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RADIOLOGY AND NUCLEAR MEDICINE (192 journals)                     

Showing 1 - 192 of 192 Journals sorted alphabetically
Abdominal Radiology     Hybrid Journal   (Followers: 20)
Academic Radiology     Hybrid Journal   (Followers: 27)
Acta Cytologica     Hybrid Journal   (Followers: 3)
Acta Radiologica     Hybrid Journal   (Followers: 2)
Acta Radiologica Open     Open Access   (Followers: 3)
Acta Radiológica Portuguesa     Open Access  
Advanced Structural and Chemical Imaging     Open Access   (Followers: 2)
Advances in Computed Tomography     Open Access   (Followers: 3)
Advances in Radiation Oncology     Open Access   (Followers: 3)
AINS - Anasthesiologie - Intensivmedizin - Notfallmedizin - Schmerztherapie     Hybrid Journal   (Followers: 5)
Alasbimn Journal     Open Access   (Followers: 2)
American Journal of Neuroradiology     Full-text available via subscription   (Followers: 20)
American Journal of Roentgenology     Full-text available via subscription   (Followers: 34)
Annals of Nuclear Medicine     Hybrid Journal   (Followers: 4)
Annals of the ICRP     Hybrid Journal   (Followers: 4)
Applied In Vitro Toxicology     Hybrid Journal   (Followers: 2)
Applied Radiology     Full-text available via subscription   (Followers: 10)
Arab Journal of Interventional Radiology     Open Access   (Followers: 1)
Asia Oceania Journal of Nuclear Medicine & Biology     Open Access   (Followers: 3)
Bangladesh Journal of Nuclear Medicine     Open Access  
Belgian Journal of Radiology     Open Access   (Followers: 3)
Biomedical Imaging and Intervention Journal     Open Access   (Followers: 4)
BJR     Hybrid Journal   (Followers: 21)
BJR | case reports     Open Access   (Followers: 6)
BMC Medical Imaging     Open Access   (Followers: 10)
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 2)
Cancer Biotherapy & Radiopharmaceuticals     Hybrid Journal   (Followers: 1)
Cancer Radiothérapie     Full-text available via subscription   (Followers: 1)
Case Reports in Radiology     Open Access   (Followers: 12)
Chinese Journal of Academic Radiology     Hybrid Journal  
Clinical and Translational Imaging     Hybrid Journal   (Followers: 1)
Clinical and Translational Radiation Oncology     Open Access   (Followers: 1)
Clinical Imaging     Hybrid Journal   (Followers: 5)
Clinical Mass Spectrometry     Open Access  
Clinical Neuroradiology     Hybrid Journal   (Followers: 3)
Clinical Nuclear Medicine     Hybrid Journal   (Followers: 2)
Clinical Radiology     Hybrid Journal   (Followers: 18)
Computerized Medical Imaging and Graphics     Hybrid Journal   (Followers: 14)
Concepts in Magnetic Resonance Part A     Open Access   (Followers: 1)
Concepts in Magnetic Resonance Part B, Magnetic Resonance Engineering     Open Access   (Followers: 1)
Concussion     Open Access  
Contemporary Diagnostic Radiology     Full-text available via subscription   (Followers: 3)
Contrast Media & Molecular Imaging     Open Access   (Followers: 2)
Critical Ultrasound Journal     Open Access   (Followers: 3)
Current Medical Imaging Reviews     Hybrid Journal   (Followers: 3)
Current Problems in Diagnostic Radiology     Hybrid Journal   (Followers: 10)
Current Radiology Reports     Hybrid Journal   (Followers: 4)
Dentomaxillofacial Radiology     Hybrid Journal   (Followers: 4)
Der Nuklearmediziner     Hybrid Journal  
Der Radiologe     Hybrid Journal   (Followers: 1)
Diagnostic and Interventional Radiology     Open Access   (Followers: 6)
Digestive Disease Interventions     Hybrid Journal  
DNA and RNA Nanotechnology     Open Access   (Followers: 6)
Egyptian Journal of Radiology and Nuclear Medicine     Open Access   (Followers: 1)
EJNMMI Radiopharmacy and Chemistry     Open Access  
Emergency Radiology     Hybrid Journal   (Followers: 8)
Endoscopic Ultrasound     Open Access  
European Journal of Nanomedicine     Hybrid Journal   (Followers: 1)
European Journal of Nuclear Medicine and Molecular Imaging     Hybrid Journal   (Followers: 12)
European Journal of Radiology     Hybrid Journal   (Followers: 21)
European Journal of Radiology Open     Open Access   (Followers: 9)
European Radiology     Hybrid Journal   (Followers: 17)
European Radiology Experimental     Open Access  
European Radiology Supplements     Hybrid Journal   (Followers: 3)
Feuillets de Radiologie     Full-text available via subscription  
Frontiers in Neurogenesis     Open Access   (Followers: 2)
IEEE Transactions on Medical Imaging     Hybrid Journal   (Followers: 28)
IEEE Transactions on Radiation and Plasma Medical Sciences     Hybrid Journal   (Followers: 3)
Imagen Diagnóstica     Full-text available via subscription  
Imaging Decisions MRI     Hybrid Journal   (Followers: 2)
Indian Journal of Nuclear Medicine     Open Access   (Followers: 2)
Indian Journal of Radiology and Imaging     Open Access   (Followers: 4)
Insights into Imaging     Open Access   (Followers: 4)
International Journal of Biomedical Nanoscience and Nanotechnology     Hybrid Journal   (Followers: 8)
International Journal of Computer Assisted Radiology and Surgery     Hybrid Journal   (Followers: 6)
International Journal of Medical Physics, Clinical Engineering and Radiation Oncology     Open Access   (Followers: 10)
International Journal of Nanomedicine     Open Access   (Followers: 2)
International Journal of Radiation Biology     Hybrid Journal   (Followers: 6)
International Journal of Radiology and Radiation Oncology     Open Access   (Followers: 1)
International Journal of Tomography & Simulation     Full-text available via subscription   (Followers: 1)
Interventional Neuroradiology     Hybrid Journal   (Followers: 1)
Interventionelle Radiologie Scan     Hybrid Journal   (Followers: 1)
Investigative Radiology     Hybrid Journal   (Followers: 10)
Iranian Journal of Medical Physics     Open Access  
Iranian Journal of Nuclear Medicine     Open Access   (Followers: 1)
Iranian Journal of Radiology     Open Access   (Followers: 5)
Japanese Journal of Radiology     Hybrid Journal   (Followers: 4)
Journal de Radiologie     Full-text available via subscription  
Journal de Radiologie Diagnostique et Interventionnelle     Full-text available via subscription   (Followers: 2)
Journal of Nanomedicine & Nanotechnology     Open Access   (Followers: 1)
Journal of Clinical Imaging Science     Open Access   (Followers: 3)
Journal of Clinical Interventional Radiology ISVIR     Open Access   (Followers: 2)
Journal of Clinical Ultrasound     Hybrid Journal   (Followers: 6)
Journal of Computer Assisted Tomography     Hybrid Journal   (Followers: 1)
Journal of Diagnostic Medical Sonography     Hybrid Journal  
Journal of Diagnostic Radiography and Imaging     Hybrid Journal   (Followers: 4)
Journal of Fetal Medicine     Hybrid Journal  
Journal of Global Radiology     Open Access   (Followers: 2)
Journal of Indian Academy of Oral Medicine and Radiology     Open Access   (Followers: 3)
Journal of Innovative Optical Health Sciences     Open Access  
Journal of Liver : Disease & Transplantation     Hybrid Journal   (Followers: 7)
Journal of Magnetic Resonance     Hybrid Journal   (Followers: 14)
Journal of Magnetic Resonance Imaging     Hybrid Journal   (Followers: 17)
Journal of Medical Imaging     Free   (Followers: 5)
Journal of Medical Imaging and Radiation Oncology     Hybrid Journal   (Followers: 3)
Journal of Medical Imaging and Radiation Sciences     Hybrid Journal   (Followers: 5)
Journal of Medical Radiation Sciences     Open Access   (Followers: 3)
Journal of Neuroradiology     Full-text available via subscription   (Followers: 4)
Journal of Nuclear Medicine     Full-text available via subscription   (Followers: 20)
Journal of Nuclear Medicine & Radiation Therapy     Open Access   (Followers: 3)
Journal of Nucleic Acids Investigation     Open Access   (Followers: 2)
Journal of Oral and Maxillofacial Radiology     Open Access   (Followers: 1)
Journal of Pediatric Neuroradiology     Hybrid Journal   (Followers: 3)
Journal of Radiation and Cancer Research     Open Access  
Journal of Radiation Research     Open Access   (Followers: 3)
Journal of Radiation Research and Applied Sciences     Open Access   (Followers: 2)
Journal of Radiobiology     Open Access   (Followers: 1)
Journal of Radiological Protection     Full-text available via subscription   (Followers: 4)
Journal of Radiology and Oncology     Open Access  
Journal of Radiology Nursing     Hybrid Journal   (Followers: 2)
Journal of Radiosurgery     Hybrid Journal   (Followers: 2)
Journal of Radiotherapy in Practice     Hybrid Journal   (Followers: 7)
Journal of the American College of Radiology     Hybrid Journal   (Followers: 10)
Journal of Thoracic Imaging     Hybrid Journal   (Followers: 3)
Journal of Vascular and Interventional Radiology     Hybrid Journal   (Followers: 13)
La radiologia medica     Hybrid Journal  
Magnetic Resonance Imaging     Hybrid Journal   (Followers: 7)
Magnetic Resonance Imaging Clinics of North America     Full-text available via subscription   (Followers: 7)
Magnetic Resonance in Medicine     Hybrid Journal   (Followers: 16)
Medical Image Analysis     Hybrid Journal   (Followers: 15)
Medical Imaging and Radiology     Open Access   (Followers: 7)
Nepalese Journal of Radiology     Open Access   (Followers: 1)
Neurographics     Free   (Followers: 3)
NeuroImage : Clinical     Open Access   (Followers: 15)
Neuroradiology     Hybrid Journal   (Followers: 9)
Neuroradiology Journal The     Hybrid Journal   (Followers: 1)
Nuclear Medicine and Biology     Hybrid Journal   (Followers: 4)
Nuclear Medicine and Molecular Imaging     Hybrid Journal   (Followers: 4)
Nuclear Medicine Communications     Hybrid Journal   (Followers: 2)
Nuclear Medicine Review     Open Access   (Followers: 2)
Nuklearmedizin / NuclearMedicine     Hybrid Journal  
Open Journal of Clinical Diagnostics     Open Access   (Followers: 1)
Open Journal of Medical Imaging     Open Access   (Followers: 1)
Open Journal of Radiology     Open Access   (Followers: 4)
Open Medical Imaging Journal     Open Access  
Oral Radiology     Hybrid Journal   (Followers: 1)
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology     Full-text available via subscription   (Followers: 9)
Pediatric Radiology     Hybrid Journal   (Followers: 6)
Physica Medica     Full-text available via subscription   (Followers: 3)
Progress in Nuclear Magnetic Resonance Spectroscopy     Full-text available via subscription   (Followers: 8)
Radiation Protection and Environment     Open Access   (Followers: 1)
Radiatsionnaya Gygiena = Radiation Hygiene     Open Access  
Radiographics     Full-text available via subscription   (Followers: 27)
Radiography     Full-text available via subscription   (Followers: 7)
Radiography Open     Open Access   (Followers: 1)
Radiología     Full-text available via subscription   (Followers: 1)
Radiología (English Edition)     Full-text available via subscription  
Radiologia Brasileira     Open Access  
Radiologic Clinics of North America     Full-text available via subscription   (Followers: 19)
Radiologie up2date     Hybrid Journal   (Followers: 1)
Radiology     Full-text available via subscription   (Followers: 42)
Radiology Case Reports     Open Access   (Followers: 2)
Radiology of Infectious Diseases     Open Access   (Followers: 3)
Radiology Research and Practice     Open Access   (Followers: 3)
Radiopraxis     Hybrid Journal  
Reports in Medical Imaging     Open Access  
Research and Reports in Nuclear Medicine     Open Access   (Followers: 1)
Research Journal of Radiology     Open Access   (Followers: 5)
Revista Argentina de Radiología / Argentinian Journal of Radiology     Open Access  
Revista Chilena de Radiologia     Open Access  
Revista Española de Medicina Nuclear e Imagen Molecular     Full-text available via subscription   (Followers: 2)
Revista Española de Medicina Nuclear e Imagen Molecular (English Edition)     Full-text available via subscription  
Revista Internacional de Ciencias Podológicas     Open Access  
Seminars in Interventional Radiology     Hybrid Journal   (Followers: 6)
Seminars in Musculoskeletal Radiology     Hybrid Journal   (Followers: 6)
Seminars in Nuclear Medicine     Hybrid Journal   (Followers: 5)
Seminars in Roentgenology     Hybrid Journal   (Followers: 3)
Seminars in Ultrasound, CT and MRI     Hybrid Journal   (Followers: 9)
Shadows : The New Zealand Journal of Medical Radiation Technology     Full-text available via subscription   (Followers: 2)
Skeletal Radiology     Hybrid Journal   (Followers: 10)
Solid State Nuclear Magnetic Resonance     Hybrid Journal   (Followers: 3)
South African Journal of Radiology     Open Access   (Followers: 1)
South African Radiographer     Full-text available via subscription  
Sri Lanka Journal of Radiology     Open Access  
Surgical and Radiologic Anatomy     Hybrid Journal   (Followers: 6)
Techniques in Vascular and Interventional Radiology     Full-text available via subscription   (Followers: 8)
Topics in Magnetic Resonance Imaging     Hybrid Journal   (Followers: 3)
Ultraschall in der Medizin - European Journal of Ultrasound     Hybrid Journal   (Followers: 2)
Ultrasonic Imaging     Hybrid Journal   (Followers: 2)
Ultrasound Quarterly     Hybrid Journal   (Followers: 2)
West African Journal of Radiology     Open Access   (Followers: 1)
World Journal of Nuclear Medicine     Open Access   (Followers: 2)


Similar Journals
Journal Cover
NeuroImage : Clinical
Journal Prestige (SJR): 2.153
Citation Impact (citeScore): 5
Number of Followers: 15  

  This is an Open Access Journal Open Access journal
ISSN (Online) 2213-1582
Published by Elsevier Homepage  [3203 journals]
  • Connectivity derived thalamic segmentation: Separating myth from reality

    • Abstract: Publication date: Available online 20 March 2019Source: NeuroImage: ClinicalAuthor(s): Harith Akram, Marwan Hariz, Ludvic Zrinzo
  • Complexities of connectivity-based DBS targeting: Rebirth of the debate on
           thalamic and subthalamic treatment of tremor

    • Abstract: Publication date: Available online 20 March 2019Source: NeuroImage: ClinicalAuthor(s): Erik H. Middlebrooks, Sanjeet S. Grewal, Vanessa M. Holanda
  • Disentangling motor planning and motor execution in unmedicated de novo
           Parkinson's disease patients: An fMRI study

    • Abstract: Publication date: Available online 19 March 2019Source: NeuroImage: ClinicalAuthor(s): Jason A. Martin, Nadine Zimmermann, Lukas Scheef, Jakob Jankowski, Sebastian Paus, Hans H. Schild, Thomas Klockgether, Henning BoeckerAbstractMany studies have used functional magnetic resonance imaging to unravel the neuronal underpinnings of motor system abnormalities in Parkinson's disease, indicating functional inhibition at the level of basal ganglia-thalamo-cortical motor networks. The study aim was to extend the characterization of functional motor changes in Parkinson's Disease by dissociating between two phases of action (i.e. motor planning and motor execution) during an automated unilateral finger movement sequence with the left and right hand, separately. In essence, we wished to identify neuronal dysfunction and potential neuronal compensation before (planning) and during (execution) automated sequential motor behavior in unmedicated early stage Parkinson's Disease patients. Twenty-two Parkinson's Disease patients (14 males; 53 ± 11 years; Hoehn and Yahr score 1.4 ± 0.6; UPDRS (part 3) motor score 16 ± 6) and 22 healthy controls (14 males; 49 ± 12 years) performed a pre-learnt four finger sequence (index, ring, middle and little finger, in order), either self-initiated (FREE) or externally triggered (REACT), within an 8-second time window. Findings were most pronounced during FREE with the clinically most affected side, where motor execution revealed significant underactivity of contralateral primary motor cortex, contralateral posterior putamen (sensorimotor territory), ipsilateral anterior cerebellum / cerebellar vermis, along with underactivity in supplementary motor area (based on ROI analyses only), corroborating previous findings in Parkinson's Disease. During motor planning, Parkinson's Disease patients showed a significant relative overactivity in dorsolateral prefrontal cortex (DLPFC), suggesting a compensatory overactivity. To a variable extent this relative overactivity in the DLPFC went along with a relative overactivity in the precuneus and the ipsilateral anterior cerebellum/cerebellar vermis Our study illustrates that a refined view of disturbances in motor function and compensatory processes can be gained from experimental designs that try to dissociate motor planning from motor execution, emphasizing that compensatory mechanisms are triggered in Parkinson's Disease when voluntary movements are conceptualized for action.
  • Resting state connectivity best predicts alcohol use severity in moderate
           to heavy alcohol users

    • Abstract: Publication date: Available online 19 March 2019Source: NeuroImage: ClinicalAuthor(s): Samantha J. Fede, Erica N. Grodin, Sarah F. Dean, Nancy Diazgranados, Reza MomenanAbstractBackgroundIn the United States, 13% of adults are estimated to have alcohol use disorder (AUD). Most studies examining the neurobiology of AUD treat individuals with this disorder as a homogeneous group; however, the theories of the neurocircuitry of AUD call for a quantitative and dimensional approach. Previous imaging studies find differences in brain structure, function, and resting-state connectivity in AUD, but few use a multimodal approach to understand the association between severity of alcohol use and the brain differences.MethodsAdults (ages 22–60) with problem drinking patterns (n = 59) completed a behavioral and neuroimaging protocol at the National Institutes of Health. Alcohol severity was quantified with the Alcohol Use Disorders Identification Test (AUDIT). In a 3 T MRI scanner, participants underwent a structural MRI as well as resting-state, monetary incentive delay, and face matching fMRI scans. Machine learning was applied and trained using the neural data from MRI scanning. The model was tested for generalizability in a validation sample (n = 24).ResultsThe resting state-connectivity features model best predicted AUD severity in the naïve sample, compared to task fMRI, structural MRI, combined MRI features, or demographic features. Network connectivity features between salience network, default mode network, executive control network, and sensory networks explained 33% of the variance associated with AUDIT in this model.ConclusionsThese findings indicate that the neural effects of AUD vary according to severity. Our results emphasize the utility of resting state fMRI as a neuroimaging biomarker for quantitative clinical evaluation of AUD.
  • Modeling grey matter atrophy as a function of time, aging or cognitive
           decline show different anatomical patterns in Alzheimer's disease

    • Abstract: Publication date: Available online 19 March 2019Source: NeuroImage: ClinicalAuthor(s): Ellen Dicks, Lisa Vermunt, Wiesje M. van der Flier, Pieter Jelle Visser, Frederik Barkhof, Philip Scheltens, Betty M. Tijms, for the Alzheimer's Disease Neuroimaging InitiativeAbstractBackgroundGrey matter (GM) atrophy in Alzheimer's disease (AD) is most commonly modeled as a function of time. However, this approach does not take into account inter-individual differences in initial disease severity or changes due to aging. Here, we modeled GM atrophy within individuals across the AD clinical spectrum as a function of time, aging and MMSE, as a proxy for disease severity, and investigated how these models influence estimates of GM atrophy.MethodsWe selected 523 individuals from ADNI (100 preclinical AD, 288 prodromal AD, 135 CE dementia) with abnormal baseline amyloid PET/CSF and ≥1 year of MRI follow-up. We calculated total and 90 regional GM volumes for 2281 MRI scans (median [IQR]; 4 [3–5] scans per individual over 2 [1.6–4] years) and used linear mixed models to investigate atrophy as a function of time, aging and decline on MMSE. Analyses included clinical stage as interaction with the predictor and were corrected for baseline age, sex, education, field strength and total intracranial volume. We repeated analyses for a sample of participants with normal amyloid (n = 387) to assess whether associations were specific for amyloid pathology.ResultsUsing time or aging as predictors, amyloid abnormal participants annually declined −1.29 ± 0.08 points and − 0.28 ± 0.03 points respectively on the MMSE and −12.23 ± 0.47 cm3 and −8.87 ± 0.34 respectively in total GM volume (p 
  • Personalized transcranial alternating current stimulation (tACS) and
           physical therapy to treat motor and cognitive symptoms in Parkinson's
           disease: A randomized cross-over trial

    • Abstract: Publication date: Available online 18 March 2019Source: NeuroImage: ClinicalAuthor(s): Alessandra Del Felice, Leonora Castiglia, Emanuela Formaggio, Manuela Cattelan, Bruno Scarpa, Paolo Manganotti, Elena Tenconi, Stefano MasieroAbstractAbnormal cortical oscillations are markers of Parkinson's Disease (PD). Transcranial alternating current stimulation (tACS) can modulate brain oscillations and possibly impact on behaviour. Mapping of cortical activity (prevalent oscillatory frequency and topographic scalp distribution) may provide a personalized neurotherapeutic target and guide non-invasive brain stimulation. This is a cross-over, double blinded, randomized trial. Electroencephalogram (EEG) from participants with PD referred to Specialist Clinic, University Hospital, were recorded. TACS frequency and electrode position were individually defined based on statistical comparison of EEG power spectra maps with normative data from our laboratory. Stimulation frequency was set according to the EEG band displaying higher power spectra (with beta excess on EEG map, tACS was set at 4 Hz; with theta excess, tACS was set at 30 Hz). Participants were randomized to tACS or random noise stimulation (RNS), 5 days/week for 2-weeks followed by ad hoc physical therapy. EEG, motor (Unified Parkinson's Disease Rating Scale-motor: UPDRS III), neuropsychological (frontal, executive and memory tests) performance and mood were measured before (T0), after (T1) and 4-weeks after treatment (T2). A linear model with random effects and Wilcoxon test were used to detect differences.Main results include a reduction of beta rhythm in theta-tACS vs. RNS group at T1 over right sensorimotor area (p = .014) and left parietal area (p = .010) and at T2 over right sensorimotor area (p = .004) and left frontal area (p = .039). Bradykinesia items improved at T1 (p = .002) and T2 (p = .047) compared to T0 in the tACS group. In the tACS group the Montréal Cognitive Assessment (MoCA) improved at T2 compared with T1 (p = .049).Individualized tACS in PD improves motor and cognitive performance. These changes are associated with a reduction of excessive fast EEG oscillations.
  • Impaired hippocampal development and outcomes in very preterm infants with
           perinatal brain injury

