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The 15q11.2 BP1-BP2 copy number variant (CNV) is associated with altered brain morphology and risk for atypical development, including increased risk for schizophrenia and learning difficulties for the deletion. However, it is still unclear whether differences in brain morphology are associated with neurodevelopmental or neurodegenerative processes. This study derived morphological brain MRI measures in 15q11.2 BP1-BP2 deletion (n = 124) and duplication carriers (n = 142), and matched deletion-controls (n = 496) and duplication-controls (n = 568) from the UK Biobank study to investigate the association with brain morphology and estimates of brain ageing. Further, we examined the ageing trajectory of age-affected measures (i.e., cortical thickness, surface area, subcortical volume, reaction time, hand grip strength, lung function, and blood pressure) in 15q11.2 BP1-BP2 CNV carriers compared to non-carriers. In this ageing population, the results from the machine learning models showed that the estimated brain age gaps did not differ between the 15q11.2 BP1-BP2 CNV carriers and non-carriers, despite deletion carriers displaying thicker cortex and lower subcortical volume compared to the deletion-controls and duplication carriers, and lower surface area compared to the deletion-controls. Likewise, the 15q11.2 BP1-BP2 CNV carriers did not deviate from the ageing trajectory on any of the age-affected measures examined compared to non-carriers. Despite altered brain morphology in 15q11.2 BP1-BP2 CNV carriers, the results did not show any clear signs of apparent altered ageing in brain structure, nor in motor, lung or heart function. The results do not indicate neurodegenerative effects in 15q11.2 BP1-BP2 CNV carriers.

Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

T1-weighted structural MRI is widely used to measure brain morphometry (e.g., cortical thickness and subcortical volumes). Accelerated scans as fast as one minute or less are now available but it is unclear if they are adequate for quantitative morphometry. Here we compared the measurement properties of a widely adopted 1.0 mm resolution scan from the Alzheimer's Disease Neuroimaging Initiative (ADNI = 5 & PRIME; 12") with two variants of highly accelerated 1.0 mm scans (compressed-sensing, CSx6 = 1 & PRIME; 12"; and wave-controlled aliasing in parallel imaging, WAVEx9 = 1 & PRIME; 09") in a test-retest study of 37 older adults aged 54 to 86 (including 19 individuals diagnosed with a neurodegenerative dementia). Rapid scans produced highly reliable morphometric measures that largely matched the quality of morphometrics derived from the ADNI scan. Regions of lower reliability and relative divergence between ADNI and rapid scan alternatives tended to occur in midline regions and regions with susceptibility -induced artifacts. Critically, the rapid scans yielded morphometric measures similar to the ADNI scan in regions of high atrophy. The results converge to suggest that, for many current uses, extremely rapid scans can replace longer scans. As a final test, we explored the possibility of a 0 & PRIME; 49" 1.2 mm CSx6 structural scan, which also showed promise. Rapid structural scans may benefit MRI studies by shortening the scan session and reducing cost, minimizing opportunity for movement, creating room for additional scan sequences, and allowing for the repetition of structural scans to increase precision of the estimates.