    • Abstract: Publication date: Available online 18 March 2019Source: NeuroImage: ClinicalAuthor(s): Jennifer M. Strahle, Regina L. Triplett, Dimitrios Alexopoulos, Tara A. Smyser, Cynthia E. Rogers, David D. Limbrick, Christopher D. SmyserAbstractPreterm infants are at high risk for brain injury during the perinatal period. Intraventricular hemorrhage and periventricular leukomalacia, the two most common patterns of brain injury in prematurely-born children, are associated with poor neurodevelopmental outcomes. The hippocampus is known to be critical for learning and memory; however, it remains unknown how these forms of brain injury affect hippocampal growth and how the resulting alterations in hippocampal development relate to childhood outcomes. To investigate these relationships, hippocampal segmentations were performed on term equivalent MRI scans from 55 full-term infants, 85 very preterm infants (born ≤32 weeks gestation) with no to mild brain injury and 73 very preterm infants with brain injury (e.g., grade III/IV intraventricular hemorrhage, post-hemorrhagic hydrocephalus, cystic periventricular leukomalacia). Infants then underwent standardized neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, 3rd edition at age 2 years, corrected for prematurity. To delineate the effects of brain injury on early hippocampal development, hippocampal volumes were compared across groups and associations between neonatal volumes and neurodevelopmental outcomes at age 2 years were explored. Very preterm infants with brain injury had smaller hippocampal volumes at term equivalent age compared to term and very preterm infants with no to mild injury, with the smallest hippocampi among those with grade III/IV intraventricular hemorrhage and post-hemorrhagic hydrocephalus. Further, larger ventricle size was associated with smaller hippocampal size. Smaller hippocampal volumes were related to worse motor performance at age 2 years across all groups. In addition, smaller hippocampal volumes in infants with brain injury were correlated with impaired cognitive scores at age 2 years, a relationship specific to this group. Consistent with our preclinical findings, these findings demonstrate that perinatal brain injury is associated with hippocampal size in preterm infants, with smaller volumes related to domain-specific neurodevelopmental impairments in this high-risk clinical population.
  • Myelin water imaging of moderate to severe diffuse traumatic brain injury

    • Abstract: Publication date: Available online 16 March 2019Source: NeuroImage: ClinicalAuthor(s): Joon Yul Choi, Tessa Hart, John Whyte, Amanda R. Rabinowitz, Se-Hong Oh, Jongho Lee, Junghoon J. KimTraumatic axonal injury (TAI), a signature injury of traumatic brain injury (TBI), is increasingly known to involve myelin damage. The objective of this study was to demonstrate the clinical relevance of myelin water imaging (MWI) by first quantifying changes in myelin water after TAI and then correlating those changes with measures of injury severity and neurocognitive performance. Scanning was performed at 3 months post-injury in 22 adults with moderate to severe diffuse TBI and 30 demographically matched healthy controls using direct visualization of short transverse component (ViSTa) MWI. Fractional anisotropy (FA) and radial diffusivity (RD) were also obtained using diffusion tensor imaging. Duration of post-traumatic amnesia (PTA) and cognitive processing speed measured by the Processing Speed Index (PSI) from Wechsler Adult Intelligence Scale-IV, were assessed. A between-group comparison using Tract-Based Spatial Statistics revealed that there was a widespread reduction of apparent myelin water fraction (aMWF) in TBI, consistent with neuropathology involving TAI. The group difference map of aMWF yielded topography that was different from FA and RD. Importantly, aMWF demonstrated significant associations with PTA (r = −0.564, p = .006) and PSI (r = 0.452, p = .035). In conclusion, reduced myelin water, quantified by ViSTa MWI, is prevalent in moderate-to-severe diffuse TBI and could serve as a potential biomarker for injury severity and prediction of clinical outcomes.Graphical abstractUnlabelled Image
  • Thalamo-cortical network hyperconnectivity in preclinical progranulin
           mutation carriers

    • Abstract: Publication date: Available online 16 March 2019Source: NeuroImage: ClinicalAuthor(s): Suzee E. Lee, Ana C. Sias, Eena L. Kosik, Taru M. Flagan, Jersey Deng, Stephanie A. Chu, Jesse A. Brown, Anna A. Vidovszky, Eliana Marisa Ramos, Maria Luisa Gorno-Tempini, Anna M. Karydas, Giovanni Coppola, Dan H. Geschwind, Rosa Rademakers, Bradley F. Boeve, Adam L. Boxer, Howard J. Rosen, Bruce L. Miller, William W. SeeleyAbstractMutations in progranulin (GRN) cause heterogeneous clinical syndromes, including behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), corticobasal syndrome (CBS) and Alzheimer-type dementia (AD-type dementia). Human studies have shown that presymptomatic GRN carriers feature reduced connectivity in the salience network, a system targeted in bvFTD. Mice with homozygous deletion of GRN, in contrast, show thalamo-cortical hypersynchrony due to aberrant pruning of inhibitory synapses onto thalamo-cortical projection neurons. No studies have systematically explored the intrinsic connectivity networks (ICNs) targeted by the four GRN-associated clinical syndromes, or have forged clear links between human and mouse model findings. We compared 17 preclinical GRN carriers (14 “presymptomatic” clinically normal and three “prodromal” with mild cognitive symptoms) to healthy controls to assess for differences in cognitive testing and gray matter volume. Using task-free fMRI, we assessed connectivity in the salience network, a non-fluent variant primary progressive aphasia network (nfvPPA), the perirolandic network (CBS), and the default mode network (AD-type dementia). GRN carriers and controls showed similar performance on cognitive testing. Although carriers showed little evidence of brain atrophy, markedly enhanced connectivity emerged in all four networks, and thalamo-cortical hyperconnectivity stood out as a unifying feature. Voxelwise assessment of whole brain degree centrality, an unbiased graph theoretical connectivity metric, confirmed thalamic hyperconnectivity. These results show that human GRN disease and the prevailing GRN mouse model share a thalamo-cortical network hypersynchrony phenotype. Longitudinal studies will determine whether this network physiology represents a compensatory response as carriers approach symptom onset, or an early and sustained preclinical manifestation of lifelong progranulin haploinsufficiency.
  • Unchanged type 1 metabotropic glutamate receptor availability in patients
           with Alzheimer's disease: A study using 11C-ITMM positron emission

    • Abstract: Publication date: Available online 16 March 2019Source: NeuroImage: ClinicalAuthor(s): Kenji Ishibashi, Yoshiharu Miura, Jun Toyohara, Kiichi Ishiwata, Kenji IshiiAbstractImaging of type 1 metabotropic glutamate receptor (mGluR1) has recently become possible using positron emission tomography (PET). To date, little evidence exists on the role of mGluR1 in the pathophysiology of Alzheimer's disease (AD). We aimed to examine mGluR1 availability in patients with AD. Ten patients with AD (78.9 ± 5.9 years) and 12 age-matched volunteers (74.6 ± 2.6 years) underwent PET using an mGluR1 radiotracer. All patients were anti-dementia drug-naive. Volumes-of-interest were placed on the anterior and posterior lobes and vermis in the cerebellum and frontal, parietal, and temporal cortices. The binding potential (BPND) was calculated to estimate mGluR1 availability, and partial volume correction was applied to the BPND values. Mini Mental State Examination (MMSE) scores were also obtained (22.0 ± 4.8). No significant difference was observed in BPND between the AD and control groups in the anterior lobe (p = .30), posterior lobe (p = .95), vermis (p = .96), frontal cortex (p = .61), parietal cortex (p = .59), or temporal cortex (p = .27). No significant correlation was observed between BPND and MMSE scores in the anterior lobe (p = .59), posterior lobe (p = .35), vermis (p = .92), frontal cortex (p = .78), parietal cortex (p = .83), or temporal cortex (p = .82). In conclusions, this study suggests that mGluR1 availability is unchanged in the relatively early stage of AD. However, because regional mGluR1 availability may change with the progression of AD, further longitudinal follow-up is necessary.
  • Altered grey matter volume, perfusion and white matter integrity in very
           low birthweight adults

    • Abstract: Publication date: Available online 15 March 2019Source: NeuroImage: ClinicalAuthor(s): Maddie J. Pascoe, Tracy R. Melzer, L. John Horwood, Lianne J. Woodward, Brian A. DarlowAbstractThis study examined the long-term effects of being born very-low-birth-weight (VLBW,
  • Erratum to 'The effect of tDCS on functional connectivity in primary
           progressive aphasia'

    • Abstract: Publication date: Available online 14 March 2019Source: NeuroImage: ClinicalAuthor(s):
  • “The effect of tDCS on functional connectivity in primary progressive
           aphasia” NeuroImage: Clinical, volume 19 (2018), pages 703–715

    • Abstract: Publication date: Available online 14 March 2019Source: NeuroImage: ClinicalAuthor(s): Bronte N. Ficek, Zeyi Wang, Yi Zhao, Kimberly T. Webster, John E. Desmond, Argye E. Hillis, Constantine Frangakis, Andreia Vasconcellos Faria, Brian Caffo, Kyrana TsapkiniAbstractTranscranial direct current stimulation (tDCS) is an innovative technique recently shown to improve language outcomes even in neurodegenerative conditions such as primary progressive aphasia (PPA), but the underlying brain mechanisms are not known. The present study tested whether the additional language gains with repetitive tDCS (over sham) in PPA are caused by changes in functional connectivity between the stimulated area (the left inferior frontal gyrus (IFG)) and the rest of the language network.We scanned 24 PPA participants (11 female) before and after language intervention (written naming/spelling) with a resting-state fMRI sequence and compared changes before and after three weeks of tDCS or sham coupled with language therapy. We correlated changes in the language network as well as in the default mode network (DMN) with language therapy outcome measures (letter accuracy in written naming).Significant tDCS effects in functional connectivity were observed between the stimulated area and other language network areas and between the language network and the DMN. TDCS over the left IFG lowered the connectivity between the above pairs. Changes in functional connectivity correlated with improvement in language scores (letter accuracy as a proxy for written naming) evaluated before and after therapy.These results suggest that one mechanism for anodal tDCS over the left IFG in PPA is a decrease in functional connectivity (compared to sham) between the stimulated site and other posterior areas of the language network. These results are in line with similar decreases in connectivity observed after tDCS over the left IFG in aging and other neurodegenerative conditions.
  • Visual network alterations in brain functional connectivity in chronic low
           back pain: A resting state functional connectivity and machine learning

    • Abstract: Publication date: Available online 14 March 2019Source: NeuroImage: ClinicalAuthor(s): Wei Shen, Yiheng Tu, Randy L. Gollub, Ana Ortiz, Vitaly Napadow, Siyi Yu, Georgia Wilson, Joel Park, Courtney Lang, Minyoung Jung, Jessica Gerber, Ishtiaq Mawla, Suk-Tak Chan, Ajay D. Wasan, Robert R. Edwards, Ted Kaptchuk, Shasha Li, Bruce Rosen, Jian KongAbstractChronic low back pain (cLBP) is associated with wide-spread brain function and structural changes. This study aims to investigate the resting state functional connectivity (rsFC) changes of visual networks in cLBP patients and the feasibility of distinguishing cLBP patients from healthy controls using machine learning methods. cLBP (n = 90) and control individuals (n = 74) were enrolled and underwent resting-state BOLD fMRI scans. Primary, dorsal, and ventral visual networks derived from independent component analysis were used as regions of interest to compare the resting state functional connectivity changes between the cLBP patients and healthy controls. We then applied a support vector machine classifier to distinguish the cLBP patients and control individuals. These results were further verified in a new cohort of subjects. We found that the functional connectivity between the primary visual network and the somatosensory & motor areas and MCC/ACC area were significantly enhanced in cLBP patients. The rsFC between the primary visual network and S1 was negatively associated with duration of cLBP. In addition, we found that the rsFC of the visual network could achieve a classification accuracy of 79.3% in distinguishing cLBP patients from HCs, and these results were further validated in an independent cohort of subjects (accuracy = 67.6%). Our results demonstrate significant changes in the rsFC of the visual networks in cLBP patients. We speculate these alternations may represent an adaptation/self-adjustment mechanism and cross-model interaction between the visual, somatosensory, motor, attention, and salient networks in response to persistent cLBP. Elucidating the role of the visual networks in cLBP may shed light on the pathophysiology and development of chronic low back pain.
  • Multi-atlas based detection and localization (MADL) for location-dependent
           quantification of white matter hyperintensities

    • Abstract: Publication date: Available online 13 March 2019Source: NeuroImage: ClinicalAuthor(s): Dan Wu, Marilyn Albert, Anja Soldan, Corinne Pettigrew, Kenichi Oishi, Yusuke Tomogane, Chenfei Ye, Ting Ma, Michael I. Miller, Susumu MoriAbstractThe extent and spatial location of white matter hyperintensities (WMH) on brain MRI may be relevant to the development of cognitive decline in older persons. Here, we introduce a new method, known as the Multi-atlas based Detection and Localization (MADL), to evaluate WMH on fluid-attenuated inversion recovery (FLAIR) data. This method simultaneously parcellates the whole brain into 143 structures and labels hyperintense areas within each WM structure. First, a multi-atlas library was established with FLAIR data of normal elderly brains; and then a multi-atlas fusion algorithm was developed by which voxels with locally abnormal intensities were detected as WMH. At the same time, brain segmentation maps were generated from the multi-atlas fusion process to determine the anatomical location of WMH. Areas identified using the MADL method agreed well with manual delineation, with an interclass correlation of 0.97 and similarity index (SI) between 0.55 and 0.72, depending on the total WMH load. Performance was compared to other state-of-the-art WMH detection methods, such as BIANCA and LST. MADL-based analyses of WMH in an older population revealed a significant association between age and WMH load in deep WM but not subcortical WM. The findings also suggested increased WMH load in selective brain regions in subjects with mild cognitive impairment compared to controls, including the inferior deep WM and occipital subcortical WM. The proposed MADL approach may facilitate location-dependent characterization of WMH in older individuals with memory impairment.
  • Attention network dysfunction underlies memory impairment in posterior
           cortical atrophy

    • Abstract: Publication date: Available online 13 March 2019Source: NeuroImage: ClinicalAuthor(s): Michele Veldsman, Giovanna Zamboni, Christopher Butler, Samrah AhmedAbstractAccumulating evidence suggests that memory is impaired in posterior cortical atrophy (PCA), alongside the early and defining visual disorder. The posterior parietal cortex is a key region of pathology in PCA and memory impairment may be the result of dysfunction of parietally dependent network function rather than the medial temporal lobe dependent dysfunction that defines the storage deficits in typical Alzheimer's disease.We assessed episodic memory performance and network function in16 PCA patients and 19 healthy controls who underwent structural and resting-state functional MRI and neuropsychological testing. Memory was assessed using the Free and Cued Selective Reminding Test (FCSRT), a sensitive test of episodic memory storage and retrieval. We examined correlations between memory performance and functional connectivity in the dorsal attention (DAN) and default mode network (DMN).Immediate recall on the FCSRT was relatively preserved in PCA patients. Total recall performance was impaired in patients relative to healthy controls and performance benefitted from retrieval cues. In patients only, disrupted connectivity in the DAN, but not the DMN, was associated with total recall.Memory impairment may arise from disruption to the dorsal attention network, subserved by the dorsal posterior parietal cortex, a key region of pathology in PCA, rather than classic medial temporal lobe memory circuitry.We propose that functional dysconnectivity in attentional circuits underpins memory impairment in PCA.
  • Association of short-term cognitive decline and MCI-to-AD dementia
           conversion with CSF, MRI, amyloid- and 18F-FDG-PET imaging

    • Abstract: Publication date: Available online 13 March 2019Source: NeuroImage: ClinicalAuthor(s): Julie Ottoy, Ellis Niemantsverdriet, Jeroen Verhaeghe, Ellen De Roeck, Hanne Struyfs, Charisse Somers, Leonie Wyffels, Sarah Ceyssens, Sara Van Mossevelde, Tobi Van den Bossche, Christine Van Broeckhoven, Annemie Ribbens, Maria Bjerke, Sigrid Stroobants, Sebastiaan Engelborghs, Steven StaelensAbstractDisease-modifying treatment trials are increasingly advanced to the prodromal or preclinical phase of Alzheimer's disease (AD), and inclusion criteria are based on biomarkers rather than clinical symptoms. Therefore, it is of great interest to determine which biomarkers should be combined to accurately predict conversion from mild cognitive impairment (MCI) to AD dementia. However, up to date, only few studies performed a complete A/T/N subject characterization using each of the CSF and imaging markers, or they only investigated long-term (≥ 2 years) prognosis. This study aimed to investigate the association between cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), amyloid- and 18F-FDG positron emission tomography (PET) measures at baseline, in relation to cognitive changes and conversion to AD dementia over a short-term (12-month) period. We included 13 healthy controls, 49 MCI and 16AD dementia patients with a clinical-based diagnosis and a complete A/T/N characterization at baseline. Global cortical amyloid-β (Aβ) burden was quantified using the 18F-AV45 standardized uptake value ratio (SUVR) with two different reference regions (cerebellar grey and subcortical white matter), whereas metabolism was assessed based on 18F-FDG SUVR. CSF measures included Aβ1–42, Aβ1–40, T-tau, P-tau181 and their ratios, and MRI markers included hippocampal volumes (HV), white matter hyperintensities, and cortical grey matter volumes. Cognitive functioning was measured by MMSE and RBANS index scores. All statistical analyses were corrected for age, sex, education, and APOE ε4 genotype. As a result, faster cognitive decline was most strongly associated with hypometabolism (posterior cingulate) and smaller hippocampal volume (e.g., Δstory recall: β = +0.43 [p 
  • Mechanisms of functional compensation, delineated by eigenvector
           centrality mapping, across the pathophysiological continuum of
           Alzheimer’s disease

    • Abstract: Publication date: Available online 12 March 2019Source: NeuroImage: ClinicalAuthor(s): Stavros Skouras, Carles Falcon, Alan Tucholka, Lorena Rami, Raquel Sanchez-Valle, Albert Lladó, Juan D. Gispert, José Luís MolinuevoAbstractBackgroundMechanisms of functional compensation throughout the progression of Alzheimer's disease (AD) remain largely underspecified. By investigating functional connectomics in relation to cerebrospinal fluid (CSF) biomarkers across the pathophysiological continuum of AD, we identify disease-stage-specific patterns of functional degradation and functional compensation.MethodsData from a sample of 96 participants, comprised of 49 controls, 11 preclinical AD subjects, 21 patients with mild cognitive impairment (MCI) due to AD and 15 patients with mild dementia due to AD, were analyzed. CSF ratio of phosphorylated tau protein over amyloid beta peptide 42 (p-tau/Aβ42) was computed and used as a marker of progression along the AD continuum. Whole-brain, voxel-wise eigenvector centrality mapping (ECM) was computed from resting-state fMRI and regression against p-tau/Aβ42 was performed. Surviving clusters were used as data-derived seeds in functional connectivity analyses and investigated in relation to memory performance scores (delayed free recall and memory alteration) via complementary regression models. To investigate disease-stage-specific effects, the whole-brain connectivity maps of each cluster were compared between progressive groups.ResultsCentrality in BA39-BA19 is negatively correlated with the p-tau/Aβ42 ratio and associated to memory function impairment across the AD continuum. The thalamus, anterior cingulate (ACC), midcingulate (MCC) and posterior cingulate cortex (PCC) show the opposite effect. The MCC shows the highest increase in centrality as memory performance decays. In the asymptomatic preclinical group, MCC shows reduced functional connectivity (FC) with the left hippocampus and stronger FC with the precuneus (PCu). Additionally, BA39-BA19 show reduced FC with the cerebellum, compensated by stronger FC between cerebellum and PCC. In the MCI group, PCC shows reduced FC with PCu, compensated by stronger FC with the left pars orbitalis, insula and temporal pole, as well as by stronger FC of MCC with its anterior and ventral neighboring areas and the cerebellum. In the mild dementia group, extensive functional decoupling occurs across the entire autobiographical memory network and functional resilience ensues in posterior regions and the cerebellum.ConclusionsFunctional decoupling in preclinical AD occurs predominantly in AD-vulnerable regions (e.g. hippocampus, cerebellar lobule VI / Crus I, visual cortex, frontal pole) and coupling between MCC and PCu, as well as between PCC and cerebellum, emerge as intrinsic mechanisms of functional compensation. At the MCI stage, the PCu can no longer compensate for hippocampal decoupling, but the compensatory role of the MCC and PCC ensue into the stage of dementia. These findings shed light on the neural mechanisms of functional compensation across the pathophysiological continuum of AD, highlighting the compensatory roles of several key brain areas.
  • CACNA1C risk variant affects microstructural connectivity of the