We present associations between neuropsychiatric symptoms (NPS) and brain morphology in a large sample of patients with mild cognitive impairment (MCI) and Alzheimer's disease with dementia (AD dementia). Several studies assessed NPS factor structure in MCI and AD dementia, but we know of no study that tested for associations between NPS factors and brain morphology. The use of factor scores increases parsimony and power. For transparency, we performed an additional analysis with selected Neuropsychiatric Inventory - Questionnaire (NPI-Q) items. Including regional cortical thickness, cortical and subcortical volumes, we examined associations between NPS and brain morphology across the whole brain in an unbiased fashion. We reported both statistical significance and effect sizes, using linear models adjusted for multiple comparisons by false discovery rate (FDR). Moreover, we included an interaction term for diagnosis and could thereby compare associations of NPS and brain morphology between MCI and AD dementia. We found an association between the factor elation and thicker right anterior cingulate cortex across MCI and AD dementia. Associations between the factors depression to thickness of the banks of the left superior temporal sulcus and psychosis to the left post-central volume depended on diagnosis: in MCI these associations were positive, in AD dementia negative. Our findings indicate that NPS in MCI and AD dementia are not exclusively associated with atrophy and support previous findings of associations between NPS and mainly frontotemporal brain structures.Objectives: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and Alzheimer's disease with dementia (AD dementia), but their brain structural correlates are unknown. We tested for associations between NPS and MRI-based cortical and subcortical morphometry in patients with MCI and AD dementia. Design: Cross-sectional. Settings: Conducted in Norway. Participants: Patients with MCI (n = 102) and AD dementia (n = 133) from the Memory Clinic and the Geriatric Psychiatry Unit at Oslo University Hospital. Measurements: Neuropsychiatric Inventory - Questionnaire (NPI-Q) severity indices were reduced using principal component analysis (PCA) and tested for associations with 170 MRI features using linear models and false discovery rate (FDR) adjustment. We also tested for differences between groups. For transparency, we added analyses with selected NPI-Q items. Results: PCA revealed four factors: elation, psychosis, depression, and motor behavior. FDR adjustment revealed a significant positive association (B = 0.20, p(FDR) < 0.005) between elation and thickness of the right caudal anterior cingulate cortex (ACC) across groups, and significant interactions between diagnosis and psychosis (B = -0.48, p(FDR) < 0.0010) on the left post-central volume and between diagnosis and depression (B = -0.40, p(FDR) < 0.005) on the thickness of the banks of the left superior temporal sulcus. Associations of apathy, anxiety, and nighttime behavior to the left temporal lobe were replicated. Conclusions: The positive association between elation and ACC thickness suggests that mechanisms other than atrophy underly elation. Interactions between diagnosis and NPS on MRI features suggest different mechanisms of NPS in our MCI and AD dementia samples. The results contribute to a better understanding of NPS brain mechanisms in MCI and AD dementia.

Funder: Evelyn Trust; doi: https://doi.org/10.13039/501100004282, Funder: James S. McDonnell Foundation (McDonnell Foundation); doi: https://doi.org/10.13039/100000913, Funder: Canadian Institute for Advanced Research (L'Institut Canadien de Recherches Avancées), The human brain entertains rich spatiotemporal dynamics, which are drastically reconfigured when consciousness is lost due to anaesthesia or disorders of consciousness (DOC). Here, we sought to identify the neurobiological mechanisms that explain how transient pharmacological intervention and chronic neuroanatomical injury can lead to common reconfigurations of neural activity. We developed and systematically perturbed a neurobiologically realistic model of whole-brain haemodynamic signals. By incorporating PET data about the cortical distribution of GABA receptors, our computational model reveals a key role of spatially-specific local inhibition for reproducing the functional MRI activity observed during anaesthesia with the GABA-ergic agent propofol. Additionally, incorporating diffusion MRI data obtained from DOC patients reveals that the dynamics that characterise loss of consciousness can also emerge from randomised neuroanatomical connectivity. Our results generalise between anaesthesia and DOC datasets, demonstrating how increased inhibition and connectome perturbation represent distinct neurobiological paths towards the characteristic activity of the unconscious brain.

Background: Substantial evidence acknowledges the complex gene-environment interplay impacting brain development and learning. Intergenerational neuroimaging allows the assessment of familial transfer effects on brain structure, function and behavior by investigating neural similarity in caregiver-child dyads. Methods: Neural similarity in the human reading network was assessed through well-used measures of brain structure (i.e., surface area (SA), gyrification (lG), sulcal morphology, gray matter volume (GMV) and cortical thickness (CT)) in 69 mother-child dyads (children's age~11 y). Regions of interest for the reading network included left-hemispheric inferior frontal gyrus, inferior parietal lobe and fusiform gyrus. Mother-child similarity was quantified by correlation coefficients and familial specificity was tested by comparison to random adult-child dyads. Sulcal morphology analyses focused on occipitotemporal sulcus interruptions and similarity was assessed by chi-square goodness of fit. Results: Significant structural brain similarity was observed for mother-child dyads in the reading network for lG, SA and GMV (r = 0.349/0.534/0.542, respectively), but not CT. Sulcal morphology associations were non-significant. Structural brain similarity in lG, SA and GMV were specific to mother-child pairs. Furthermore, structural brain similarity for SA and GMV was higher compared to CT. Conclusion: Intergenerational neuroimaging techniques promise to enhance our knowledge of familial transfer effects on brain development and disorders., Developmental Cognitive Neuroscience, 53, ISSN:1878-9293, ISSN:1878-9307