    • Abstract: Publication date: Available online 12 March 2019Source: NeuroImage: ClinicalAuthor(s): Katharina Koch, Sophia Stegmaier, Lena Schwarz, Michael Erb, Mara Thomas, Klaus Scheffler, Dirk Wildgruber, Vanessa Nieratschker, Thomas EthoferAbstractDeficits in perception of emotional prosody have been described in patients with affective disorders at behavioral and neural level. In the current study, we use an imaging genetics approach to examine the impact of CACNA1C, one of the most promising genetic risk factors for psychiatric disorders, on prosody processing on a behavioral, functional and microstructural level. Using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) we examined key areas involved in prosody processing, i.e. the amygdala and voice areas, in a healthy population. We found stronger activation to emotional than neutral prosody in the voice areas and the amygdala, but CACNA1C rs1006737 genotype had no influence on fMRI activity. However, significant microstructural differences (i.e. mean diffusivity) between CACNA1C rs1006737 risk allele carriers and non carriers were found in the amygdala, but not the voice areas. These modifications in brain architecture associated with CACNA1C might reflect a neurobiological marker predisposing to affective disorders and concomitant alterations in emotion perception.
  • Spectral entropy indicates electrophysiological and hemodynamic changes in
           drug-resistant epilepsy – A multimodal MREG study

    • Abstract: Publication date: Available online 12 March 2019Source: NeuroImage: ClinicalAuthor(s): H. Helakari, J. Kananen, N. Huotari, L. Raitamaa, T. Tuovinen, V. Borchardt, A. Rasila, V. Raatikainen, T. Starck, T. Hautaniemi, T. Myllylä, O. Tervonen, S. Rytky, T. Keinänen, V. Korhonen, V. Kiviniemi, H. AnsakorpiAbstractObjectiveEpilepsy causes measurable irregularity over a range of brain signal frequencies, as well as autonomic nervous system functions that modulate heart and respiratory rate variability. Imaging dynamic neuronal signals utilizing simultaneously acquired ultra-fast 10 Hz magnetic resonance encephalography (MREG), direct current electroencephalography (DC-EEG), and near-infrared spectroscopy (NIRS) can provide a more comprehensive picture of human brain function. Spectral entropy (SE) is a nonlinear method to summarize signal power irregularity over measured frequencies. SE was used as a joint measure to study whether spectral signal irregularity over a range of brain signal frequencies based on synchronous multimodal brain signals could provide new insights in the neural underpinnings of epileptiform activity.MethodsTen patients with focal drug-resistant epilepsy (DRE) and ten healthy controls (HC) were scanned with 10 Hz MREG sequence in combination with EEG, NIRS (measuring oxygenated, deoxygenated, and total hemoglobin: HbO, Hb, and HbT, respectively), and cardiorespiratory signals. After pre-processing, voxelwise SEMREG was estimated from MREG data. Different neurophysiological and physiological subfrequency band signals were further estimated from MREG, DC-EEG, and NIRS: fullband (0–5 Hz, FB), near FB (0.08–5 Hz, NFB), brain pulsations in very-low (0.009–0.08 Hz, VLFP), respiratory (0.12–0.4 Hz, RFP), and cardiac (0.7–1.6 Hz, CFP) frequency bands. Global dynamic fluctuations in MREG and NIRS were analyzed in windows of 2 min with 50% overlap.ResultsRight thalamus, cingulate gyrus, inferior frontal gyrus, and frontal pole showed significantly higher SEMREG in DRE patients compared to HC. In DRE patients, SE of cortical Hb was significantly reduced in FB (p = .045), NFB (p = .017), and CFP (p = .038), while both HbO and HbT were significantly reduced in RFP (p = .038, p = .045, respectively). Dynamic SE of HbT was reduced in DRE patients in RFP during minutes 2 to 6. Fitting to the frontal MREG and NIRS results, DRE patients showed a significant increase in SEEEG in FB in fronto-central and parieto-occipital regions, in VLFP in parieto-central region, accompanied with a significant decrease in RFP in frontal pole and parietal and occipital (O2, Oz) regions.ConclusionThis is the first study to show altered spectral entropy from synchronous MREG, EEG, and NIRS in DRE patients. Higher SEMREG in DRE patients in anterior cingulate gyrus together with SEEEG and SENIRS results in 0.12–0.4 Hz can be linked to altered parasympathetic function and respiratory pulsations in the brain. Higher SEMREG in thalamus in DRE patients is connected to disturbances in anatomical and functional connections in epilepsy. Findings suggest that spectral irregularity of both electrophysiological and hemodynamic signals are altered in specific way depending on the physiological frequency range.
  • Attenuated mismatch negativity in patients with first-episode
           antipsychotic-naive schizophrenia using a source-resolved method

    • Abstract: Publication date: Available online 12 March 2019Source: NeuroImage: ClinicalAuthor(s): M. Randau, B. Oranje, M. Miyakoshi, S. Makeig, B. Fagerlund, B. Glenthøj, N. BakAbstractBackgroundMismatch negativity (MMN) is a measure of pre-attentive auditory information processing related to change detection. Traditional scalp-level EEG methods consistently find attenuated MMN in patients with chronic but not first-episode schizophrenia. In the current paper, we use a source-resolved method to assess MMN and hypothesize that more subtle changes can be identified with this analysis method.MethodFifty-six first-episode antipsychotic-naïve schizophrenia (FEANS) patients (31 males, 25 females, mean age 24.6) and 64 matched controls (37 males, 27 females, mean age 24.8) were assessed for duration-, frequency- and combined-type MMN and P3a as well as 4 clinical, 3 cognitive and 3 psychopathological measures. To evaluate and correlate MMN at source-level, independent component analysis (ICA) was applied to the continuous EEG data to derive equivalent current dipoles which were clustered into 19 clusters based on cortical location.ResultsNo scalp channel group MMN or P3a amplitude differences were found. Of the localized clusters, several were in or near brain areas previously suggested to be involved in the MMN response, including frontal and anterior cingulate cortices and superior temporal and inferior frontal gyri. For duration deviants, MMN was attenuated at the right superior temporal gyrus in patients compared to healthy controls (p = 0.01), as was P3a at the superior frontal cortex (p = 0.01). No individual patient correlations with clinical, cognitive, or psychopathological measures survived correction for multiple comparisons.ConclusionAttenuated source-localized MMN and P3a peak contributions can be identified in FEANS patients using a method based on independent component analysis (ICA). This indicates that deficits in pre-attentive auditory information processing are present at this early stage of schizophrenia and are not the result of disease chronicity or medication. This is to our knowledge the first study on FEANS patients using this more detailed method.
  • Longitudinal analysis of structural changes following unilateral focused
           ultrasound thalamotomy

    • Abstract: Publication date: Available online 12 March 2019Source: NeuroImage: ClinicalAuthor(s): Francesco Sammartino, Fang-Cheng Yeh, Vibhor KrishnaAbstractObjectiveFocused ultrasound thalamotomy is an emerging treatment for essential tremor, and it is ideal for studying reorganization the in human brain after acute injury because it creates a controlled thalamic ablation without breaching the cortex. However, there is not yet a metric capable of detecting microstructural changes in the presence of acute phase edema with good sensitivity in the chronic phase, when the lesion boundaries become inconspicuous.MethodsWe prospectively studied microstructural changes at the lesion site using generalized q-sampling imaging with restricted diffusion imaging. We obtained diffusion-weighted MRI scans preoperatively, 1 day after (n = 18), and 1 year after (n = 9) focused ultrasound thalamotomy. The restricted diffusion imaging maps were compared at the group level, controlling for improvement in contralateral hand tremor.ResultsThe restricted diffusion imaging metric significantly increased in the 1 day post images, and the area with restricted diffusivity extended beyond the lesion boundaries identified on T2-weighted imaging. Two distinct zones of microstructural changes were identified, and the lesion area was identifiable at 1 year. The anterior and medial aspects of the lesion had a significant changes in RDI at 1 year, potentially signifying reorganization. The voxels with significant changes in restricted diffusion imaging values (accounting for tremor reduction) extend beyond the VIM into the surrounding white matter.InterpretationCorrecting for free water contamination allowed us to study microstructural changes after focused ultrasound thalamotomy. We observed statistically significant changes in RDI in the anterior and medial aspect of the lesion at 1 year. Whether these changes represent tissue reorganization remains to be confirmed in future studies. These findings may support performing additional ablations antero-medially for durable efficacy.
  • GABA and glutamate moderate beta-amyloid related functional connectivity
           in cognitively unimpaired old-aged adults

    • Abstract: Publication date: Available online 12 March 2019Source: NeuroImage: ClinicalAuthor(s): F.C. Quevenco, S.J. Schreiner, M.G. Preti, J.M.G. van Bergen, T. Kirchner, M. Wyss, S.C. Steininger, A. Gietl, S.E. Leh, A. Buck, K.P. Pruessmann, C. Hock, R.M. Nitsch, A. Henning, D. Van De Ville, P.G. UnschuldAbstractBackgroundEffects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer's disease (AD) by years and affect distinct cognitive brain networks. As previous studies suggest a link between beta-amyloid and dysregulation of excitatory and inhibitory neurotransmitters, we aimed to investigate the impact of GABA and glutamate on beta-amyloid related functional connectivity.Methods29 cognitively unimpaired old-aged adults (age = 70.03 ± 5.77 years) were administered 11C-Pittsburgh Compound B (PiB) positron-emission tomography (PET), and MRI at 7 Tesla including blood oxygen level dependent (BOLD) functional MRI (fMRI) at rest for measuring static and dynamic functional connectivity. MR spectroscopic imaging (MRSI) using ‘free induction decay acquisition localized by outer volume suppression’ (FIDLOVS) was used for gray matter specific measures of GABA and glutamate in the posterior cingulate and precuneus (PCP) region.ResultsGABA and glutamate indicated significantly higher levels in gray matter than in white matter. A global effect of beta-amyloid on functional connectivity in the frontal, occipital and inferior temporal lobes was observable. Interactive effects of beta-amyloid with gray matter GABA displayed positive PCP connectivity to the frontomedial regions, and the interaction of beta-amyloid with gray matter glutamate indicated positive PCP connectivity to frontal and cerebellar regions. Furthermore, decreased whole-brain but increased fronto-occipital and temporo-parietal dynamic connectivity was found, when GABA interacted with regional beta-amyloid deposits in the amygdala, frontal lobe, hippocampus, insula and striatum.ConclusionsGABA, and less so glutamate, may moderate beta-amyloid related functional connectivity. Additional research is needed to better characterize their interaction, and its potential impact on AD.
  • Sex differences in the association between amyloid and longitudinal brain
           volume change in cognitively Normal older adults

    • Abstract: Publication date: Available online 11 March 2019Source: NeuroImage: ClinicalAuthor(s): Nicole M. Armstrong, Chiung-Wei Huang, Owen Williams, Murat Bilgel, Yang An, Jimit Doshi, Guray Erus, Christos Davatzikos, Dean F. Wong, Luigi Ferrucci, Susan ResnickAbstractObjectiveAmyloid positivity is a biomarker of AD pathology, yet the associations between amyloid positivity and brain volumetric changes, especially in the hippocampus, are inconsistent. We hypothesize that sex differences in associations may contribute to inconsistent findings among cognitively normal older adults.MethodsUsing linear mixed effects models, we examined the association of amyloid positivity with prospective volumetric changes (mean = 3.3 visits) of parahippocampal gyrus (phg), hippocampus, entorhinal cortex (erc), precuneus, and fusiform among 171 Baltimore Longitudinal Study of Aging participants aged ≥55 years. Amyloid positivity was defined by a mean 11C-Pittsburgh Compound B (PiB) distribution volume ratio (DVR) cut-off of 1.062. All analyses included age, race, sex, education, APOE e4 carrier status, and two-way interactions of these covariates with time. Two-way interaction between sex and PiB+/− status and three-way interaction of sex and PiB+/− status with time was added to assess whether sex modified associations.ResultsPiB+ status was associated with greater volumetric declines in the phg (β = −0.036, SE = 0.011, p = 0.001) and erc (β = −0.019, SE = 0.009, p = 0.045). Sex modified the association of PiB+ status and rates of volumetric declines in fusiform (β = −0.117, SE = 0.049, p = 0.019). PiB+ males had steeper rates of volumetric declines in phg (β = −0.051, SE = 0.013, p 
  • Group ICA for identifying biomarkers in schizophrenia: ‘Adaptive’
           networks via spatially constrained ICA show more sensitivity to group
           differences than spatio-temporal regression

    • Abstract: Publication date: Available online 5 March 2019Source: NeuroImage: ClinicalAuthor(s): Mustafa S. Salman, Yuhui Du, Dongdong Lin, Zening Fu, Alex Fedorov, Eswar Damaraju, Jing Sui, Jiayu Chen, Andrew Mayer, Stefan Posse, Daniel Mathalon, Judith M. Ford, Theodorus Van Erp, Vince D. CalhounAbstractBrain functional networks identified from fMRI data can provide potential biomarkers for brain disorders. Group independent component analysis (GICA) is popular for extracting brain functional networks from multiple subjects. In GICA, different strategies exist for reconstructing subject-specific networks from the group-level networks. However, it is unknown whether these strategies have different sensitivities to group differences and abilities in distinguishing patients. Among GICA, spatio-temporal regression (STR) and spatially constrained ICA approaches such as group information guided ICA (GIG-ICA) can be used to propagate components (indicating networks) to a new subject that is not included in the original subjects. In this study, based on the same a priori network maps, we reconstructed subject-specific networks using these two methods separately from resting-state fMRI data of 151 schizophrenia patients (SZs) and 163 healthy controls (HCs). We investigated group differences in the estimated functional networks and the functional network connectivity (FNC) obtained by each method. The networks were also used as features in a cross-validated support vector machine (SVM) for classifying SZs and HCs. We selected features using different strategies to provide a comprehensive comparison between the two methods. GIG-ICA generally showed greater sensitivity in statistical analysis and better classification performance (accuracy 76.45 ± 8.9%, sensitivity 0.74 ± 0.11, specificity 0.79 ± 0.11) than STR (accuracy 67.45 ± 8.13%, sensitivity 0.65 ± 0.11, specificity 0.71 ± 0.11). Importantly, results were also consistent when applied to an independent dataset including 82 HCs and 82 SZs. Our work suggests that the functional networks estimated by GIG-ICA are more sensitive to group differences, and GIG-ICA is promising for identifying image-derived biomarkers of brain disease.
  • Single-subject classification of presymptomatic frontotemporal dementia
           mutation carriers using multimodal MRI

    • Abstract: Publication date: Available online 1 March 2019Source: NeuroImage: ClinicalAuthor(s): Rogier A. Feis, Mark J.R.J. Bouts, Jessica L. Panman, Lize C. Jiskoot, Elise G.P. Dopper, Tijn M. Schouten, Frank de Vos, Jeroen van der Grond, John C. van Swieten, Serge A.R.B. RomboutsAbstractBackgroundClassification models based on magnetic resonance imaging (MRI) may aid early diagnosis of frontotemporal dementia (FTD) but have only been applied in established FTD cases. Detection of FTD patients in earlier disease stages, such as presymptomatic mutation carriers, may further advance early diagnosis and treatment. In this study, we aim to distinguish presymptomatic FTD mutation carriers from controls on an individual level using multimodal MRI-based classification.MethodsAnatomical MRI, diffusion tensor imaging (DTI) and resting-state functional MRI data were collected in 55 presymptomatic FTD mutation carriers (8 microtubule-associated protein Tau, 35 progranulin, and 12 chromosome 9 open reading frame 72) and 48 familial controls. We calculated grey and white matter density features from anatomical MRI scans, diffusivity features from DTI, and functional connectivity features from resting-state functional MRI. These features were applied in a recently introduced multimodal behavioural variant FTD (bvFTD) classification model, and were subsequently used to train and test unimodal and multimodal carrier-control models. Classification performance was quantified using area under the receiver operator characteristic curves (AUC).ResultsThe bvFTD model was not able to separate presymptomatic carriers from controls beyond chance level (AUC = 0.582, p = 0.078). In contrast, one unimodal and several multimodal carrier-control models performed significantly better than chance level. The unimodal model included the radial diffusivity feature and had an AUC of 0.642 (p = 0.032). The best multimodal model combined radial diffusivity and white matter density features (AUC = 0.684, p = 0.004).ConclusionsFTD mutation carriers can be separated from controls with a modest AUC even before symptom-onset, using a newly created carrier-control classification model, while this was not possible using a recent bvFTD classification model. A multimodal MRI-based classification score may therefore be a useful biomarker to aid earlier FTD diagnosis. The exclusive selection of white matter features in the best performing model suggests that the earliest FTD-related pathological processes occur in white matter.
  • Corrigendum to 'Single-subject classification of presymptomatic
           frontotemporal dementia mutation carriers using multimodal MRI'

    • Abstract: Publication date: Available online 21 February 2019Source: NeuroImage: ClinicalAuthor(s):
  • Divergent patterns of loss of interpersonal warmth in frontotemporal
           dementia syndromes are predicted by altered intrinsic network connectivity

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Gianina Toller, Winson F.Z. Yang, Jesse A. Brown, Kamalini G. Ranasinghe, Suzanne M. Shdo, Joel H. Kramer, William W. Seeley, Bruce L. Miller, Katherine P. RankinAbstractLoss of warmth is well-documented in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) at a group level, and has been linked to salience (SN) and semantic-appraisal (SAN) network atrophy. However, clinical observations of individual patients show much greater heterogeneity, thus measuring this clinical variability and identifying the underlying neurologic mechanisms is a critical step for understanding the symptom profile of any one patient. We used reliable change indexes with premorbid and current informant-based evaluations to characterize patterns of change on the warmth subscale of the Interpersonal Adjective Scale (IAS) questionnaire in 132 patients (21 bvFTD, 19 svPPA, 22 nonfluent variant primary progressive aphasia [nfvPPA], 37 Alzheimer's disease [AD]) and 33 healthy older adults. We investigated whether individual differences in warmth change were reflected in SN or SAN functional connectivity, or structural volume of individual brain regions in these two networks. Though one subset of patients showed significant drop in warmth to abnormally low levels (bvFTD: 38%; svPPA: 21%; nfvPPA: 5%; AD: 11%), a second subset significantly dropped but remained within the clinically normal range (bvFTD: 33%; svPPA: 21%; nfvPPA: 9%; AD: 5%), and a third subset did not drop and stayed in the clinically normal range (bvFTD: 29%; svPPA: 58%; nfvPPA: 86%; AD: 84%). Furthermore, interpersonal warmth score was strongly predicted by SN functional connectivity (p 
  • Phasic amygdala and BNST activation during the anticipation of temporally
           unpredictable social observation in social anxiety disorder patients

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Benedikt Figel, Leonie Brinkmann, Christine Buff, Carina Y. Heitmann, David Hofmann, Maximilian Bruchmann, Michael P.I. Becker, Martin J. Herrmann, Thomas StraubeAbstractAnticipation of potentially threatening social situations is a key process in social anxiety disorder (SAD). In other anxiety disorders, recent research of neural correlates of anticipation of temporally unpredictable threat suggests a temporally dissociable involvement of amygdala and bed nucleus of the stria terminalis (BNST) with phasic amygdala responses and sustained BNST activation. However, the temporal profile of amygdala and BNST responses during temporal unpredictability of threat has not been investigated in patients suffering from SAD. We used functional magnetic resonance imaging (fMRI) to investigate neural activation in the central nucleus of the amygdala (CeA) and the BNST during anticipation of temporally unpredictable aversive (video camera observation) relative to neutral (no camera observation) events in SAD patients compared to healthy controls (HC). For the analysis of fMRI data, we applied two regressors (phasic/sustained) within the same model to detect temporally dissociable brain responses. The aversive condition induced increased anxiety in patients compared to HC. SAD patients compared to HC showed increased phasic activation in the CeA and the BNST for anticipation of aversive relative to neutral events. SAD patients as well as HC showed sustained activity alterations in the BNST for aversive relative to neutral anticipation. No differential activity during sustained threat anticipation in SAD patients compared to HC was found. Taken together, our study reveals both CeA and BNST involvement during threat anticipation in SAD patients. The present results point towards potentially SAD-specific threat processing marked by elevated phasic but not sustained CeA and BNST responses when compared to HC.
  • pH-weighted molecular MRI in human traumatic brain injury (TBI) using
           amine proton chemical exchange saturation transfer echoplanar imaging
           (CEST EPI)

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Benjamin M. Ellingson, Jingwen Yao, Catalina Raymond, Ararat Chakhoyan, Kasra Khatibi, Noriko Salamon, J. Pablo Villablanca, Ina Wanner, Courtney R. Real, Azim Laiwalla, David L. McArthur, Martin M. Monti, David A. Hovda, Paul M. VespaAbstractCerebral acidosis is a consequence of secondary injury mechanisms following traumatic brain injury (TBI), including excitotoxicity and ischemia, with potentially significant clinical implications. However, there remains an unmet clinical need for technology for non-invasive, high resolution pH imaging of human TBI for studying metabolic changes following injury. The current study examined 17 patients with TBI and 20 healthy controls using amine chemical exchange saturation transfer echoplanar imaging (CEST EPI), a novel pH-weighted molecular MR imaging technique, on a clinical 3T MR scanner. Results showed significantly elevated pH-weighted image contrast (MTRasym at 3 ppm) in areas of T2 hyperintensity or edema (P 
  • Altered default mode network connectivity in adolescents with
           post-traumatic stress disorder

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Armelle Viard, Justine Mutlu, Sandra Chanraud, Fabian Guenolé, Pierre-Jean Egler, Priscille Gérardin, Jean-Marc Baleyte, Jacques Dayan, Francis Eustache, Bérengère Guillery-GirardAbstractPost-traumatic stress disorder (PTSD) is characterized by intrusions, re-experiencing, avoidance and hyperarousal. These symptoms might be linked to dysfunction in core neurocognitive networks subserving self-referential mental processing (default mode network, DMN), detection of salient stimuli (salience network, SN) and cognitive dysfunction (central executive network, CEN). Resting state studies in adolescent PTSD are scarce and findings are inconsistent, probably due to differences in patient symptom severity. Resting state brain activity was measured in 14 adolescents with severe PTSD and 24 age-matched controls. Seed-based connectivity analyses were used to examine connectivity between the DMN and the whole brain, including regions from other networks (SN and CEN). The relationships of network properties with symptom dimensions (severity, anxiety and depression) and episodic memory were also examined. Analyses revealed decreased within-DMN connectivity (between PCC and occipital cortex) in patients compared to controls. Furthermore, within-DMN connectivity (between PCC and hippocampus) correlated negatively with symptom dimensions (severity and anxiety), while increased connectivity (DMN-SN and DMN-CEN) correlated positively with episodic memory measures. These abnormal network properties found in adolescent PTSD corroborate those previously reported in adult PTSD. Decreased within-DMN connectivity and disrupted DMN-SN and DMN-CEN coupling could form the basis for intrusive trauma recollection and impaired episodic autobiographical recall in PTSD.
  • Inter-rater agreement in glioma segmentations on longitudinal MRI