Contains fulltext : 251394.pdf (Publisher’s version ) (Open Access) Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

Previous cross-sectional research has largely associated binge drinking (BD) with changes in volume and thickness during adolescence and early adulthood. Nevertheless, the long-term alcohol-related effects on gray matter features in youths who had maintained a BD pattern over time have not yet been sufficiently explored. The present study aimed to assess group differences both cross-sectionally and longitudinally [using symmetric percent change (SPC)] on several structural measures (i.e., thickness, surface area, volume). For this purpose, magnetic resonance imaging was recorded twice within a 2-year interval; at baseline (18–19 years) and a follow-up (20–21 years). The sample included 44 university students who were classified as 16 stable binge drinkers (8 females) and 28 stable controls (13 females). Whole-brain analysis showed larger insular surface area in binge drinkers relative to controls at follow-up (cluster-wise p = 0.045). On the other hand, region of interest (ROI) analyses on thickness also revealed a group by sex interaction at follow-up (p = 0.005), indicating that BD males had smaller right rostral middle frontal gyrus thickness than both control males (p = 0.011) and BD females (p = 0.029). Similarly, ROI-based analysis on longitudinal data showed a group by sex interaction in the right nucleus accumbens (p = 0.009) which revealed a decreased volume across time in BD males than in control males (p = 0.007). Overall, continued BD pattern during emerging adulthood appears to lead to gray matter abnormalities in regions intimately involved in reward processing, emotional regulation and executive functions. Notably, some anomalies varied significantly depending on sex, suggesting a sex-specific impact of BD on typical neurodevelopment processes This work was supported by grants from the Spanish Ministerio de Sanidad, Servicios Sociales e Igualdad, Plan Nacional sobre Drogas (PNSD 2015/034), Ministerio de Economìa y Competitividad (PSI2015-70525-P) co-funded for European Regional Development Fund, MCIN/ AEI/10.13039/501100011033 (grant PID2020-113487RB-I00), and Xunta de Galicia (GRC ED431C 2017/06; ED431C 2021/08). JP-G was supported by the FPU program from the Spanish Ministerio de Educacion, Cultura y Deporte (FPU16/01573). EC-R was supported by the Swiss National Science Foundation (SNSF, Ambizione grant PZ00P2 185814). SI

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is associated with a variety of structural and psychological alterations. Recently, there has been renewed interest in using brain tissue resected during epilepsy surgery, in particular 'non-epileptic' brain samples with normal histology that can be found alongside epileptic tissue in the same epileptic patients - with the aim being to study the normal human brain organization using a variety of methods. An important limitation is that different medical characteristics of the patients may modify the brain tissue. Thus, to better determine how 'normal' the resected tissue is, it is fundamental to know certain clinical, anatomical and psychological characteristics of the patients. Unfortunately, this information is frequently not fully available for the patient from which the resected tissue has been obtained - or is not fully appreciated by the neuroscientists analyzing the brain samples, who are not necessarily experts in epilepsy. In order to present the full picture of TLE in a way that would be accessible to multiple communities (e.g., basic researchers in neuroscience, neurologists, neurosurgeons and psychologists), we have reviewed 34 TLE patients, who were selected due to the availability of detailed clinical, anatomical, and psychological information for each of the patients. Our aim was to convey the full complexity of the disorder, its putative anatomical substrates, and the wide range of individual variability, with a view toward: (1) emphasizing the importance of considering critical patient information when using brain samples for basic research and (2) gaining a better understanding of normal and abnormal brain functioning. In agreement with a large number of previous reports, this study (1) reinforces the notion of substantial individual variability among epileptic patients, and (2) highlights the common but overlooked psychopathological alterations that occur even in patients who become seizure-free after surgery. The first point is based on pre- and post-surgical comparisons of patients with hippocampal sclerosis and patients with normal-looking hippocampus in neuropsychological evaluations. The second emerges from our extensive battery of personality and projective tests, in a two-way comparison of these two types of patients with regard to pre- and post-surgical performance.

Description, The first genome-wide study of sulcal depth shows that it is highly genetically discoverable, associated with neurodevelopment., The folding of the human cerebral cortex is a highly genetically regulated process that allows for a much larger surface area to fit into the cranial vault and optimizes functional organization. Sulcal depth is a robust yet understudied measure of localized folding, previously associated with multiple neurodevelopmental disorders. Here, we report the first genome-wide association study of sulcal depth. Through the multivariate omnibus statistical test (MOSTest) applied to vertex-wise measures from 33,748 U.K. Biobank participants (mean age, 64.3 years; 52.0% female), we identified 856 genome-wide significant loci (P < 5 × 10−8). Comparisons with cortical thickness and surface area indicated that sulcal depth has higher locus yield, heritability, and effective sample size. There was a large amount of genetic overlap between these traits, with gene-based analyses indicating strong associations with neurodevelopmental processes. Our findings demonstrate sulcal depth is a promising neuroimaging phenotype that may enhance our understanding of cortical morphology.

There is compelling evidence that head injury is a significant environmental risk factor for Alzheimer’s disease (AD) and that a history of traumatic brain injury (TBI) accelerates the onset of AD. Amyloid-β plaques and tau aggregates have been observed in the post-mortem brains of TBI patients; however, the mechanisms leading to AD neuropathology in TBI are still unknown. In this study, we hypothesized that focal TBI induces changes in miRNA expression in and around affected areas, resulting in the altered expression of genes involved in neurodegeneration and AD pathology. For this purpose, we performed a miRNA array in extracts from rats subjected to experimental TBI, using the controlled cortical impact (CCI) model. In and around the contusion, we observed alterations of miRNAs associated with dementia/AD, compared to the contralateral side. Specifically, the expression of miR-9 was significantly upregulated, while miR-29b, miR-34a, miR-106b, miR-181a and miR-107 were downregulated. Via qPCR, we confirmed these results in an additional group of injured rats when compared to naïve animals. Interestingly, the changes in those miRNAs were concomitant with alterations in the gene expression of mRNAs involved in amyloid generation and tau pathology, such as β-APP cleaving enzyme (BACE1) and Glycogen synthase-3-β (GSK3β). In addition increased levels of neuroinflammatory markers (TNF-α), glial activation, neuronal loss, and tau phosphorylation were observed in pericontusional areas. Therefore, our results suggest that the secondary injury cascade in TBI affects miRNAs regulating the expression of genes involved in AD dementia.

N.H. is supported by funding from an International Max Planck Research School (IMPRS) for language sciences fellowship grant, and the work of N.H. and S.C.V. was supported by a Max Planck Research Group (MPRG) awarded to S.C.V. The work of L.V. and A.R. was supported by a Max Planck Research Group (MPRG) awarded to A.R. S.C.V. was also supported by a Human Frontiers Science Program (HFSP) Research grant (grant no. RGP0058/2016) and a UKRI Future Leaders Fellowship (grant no. MR/T021985/1). Comparative animal studies of complex behavioural traits, and their neurobiological underpinnings, can increase our understanding of their evolution, including in humans. Vocal learning, a potential precursor to human speech, is one such trait. Mammalian vocal learning is under-studied: most research has either focused on vocal learning in songbirds or its absence in non-human primates. Here, we focus on a highly promising model species for the neurobiology of vocal learning: grey seals (Halichoerus grypus). We provide a neuroanatomical atlas (based on dissected brain slices and magnetic resonance images), a labelled MRI template, a three-dimensional model with volumetric measurements of brain regions, and histological cortical stainings. Four main features of the grey seal brain stand out: (i) it is relatively big and highly convoluted; (ii) it hosts a relatively large temporal lobe and cerebellum; (iii) the cortex is similar to that of humans in thickness and shows the expected six-layered mammalian structure; (iv) there is expression of FoxP2 present in deeper layers of the cortex; FoxP2 is a gene involved in motor learning, vocal learning, and spoken language. Our results could facilitate future studies targeting the neural and genetic underpinnings of mammalian vocal learning, thus bridging the research gap from songbirds to humans and non-human primates. Our findings are relevant not only to vocal learning research but also to the study of mammalian neurobiology and cognition more in general. Postprint