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): M. Visser, D.M.J. Müller, R.J.M. van Duijn, M. Smits, N. Verburg, E.J. Hendriks, R.J.A. Nabuurs, J.C.J. Bot, R.S. Eijgelaar, M. Witte, M.B. van Herk, F. Barkhof, P.C. de Witt Hamer, J.C. de MunckBackgroundTumor segmentation of glioma on MRI is a technique to monitor, quantify and report disease progression. Manual MRI segmentation is the gold standard but very labor intensive. At present the quality of this gold standard is not known for different stages of the disease, and prior work has mainly focused on treatment-naive glioblastoma. In this paper we studied the inter-rater agreement of manual MRI segmentation of glioblastoma and WHO grade II-III glioma for novices and experts at three stages of disease. We also studied the impact of inter-observer variation on extent of resection and growth rate.MethodsIn 20 patients with WHO grade IV glioblastoma and 20 patients with WHO grade II-III glioma (defined as non-glioblastoma) both the enhancing and non-enhancing tumor elements were segmented on MRI, using specialized software, by four novices and four experts before surgery, after surgery and at time of tumor progression. We used the generalized conformity index (GCI) and the intra-class correlation coefficient (ICC) of tumor volume as main outcome measures for inter-rater agreement.ResultsFor glioblastoma, segmentations by experts and novices were comparable. The inter-rater agreement of enhancing tumor elements was excellent before surgery (GCI 0.79, ICC 0.99) poor after surgery (GCI 0.32, ICC 0.92), and good at progression (GCI 0.65, ICC 0.91). For non-glioblastoma, the inter-rater agreement was generally higher between experts than between novices. The inter-rater agreement was excellent between experts before surgery (GCI 0.77, ICC 0.92), was reasonable after surgery (GCI 0.48, ICC 0.84), and good at progression (GCI 0.60, ICC 0.80). The inter-rater agreement was good between novices before surgery (GCI 0.66, ICC 0.73), was poor after surgery (GCI 0.33, ICC 0.55), and poor at progression (GCI 0.36, ICC 0.73). Further analysis showed that the lower inter-rater agreement of segmentation on postoperative MRI could only partly be explained by the smaller volumes and fragmentation of residual tumor. The median interquartile range of extent of resection between raters was 8.3% and of growth rate was 0.22 mm/year.ConclusionManual tumor segmentations on MRI have reasonable agreement for use in spatial and volumetric analysis. Agreement in spatial overlap is of concern with segmentation after surgery for glioblastoma and with segmentation of non-glioblastoma by non-experts.Graphical abstractUnlabelled Image
  • Decreased peak alpha frequency and impaired visual evoked potentials in
           first episode psychosis

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Michael Murphy, Dost ÖngürAbstractAbnormal spontaneous and evoked oscillations have been reported in several studies of patients with psychotic disorders. Resting alpha power and peak alpha frequency may be decreased in patients with psychosis. We used high-density EEG (hd-EEG) to record resting-state data and steady-state visual evoked potentials (SSVEPs) in patients with first episode psychosis (FEP) and healthy controls to compare brain resonances across multiple frequencies. We recorded hd-EEG (128 channels) from 22 FEP patients and 22 healthy controls during eyes-closed resting state and eyes-closed photic stimulation at 1 Hz, 4 Hz, 10 Hz, 20 Hz, and 40 Hz. Alpha power, peak alpha frequency, and SSVEP amplitude were analyzed using ANOVA and statistical non-parametric mapping. We found that FEP patients had lower peak alpha frequencies (9.72 Hz vs 10.40 Hz, p = .02, Cohen's d = 0.73) and this decrease was driven by slowing over the central and posterior scalp. There was no difference in alpha power. Alpha waves propagated primarily from anterior to posterior and that propagation was slowed in patients. During SSVEP, patients had smaller increases in EEG power in the stimulation band (F(1,184) = 5.3, p = .02). Patients had attenuated responses to SSVEP stimulation at alpha, beta and gamma frequencies. The gamma response was partially preserved in patients who also had depressive symptoms. We conclude that even in early stages of illness, psychotic disorders are associated with decreased alpha peak frequency and impaired evoked resonances. These findings implicate multiple patterns of dysconnectivity in cortico-cortico and cortico-thalamic networks in FEP.
  • The neural correlations of spatial attention and working memory deficits
           in adults with ADHD

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Xiangsheng Luo, Jialiang Guo, Lu Liu, Xixi Zhao, Dongwei Li, Hui Li, Qihua Zhao, Yanfei Wang, Qiujin Qian, Yufeng Wang, Yan Song, Li SunAbstractWorking memory impairment is a typical cognitive abnormality in patients with attention-deficit/hyperactivity disorder (ADHD) and is closely related to attention. Exploring the interaction between working memory and attention in patients with ADHD is of great significance for studying the pathological mechanism of this disease. In this study, electrophysiological markers of attention, posterior contralateral N2 (N2pc), and working memory, contralateral delay activity (CDA), were used to explore the relationship between these two cognitive abilities in patients with ADHD. EEG data were collected from adults with ADHD and age-, sex-, and IQ-matched normal controls while performing a classical visuospatial working memory task that consisted of low-load and high-load memory conditions. In different memory load conditions, the memory array elicited a smaller N2pc (220–260 ms) and a smaller CDA (400–800 ms) in adults with ADHD than in normal controls. Further analysis revealed that the reduced CDA amplitude could be significantly predicted by the earlier and reduced N2pc amplitude in adults with ADHD. Moreover, when the number of memory items increased, the increase in N2pc highly predicted the increases in CDA. Our findings illustrate the relationship between spatial working memory and attention ability in ADHD adults from the neurophysiological aspect that reduced working memory is closely related to insufficient attention ability and provide a potential physiological basis for the pathological mechanism of ADHD.
  • Connectome-wide network analysis of white matter connectivity in
           Alzheimer's disease

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Chenfei Ye, Susumu Mori, Piu Chan, Ting MaAbstractA multivariate analytical strategy may pinpoint the structural connectivity patterns associated with Alzheimer's disease (AD) pathology in connectome-wide association studies. Diffusion magnetic resonance imaging data from 161 participants including subjects with healthy controls, AD, stable and converting mild cognitive impairment, were selected for group-wise comparisons. A multivariate distance matrix regression (MDMR) analysis was performed to detect abnormality in brain structural network along with disease progression. Based on the seed regions returned by the MDMR analysis, supervised learning was applied to evaluate the disease predictive performance. Nine brain regions, including the left orbital part of superior and middle frontal gyrus, the bilateral supplementary motor area, the bilateral insula, the left hippocampus, the left putamen, and the left thalamus demonstrated extremely significant structural pattern changes along with the progression of AD. The disease classification was more efficient when based on the key connectivity related to these seed regions than when based on whole-brain structural connectivity. MDMR analysis reveals brain network reorganization caused by AD pathology. The key structural connectivity detected in this study exhibits promising distinguishing capability to predict prodromal AD patients.
  • Validations of apomorphine-induced BOLD activation correlations in
           hemiparkinsonian rhesus macaques

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): J.E. Quintero, Yi Ai, A.H. Andersen, P. Hardy, R. Grondin, Z. Guduru, D.M. Gash, G.A. Gerhardt, Z. ZhangAbstractIdentification of Parkinson's disease at the earliest possible stage of the disease may provide the best opportunity for the use of disease modifying treatments. However, diagnosing the disease during the pre-symptomatic period remains an unmet goal. To that end, we used pharmacological MRI (phMRI) to assess the function of the cortico-basal ganglia circuit in a non-human primate model of dopamine deficiency to determine the possible relationships between phMRI signals with behavioral, neurochemical, and histological measurements. Animals with unilateral treatments with the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), that expressed stable, long-term hemiparkinsonism were challenged with the dopaminergic receptor agonist, apomorphine, and structure-specific phMRI blood oxygen level-dependent (BOLD) activation responses were measured. Behavioral, histopathological, and neurochemical measurements were obtained and correlated with phMRI activation of structures of the cortico-basal ganglia system. Greater phMRI activations in the basal ganglia and cortex were associated with slower movement speed, decreased daytime activity, or more pronounced parkinsonian features. Animals showed decreased stimulus-evoked dopamine release in the putamen and substantia nigra pars compacta and lower basal glutamate levels in the motor cortex on the MPTP-lesioned hemisphere compared to the contralateral hemisphere. The altered neurochemistry was significantly correlated with phMRI signals in the motor cortex and putamen. Finally, greater phMRI activations in the caudate nucleus correlated with fewer tyrosine hydroxylase-positive (TH+) nigral cells and decreased TH+ fiber density in the putamen. These results reveal the correlation of phMRI signals with the severity of the motor deficits and pathophysiological changes in the cortico-basal ganglia circuit.
  • Structural brain correlates of fatigue in older adults with and without
           Parkinson's disease

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Benzi M. Kluger, Qing Zhao, Jared J. Tanner, Nadine A. Schwab, Shellie-Anne Levy, Sarah E. Burke, Haiqing Huang, Mingzhou Ding, Catherine PriceFatigue is one of the most common and disabling nonmotor symptoms seen in Parkinson's disease (PD) and is also commonly seen in healthy older adults. Our understanding of the etiology of fatigue in older adults with or without PD is limited and it remains unclear whether fatigue in PD is specifically related to PD pathology. The objective of this study was thus to determine whether fatigue in PD was associated with structural changes in gray or white matter and explore whether these changes were similar in older adults without PD. Magnetic resonance imaging (T1 weighted) and diffusion tensor imaging were performed in 60 patients with PD (17 females; age = 67.58 ± 5.51; disease duration = 5.67 ± 5.83 years) and 41 age- and sex- matched healthy controls. FSL image processing was used to measure gray matter volume, fractional anisotropy, and leukoariosis differences. Voxel-based morphometry confirmed gray matter loss across the dorsal striatum and insula in the PD patient cohort. PD patients with fatigue had reduced gray matter volume in dorsal striatum relative to PD patients without fatigue (P 
  • Low-rank network signatures in the triple network separate schizophrenia
           and major depressive disorder

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Wei Han, Christian Sorg, Changgang Zheng, Qinli Yang, Xiaosong Zhang, Arvid Ternblom, Cobbinah Bernard Mawuli, Lianli Gao, Cheng Luo, Dezhong Yao, Tao Li, Sugai Liang, Junming ShaoAbstractBrain imaging studies have revealed that functional and structural brain connectivity in the so-called triple network (i.e., default mode network (DMN), salience network (SN) and central executive network (CEN)) are consistently altered in schizophrenia. However, similar changes have also been found in patients with major depressive disorder, prompting the question of specific triple network signatures for the two disorders. In this study, we proposed Supervised Convex Nonnegative Matrix Factorization (SCNMF) to extract distributed multi-modal brain patterns. These patterns distinguish schizophrenia and major depressive disorder in a latent low-dimensional space of the triple brain network. Specifically, 21 patients of schizophrenia and 25 patients of major depressive disorder were assessed by T1-weighted, diffusion-weighted, and resting-state functional MRIs. Individual structural and functional connectivity networks, based on pre-defined regions of the triple network were constructed, respectively. Afterwards, SCNMF was employed to extract the discriminative patterns. Experiments indicate that SCNMF allows extracting the low-rank discriminative patterns between the two disorders, achieving a classification accuracy of 82.6% based on the extracted functional and structural abnormalities with support vector machine. Experimental results show the specific brain patterns for schizophrenia and major depressive disorder that are multi-modal, complex, and distributed in the triple network. Parts of the prefrontal cortex including superior frontal gyri showed variation between patients with schizophrenia and major depression due to structural properties. In terms of functional properties, the middle cingulate cortex, inferior parietal lobule, and cingulate cortex were the most discriminative regions.
  • Characterization of white matter changes along fibers by automated fiber
           quantification in the early stages of Alzheimer's disease

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Xin Zhang, Yu Sun, Weiping Li, Bing Liu, Wenbo Wu, Hui Zhao, Renyuan Liu, Yue Zhang, Zhenyu Yin, Tingting Yu, Zhao Qing, Bin Zhu, Yun Xu, Zuzana Nedelska, Jakub Hort, Bing Zhang, for the Alzheimer's Disease Neuroimaging InitiativeAbstractBrain white matter fiber bundles in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) have abnormalities not usually seen in unaffected subjects. Ideal algorithm of the localization-specific properties in white matter integrity might reveal the changes of tissue properties varying along each tract, while previous studies only detected the mean DTI parameters of each fiber. The aim of this study was to investigate whether these abnormalities of nerve fiber tracts are localized to specific regions of the tracts or spread throughout and to analyze which of the examined fiber tracts are involved in the early stages of Alzheimer's disease. In this study, we utilized VBA, TBSS as well as AFQ together to comprehensively investigate the white matter fiber impairment on 25 CE patients, 29 MCI patients and 34 normal control (NC) subjects. Two tract profiles, fractional anisotropy (FA) and mean diffusivity (MD), were extracted to evaluate the white matter integrity at 100 locations along each of 20 fiber tracts and then we validated the results with 27 CE patients, 21 MCI patients and 22 NC from the ADNI cohort. Also, we compare the AFQ with VBA and TBSS in our cohort. In comparison with NC, AD patients showed widespread FA reduction in 25% (5 /20) and MD increase in 65%(13/20) of the examined fiber tracts. The MCI patients showed a regional FA reduction in 5% (1/20) of the examined fiber tracts (right cingulum cingulate) and MD increase in 5%(1/20) of the examined fiber tracts (left arcuate fasciculus). Among these changed tracts, only the right cingulum cingulate showed widespread disruption of myelin or/and fiber axons in MCI and aggravated deterioration in AD, findings supported by FA/MD changes both by the mean and FA changes by point wise methods and TBSS. And the AFQ findings from ADNI cohort showed some similarity with our cohort, especially in the pointwise comparison of MD profiles between AD vs NC. Furthermore, the pattern of white matter abnormalities was different across neuronal fiber tracts; for example, the MCI and AD patients showed similar FA reduction in the middle part of the right cingulum cingulate, and the anterior part were not damaged. However, the left arcuate fasciculus showed MD elevation located at the temporal part of the fibers in the MCI patients and expanding to the temporal and middle part of the fibers in AD patients. So, the AFQ may be an alternative complementary method of VBA and TBSS, and may provide new insights into white matter degeneration in MCI and its association with AD.
  • Individuals with 22q11.2 deletion syndrome show intact prediction but
           reduced adaptation in responses to repeated sounds: Evidence from Bayesian

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Kit Melissa Larsen, Morten Mørup, Michelle Rosgaard Birknow, Elvira Fischer, Line Olsen, Michael Didriksen, William Frans Christiaan Baaré, Thomas Mears Werge, Marta Isabel Garrido, Hartwig Roman SiebnerAbstractOne of the most common copy number variants, the 22q11.2 microdeletion, confers an increased risk for schizophrenia. Since schizophrenia has been associated with an aberrant neural response to repeated stimuli through both reduced adaptation and prediction, we here hypothesized that this may also be the case in nonpsychotic individuals with a 22q11.2 deletion.We recorded high-density EEG from 19 individuals with 22q11.2 deletion syndrome (12–25 years), as well as 27 healthy volunteers with comparable age and sex distribution, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Using posterior probability maps and dynamic causal modelling we tested three different models accounting for repetition dependent changes in cortical responses as well as in effective connectivity; namely an adaptation model, a prediction model, and a model including both adaptation and prediction.Repetition-dependent changes were parametrically modulated by a combination of adaptation and prediction and were apparent in both cortical responses and in the underlying effective connectivity. This effect was reduced in individuals with a 22q11.2 deletion and was negatively correlated with negative symptom severity. Follow-up analysis showed that the reduced effect of the combined adaptation and prediction model seen in individuals with 22q11.2 deletion was driven by reduced adaptation rather than prediction failure. Our findings suggest that adaptation is reduced in individuals with a 22q11.2 deletion, which can be interpreted in light of the framework of predictive coding as a failure to suppress prediction errors.
  • Disrupted left fusiform response to print in beginning kindergartners is
           associated with subsequent reading

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Tracy M. Centanni, Elizabeth S. Norton, Ola Ozernov-Palchik, Anne Park, Sara D. Beach, Kelly Halverson, Nadine Gaab, John D.E. GabrieliAbstractDyslexia is a common neurobiological disorder in which a child fails to acquire typical word reading skills despite adequate opportunity and intelligence. The visual word form area (VWFA) is a region within the left fusiform gyrus that specializes for print over the course of reading acquisition and is often hypoactivated in individuals with dyslexia. It is currently unknown whether atypicalities in this brain region are already present in kindergarten children who will subsequently develop dyslexia. Here, we measured fMRI activation in response to letters and false fonts in bilateral fusiform gyrus in children with and without risk for dyslexia (defined by family history or low scores on assessments of pre-reading skills, such as phonological awareness). We then followed these children longitudinally through the end of second grade to evaluate whether brain activation patterns in kindergarten were related to second-grade reading outcomes. Compared to typical readers who exhibited no risk factors for reading impairment in kindergarten, there was significant hypoactivation to both letters and false-fonts in the left fusiform gyrus in at-risk children who subsequently developed reading impairment, but not in at-risk children who developed typical reading skills. There were no significant differences in letter- or false-font responses in the right fusiform gyrus among the groups. The finding that hypoactivation to print in the VWFA is present in children who subsequently develop reading impairment even prior to the onset of formal reading instruction suggests that atypical responses to print play an early role in the development of reading impairments such as dyslexia.
  • Frontal brain activity and cognitive processing speed in multiple
           sclerosis: An exploration of EEG neurofeedback training

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Philipp M. Keune, Sascha Hansen, Torsten Sauder, Sonja Jaruszowic, Christina Kehm, Jana Keune, Emily Weber, Michael Schönenberg, Patrick OschmannAbstractBackgroundCognitive deficits including impaired information processing speed as assessed by the Symbol Digit Modalities Test (SDMT) are common in multiple sclerosis (MS). Oscillatory markers of processing speed may be extracted from magnetoencephalographic (MEG) and electroencephalographic (EEG) resting-state recordings. In this context, an increased proportion of frontal slow-wave (theta, 4–8 Hz) to fast-wave (beta, 13–30 Hz) EEG activity was indicative of impaired SDMT performance. Such an increased theta/beta ratio may reflect oscillatory slowing associated with deficits in attention control. Therapeutic approaches that consider atypical oscillatory activity in MS remain sparse.ObjectivesIn a cross-sectional design, we examined the relation between SDMT performance, the EEG theta/beta ratio and its components. We also explored longitudinally, whether EEG neurofeedback could be used to induce a putatively adaptive alteration in these EEG parameters, toward a pattern indicative of improved processing speed.MethodsN = 58 MS patients (RRMS/SPMS/PPMS N: 18/35/3, 2 cases excluded) participated in a neuropsychological examination and a resting-state EEG recording. Subsequently, N = 10 patients received neurofeedback training for two weeks in a hospitalized setting. The purpose was to reduce the frontal theta/beta ratio through operant conditioning.ResultsIn the cross-sectional examination, patients with slow SDMT speed displayed an increased theta/beta ratio, relative to those with normal speed. This involved increased frontal theta power, whereas beta power was equal across groups. The theta/beta ratio remained stable during neurofeedback across sessions of the two-week training period. In an exploratory secondary analysis, within sessions a reduction in the theta/beta ratio during active training blocks relative pre/post session resting-states was observed, driven by reduced theta power.ConclusionsThese findings provide support for utilizing frontal EEG theta activity as an inverse marker of processing speed in MS. Across sessions, there was no support for successful operant conditioning of the theta/beta ratio during the two-week training period. The observed state-specific shift within sessions, involving a transient reduction in theta activity, nevertheless may provide a rationale for a further investigation of neurofeedback as a treatment approach in MS.
  • Brain structure segmentation in the presence of multiple sclerosis lesions

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Sandra González-Villà, Arnau Oliver, Yuankai Huo, Xavier Lladó, Bennett A. LandmanAbstractIntensity-based multi-atlas segmentation strategies have shown to be particularly successful in segmenting brain images of healthy subjects. However, in the same way as most of the methods in the state of the art, their performance tends to be affected by the presence of MRI visible lesions, such as those found in multiple sclerosis (MS) patients. Here, we present an approach to minimize the effect of the abnormal lesion intensities on multi-atlas segmentation. We propose a new voxel/patch correspondence model for intensity-based multi-atlas label fusion strategies that leads to more accurate similarity measures, having a key role in the final brain segmentation. We present the theory of this model and integrate it into two well-known fusion strategies: Non-local Spatial STAPLE (NLSS) and Joint Label Fusion (JLF). The experiments performed show that our proposal improves the segmentation performance of the lesion areas. The results indicate a mean Dice Similarity Coefficient (DSC) improvement of 1.96% for NLSS (3.29% inside and 0.79% around the lesion masks) and, an improvement of 2.06% for JLF (2.31% inside and 1.42% around lesions). Furthermore, we show that, with the proposed strategy, the well-established preprocessing step of lesion filling can be disregarded, obtaining similar or even more accurate segmentation results.
  • Cerebellar resting-state functional connectivity in Parkinson's disease
           and multiple system atrophy: Characterization of abnormalities and
           potential for differential diagnosis at the single-patient level