Funding Information: L.F., D.M., and T.P. acknowledge the support of the Cluster of Excellence Matters of Activity. Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy—EXC 2025—390648296. T.R. received support from the Finnish Cultural Foundation. Figure 2 was visualized with the BrainNet Viewer toolbox (86). Funding was provided by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy—EXC 2025—390648296. Publisher Copyright: © 2022, The Author(s). Gliomas that infiltrate networks and systems, such as the motor system, often lead to substantial functional impairment in multiple systems. Network-based statistics (NBS) allow to assess local network differences and graph theoretical analyses enable investigation of global and local network properties. Here, we used network measures to characterize glioma-related decreases in structural connectivity by comparing the ipsi- with the contralesional hemispheres of patients and correlated findings with neurological assessment. We found that lesion location resulted in differential impairment of both short and long connectivity patterns. Network analysis showed reduced global and local efficiency in the ipsilesional hemisphere compared to the contralesional hemispheric networks, which reflect the impairment of information transfer across different regions of a network.

IMPORTANCE The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.OBJECTIVE To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).DESIGN, SETTING, AND PARTICIPANTS In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.MAIN OUTCOMES AND MEASURES Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).RESULTS Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (rho = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (rho = 0.43; 95% CI, 0.20 to 0.61; P = .001).CONCLUSIONS AND RELEVANCE This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.Question How are brain morphometric features associated with later psychosis conversion in individuals at clinical high risk (CHR) for developing psychosis?Findings In this case-control study including 3169 participants, lower cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in individuals at CHR in a manner highly consistent with thinner cortex in individuals with established psychosis. Regions that displayed lower cortical thickness in individuals at CHR who later developed a psychotic disorder additionally displayed abnormal associations with age.Meaning In this study, CHR status and later transition to psychosis was robustly associated with lower cortical thickness; abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in individuals at CHR, including pruning and myelination.This case-control study investigates baseline structural magnetic resonance imaging (MRI) differences between individuals at clinical high risk and healthy controls as well as between participants at clinical high risk who later developed a psychotic disorder and those who did not.

Mercury is a neurotoxic chemical that represents one of the greatest pollution threats to Arctic ecosystem health. Evaluating the direct neurotoxic effects of mercury in free ranging wildlife is challenging, necessitating the use of neurochemical biomarkers to assess potential sub-clinical neurological changes. The objective of this study was to characterize the distribution and speciation of mercury, as well as exposure-associated changes in neurochemistry, across multiple brain regions (n = 10) and marine mammal species (n = 5) that each occupy a trophic niche in the Arctic ecosystem. We found consistent species differences in mean brain and brain region-specific concentrations of total mercury (THg) and methyl mercury (MeHg), with higher concentrations in toothed whales (narwhal, pilot whales and harbour porpoise) compared to fur-bearing mammals (polar bear and ringed seal). Mean THg (μg/g dw) in decreasing rank order was: pilot whale (11.9) > narwhal (7.7) > harbour porpoise (3.6) > polar bear (0.6) > ringed seal (0.2). The higher THg concentrations in toothed whales was associated with a marked reduction in the percentage of MeHg (70 %) that had lower brain THg concentrations. This pattern in mercury concentration and speciation corresponded broadly to an overall higher number of mercury-associated neurochemical biomarker correlations in toothed whales. Of the 226 correlations between mercury and neurochemical biomarkers across brain regions, we found 60 (27 %) meaningful relationships (r>0.60 or p < 0.10). We add to the growing weight of evidence that wildlife accumulate mercury in their brains and demonstrate that there is variance in accumulation across species as well as across distinct brain regions, and that some of these exposures may be associated with sub-clinical changes in neurochemistry.

[Importance] Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood., [Objective] To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia., [Design, Setting, and Participants] Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244., [Main Outcomes and Measures] Interregional profiles of group difference in cortical thickness between cases and controls., [Results] A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders., [Conclusions and Relevance] In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

Determining the impact that the KIAA0319 gene has on primate brain morphology can provide insight into the evolution of human cognition and language systems. Here, we tested whether polymorphisms in KIAA0319 in chimpanzees account for gray matter volumetric variation in brain regions implicated in language and communication (particularly within the posterior superior temporal gyrus and inferior frontal gyrus). First, we identified the nature and frequencies of single nucleotide variants (SNVs) in KIAA0319 in a sample of unrelated chimpanzees (Pan troglodytes spp.). Next, we genotyped a subset of SNVs (those important for gene regulation or likely to alter protein structure/function) in a sample of chimpanzees for which in vivo T1-structural magnetic resonance imaging scans had been obtained. We then used source-based morphometry (SBM) to test for whole-brain gray matter covariation differences between chimpanzees with different KIAA0319 alleles. Finally, using histologic sections of 15 postmortem chimpanzee brains, we analyzed microstructural variation related to KIAA0319 polymorphisms in the posterior superior temporal cortex. We found that the SNVs were associated with variation in gray matter within several brain regions, including the posterior superior temporal gyrus (a region associated with language comprehension and production in humans). The microstructure analysis further revealed hemispheric differences in neuropil fraction, indicating that KIAA0319 expression may be involved in regulation of processes related to the formation and maintenance of synapses, dendrites, or axons within regions associated with communication. Significance Statement Studying the impact of language-related genes on primate brain morphology can provide insight into the evolution of human cognition and language systems. Here, we show that two KIAA0319 variants in chimpanzees are linked to differences in gray matter volume of the posterior superior temporal gyrus, a region associated with language comprehension and production in humans. Examination of the microstructure of this region showed that one KIAA0319 variant is associated with hemispheric differences in neuropil fraction, indicating that KIAA0319 expression may be involved in the formation and maintenance of synapses, dendrites, or axons within a region directly involved in communication. Together, these findings suggest that KIAA0319 variants may underlie individual variation in auditory processing and associated brain regions in nonhuman primates.

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen’s d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = −1.01/−1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

Brain networks are complex dynamical systems in which directed interactions between different areas evolve at the sub-second scale of sensory, cognitive and motor processes. Due to the highly non-stationary nature of neural signals and their unknown noise components, however, modeling dynamic brain networks has remained one of the major challenges in contemporary neuroscience. Here, we present a new algorithm based on an innovative formulation of the Kalman filter that is optimized for tracking rapidly evolving patterns of directed functional connectivity under unknown noise conditions. The Self-Tuning Optimized Kalman filter (STOK) is a novel adaptive filter that embeds a self-tuning memory decay and a recursive regularization to guarantee high network tracking accuracy, temporal precision and robustness to noise. To validate the proposed algorithm, we performed an extensive comparison against the classical Kalman filter, in both realistic surrogate networks and real electroencephalography (EEG) data. In both simulations and real data, we show that the STOK filter estimates time-frequency patterns of directed connectivity with significantly superior performance. The advantages of the STOK filter were even clearer in real EEG data, where the algorithm recovered latent structures of dynamic connectivity from epicranial EEG recordings in rats and human visual evoked potentials, in excellent agreement with known physiology. These results establish the STOK filter as a powerful tool for modeling dynamic network structures in biological systems, with the potential to yield new insights into the rapid evolution of network states from which brain functions emerge., Author summary During normal behavior, brains transition between functional network states several times per second. This allows humans to quickly read a sentence, and a frog to catch a fly. Understanding these fast network dynamics is fundamental to understanding how brains work, but up to now it has proven very difficult to model fast brain dynamics for various methodological reasons. To overcome these difficulties, we designed a new Kalman filter (STOK) by innovating on previous solutions from control theory and state-space modelling. We show that STOK accurately models fast network changes in simulations and real neural data, making it an essential new tool for modelling fast brain networks in the time and frequency domain.

Human brain development involves spatially and temporally heterogeneous changes, detectable across a wide range of magnetic resonance imaging (MRI) measures. Investigating the interplay between multimodal MRI and polygenic scores (PGS) for personality traits associated with mental disorders in youth may provide new knowledge about typical and atypical neurodevelopment. We derived independent components across cortical thickness, cortical surface area, and grey/white matter contrast (GWC) (n = 2596, 3–23 years), and tested for associations between these components and age, sex and-, in a subsample (n = 878), PGS for neuroticism. Age was negatively associated with a single-modality component reflecting higher global GWC, and additionally with components capturing common variance between global thickness and GWC, and several multimodal regional patterns. Sex differences were found for components primarily capturing global and regional surface area (boys > girls), but also regional cortical thickness. For PGS for neuroticism, we found weak and bidirectional associations with a component reflecting right prefrontal surface area. These results indicate that multimodal fusion is sensitive to age and sex differences in brain structure in youth, but only weakly to polygenic load for neuroticism.