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Hugo C. Baggio, Alexandra Abos, Barbara Segura, Anna Campabadal, Carme Uribe, Darly M. Giraldo, Alexandra Perez-Soriano, Esteban Muñoz, Yaroslau Compta, Carme Junque, Maria Jose MartiAbstractBackgroundRecent studies using resting-state functional connectivity and machine-learning to distinguish patients with neurodegenerative diseases from other groups of subjects show promising results. This approach has not been tested to discriminate between Parkinson's disease (PD) and multiple system atrophy (MSA) patients.ObjectivesOur first aim is to characterize possible abnormalities in resting-state functional connectivity between the cerebellum and a set of intrinsic-connectivity brain networks and between the cerebellum and different regions of the striatum in PD and MSA. The second objective of this study is to assess the potential of cerebellar connectivity measures to distinguish between PD and MSA patients at the single-patient level.MethodsFifty-nine healthy controls, 62 PD patients, and 30 MSA patients underwent resting-state functional MRI with a 3T scanner. Independent component analysis and dual regression were used to define seven resting-state networks of interest. To assess striatal connectivity, a seed-to-voxel approach was used after dividing the striatum into six regions bilaterally. Measures of cerebellar-brain network and cerebellar-striatal connectivity were then used as features in a support vector machine to discriminate between PD and MSA patients.ResultsMSA patients displayed reduced cerebellar connectivity with different brain networks and with the striatum compared with PD patients and with controls. The classification procedure achieved an overall accuracy of 77.17% with 83.33% of the MSA subjects and 74.19% of the PD patients correctly classified.ConclusionOur findings suggest that measures of cerebellar functional connectivity have the potential to distinguish between PD and MSA patients.
  • Segregation of salience network predicts treatment response of depression
           to repetitive transcranial magnetic stimulation

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Jie Fan, Ivy F. Tso, Daniel F. Maixner, Tessa Abagis, Luis Hernandez-Garcia, Stephan F. TaylorAbstractBackgroundThe present study tested the hypothesis that network segregation, a graph theoretic measure of functional organization of the brain, is correlated with treatment response in patients with major depressive disorder (MDD) undergoing repetitive transcranial magnetic stimulation (rTMS).MethodsNetwork segregation, calculated from resting state functional magnetic resonance imaging scans, was measured in 32 patients with MDD who entered a sham-controlled, double-blinded, randomized trial of rTMS to the left dorsolateral prefrontal cortex, and a cohort of 20 healthy controls (HCs). Half of the MDD patients received sham treatment in the blinded phase, followed by active rTMS in the open-label phase. The analyses focused on segregation of the following networks: default mode (DMN), salience (SN), fronto-parietal (FPN), cingulo-opercular (CON), and memory retrieval (MRN).ResultsThere was no differential change in network segregation comparing sham to active treatment. However, in the combined group of patients who completed active rTMS treatment (in the blinded plus open-label phases), higher baseline segregation of SN significantly predicted more symptom improvement after rTMS. Compared to HCs at baseline, MDD patients showed decreased segregation in DMN, and trend-level decreases in SN and MRN.ConclusionThe results highlight the importance of network segregation in MDD, particularly in the SN, where more normal baseline segregation of SN may predict better treatment response to rTMS in depression.
  • Structural brain network measures are superior to vascular burden scores
           in predicting early cognitive impairment in post stroke patients with
           small vessel disease

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Jing Du, Yao Wang, Nan Zhi, Jieli Geng, Wenwei Cao, Ling Yu, Jianhua Mi, Yan Zhou, Qun Xu, Wei Wen, Perminder SachdevAbstractObjectivesIn this cross-sectional study, we aimed to explore the mechanisms of early cognitive impairment in a post stroke non-dementia cerebral small vessel disease (SVD) cohort by comparing the SVD score with the structural brain network measures.Method127 SVD patients were recruited consecutively from a stroke clinic, comprising 76 individuals with mild cognitive impairment (MCI) and 51 with no cognitive impairment (NCI). Detailed neuropsychological assessments and multimodal MRI were performed. SVD scores were calculated on a standard scale, and structural brain network measures were analyzed by diffusion tensor imaging (DTI). Between-group differences were analyzed, and logistic regression was applied to determine the predictive value of SVD and network measures for cognitive status. Mediation analysis with structural equation modeling (SEM) was used to better understand the interactions of SVD burden, brain networks and cognitive deficits.ResultsGroup difference was found on all global brain network measures. After adjustment for age, gender, education and depression, significant correlations were found between global brain network measures and diverse neuropsychological tests, including TMT-B (r = −0.209, p 
  • Glutamate weighted imaging contrast in gliomas with 7 Tesla magnetic
           resonance imaging

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Andrew Neal, Bradford A. Moffat, Joel M. Stein, Ravi Prakash Reddy Nanga, Patricia Desmond, Russell T. Shinohara, Hari Hariharan, Rebecca Glarin, Katharine Drummond, Andrew Morokoff, Patrick Kwan, Ravinder Reddy, Terence J. O'Brien, Kathryn A. DavisIntroductionDiffuse gliomas are incurable malignancies, which undergo inevitable progression and are associated with seizure in 50–90% of cases. Glutamate has the potential to be an important glioma biomarker of survival and local epileptogenicity if it can be accurately quantified noninvasively.MethodsWe applied the glutamate-weighted imaging method GluCEST (glutamate chemical exchange saturation transfer) and single voxel MRS (magnetic resonance spectroscopy) at 7 Telsa (7 T) to patients with gliomas. GluCEST contrast and MRS metabolite concentrations were quantified within the tumour region and peritumoural rim. Clinical variables of tumour aggressiveness (prior adjuvant therapy and previous radiological progression) and epilepsy (any prior seizures, seizure in last month and drug refractory epilepsy) were correlated with respective glutamate concentrations. Images were separated into post-hoc determined patterns and clinical variables were compared across patterns.ResultsTen adult patients with a histo-molecular (n = 9) or radiological (n = 1) diagnosis of grade II-III diffuse glioma were recruited, 40.3 +/− 12.3 years. Increased tumour GluCEST contrast was associated with prior adjuvant therapy (p = .001), and increased peritumoural GluCEST contrast was associated with both recent seizures (p = .038) and drug refractory epilepsy (p = .029). We distinguished two unique GluCEST contrast patterns with distinct clinical and radiological features. MRS glutamate correlated with GluCEST contrast within the peritumoural voxel (R = 0.89, p = .003) and a positive trend existed in the tumour voxel (R = 0.65, p = .113).ConclusionThis study supports the role of glutamate in diffuse glioma biology. It further implicates elevated peritumoural glutamate in epileptogenesis and altered tumour glutamate homeostasis in glioma aggressiveness. Given the ability to non-invasively visualise and quantify glutamate, our findings raise the prospect of 7 T GluCEST selecting patients for individualised therapies directed at the glutamate pathway. Larger studies with prospective follow-up are required.Graphical abstractUnlabelled Image
  • The organization of the basal ganglia functional connectivity network is
           non-linear in Parkinson's disease

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Clara Rodriguez-Sabate, Ingrid Morales, Jesus N. Lorenzo, Manuel RodriguezThe motor symptoms in Parkinson's disease (PD) have been linked to changes in the excitatory/inhibitory interactions of centers involved in the cortical-subcortical closed-loop circuits which connect basal ganglia (BG) and the brain cortex. This approach may explain some motor symptoms of PD but not others, which has driven the study of BG from new perspectives. Besides their cortical-subcortical linear circuits, BG have a number of subcortical circuits which directly or indirectly connect each BG with all the others. This suggests that BG may work as a complex network whose output is the result of massive functional interactions between all of their nuclei (decentralized network; DCN), more than the result of the linear excitatory/inhibitory interactions of the cortical-subcortical closed-loops. The aim of this work was to study BG as a DCN, and to test whether the DCN behavior of BG changes in PD. BG activity was recorded with MRI methods and their complex interactions were studied with a procedure based on multiple correspondence analysis, a data-driven multifactorial method which can work with non-linear multiple interactions. The functional connectivity of twenty parkinsonian patients and eighteen age-matched controls were studied during resting and when they were performing sequential hand movements. Seven functional configurations were identified in the control subjects during resting, and some of these interactions changed with motor activity. Five of the seven interactions found in control subjects changed in Parkinson's disease. The BG response to the motor task was also different in PD patients and controls. These data show the basal ganglia as a decentralized network where each region can perform multiple functions and each function is performed by multiple regions. This framework of BG interactions may provide new explanations concerning motor symptoms of PD which are not explained by current BG models.Graphical abstractUnlabelled Image
  • Volume alterations of brainstem subregions in migraine with aura

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Igor Petrusic, Marko Dakovic, Jasna Zidverc-TrajkovicAbstractBackgroundThe brainstem plays a significant role in migraine pathogenesis, but a relationship between volume alterations of brainstem subregions and migraine aura characteristics has not been sufficiently investigated. The aim of this study is to compare the volume of the brainstem, and its subregions, between patients with a migraine with aura (MwA) and healthy controls (HC), and also to correlate characteristics of MwA and the volume of the brainstem subregions.MethodsForty-two MwA and 42 HCs, balanced by sex and age, were selected for this study. Total brainstem volume changes as well as volume changes in the pons, medulla, midbrain and the superior cerebellar peduncles were investigated in MwA relative to HCs. In addition, the relationships between brainstem subregions and aura characteristics (aura duration, the frequency of the aura, occurrence of somatosensory and dysphasic aura, duration of a headache, intensity of headache pain and disease duration) were explored in MwA.ResultsMwA patients had a larger brainstem volume relative to HCs (25,941.35 ± 2559.2 mm3 vs. 25,179.32 ± 2019.1 mm3; p = .008), as well as the midbrain and pons (6155.98 ± 565.7 mm3 vs. 5964.22 ± 457.0 mm3, p = .002; 15,105.13 ± 1765.5 mm3 vs. 14,539.89 ± 1408.4 mm3, p = .007, respectively). Total brainstem volume, as well as volumes of brainstem subregions, were not significantly correlated to the MwA characteristics.ConclusionThe results of this study reveal that a migraine with aura is associated with a larger volume of the brainstem with a particular involvement of the midbrain and pons.
  • White matter microstructure correlates of general and specific
           second-order factors of psychopathology

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Kendra E. Hinton, Benjamin B. Lahey, Victoria Villalta-Gil, Francisco A.C. Meyer, Leah L. Burgess, Laura K. Chodes, Brooks Applegate, Carol A. Van Hulle, Bennett A. Landman, David H. ZaldAbstractIncreasing data indicate that prevalent forms of psychopathology can be organized into second-order dimensions based on their correlations, including a general factor of psychopathology that explains the common variance among all disorders and specific second-order externalizing and internalizing factors. Nevertheless, most existing studies on the neural correlates of psychopathology employ case-control designs that treat diagnoses as independent categories, ignoring the highly correlated nature of psychopathology. Thus, for instance, although perturbations in white matter microstructure have been identified across a range of mental disorders, nearly all such studies used case-control designs, leaving it unclear whether observed relations reflect disorder-specific characteristics or transdiagnostic associations. Using a representative sample of 410 young adult twins oversampled for psychopathology risk, we tested the hypothesis that some previously observed relations between white matter microstructure properties in major tracts and specific disorders are related to second-order factors of psychopathology. We examined fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). White matter correlates of all second-order factors were identified after controlling for multiple statistical tests, including the general factor (FA in the body of the corpus callosum), specific internalizing (AD in the fornix), and specific externalizing (AD in the splenium of the corpus callosum, sagittal stratum, anterior corona radiata, and internal capsule). These findings suggest that some features of white matter within specific tracts may be transdiagnostically associated multiple forms of psychopathology through second-order factors of psychopathology rather with than individual mental disorders.
  • Detecting frontotemporal dementia syndromes using MRI biomarkers

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Marie Bruun, Juha Koikkalainen, Hanneke F.M. Rhodius-Meester, Marta Baroni, Le Gjerum, Mark van Gils, Hilkka Soininen, Anne M. Remes, Päivi Hartikainen, Gunhild Waldemar, Patrizia Mecocci, Frederik Barkhof, Yolande Pijnenburg, Wiesje M. van der Flier, Steen G. Hasselbalch, Jyrki Lötjönen, Kristian S. FrederiksenAbstractBackgroundDiagnosing frontotemporal dementia may be challenging. New methods for analysis of regional brain atrophy patterns on magnetic resonance imaging (MRI) could add to the diagnostic assessment. Therefore, we aimed to develop automated imaging biomarkers for differentiating frontotemporal dementia subtypes from other diagnostic groups, and from one another.MethodsIn this retrospective multicenter cohort study, we included 1213 patients (age 67 ± 9, 48% females) from two memory clinic cohorts: 116 frontotemporal dementia, 341 Alzheimer's disease, 66 Dementia with Lewy bodies, 40 vascular dementia, 104 other dementias, 229 mild cognitive impairment, and 317 subjective cognitive decline. Three MRI atrophy biomarkers were derived from the normalized volumes of automatically segmented cortical regions: 1) the anterior vs. posterior index, 2) the asymmetry index, and 3) the temporal pole left index. We used the following performance metrics: area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. To account for the low prevalence of frontotemporal dementia we pursued a high specificity of 95%. Cross-validation was used in assessing the performance. The generalizability was assessed in an independent cohort (n = 200).ResultsThe anterior vs. posterior index performed with an AUC of 83% for differentiation of frontotemporal dementia from all other diagnostic groups (Sensitivity = 59%, Specificity = 95%, positive likelihood ratio = 11.8, negative likelihood ratio = 0.4). The asymmetry index showed highest performance for separation of primary progressive aphasia and behavioral variant frontotemporal dementia (AUC = 85%, Sensitivity = 79%, Specificity = 92%, positive likelihood ratio = 9.9, negative likelihood ratio = 0.2), whereas the temporal pole left index was specific for detection of semantic variant primary progressive aphasia (AUC = 85%, Sensitivity = 82%, Specificity = 80%, positive likelihood ratio = 4.1, negative likelihood ratio = 0.2). The validation cohort provided corresponding results for the anterior vs. posterior index and temporal pole left index.ConclusionThis study presents three quantitative MRI biomarkers, which could provide additional information to the diagnostic assessment and assist clinicians in diagnosing frontotemporal dementia.
  • Hypercapnic BOLD MRI compared to H2 15O PET/CT for the hemodynamic
           evaluation of patients with Moyamoya Disease

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Till-Karsten Hauser, Achim Seeger, Benjamin Bender, Uwe Klose, Johannes Thurow, Ulrike Ernemann, Marcos Tatagiba, Philipp T. Meyer, Nadia Khan, Constantin RoderAbstractBackground and purposePatients with Moyamoya Disease (MMD) need hemodynamic evaluation of vascular territories at risk of stroke. Today's investigative standards include H215O PET/CT with pharmacological challenges with acetazolamide (ACZ). Recent developments suggest that CO2-triggered blood‑oxygen-level-dependent (BOLD) functional MRI might provide comparable results to current standard methods for evaluation of territorial hemodynamics, while being a more widely available and easily implementable method. This study examines results of a newly developed quantifiable analysis algorithm for CO2-triggered BOLD MRI in Moyamoya patients and correlates the results with H215O PET/CT with ACZ challenge to assess comparability between both modalities.MethodsCO2-triggered BOLD MRI was performed and compared to H215O PET/CT with ACZ challenge in patients with angiographically proven MMD. Images of both modalities were analyzed retrospectively in a blinded, standardized fashion by visual inspection, as well as with a semi-quantitative analysis using stimuli-induced approximated regional perfusion-weighted data and BOLD-signal changes with reference to cerebellum.Results20 consecutive patients fulfilled the inclusion criteria, a total of 160 vascular territories were analyzed retrospectively. Visual analysis (4-step visual rating system) of standardized, color-coded cerebrovascular reserve/reactivity maps showed a very strong correlation (Spearman's rho = 0.9, P 
  • Identifying brain changes related to cognitive aging using VBM and visual
           rating scales

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Valentina Pergher, Philippe Demaerel, Olivier Soenen, Carina Saarela, Jos Tournoy, Birgitte Schoenmakers, Mira Karrasch, Marc M. Van HulleAbstractAging is often associated with changes in brain structures as well as in cognitive functions. Structural changes can be visualized with Magnetic Resonance Imaging (MRI) using voxel-based grey matter morphometry (VBM) and visual rating scales to assess atrophy level. Several MRI studies have shown that possible neural correlates of cognitive changes can be seen in normal aging. It is still not fully understood how cognitive function as measured by tests and demographic factors are related to brain changes in the MRI. We recruited 55 healthy elderly subjects aged 50–79 years. A battery of cognitive tests was administered to all subjects prior to MRI scanning. Our aim was to assess correlations between age, sex, education, cognitive test performance, and the said two MRI-based measures. Our results show significant differences in VBM grey matter volume for education level (≤ 12 vs.> 12 years), with a smaller amount of grey matter volume in subjects with lower educational levels, and for age in interaction with education, indicating larger grey matter volume for young, higher educated adults. Also, grey matter volume was found to be correlated with working memory function (Digit Span Backward). Furthermore, significant positive correlations were found between visual ratings and both age and education, showing larger atrophy levels with increasing age and decreasing level of education. These findings provide supportive evidence that MRI-VBM detects structural differences for education level, and correlates with educational level and age, and working memory task performance.
  • Cortical thickness and surface area as an endophenotype in bipolar
           disorder type I patients and their first-degree relatives

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Nefize Yalin, Aybala Saricicek, Ceren Hidiroglu, Andre Zugman, Nese Direk, Emel Ada, Berrin Cavusoglu, Ayşe Er, Gizem Isik, Deniz Ceylan, Zeliha Tunca, Matthew J. Kempton, Aysegul OzerdemAbstractObjectivesSo far, few studies have investigated cortical thickness (CT) and surface area (SA) measures in bipolar disorder type I (BDI) in comparison to a high genetic risk group such as first-degree relatives (FR). This study aimed to examine CT and SA differences between BDI, FR and healthy controls (HC).Methods3D T1 magnetic resonance images were acquired from 27 euthymic BDI patients, 24 unaffected FR and 29 HC. CT and SA measures were obtained with FreeSurfer version 5.3.0. Generalized estimating equations were used to compare CT and SA between groups. Group comparisons were repeated with restricting the FR group to 17 siblings (FR-SB) only.Results\Mean age in years was 36.3 ± 9.5 for BDI, 32.1 ± 10.9 for FR, 34.7 ± 9.8 for FR-SB and 33.1 ± 9.0 for HC group respectively. BDI patients revealed larger SA of left pars triangularis (LPT) compared to HC (p = .001). In addition, increased SA in superior temporal cortex (STC) in FR-SB group compared to HC was identified (p = .0001).ConclusionsOur result of increased SA in LPT of BDI could be a disease marker and increased SA in STC of FR-SB could be a marker related with resilience to illness.
  • Increased heartbeat-evoked potential during REM sleep in nightmare

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Lampros Perogamvros, Hyeong-Dong Park, Laurence Bayer, Aurore A. Perrault, Olaf Blanke, Sophie SchwartzAbstractNightmares are characterized by the experience of strong negative emotions occurring mainly during REM sleep. Some people suffer from nightmare disorder, which is defined by the repeated occurrence of nightmares and by significant distress in wakefulness. Yet, whether frequent nightmares relate to a general increase in emotional reactivity or arousal during sleep remains unclear. To address this question, we recorded heartbeat-evoked potentials (HEPs) during wakefulness, NREM and REM sleep in patients with nightmare disorder and healthy participants. The HEP represents a cortical (EEG) response to the heartbeat and indexes brain-body interactions, such as interoceptive processing and intrinsic levels of arousal. HEP amplitude is typically increased during states of high emotional arousal and motivation, and is decreased in depression. Here we compared the amplitude of HEPs between nightmare patients and healthy controls separately during AWAKE, NREM, REM periods, and found higher HEP amplitude in nightmare patients compared to healthy controls over a cluster of frontal regions only during REM sleep. This effect was not paralleled by any group difference in cardiac control measures (e.g. heart rate variability, interbeat interval). These findings corroborate the notion that nightmares are essentially a REM pathology and suggest that increased emotional arousal during REM sleep, as measured by HEP, is a physiological condition responsible for frequent nightmares. This result also supports that HEP may be used as a biomarker of increased emotional and sensory processing during REM sleep in these patients.
  • Neurophysiological markers of network dysfunction in neurodegenerative

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Roisin McMackin, Peter Bede, Niall Pender, Orla Hardiman, Bahman NasseroleslamiAbstractThere is strong clinical, imaging and pathological evidence that neurodegeneration is associated with altered brain connectivity. While functional imaging (fMRI) can detect resting and activated states of metabolic activity, its use is limited by poor temporal resolution, cost and confounding vascular parameters. By contrast, electrophysiological (e.g. EEG/MEG) recordings provide direct measures of neural activity with excellent temporal resolution, and source localization methodologies can address problems of spatial resolution, permitting measurement of functional activity of brain networks with a spatial resolution similar to that of fMRI. This opens an exciting therapeutic approach focussed on pharmacological and physiological modulation of brain network activity.This review describes current neurophysiological approaches towards evaluating cortical network dysfunction in common neurodegenerative disorders. It explores how modern neurophysiologic tools can provide markers for diagnosis, prognosis, subcategorization and clinical trial outcome measures, and how modulation of brain networks can contribute to new therapeutic approaches.
  • Dysfunction of attention switching networks in amyotrophic lateral

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Roisin McMackin, Stefan Dukic, Michael Broderick, Parameswaran M. Iyer, Marta Pinto-Grau, Kieran Mohr, Rangariroyashe Chipika, Amina Coffey, Teresa Buxo, Christina Schuster, Brighid Gavin, Mark Heverin, Peter Bede, Niall Pender, Edmund C. Lalor, Muthuraman Muthuraman, Orla Hardiman, Bahman NasseroleslamiAbstractObjectiveTo localise and characterise changes in cognitive networks in Amyotrophic Lateral Sclerosis (ALS) using source analysis of mismatch negativity (MMN) waveforms.RationaleThe MMN waveform has an increased average delay in ALS. MMN has been attributed to change detection and involuntary attention switching. This therefore indicates pathological impairment of the neural network components which generate these functions. Source localisation can mitigate the poor spatial resolution of sensor-level EEG analysis by associating the sensor-level signals to the contributing brain sources. The functional activity in each generating source can therefore be individually measured and investigated as a quantitative biomarker of impairment in ALS or its sub-phenotypes.MethodsMMN responses from 128-channel electroencephalography (EEG) recordings in 58 ALS patients and 39 healthy controls were localised to source by three separate localisation methods, including beamforming, dipole fitting and exact low resolution brain electromagnetic tomography.ResultsCompared with controls, ALS patients showed significant increase in power of the left posterior parietal, central and dorsolateral prefrontal cortices (false discovery rate = 0.1). This change correlated with impaired cognitive flexibility (rho = 0.45, 0.45, 0.47, p = .042, .055, .031 respectively). ALS patients also exhibited a decrease in the power of dipoles representing activity in the inferior frontal (left: p = 5.16 × 10−6, right: p = 1.07 × 10−5) and left superior temporal gyri (p = 9.30 × 10−6). These patterns were detected across three source localisation methods. Decrease in right inferior frontal gyrus activity was a good discriminator of ALS patients from controls (AUROC = 0.77) and an excellent discriminator of C9ORF72 expansion-positive patients from controls (AUROC = 0.95).InterpretationSource localization of evoked potentials can reliably discriminate patterns of functional network impairment in ALS and ALS subgroups during involuntary attention switching. The discriminative ability of the detected cognitive changes in specific brain regions are comparable to those of functional magnetic resonance imaging (fMRI).Source analysis of high-density EEG patterns has excellent potential to provide non-invasive, data-driven quantitative biomarkers of network disruption that could be harnessed as novel neurophysiology-based outcome measures in clinical trials.
  • The structural brain correlates of callous-unemotional traits in
           incarcerated male adolescents

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Brendan M. Caldwell, Nathaniel E. Anderson, Keith A. Harenski, Miranda H. Sitney, Michael F. Caldwell, Greg J. Van Rybroek, Kent A. KiehlAbstractYouth with severe conduct problems impose a significant cost on society by engaging in high levels of antisocial and aggressive behavior. Within this group, adolescents with high levels of callous- unemotional traits have been found to exhibit more severe and persistent patterns of antisocial behavior than youth with severe conduct problems but normative levels of callous-unemotional traits. Existing neuroimaging studies, along with theoretical accounts of psychopathology, suggest that dysfunction within the paralimbic cortex and limbic system may underlie elevated levels of callous-unemotional traits. The present study examines this hypothesis by investigating gray matter correlates associated with callous-unemotional traits. A sample of incarcerated male adolescents (N = 269), were assessed using voxel-based morphometry. Callous-unemotional traits were assessed using the Inventory of Callous-Unemotional traits (Frick 2004). Total callous-unemotional traits were negatively correlated with anterior temporal lobe gray matter volume (GMV). Callous traits in particular exhibited a reliable negative correlation with gray matter volume in nearly every paralimbic brain region examined. Uncaring traits were positively correlated with GMV in the orbitofrontal and anterior cingulate cortices. These findings demonstrate specific neural features within the paralimbic cortex and limbic system that accompany elevated callous-unemotional traits and serves to expand our understanding of pathophysiological mechanisms that may give rise to severe conduct problems in youth.
  • Evidence of early microstructural white matter abnormalities in multiple
           sclerosis from multi-shell diffusion MRI

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Silvia De Santis, Tobias Granberg, Russell Ouellette, Constantina A. Treaba, Elena Herranz, Qiuyun Fan, Caterina Mainero, Nicola ToschiAbstractIrreversible white matter (WM) damage, including severe demyelination and axonal loss, is a main determinant of long-term disability in multiple sclerosis (MS). Non-invasive detection of changes in microstructural WM integrity in the disease is challenging since commonly used imaging metrics lack the necessary sensitivity, especially in the early phase of the disease. This study aims at assessing microstructural WM abnormalities in early-stage MS by using ultra-high gradient strength multi-shell diffusion MRI and the restricted signal fraction (FR) from the Composite Hindered and Restricted Model of Diffusion (CHARMED), a metric sensitive to the volume fraction of axons.In 22 early MS subjects (disease duration ≤5 years) and 15 age-matched healthy controls, restricted fraction estimates were obtained through the CHARMED model along with conventional Diffusion Tensor Imaging (DTI) metrics. All imaging parameters were compared cross-sectionally between the MS subjects and controls both in WM lesions and normal-appearing white matter (NAWM).We found a significant reduction in FR focally in WM lesions and widespread in the NAWM in MS patients relative to controls (corrected p 
  • White-matter pathways and semantic processing: intrasurgical and
           lesion-symptom mapping evidence

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Joanna Sierpowska, Andreu Gabarrós, Alejandro Fernández-Coello, Àngels Camins, Sara Castañer, Montserrat Juncadella, Clément François, Antoni Rodríguez-FornellsAbstractIn the present study, we aimed to test the association between the correct function of the left ventral white matter pathways and semantic processing (dual stream models for language processing, Hickok & Poeppel, 2004), using a new set of language tasks during intraoperative electrical stimulation at white matter level. Additionally, we evaluated brain regions needed for correct performance on the different semantic tasks using lesion-symptom analyses (voxel lesion-symptom mapping and track-wise lesion analysis) in a sample of 62 candidates for the awake brain surgery. We found that electrical stimulation in the vicinity of the inferior longitudinal and inferior fronto-occipital fasciculi disturbed performance on semantic processing tasks. Individuals presented with significantly more semantic paraphasias during brain tumor resection than during the electrical stimulation at the cortex level. Track-wise analyses confirmed the role of these left ventral pathways in semantic processing: a significant relationship was observed between the probability of inferior fronto-occipital fasciculus disconnection/damage and the semantic matching tasks, as well as the number of semantic paraphasias in naming. Importantly, the same analyses for the total score of the Boston Naming Test confirmed significant relationships between this test score and the integrity of the inferior fronto-occipital, inferior longitudinal and uncinate fasciculi. This was further supported by the results of VLSM analyses showing a significant relationship between BNT and the presence of lesion within left middle and inferior temporal gyri. The present findings provide new intraoperative evidence for the role of the white-matter ventral pathways in semantic processing, while at the same time emphasizing the need to include a broader assessment of semantic-conceptual aspects during the awake neurosurgical intervention. This approach will ensure better preservation of functional tissue in the tumoral vicinity and therefore substantially diminish post-surgical language impairments.
  • Structural connectome alterations in patients with disorders of
           consciousness revealed by 7-tesla magnetic resonance imaging

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Xufei Tan, Zhen Zhou, Jian Gao, Fanxia Meng, Yamei Yu, Jie Zhang, Fangping He, Ruili Wei, Junyang Wang, Guoping Peng, Xiaotong Zhang, Gang Pan, Benyan LuoAbstractAlthough the functional connectivity of patients with disorders of consciousness (DOC) has been widely examined, less is known about brain white matter connectivity. The aim of this study was to explore structural network alterations for the diagnosis and prognosis of patients with chronic DOC. Eleven DOC patients and 11 sex- and age-matched controls were included in the study. Participants underwent diffusion magnetic resonance imaging (MRI) and T1-weighted structural MRI at 7 tesla (7 T). Graph-theoretical analysis and network-based statistics were used to analyze the group differences. Two patients were scanned twice for a longitudinal study to examine the relationship between connectome metrics and the patients' prognoses. Compared with healthy controls, DOC patients showed significantly elevated transitivity (p 
  • Arterial spin labelling and diffusion-weighted imaging in paediatric brain

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Patrick W. Hales, Felice d'Arco, Jessica Cooper, Josef Pfeuffer, Darren Hargrave, Kshitij Mankad, Chris ClarkBackgroundDiffusion- and perfusion-weighted MRI are valuable tools for measuring the cellular and vascular properties of brain tumours. This has been well studied in adult patients, however, the biological features of childhood brain tumours are unique, and paediatric-focused studies are less common. We aimed to assess the diagnostic utility of apparent diffusion coefficient (ADC) values derived from diffusion-weighted imaging (DWI) and cerebral blood flow (CBF) values derived from arterial spin labelling (ASL) in paediatric brain tumours.MethodsWe performed a meta-analysis of published studies reporting ADC and ASL-derived CBF values in paediatric brain tumours. Data were combined using a random effects model in order to define typical parameter ranges for different histological tumour subtypes and WHO grades. New data were also acquired in a ‘validation cohort’ at our institution, in which ADC and CBF values in treatment naïve paediatric brain tumour patients were measured, in order to test the validity of the findings from the literature in an un-seen cohort. ADC and CBF quantification was performed by two radiologists via manual placement of tumour regions of interest (ROIs), in addition to an automated approach to tumour ROI placement.ResultsA total of 14 studies met the inclusion criteria for the meta-analysis, constituting data acquired in 542 paediatric patients. Parameters of interest were based on measurements from ROIs placed within the tumour, including mean and minimum ADC values (ADCROI-mean, ADCROI-min) and the maximum CBF value normalised to grey matter (nCBFROI-max). After combination of the literature data, a number of histological tumour subtype groups showed significant differences in ADC values, which were confirmed, where possible, in our validation cohort of 32 patients. In both the meta-analysis and our cohort, diffuse midline glioma was found to be an outlier among high-grade tumour subtypes, with ADC and CBF values more similar to the low-grade tumours. After grouping patients by WHO grade, significant differences in grade groups were found in ADCROI-mean, ADCROI-min, and nCBFROI-max, in both the meta-analysis and our validation cohort. After excluding diffuse midline glioma, optimum thresholds (derived from ROC analysis) for separating low/high-grade tumours were 0.95 × 10−3 mm2/s (ADCROI-mean), 0.82 × 10−3 mm2/s (ADCROI-min) and 1.45 (nCBFROI-max). These thresholds were able to identify low/high-grade tumours with 96%, 83%, and 83% accuracy respectively in our validation cohort, and agreed well with the results from the meta-analysis. Diagnostic power was improved by combining ADC and CBF measurements from the same tumour, after which 100% of tumours in our cohort were correctly classified as either low- or high-grade (excluding diffuse midline glioma).ConclusionADC and CBF values are useful for differentiating certain histological subtypes, and separating low- and high-grade paediatric brain tumours. The threshold values presented here are in agreement with previously published studies, as well as a new patient cohort. If ADC and CBF values acquired in the same tumour are combined, the diagnostic accuracy is optimised.Graphical abstractUnlabelled Image
  • Region-specific association between basal blood insulin and cerebral
           glucose metabolism in older adults

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Min Soo Byun, Hyun Jung Kim, Dahyun Yi, Hyo Jung Choi, Hyewon Baek, Jun Ho Lee, Young Min Choe, Seung Hoon Lee, Kang Ko, Bo Kyung Sohn, Jun-Young Lee, Younghwa Lee, Yu Kyeong Kim, Yun-Sang Lee, Dong Young Lee, for the KBASE Research GroupAbstractBackgroundAlthough previous studies have suggested that insulin plays a role in brain function, it still remains unclear whether or not insulin has a region-specific association with neuronal and synaptic activity in the living human brain. We investigated the regional pattern of association between basal blood insulin and resting-state cerebral glucose metabolism (CMglu), a proxy for neuronal and synaptic activity, in older adults.MethodA total of 234 nondiabetic, cognitively normal (CN) older adults underwent comprehensive clinical assessment, resting-state 18F-fluodeoxyglucose (FDG)-positron emission tomography (PET) and blood sampling to determine overnight fasting blood insulin and glucose levels, as well as apolipoprotein E (APOE) genotyping.ResultsAn exploratory voxel-wise analysis of FDG-PET without a priori hypothesis demonstrated a positive association between basal blood insulin levels and resting-state CMglu in specific cerebral cortices and hippocampus, rather than in non-specific overall cerebral regions, even after controlling for the effects of APOE e4 carrier status, vascular risk factor score, body mass index, fasting blood glucose, and demographic variables. Particularly, a positive association of basal blood insulin with CMglu in the right posterior hippocampus and adjacent parahippocampal region as well as in the right inferior parietal region remained significant after multiple comparison correction. Conversely, no region showed negative association between basal blood insulin and CMglu.ConclusionsOur finding suggests that basal fasting blood insulin may have association with neuronal and synaptic activity in specific cerebral regions, particularly in the hippocampal/parahippocampal and inferior parietal regions.
  • Mapping acute lesion locations to physiological swallow impairments after

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Janina Wilmskoetter, Leonardo Bonilha, Bonnie Martin-Harris, Jordan J. Elm, Janet Horn, Heather S. BonilhaAbstractDysphagia is a common deficit after a stroke, and it is frequently associated with pneumonia, malnutrition, dehydration, and poor quality of life. It is not yet fully clear which brain regions are directly related to swallowing, and how lesions affect swallow physiology. This study aimed to assess the statistical relationship between acute stroke lesion locations and impairment of specific aspects of swallow physiology. We performed lesion symptom mapping with 68 retrospectively recruited, acute, first-ever ischemic stroke patients. Lesions were determined on diffusion weighted MRI scans. Post-stroke swallow physiology was determined using the Modified Barium Swallow Study Impairment Profile (MBSImP©™). The relationship between brain lesion location and 17 physiological aspects of swallowing were tested using voxel-based and region-based statistical associations corrected for multiple comparisons using permutation thresholding. We found that laryngeal elevation, anterior hyoid excursion, laryngeal vestibular closure, and pharyngeal residue were associated with lesioned voxels or regions of interests. All components showed distinct and overlapping lesion locations, mostly in the right hemisphere, and including cortical regions (inferior frontal gyrus, pre- and postcentral gyrus, supramarginal gyrus, angular gyrus, superior temporal gyrus, insula), subcortical regions (thalamus, amygdala) and white matter tracts (superior longitudinal fasciculus, corona radiata, internal capsule, external capsule, ansa lenticularis, lenticular fasciculus). Our findings indicate that different aspects of post-stroke swallow physiology are associated with distinct lesion locations, primarily in the right hemisphere, and primarily including sensory-motor integration areas and their corresponding white matter tracts. Future studies are needed to expand on our findings and thus, support the development of a neuroanatomical model of post-stroke swallow physiology and treatment approaches targeting the neurophysiological underpinnings of swallowing post stroke.
  • Reduced higher dimensional temporal dynamism in neurofibromatosis type 1

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Eva Mennigen, Peter Schuette, Ariana Vajdi, Laura Pacheco, Tena Rosser, Carrie E. BeardenAbstractNeurofibromatosis type 1 (NF1) is a common single gene disorder resulting in multi-organ involvement. In addition to physical manifestations such as characteristic pigmentary changes, nerve sheath tumors, and skeletal abnormalities, NF1 is also associated with increased rates of learning disabilities, attention deficit hyperactivity disorder, and autism spectrum disorder. While there are established NF1-related structural brain anomalies, including brain overgrowth and white matter disruptions, little is known regarding patterns of functional connectivity in NF1. Here, we sought to investigate functional network connectivity (FNC) in a well-characterized sample of NF1 participants (n = 30) vs. age- and sex-matched healthy controls (n = 30). We conducted a comprehensive investigation of both static as well as dynamic FNC and meta-state analysis, a novel approach to examine higher-dimensional temporal dynamism of whole-brain connectivity.We found that static FNC of the cognitive control domain is altered in NF1 participants. Specifically, connectivity between anterior cognitive control areas and the cerebellum is decreased, whereas connectivity within the cognitive control domain is increased in NF1 participants relative to healthy controls. These alterations are independent of IQ.Dynamic FNC analysis revealed that NF1 participants spent more time in a state characterized by whole-brain hypoconnectivity relative to healthy controls. However, connectivity strength of dynamic states did not differ between NF1 participants and healthy controls.NF1 participants exhibited also reduced higher-dimensional dynamism of whole-brain connectivity, suggesting that temporal fluctuations of FNC are reduced. Given that similar findings have been observed in individuals with schizophrenia, higher occurrence of hypoconnected dynamic states and reduced temporal dynamism may be more general indicators of global brain dysfunction and not specific to either disorder.
  • Functional correlates of strategy formation and verbal suppression in
           Parkinson's disease

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Megan L. Isaacs, Katie L. McMahon, Anthony J. Angwin, Bruce Crosson, David A. CoplandAbstractIndividuals with Parkinson's disease (PD) have shown impaired performance on the verbal suppression component of the Haylings Sentence Completion Test (HSCT). The present study aimed to determine whether this performance related to (i) the inability to suppress a pre-potent response or (ii) difficulty in the generation of a strategy to facilitate task execution. The study adopted a novel variation of the HSCT that isolated each process and employed fMRI to examine the associated neural correlates in a comparison of individuals with PD and matched healthy controls. No significant behavioral differences were detected between these two groups. However, fMRI results revealed atypical underlying neural activity in the PD group. Controls exhibited increased activation in the left dorsolateral prefrontal cortex and striatum when generating a response independently, relative to generation when a supporting strategy was provided. The PD group demonstrated the opposite pattern of activation, in addition to greater recruitment of right hemisphere regions. This pattern of activation was postulated to be evidence of compensatory mechanisms, acting to bolster the output of frontostriatal circuits compromised by disease pathology.
  • Multiparametric graph theoretical analysis reveals altered structural and
           functional network topology in Alzheimer's disease

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Shih-Yen Lin, Chen-Pei Lin, Tsung-Jen Hsieh, Chung-Fen Lin, Sih-Huei Chen, Yi-Ping Chao, Yong-Sheng Chen, Chih-Cheng Hsu, Li-Wei KuoAbstractAlzheimer's disease (AD), an irreversible neurodegenerative disease, is the most common type of dementia in elderly people. This present study incorporated multiple structural and functional connectivity metrics into a graph theoretical analysis framework and investigated alterations in brain network topology in patients with mild cognitive impairment (MCI) and AD. By using this multiparametric analysis, we expected different connectivity metrics may reflect additional or complementary information regarding the topological changes in brain networks in MCI or AD. In our study, a total of 73 subjects participated in this study and underwent the magnetic resonance imaging scans. For the structural network, we compared commonly used connectivity metrics, including fractional anisotropy and normalized streamline count, with multiple diffusivity-based metrics. We compared Pearson correlation and covariance by investigating their sensitivities to functional network topology. Significant disruption of structural network topology in MCI and AD was found predominantly in regions within the limbic system, prefrontal and occipital regions, in addition to widespread alterations of local efficiency. At a global scale, our results showed that the disruption of the structural network was consistent across different edge definitions and global network metrics from the MCI to AD stages. Significant changes in connectivity and tract-specific diffusivity were also found in several limbic connections. Our findings suggest that tract-specific metrics (e.g., fractional anisotropy and diffusivity) provide more sensitive and interpretable measurements than does metrics based on streamline count. Besides, the use of inversed radial diffusivity provided additional information for understanding alterations in network topology caused by AD progression and its possible origins. Use of this proposed multiparametric network analysis framework may facilitate early MCI diagnosis and AD prevention.
  • Optimal timing of tau pathology imaging and automatic extraction of a
           reference region using dynamic [18F]THK5317 PET

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): My Jonasson, Anders Wall, Konstantinos Chiotis, Antoine Leuzy, Jonas Eriksson, Gunnar Antoni, Agneta Nordberg, Mark LubberinkAbstract[18F]THK5317 is a PET tracer for in-vivo imaging of tau associated with Alzheimer's disease (AD). This work aimed to evaluate optimal timing for standardized uptake value ratio (SUVR) measures with [18F]THK5317 and automated generation of SUVR-1 and relative cerebral blood flow (R1) parametric images. Nine AD patients and nine controls underwent 90 min [18F]THK5317 scans. SUVR-1 was calculated at transient equilibrium (TE) and for seven different 20 min intervals and compared with distribution volume ratio (DVR; reference Logan). Cerebellar grey matter (MRI) was used as reference region. A supervised cluster analysis (SVCA) method was implemented to automatically generate a reference region, directly from the dynamic PET volume without the need of a structural MRI scan, for computation of SUVR-1 and R1 images for a scan duration matching the optimal timing. TE was reached first in putamen, frontal- and parietal cortex at 22 ± 4 min for AD patients and in putamen at 20 ± 0 min in controls. Over all regions and subjects, SUVR20–40-1 correlated best with DVR-1, R2 = 0.97. High correlation was found between values generated using MRI- and SVCA-based reference (R2 = 0.93 for SUVR20–40-1; R2 = 0.94 for R1). SUVR20–40 allows for accurate semi-quantitative assessment of tau pathology and SVCA may be used to obtain a reference region for calculation of both SUVR-1 and R1 with 40 min scan duration.
  • Structural covariance in subcortical stroke patients measured by automated
           MRI-based volumetry

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Caihong Wang, Lei Zhao, Yishan Luo, Jingchun Liu, Peifang Miao, Sen Wei, Lin Shi, Jingliang ChengAbstractA network-level investigation of the volumetric changes of subcortical stroke patients is still lacking. Here, we explored the alterations of structural covariance caused by subcortical stroke with automated brain volumetry. T1-weighed brain MRI scans were obtained from 63 normal controls (NC), 46 stroke patients with infarct in left internal capsule (CI_L), 33 stroke patients with infarct in right internal capsule (CI_R). We performed automatic anatomical segmentation of the T1-weighted brain images with AccuBrain. Volumetric structural covariance analyses were first performed within the basal ganglia structures that were both identified by voxel-based morphometry with AAL atlas and AccuBrain. Subsequently, we additionally included the infratentorial regions that were particularly quantified by AccuBrain for the structural covariance analyses and investigated the alterations of anatomical connections within these subcortical regions in CI_L and CI_R compared with NC. The association between the regional brain volumetry and motor function was also evaluated in stroke groups. There were significant and extensive volumetric differences in stroke patients. These significant regions were generally symmetric for CI_L and CI_R group depending on the side of stroke, involving both regions close to lesions and remote regions. The structural covariance analyses revealed the synergy volume alteration in subcortical regions both in CI_L and CI_R group. In addition, the alterations of volumetric structural covariance were more extensive in CI_L group than CI_R group. Moreover, we found that the subcortical regions with atrophy contributed to the deficits of motor function in CI_R group but not CI_L group, indicating a lesion-side effect of brain volumetric changes after stroke. These findings indicated that the chronic subcortical stroke patients have extensive disordered anatomical connections involving the whole-brain level network, and the connections patterns depend on the lesion-side.
  • Seizure detection by convolutional neural network-based analysis of scalp
           electroencephalography plot images

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Ali Emami, Naoto Kunii, Takeshi Matsuo, Takashi Shinozaki, Kensuke Kawai, Hirokazu TakahashiWe hypothesized that expert epileptologists can detect seizures directly by visually analyzing EEG plot images, unlike automated methods that analyze spectro-temporal features or complex, non-stationary features of EEG signals. If so, seizure detection could benefit from convolutional neural networks because their visual recognition ability is comparable to that of humans. We explored image-based seizure detection by applying convolutional neural networks to long-term EEG that included epileptic seizures. After filtering, EEG data were divided into short segments based on a given time window and converted into plot EEG images, each of which was classified by convolutional neural networks as ‘seizure’ or ‘non-seizure’. These resultant labels were then used to design a clinically practical index for seizure detection. The best true positive rate was obtained using a 1-s time window. The median true positive rate of convolutional neural networks labelling by seconds was 74%, which was higher than that of commercially available seizure detection software (20% by BESA and 31% by Persyst). For practical use, the median of detected seizure rate by minutes was 100% by convolutional neural networks, which was higher than the 73.3% by BESA and 81.7% by Persyst. The false alarm of convolutional neural networks' seizure detection was issued at 0.2 per hour, which appears acceptable for clinical practice. Moreover, we demonstrated that seizure detection improved when training was performed using EEG patterns similar to those of testing data, suggesting that adding a variety of seizure patterns to the training dataset will improve our method. Thus, artificial visual recognition by convolutional neural networks allows for seizure detection, which otherwise currently relies on skillful visual inspection by expert epileptologists during clinical diagnosis.Graphical abstractUnlabelled Image
  • Resting state network modularity along the prodromal late onset
           Alzheimer's disease continuum

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Joey A. Contreras, Andrea Avena-Koenigsberger, Shannon L. Risacher, John D. West, Eileen Tallman, Brenna C. McDonald, Martin R. Farlow, Liana G. Apostolova, Joaquín Goñi, Mario Dzemidzic, Yu-Chien Wu, Daniel Kessler, Lucas Jeub, Santo Fortunato, Andrew J. Saykin, Olaf SpornsAbstractAlzheimer's disease is considered a disconnection syndrome, motivating the use of brain network measures to detect changes in whole-brain resting state functional connectivity (FC). We investigated changes in FC within and among resting state networks (RSN) across four different stages in the Alzheimer's disease continuum. FC changes were examined in two independent cohorts of individuals (84 and 58 individuals, respectively) each comprising control, subjective cognitive decline, mild cognitive impairment and Alzheimer's dementia groups. For each participant, FC was computed as a matrix of Pearson correlations between pairs of time series from 278 gray matter brain regions. We determined significant differences in FC modular organization with two distinct approaches, network contingency analysis and multiresolution consensus clustering. Network contingency analysis identified RSN sub-blocks that differed significantly across clinical groups. Multiresolution consensus clustering identified differences in the stability of modules across multiple spatial scales. Significant modules were further tested for statistical association with memory and executive function cognitive domain scores. Across both analytic approaches and in both participant cohorts, the findings converged on a pattern of FC that varied systematically with diagnosis within the frontoparietal network (FP) and between the FP network and default mode network (DMN). Disturbances of modular organization were manifest as greater internal coherence of the FP network and stronger coupling between FP and DMN, resulting in less segregation of these two networks. Our findings suggest that the pattern of interactions within and between specific RSNs offers new insight into the functional disruption that occurs across the Alzheimer's disease spectrum.
  • Anodal tDCS modulates cortical activity and synchronization in Parkinson's
           disease depending on motor processing

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Anna Schoellmann, Marlieke Scholten, Barbara Wasserka, Rathinaswamy B. Govindan, Rejko Krüger, Alireza Gharabaghi, Christian Plewnia, Daniel WeissAbstractBackgroundTranscranial direct current stimulation (tDCS) may alleviate motor symptoms in Parkinson's disease (PD). However, the neurophysiological effects of tDCS on cortical activation, synchronization, and the relation to clinical motor symptoms and motor integration need characterization.ObjectiveWe aimed to explore the effect of tDCS over the left sensorimotor area on clinical motor outcome, right hand fine motor performance as well as cortical activity and synchronization in the high beta range.MethodsIn this double-blind randomized sham-controlled clinico-neurophysiological study we investigated ten idiopathic PD patients and eleven matched healthy controls (HC) on two days during an isometric precision grip task and at rest before and after ‘verum’ and ‘sham’ anodal tDCS (20 min; 1 mA; anode [C3], cathode [Fp2]). We measured clinical outcome, fine motor performance, and analysed both cortical frequency domain activity and corticocortical imaginary coherence.ResultstDCS improved PD motor symptoms. Neurophysiological features indicated a motor-task-specific modulation of activity and coherence from 22 to 27 Hz after ‘verum’ stimulation in PD. Activity was significantly reduced over the left sensorimotor and right frontotemporal area. Before stimulation, PD patients showed reduced coherence over the left sensorimotor area during motor task compared to HC, and this increased after ‘verum’ stimulation in the motor task. The activity and synchronization modulation were neither observed at rest, after sham stimulation nor in healthy controls.ConclusionVerum tDCS modulated the PD cortical network specifically during fine motor integration. Cortical oscillatory features were not in general deregulated in PD, but depended on motor processing.
  • Computerized cognitive training for Chinese mild cognitive impairment
           patients: A neuropsychological and fMRI study

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 22Author(s): Bin-Yin Li, Na-Ying He, Yuan Qiao, Hong-Min Xu, Yi-Zhou Lu, Pei-Jing Cui, Hua-Wei Ling, Fu-Hua Yan, Hui-Dong Tang, Sheng-Di ChenAbstractBackgroundComputerized multi-model training has been widely studied for its effect on delaying cognitive decline. In this study, we designed the first Chinese-version computer-based multi-model cognitive training for mild cognitive impairment (MCI) patients. Neuropsychological effects and neural activity changes assessed by functional MRI were both evaluated.MethodMCI patients in the training group were asked to take training 3–4 times per week for 6 months. Neuropsychological and resting-state fMRI assessment were performed at baseline and at 6 months. Patients in both groups were continuously followed up for another 12 months and assessed by neuropsychological tests again.Results78 patients in the training group and 63 patients in the control group accomplished 6-month follow-up. Training group improved 0.23 standard deviation (SD) of mini-mental state examination, while control group had 0.5 SD decline. Addenbrooke's cognitive examination-revised scores in attention (p = 0.002) and memory (p = 0.006), as well as stroop color-word test interference index (p = 0.038) and complex figure test-copy score (p = 0.035) were also in favor of the training effect. Difference between the changes of two groups after training was not statistically significant. The fMRI showed increased regional activity at bilateral temporal poles, insular cortices and hippocampus. However, difference between the changes of two groups after another 12 months was not statistically significant.ConclusionsMulti-model cognitive training help MCI patients to gained cognition benefit, especially in memory, attention and executive function. Functional neuroimaging provided consistent neural activation evidence. Nevertheless, after one-year follow up after last training, training effects were not significant. The study provided new evidence of beneficial effect of multi-model cognitive training.
  • Publisher’s Note

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s):
  • Erratum to typical asymmetry in the hemispheric activation during an fMRI
           verbal comprehension paradigm is related to better performance in verbal
           and non-verbal tasks in patients with epilepsy. NeuroImage: Clinical 20
           (2018) 742–752

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Irene Cano-López, Anna Calvo, Teresa Boget, Mar Carreño, Antonio Donaire, Xavier Setoain, Luis Pintor, Jordi Rumià, Esperanza González-Bono, Carme Junqué, Núria Bargalló
  • Subjective memory complaints are associated with altered resting-state
           functional connectivity but not structural atrophy

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Toshikazu Kawagoe, Keiichi Onoda, Shuhei YamaguchiAbstractResearch indicates that a subtle cognitive decline, accompanied by pathological changes, occurs in individuals with subjective memory complaints (SMC). However, there is less evidence regarding the measurement of resting-state functional connectivity to detect subtle brain network alterations in neurodegenerative illnesses before cognitive change manifestation. We investigated the correlation between SMC and cognitive performance and explored functional and structural brain changes underlying SMC severity, using behavioral and brain imaging data-driven approaches. We observed that SMC was associated with depression but not with cognitive test scores, implying that SMC represent the “worried-well”; however, this model explains only 15% of the target variance. Using a conservative threshold, we observed connectivity related to SMC severity in the lingual gyrus, cuneus, anterior insula, and superior parietal lobule. Post-hoc analysis indicated that occipital and parietal functional connectivity increased with SMC severity. In contrast, volumetric alterations were not associated with SMC, even after applying a liberal threshold. Our findings suggest that altered resting-state functional connectivity in regions associated with SMC might reflect early compensatory changes that occur before cognitive and structural abnormalities develop.
  • Reorganization of the somatosensory pathway after subacute incomplete
           cervical cord injury

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Qian Chen, Weimin Zheng, Xin Chen, Xuejing Li, Ling Wang, Wen Qin, Kuncheng Li, Nan ChenAbstractObjectiveThe main purpose of the present study was to investigate the possible somatosensory-related brain functional reorganization after traumatic spinal cord injury (SCI).MethodsThirteen patients with subacute incomplete cervical cord injury (ICCI) and thirteen age- and sex-matched healthy controls (HCs) were recruited. Eleven patients and all the HCs underwent both sensory task-related brain functional scanning and whole brain structural scanning on a 3.0 Tesla MRI system, and two patients underwent only structural scanning; the process of structural scanning was completed on thirteen patients, while functional scanning was only applied to eleven patients. We performed sensory task-related functional MRI (fMRI) to investigate the functional changes in the brain. In addition, voxel-based morphometry (VBM) was applied to explore whether any sensory-related brain structural changes occur in the whole brain after SCI.ResultsCompared with HCs, ICCI patients exhibited decreased activation in the left postcentral gyrus (postCG), the brainstem (midbrain and right pons) and the right cerebellar lobules IV-VI. Moreover, a significant positive association was found between the activation in the left PostCG and the activation in both the brainstem and the right cerebellar lobules IV-VI. Additionally, the decrease in gray matter volume (GMV) was detected in the left superior parietal lobule (SPL). The decrease of white matter volume (WMV) was observed in the right temporal lobe, the right occipital lobe, and the right calcarine gyrus. No structural change in the primary sensory cortex (S1), the secondary somatosensory cortex (S2) or the thalamus was detected.ConclusionThese functional and structural findings may demonstrate the existence of an alternative pathway in the impairment of somatosensory function after SCI, which consists of the ipsilateral cerebellum, the brainstem and the contralateral postCG. It provides a new theoretical basis for the mechanism of sensory-related brain alteration in SCI patients and the rehabilitation therapy based on this pathway in the future.
  • Graph theory analysis of DTI tractography in children with traumatic

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Christopher G. Watson, Dana DeMaster, Linda Ewing-CobbsAbstractObjectiveTo evaluate brai structural connectivity in children with traumatic injury (TI) following a motor vehicle accident using graph theory analysis of DTI tractography data.MethodsDTI scans were acquired on a 3 T Philips scanner from children aged 8–15 years approximately 2 months post-injury. The TI group consisted of children with traumatic brain injury (TBI; n = 44) or extracranial injury (EI; n = 23). Healthy control children (n = 36) were included as an age-matched comparison group. A graph theory approach was applied to DTI tractography data to investigate injury-related differences in connectivity network characteristics. Group differences in structural connectivity evidenced by graph metrics including efficiency, strength, and modularity were assessed using the multi-threshold permutation correction (MTPC) and network-based statistic (NBS) methods.ResultsAt the global network level, global efficiency and mean network strength were lower, and modularity was higher, in the TBI than in the control group. Similarly, strength was lower and modularity higher when comparing the EI to the control group. At the vertex level, nodal efficiency, vertex strength, and average shortest path length were different between all pairwise comparisons of the three groups. Both nodal efficiency and vertex strength were higher in the control than in the EI group, which in turn were higher than in the TBI group. The opposite between-group relationships were seen with path length. These between-group differences were distributed throughout the brain, in both hemispheres. NBS analysis resulted in a cluster of 22 regions and 21 edges with significantly lower connectivity in the TBI group compared to controls. This cluster predominantly involves the frontal lobe and subcortical gray matter structures in both hemispheres.ConclusionsGraph theory analysis of DTI tractography showed diffuse differences in structural brain network connectivity in children 2 months post-TI. Network differences were consistent with lower network integration and higher segregation in the injured groups compared to healthy controls. Findings suggest that inclusion of trauma-exposed comparison groups in studies of TBI outcome is warranted to better characterize the indirect effect of stress on brain networks.
  • Nuclei-specific thalamic connectivity predicts seizure frequency in
           drug-resistant medial temporal lobe epilepsy

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Hang Joon Jo, Daniel L. Kenny-Jung, Irena Balzekas, Eduardo E. Benarroch, David T. Jones, Benjamin H. Brinkmann, S. Matt Stead, Jamie J. Van Gompel, Kirk M. Welker, Gregory A. WorrellAbstractBackground and objectivesWe assessed correlations between the resting state functional connectivity (RSFC) of different thalamic nuclei and seizure frequency in patients with drug-resistant medial temporal lobe epilepsy (mTLE).MethodsSeventeen patients with mTLE and 17 sex-/age-/handedness-matched controls participated. A seed-based correlation method for the resting-state FMRI data was implemented to get RSFC maps of 70 thalamic nuclei seed masks. Group statistics for individual RSFC for subjects and seed masks were performed to obtain within-group characteristics and between-group differences with age covariates. A linear regression was applied to test whether seizure frequency correlated with thalamic nuclear RSFC with the whole brain in mTLE patients.ResultsRSFC of thalamic nuclei showed spatially distinguishable connectivity patterns that reflected principal inputs and outputs that were derived from priori anatomical knowledge. We found group differences between normal control and mTLE groups in RSFC for nuclei seeds located in various subdivisions of thalamus. The RSFCs in some of those nuclei were strongly correlated with seizure frequency.ConclusionsMediodorsal thalamic nuclei may play important roles in seizure activity or in the regulation of neuronal activity in the limbic system. The RSFC of motor- and sensory-relay nuclei may help elucidate sensory-motor deficits associated with chronic seizure activity. RSFC of the pulvinar nuclei of the thalamus could also be a key reflection of symptom-related functional deficits in mTLE.
  • Sensory-motor network functional connectivity in children with unilateral
           cerebral palsy secondary to perinatal stroke

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): K.E. Woodward, H.L. Carlson, A. Kuczynski, J. Saunders, J. Hodge, A. KirtonAbstractBackgroundPerinatal stroke is the most common cause of unilateral cerebral palsy. Mechanisms of post-stroke developmental plasticity in children are poorly understood. To better understand the relationship between functional connectivity and disability, we used resting-state fMRI to compare sensorimotor connectivity with clinical dysfunction.MethodsSchool-aged children with periventricular venous infarction (PVI) and unilateral cerebral palsy were compared to controls. Resting-state BOLD signal was acquired on 3 T MRI and analyzed using CONN in SPM12. Functional connectivity was computed between S1, M1, supplementary motor area (SMA), and thalamus of the left/non-lesioned and right/lesioned hemisphere. Primary outcome was connectivity expressed as a Fisher-transformed correlation coefficient. Motor function was measured using the Assisting Hand Assessment (AHA), and Melbourne Assessment (MA). Proprioceptive function was measured using a robotic position matching task (VarXY).ResultsParticipants included 15 PVI and 21 controls. AHA and MA in stroke patients were negatively correlated with connectivity (increased connectivity = poorer performance). Position sense was inversely correlated with connectivity (increased connectivity = improved performance) between the non-lesioned S1 and thalamus/SMA. In controls, VarXY was positively correlated with connectivity between the thalamus and bilateral sensorimotor regions.ConclusionsResting state fMRI measures of sensorimotor connectivity are associated with clinical sensorimotor function in children with unilateral cerebral palsy secondary to PVI. Greater insight into understanding reorganization of brain networks following perinatal stroke may facilitate personalized rehabilitation.
  • Dynamic changes in hippocampal diffusion and kurtosis metrics following
           experimental mTBI correlate with glial reactivity

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Kim Braeckman, Benedicte Descamps, Leen Pieters, Anne Vral, Karen Caeyenberghs, Christian VanhoveAbstractDiffusion magnetic resonance imaging biomarkers can provide quantifiable information of the brain tissue after a mild traumatic brain injury (mTBI). However, the commonly applied diffusion tensor imaging (DTI) model is not very specific to changes in the underlying cellular structures. To overcome these limitations, other diffusion models have recently emerged to provide a more complete view on the damage profile following TBI. In this study, we investigated longitudinal changes in advanced diffusion metrics following experimental mTBI, utilising three different diffusion models in a rat model of mTBI, including DTI, diffusion kurtosis imaging and a white matter model. Moreover, we investigated the association between the diffusion metrics with histological markers, including glial fibrillary acidic protein (GFAP), neurofilaments and synaptophysin in order to investigate specificity. Our results revealed significant decreases in mean diffusivity in the hippocampus and radial diffusivity and radial extra axonal diffusivity (RadEAD) in the cingulum one week post injury. Furthermore, correlation analysis showed that increased values of fractional anisotropy one day post injury in the hippocampus was highly correlated with GFAP reactivity three months post injury. Additionally, we observed a positive correlation between GFAP on one hand and the kurtosis parameters in the hippocampus on the other hand three months post injury. This result indicated that prolonged glial activation three months post injury is related to higher kurtosis values at later time points. In conclusion, our findings point out to the possible role of kurtosis metrics as well as metrics from the white matter model as prognostic biomarker to monitor prolonged glial reactivity and inflammatory responses after a mTBI not only at early timepoints but also several months after injury.
  • 7T MRI allows detection of disturbed cortical lamination of the medial
           temporal lobe in patients with Alzheimer's disease

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Boyd Kenkhuis, Laura E. Jonkman, Marjolein Bulk, Mathijs Buijs, Baayla D.C. Boon, Femke H. Bouwman, Jeroen J.G. Geurts, Wilma D.J. van de Berg, Louise van der WeerdAbstractUsing 7T T2⁎-weighted imaging, we scanned post-mortem hemispheres of Alzheimer patients and age-matched controls to describe the patterns of appearance of cortical lamination on T2*-weighted MRI in the medial temporal lobe and to assess the changes in Alzheimer patients versus controls. While controls showed a hypointense line of Baillarger in the majority of the cases, appearance of cortical lamination varied to a greater extent in the Alzheimer patients. Severely distorted cortical lamination was also observed in advanced stage Alzheimer patients and presented itself as a broad hypointense inhomogeneous band, covering a large part of the cortical width. Histology indicated that the changes in the appearance of visible cortical lamination were not only associated with myelin changes, but also with diffuse cortical iron alterations and depositions. Therefore, imaging cortical lamination alterations in Alzheimer patients using T2*-weighted MRI might provide new information on involved neuroanatomical structures in an advanced neurodegenerative stage.
  • Increased brain age in adults with Prader-Willi syndrome

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Adriana M. Azor, James H. Cole, Anthony J. Holland, Maureen Dumba, Maneesh C. Patel, Angelique Sadlon, Anthony P. Goldstone, Katherine E. ManningAbstractPrader-Willi syndrome (PWS) is the most common genetic obesity syndrome, with associated learning difficulties, neuroendocrine deficits, and behavioural and psychiatric problems. As the life expectancy of individuals with PWS increases, there is concern that alterations in brain structure associated with the syndrome, as a direct result of absent expression of PWS genes, and its metabolic complications and hormonal deficits, might cause early onset of physiological and brain aging.In this study, a machine learning approach was used to predict brain age based on grey matter (GM) and white matter (WM) maps derived from structural neuroimaging data using T1-weighted magnetic resonance imaging (MRI) scans. Brain-predicted age difference (brain-PAD) scores, calculated as the difference between chronological age and brain-predicted age, are designed to reflect deviations from healthy brain aging, with higher brain-PAD scores indicating premature aging.Two separate adult cohorts underwent brain-predicted age calculation. The main cohort consisted of adults with PWS (n = 20; age mean 23.1 years, range 19.8–27.7; 70.0% male; body mass index (BMI) mean 30.1 kg/m2, 21.5–47.7; n = 19 paternal chromosome 15q11–13 deletion) and age- and sex-matched controls (n = 40; age 22.9 years, 19.6–29.0; 65.0% male; BMI 24.1 kg/m2, 19.2–34.2) adults (BMI PWS vs. control P = .002). Brain-PAD was significantly greater in PWS than controls (effect size mean ± SEM +7.24 ± 2.20 years [95% CI 2.83, 11.63], P = .002). Brain-PAD remained significantly greater in PWS than controls when restricting analysis to a sub-cohort matched for BMI consisting of n = 15 with PWS with BMI range 21.5–33.7 kg/m2, and n = 29 controls with BMI 21.7–34.2 kg/m2 (effect size +5.51 ± 2.56 years [95% CI 3.44, 10.38], P = .037). In the PWS group, brain-PAD scores were not associated with intelligence quotient (IQ), use of hormonal and psychotropic medications, nor severity of repetitive or disruptive behaviours. A 24.5 year old man (BMI 36.9 kg/m2) with PWS from a SNORD116 microdeletion also had increased brain PAD of 12.87 years, compared to 0.84 ± 6.52 years in a second control adult cohort (n = 95; age mean 34.0 years, range 19.9–55.5; 38.9% male; BMI 28.7 kg/m2, 19.1–43.1).This increase in brain-PAD in adults with PWS indicates abnormal brain structure that may reflect premature brain aging or abnormal brain development. The similar finding in a rare patient with a SNORD116 microdeletion implicates a potential causative role for this PWS region gene cluster in the structural brain abnormalities associated primarily with the syndrome and/or its complications. Further longitudinal neuroimaging studies are needed to clarify the natural history of this increase in brain age in PWS, its relationship with obesity, and whether similar findings are seen in those with PWS from maternal uniparental disomy.
  • Identifying lesions in paediatric epilepsy using morphometric and textural
           analysis of magnetic resonance images

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Sancgeetha Kulaseharan, Azad Aminpour, Mehran Ebrahimi, Elysa WidjajaAbstractWe seek to examine the use of an image processing pipeline on Magnetic Resonance Imaging (MRI) to identify features of Focal Cortical Dysplasia (FCD) in children who were suspected to have FCD on MRI (MRI-positive) and those with MRI-negative epilepsy. We aim to use a computer-aided diagnosis system to identify epileptogenic lesions with a combination of established morphometric features and textural analysis using Gray-Level Co-occurrence Matrices (GLCM) on MRI sequences. We implemented a modified version of the 2-Step Bayesian classifier method to a paediatric cohort with medically intractable epilepsy with MRI-positive and MRI-negative epilepsy, and evaluated the performance of the algorithm trained on textural features derived from T1-weighted (T1-w), T2-weighted (T2-w), and FLAIR (Fluid Attenuated Inversion Recovery) sequences. For MRI-positive cases, T1-w has the highest subjectwise sensitivity relative to T2-w and FLAIR (94% vs. 90% vs. 71% respectively), and also the highest lesional sensitivity (63% vs. 60% vs. 42% respectively), but the lowest lesional specificity (75% vs. 80% vs. 89% respectively). Combination of all three sequences improved the performance of the algorithm, with 97% subjectwise sensitivity. For MRI-negative cases, T1-w has the highest subjectwise sensitivity relative to T2-w and FLAIR (48% vs. 30% vs. 39% respectively), and also the highest lesional sensitivity (31% vs. 22% vs. 28% respectively). However, T2-w has the highest lesional specificity relative to T1-w and FLAIR (95% vs. 94% vs. 92% respectively) for MRI-negative cases. Combination of all three sequences improved the performance of the algorithm, with 70% subjectwise sensitivity. The 2-Step Naïve Bayes classifier correctly rejected 100% of the healthy subjects for all three sequences. Using combined morphometric and textural analysis in a 2-Step Bayesian classifier, applied to multiple MRI sequences, can assist with lesion detection in children with intractable epilepsy.
  • Lack of response to disgusting food in the hypothalamus and related
           structures in Prader Willi syndrome

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Laura Blanco-Hinojo, Jesus Pujol, Susanna Esteba-Castillo, Gerard Martínez-Vilavella, Olga Giménez-Palop, Elisabeth Gabau, Laia Casamitjana, Joan Deus, Ramón Novell, Assumpta CaixàsAbstractObjectiveTo investigate, based on a putative abnormal neural processing of disgusting signals in Prader Willi syndrome (PWS) patients, the brain response to visual representations of disgusting food in PWS using functional MRI (fMRI).MethodsTwenty-one genetically-confirmed PWS patients, 30 age- and sex-matched and 28 BMI-matched control subjects viewed a movie depicting disgusting food-related scenes interspersed with scenes of appetizing food while fMRI was acquired. Brain activation maps were compared between groups and correlated with disgust and hunger ratings.ResultsAt the cortical level, the response to disgusting food representations in PWS patients was qualitatively similar to that of control subjects, albeit less extensive, and engaged brain regions typically related to visually-evoked disgust, such as the anterior insula/frontal operculum, the lateral frontal cortex and visual areas. By contrast, activation was almost absent in limbic structures directly concerned with the regulation of instinctive behavior robustly activated in control subjects, such as the hypothalamus, amygdala/hippocampus and periaqueductal gray.ConclusionsOur study provides novel insights into the neural substrates of appetite control in a genetically-mediated cause of obesity. The presence of significant cortical changes further indicates that PWS patients consciously process disgusting stimuli, but the virtual absence of response in deep, limbic structures suggests that disgusting signals do not adequately reach the primary brain system for the appetite control.
  • Thalamic diaschisis following perinatal stroke is associated with clinical

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Brandon T. Craig, Helen L. Carlson, Adam KirtonAbstractBackgroundPerinatal stroke causes most hemiparetic cerebral palsy and leads to lifelong disability. Understanding developmental neuroplasticity following early stroke is increasingly translated into novel therapies. Diaschisis refers to alterations brain structures remote from, but connected to, stroke lesions. Ipsilesional thalamic diaschisis has been described following adult stroke but has not been investigated in perinatal stroke. We hypothesized that thalamic diaschisis occurs in perinatal stroke and its degree would be inversely correlated with clinical motor function.MethodsPopulation-based, controlled cohort study. Participants were children (6 months of age, symptomatic hemiparetic cerebral palsy, and no additional neurologic disorders. Typically developing controls had comparable age and gender proportions. T1-weighted anatomical scans were parcellated into 99 regions of interest followed by generation of regional volumes. The primary outcome was thalamic volume expressed as ipsilesional (ILTV), contralesional (CLTV) and thalamic ratio (CLTV/ILTV). Standardized clinical motor assessments were correlated with thalamic volume metrics.ResultsFifty-nine participants (12.9 years old ±4.0 years, 46% female) included 20 AIS, 11 PVI, and 28 controls. ILTV was reduced in both AIS and PVI compared to controls (p 
  • Diffusion tensor imaging in anterior interosseous nerve syndrome –
           functional MR Neurography on a fascicular level

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Tim Godel, Mirko Pham, Henrich Kele, Moritz Kronlage, Daniel Schwarz, Merle Brunée, Sabine Heiland, Martin Bendszus, Philipp BäumerAbstractPurposeBy applying diffusor tensor imaging (DTI) in patients with anterior interosseous nerve syndrome (AINS), this proof of principle study aims to quantify the extent of structural damage of a peripheral nerve at the anatomical level of individual fascicles.MethodsIn this institutional review board approved prospective study 13 patients with spontaneous AINS were examined at 3 Tesla including a transversal T2-weighted turbo-spin-echo and a spin-echo echo-planar-imaging pulse sequence of the upper arm level. Calculations of quantitative DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for median nerve lesion and non-lesion fascicles as well as ulnar and radial nerve were obtained. DTI values were compared to each other and to a previously published dataset of 58 healthy controls using one-way Analysis of Variance with Bonferroni correction and p-values
  • Brain atlas for assessing the impact of tumor location on perioperative
           quality of life in patients with high-grade glioma: A prospective
           population-based cohort study

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Lisa Millgård Sagberg, Daniel Høyer Iversen, Even Hovig Fyllingen, Asgeir Store Jakola, Ingerid Reinertsen, Ole SolheimAbstractBackgroundTumor location is important for surgical decision making. Particular attention is paid to regions that contain sensorimotor and language functions, but it is unknown if these are the most important regions from the patients' perspective.ObjectiveTo develop an atlas for depicting and assessing the potential importance of tumor location for perioperative health-related quality of life (HRQoL) in patients with newly diagnosed high-grade glioma.MethodsPatient-reported HRQoL data and semi-automatically segmented preoperative 3D MRI-images were combined in 170 patients. The images were registered to a standardized space where the individual tumors were given the values and color intensity of the corresponding HRQoL. Descriptive brain maps of HRQoL, defined quantitative analyses, and voxel-based lesion symptom mapping comparing patients with tumors in different locations were made.ResultsThere was no statistical difference in overall perioperative HRQoL between patients with tumors located in left or right hemisphere, between patients with tumors in different lobes, or between patients with tumors located in non-eloquent, near eloquent, or eloquent areas. Patients with tumors involving the internal capsule, and patients with preoperative motor symptoms and postoperative motor deficits, reported significantly worse overall HRQoL-scores.ConclusionsThe impact of anatomical tumor location on overall perioperative HRQoL seems less than frequently believed, and the distinction between critical and less critical brain regions seems more unclear according to the patients than perhaps when judged by physicians. However, worse HRQoL was found in patients with tumors in motor-related regions, indicating that these areas are crucial also from the patients' perspective.
  • Optimized preoperative motor cortex mapping in brain tumors using advanced
           processing of transcranial magnetic stimulation data

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Laura Seynaeve, Tom Haeck, Markus Gramer, Frederik Maes, Steven De Vleeschouwer, Wim Van PaesschenAbstractBackground and objectiveTranscranial magnetic stimulation (TMS) is a useful technique to help localize motor function prior to neurosurgical procedures. Adequate modelling of the effect of TMS on the brain is a prerequisite to obtain reliable data.MethodsTwelve patients were included with perirolandic tumors to undergo TMS-based motor mapping. Several models were developed to analyze the mapping data, from a projection to the nearest brain surface to motor evoked potential (MEP) amplitude informed weighted average of the induced electric fields over a multilayer detailed individual head model. The probability maps were compared with direct cortical stimulation (DCS) data in all patients for the hand and in three for the foot. The gold standard was defined as the results of the DCS sampling (with on average 8 DCS-points per surgery) extrapolated over the exposed cortex (of the tailored craniotomy), and the outcome parameters were based on the similarity of the probability maps with this gold standard.ResultsAll models accurately gauge the location of the motor cortex, with point-cloud based mapping algorithms having an accuracy of 83–86%, with similarly high specificity. To delineate the whole area of the motor cortex representation, the model based on the weighted average of the induced electric fields calculated with a realistic head model performs best. The optimal single threshold to visualize the field based maps is 40% of the maximal value for the anisotropic model and 50% for the isotropic model, but dynamic thresholding adds information for clinical practice.ConclusionsThe method with which TMS mapping data are analyzed clearly affects the predicted area of the primary motor cortex representation. Realistic electric field based modelling is feasible in clinical practice and improves delineation of the motor cortex representation compared to more simple point-cloud based methods.
  • Interhemispheric connectivity and hemispheric specialization in
           schizophrenia patients and their unaffected siblings

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Xiao Chang, Guusje Collin, René C.W. Mandl, Wiepke Cahn, René S. KahnAbstractHemispheric integration and specialization are two prominent organizational principles for macroscopic brain function. Impairments of interhemispheric cooperation have been reported in schizophrenia patients, but whether such abnormalities should be attributed to effects of illness or familial risk remains inconclusive. Moreover, it is unclear how abnormalities in interhemispheric connectivity impact hemispheric specialization. To address these questions, we performed magnetic resonance imaging (MRI) in a large cohort of 253 participants, including 84 schizophrenia patients, 106 of their unaffected siblings and 63 healthy controls. Interhemispheric connectivity and hemispheric specialization were calculated from resting-state functional connectivity, and compared across groups. Results showed that schizophrenia patients exhibit lower interhemispheric connectivity as compared to controls and siblings. In addition, patients showed higher levels of hemispheric specialization as compared to siblings. Level of interhemispheric connectivity and hemispheric specialization correlated with duration of illness in patients. No significant alterations were identified in siblings relative to controls on both measurements. Furthermore, alterations in interhemispheric connectivity correlated with changes in hemispheric specialization in patients relative to controls and siblings. Taken together, these results suggest that lower interhemispheric connectivity and associated abnormalities in hemispheric specialization are features of established illness, rather than an expression of preexistent familial risk for schizophrenia.
  • Brain connectivity tracks effects of chemotherapy separately from
           behavioral measures

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Omid Kardan, Patricia A. Reuter-Lorenz, Scott Peltier, Nathan W. Churchill, Bratislav Misic, Mary K. Askren, Mi Sook Jung, Bernadine Cimprich, Marc G. BermanAbstractSeveral studies in cancer research have suggested that cognitive dysfunction following chemotherapy, referred to in lay terms as “chemobrain”, is a serious problem. At present, the changes in integrative brain function that underlie such dysfunction remain poorly understood. Recent developments in neuroimaging suggest that patterns of functional connectivity can provide a broadly applicable neuromarker of cognitive performance and other psychometric measures. The current study used multivariate analysis methods to identify patterns of disruption in resting state functional connectivity of the brain due to chemotherapy and the degree to which the disruptions can be linked to behavioral measures of distress and cognitive performance. Sixty two women (22 healthy control, 18 patients treated with adjuvant chemotherapy, and 22 treated without chemotherapy) were evaluated with neurocognitive measures followed by self-report questionnaires and open eyes resting-state fMRI scanning at three time points: diagnosis (M0, pre-adjuvant treatment), 1 month (M1), and 7 months (M7) after treatment. The results indicated deficits in cognitive health of breast cancer patients immediately after chemotherapy that improved over time. This psychological trajectory was paralleled by a disruption and later recovery of resting-state functional connectivity, mostly in the parietal and frontal brain regions. Mediation analysis showed that the functional connectivity alteration pattern is a separable treatment symptom from the decreased cognitive health. Current study indicates that more targeted support for patients should be developed to ameliorate these multi-faceted side effects of chemotherapy treatment on neural functioning and cognitive health.
  • Longitudinal changes in cocaine intake and cognition are linked to
           cortical thickness adaptations in cocaine users

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Sarah Hirsiger, Jürgen Hänggi, Jürgen Germann, Matthias Vonmoos, Katrin H. Preller, Etna J.E. Engeli, Matthias Kirschner, Caroline Reinhard, Lea M. Hulka, Markus R. Baumgartner, Mallar M. Chakravarty, Erich Seifritz, Marcus Herdener, Boris B. QuednowAbstractBackgroundCocaine use has been consistently associated with decreased gray matter volumes in the prefrontal cortex. However, it is unclear if such neuroanatomical abnormalities depict either pre-existing vulnerability markers or drug-induced consequences. Thus, this longitudinal MRI study investigated neuroplasticity and cognitive changes in relation to altered cocaine intake.MethodsSurface-based morphometry, cocaine hair concentration, and cognitive performance were measured in 29 cocaine users (CU) and 38 matched controls at baseline and follow-up. Based on changes in hair cocaine concentration, CU were classified either as Decreasers (n = 15) or Sustained Users (n = 14). Surface-based morphometry measures did not include regional tissue volumes.ResultsAt baseline, CU displayed reduced cortical thickness (CT) in lateral frontal regions, and smaller cortical surface area (CSA) in the anterior cingulate cortex, compared to controls. In Decreasers, CT of the lateral frontal cortex increased whereas CT within the same regions tended to further decrease in Sustained Users. In contrast, no changes were found for CSA and subcortical structures. Changes in CT were linked to cognitive performance changes and amount of cocaine consumed over the study period.ConclusionsThese results suggest that frontal abnormalities in CU are partially drug-induced and can recover with decreased substance use. Moreover, recovery of frontal CT is accompanied by improved cognitive performance confirming that cognitive decline associated with cocaine use is potentially reversible.
  • Positron emission tomography of tau in Iraq and Afghanistan Veterans with
           blast neurotrauma

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Meghan E. Robinson, Ann C. McKee, David H. Salat, Ann M. Rasmusson, Lauren J. Radigan, Ciprian Catana, William P. Milberg, Regina E. McGlincheyAbstractMilitary personnel are often exposed to multiple instances of various types of head trauma. As a result, there has been increasing concern recently over identifying when head trauma has resulted in a brain injury and what, if any, long-term consequences those brain injuries may have. Efforts to develop equipment to protect soldiers from these long-term consequences will first require understanding the types of head trauma that are likely responsible. In this study, we sought to identify the types of head trauma most likely to lead to the deposition of tau, a protein identified as a likely indicator of long-term negative consequences of brain injury. To define the types of head trauma in a military population, we applied a factor analysis to interviews from a larger cohort of 428 Veterans enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders. Three factors were identified: Blast Exposure, Symptom Duration, and Blunt Concussion. Sixteen male Veterans from this study and one additional male civilian (aged 25–69, mean 35.2 years) underwent simultaneous positron emission tomography/magnetic resonance imaging using a tracer that binds to tau protein, the ligand T807/AV-1451 (Flortaucipir). Standard uptake value ratios to the isthmus of the cingulate were calculated from a 20-minute time frame 70 min post-injection. We found that tracer uptake throughout the brain was associated with Blast Exposure factor beta weights, but not with either Symptom Duration or Blunt Concussion. Associations with uptake were located primarily in the cerebellar, occipital, inferior temporal and frontal regions. The data suggest that in this small, relatively young cohort of Veterans, elevated T807/AV-1451 uptake is associated with exposure to blast neurotrauma. These findings are unanticipated, as they do not match histopathological descriptions of tau pathology associated with head trauma. Continued work will be necessary to understand the nature of the regional T807/AV-1451 uptake and any associations with clinical symptoms.
  • Girls' internalizing symptoms and white matter tracts in Cortico-Limbic

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Ola Mohamed Ali, Matthew R.J. Vandermeer, Haroon I. Sheikh, Marc F. Joanisse, Elizabeth P. HaydenAbstractDysfunction in cortico-limbic circuitry is implicated in internalizing disorders (i.e., depressive and anxious disorders), but less is known about whether structural variations precede frank disorder and thus potentially mark risk. We therefore examined associations between white matter (WM) tract microstructure in cortico-limbic circuitry at age 7 and concurrent and longitudinal patterns of internalizing symptoms in 42 typically developing girls using Diffusion Tensor Imaging (DTI). Girls' internalizing symptoms were concurrently associated with reduced fractional anisotropy (FA) in segments of the cingulum bundle (CB) and the uncinate fasciculus (UF), bilaterally. Moreover, latent profile analysis showed that girls with increasing internalizing symptoms, based on assessments at ages 3, 6, 7, and 8, had reduced FA in these segments compared to girls with stably low symptoms. These results point to a putative neural mechanism underlying the course of childhood internalizing symptoms.
  • White matter integrity in schizophrenia and bipolar disorder: Tract- and
           voxel-based analyses of diffusion data from the Connectom scanner

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Daniel Mamah, Andrew Ji, Jerrel Rutlin, Joshua S. ShimonyAbstractBackgroundDiffusion imaging abnormalities have been associated with schizophrenia (SZ) and bipolar disorder (BD), indicating impaired structural connectivity. Newer methods permit the automated reconstruction of major white matter tracts from diffusion-weighted MR images in each individual's native space. Using high-definition diffusion data from SZ and BP subjects, we investigated brain white matter integrity using both an automated tract-based and voxel-based methods.MethodsUsing a protocol matched to the NIH (Young-Adult) Human Connectome Project (and collected on the same customized ‘Connectom’ scanner), diffusion scans were acquired from 87 total participants (aged 18–30), grouped as SZ (n = 24), BD (n = 33) and healthy controls (n = 30). Fractional anisotropy (FA) of eighteen white matter tracks were analyzed using the TRACULA software. Voxel-wise statistical analyses of diffusion data was carried out using the tract-based spatial statistics (TBSS) software. TRACULA group effects and clinical correlations were investigated using analyses of variance and multiple regression.ResultsTRACULA analysis identified a trend towards lower tract FA in SZ patients, most significantly in the left anterior thalamic radiation (ATR; p = .04). TBSS results showed significantly lower FA voxels bilaterally within the cerebellum and unilaterally within the left ATR, posterior thalamic radiation, corticospinal tract, and superior longitudinal fasciculus in SZ patients compared to controls (FDR corrected p 
  • Tissue-type mapping of gliomas

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Felix Raschke, Thomas R. Barrick, Timothy L. Jones, Guang Yang, Xujiong Ye, Franklyn A. HoweAbstractPurposeTo develop a statistical method of combining multimodal MRI (mMRI) of adult glial brain tumours to generate tissue heterogeneity maps that indicate tumour grade and infiltration margins.Materials and methodsWe performed a retrospective analysis of mMRI from patients with histological diagnosis of glioma (n = 25). 1H Magnetic Resonance Spectroscopic Imaging (MRSI) was used to label regions of “pure” low- or high-grade tumour across image types. Normal brain and oedema characteristics were defined from healthy controls (n = 10) and brain metastasis patients (n = 10) respectively. Probability density distributions (PDD) for each tissue type were extracted from intensity normalised proton density and T2-weighted images, and p and q diffusion maps. Superpixel segmentation and Bayesian inference was used to produce whole-brain tissue-type maps.ResultsTotal lesion volumes derived automatically from tissue-type maps correlated with those from manual delineation (p 
  • Brain processing of pictures of children in men with pedophilic disorder:
           A positron emission tomography study

    • Abstract: Publication date: 2019Source: NeuroImage: Clinical, Volume 21Author(s): Véronique Fonteille, Jérôme Redouté, Pierre Lamothe, Dominique Straub, Frank Lavenne, Didier Le Bars, Véronique Raverot, Virginie Moulier, Jean-Jacques Marchand, Aurélie Vittoz, Charlotte Leriche, Michel Pugeat, Serge StoléruAbstractAlthough structural and functional neuroimaging techniques have recently been used to investigate the mechanisms of sexual attraction to children, a hallmark of pedophilic disorder, the differences in the processing of child sexual stimuli between men attracted to children and those attracted to adults remain unclear. Here, our purpose was to identify through positron emission tomography the brain responses of 15 male outpatients with pedophilic disorder to validated visual sexual stimuli depicting children (VSSc) and to compare them with 15 male healthy controls matched for sexual orientation (to female or male adults), age, and handedness. The patients' sample comprised both offenders and non-offenders. In response to VSSc, the between-groups analysis showed that activation in the right inferior temporal cortex [Brodmann area (BA) 20] was lower in patients than in controls. Moreover, in patients but not in controls, the presentation of VSSc induced an activation in a more caudal region of the right inferior temporal gyrus (BA 37) and in the left middle occipital gyrus (BA 19). In addition, in patients the level of activation in the caudal right inferior temporal gyrus was positively correlated with ratings of sexual arousal elicited by VSSc, whereas this correlation was negative in BA 20. These results implicate the right inferior temporal gyrus as a possible candidate area mediating sexual arousal in patients with pedophilic disorder and suggest that two of its areas play opposite, i.e., activating and inhibitory, roles.
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