Understanding complex body-brain processes and the interplay between adipose tissue and brain health is important for understanding comorbidity between psychiatric and cardiometabolic disorders. We investigated associations between brain structure and anthropometric and body composition measures using brain magnetic resonance imaging (MRI; n=24,728) and body MRI (n=4973) of generally healthy participants in the UK Biobank. We derived regional and global measures of brain morphometry using FreeSurfer and tested their association with (i) anthropometric measures, and (ii) adipose and muscle tissue measured from body MRI. We identified several significant associations with small effect sizes. Anthropometric measures showed negative, nonlinear, associations with cerebellar/cortical gray matter, and brain stem structures, and positive associations with ventricular volumes. Subcortical structures exhibited mixed effect directionality, with strongest positive association for accumbens. Adipose tissue measures, including liver fat and muscle fat infiltration, were negatively associated with cortical/cerebellum structures, while total thigh muscle volume was positively associated with brain stem and accumbens. Regional investigations of cortical area, thickness, and volume indicated widespread and largely negative associations with anthropometric and adipose tissue measures, with an opposite pattern for thigh muscle volume. Self-reported diabetes, hypertension, or hypercholesterolemia were associated with brain structure. The findings provide new insight into physiological body-brain associations suggestive of shared mechanisms between cardiometabolic risk factors and brain health. Whereas the causality needs to be determined, the observed patterns of body-brain relationships provide a foundation for understanding the underlying mechanisms linking psychiatric disorders with obesity and cardiovascular disease, with potential for the development of new prevention strategies. Funding Agencies|Research Council of NorwayResearch Council of Norway [223273, 276082]; South-Eastern Norway Regional Health Authority [2017112, 2020060]; Kristian Gerhard Jebsen Stiftelsen [SKGJ-MED-021]; European UnionEuropean Commission [847776]; European Research Council (ERC) StGEuropean Research Council (ERC) [802998]

During the sleep-wake cycle, the brain undergoes profound dynamical changes, which manifest subjectively as transitions between conscious experience and unconsciousness. Yet, neurophysiological signatures that can objectively distinguish different consciousness states based are scarce. Here, we show that differences in the level of brain-wide signals can reliably distinguish different stages of sleep and anesthesia from the awake state in human and monkey fMRI resting state data. Moreover, a whole-brain computational model can faithfully reproduce changes in global synchronization and other metrics such as functional connectivity, structure-function relationship, integration and segregation across vigilance states. We demonstrate that the awake brain is close to a Hopf bifurcation, which naturally coincides with the emergence of globally correlated fMRI signals. Furthermore, simulating lesions of individual brain areas highlights the importance of connectivity hubs in the posterior brain and subcortical nuclei for maintaining the model in the awake state, as predicted by graph-theoretical analyses of structural data. G.D. was supported by the Spanish Research Project AWAKENING: using whole-brain models perturbational approaches for predicting external stimulation to force transitions between different brain states, ref. PID2019-105772GB-I00 /AEI/10.13039/501100011033, financed by the Spanish Ministry of Science, Innovation and Universities (MCIU), State Research Agency (AEI), and by the Catalan AGAUR program 2017 SGR 1545. G.D., G.H. and G.Z. received support from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 720270 (Human Brain Project SGA1), No. 785907 (Human Brain Project SGA2) and No. 945539 (Human Brain Project SGA3). G.H. was funded by the grant CONSCBRAIN (n. 661583) of the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie action. G.D. and G.H. received funding from the German Research Council (DFG, No. KN 588/7 – 1) within the priority program Computational Connectomics (SPP 2041). E.T. and H.L. were supported by the Bundesministerium für Bildung und Forschung (grant number 01 EV 0703) and the LOEWE Neuronale Koordination Forschungsschwerpunkt Frankfurt (NeFF). M.L.K. is supported by the ERC Consolidator Grant: CAREGIVING (n. 615539), Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117), and centre for Eudaimonia and Human Flourishing funded by the Pettit and Carlsberg Foundations.

Dmrt5 (Dmrta2) and Dmrt3 are key regulators of cortical patterning and progenitor proliferation and differentiation. In this study, we show an altered apical to intermediate progenitor transition, with a delay in SP neurogenesis and premature birth of Ctip2+ cortical neurons in Dmrt5-/- mice. In addition to the cortical progenitors, DMRT5 protein appears present in postmitotic subplate (SP) and marginal zone neurons together with some migrating cortical neurons. We observed the altered split of preplate and the reduced SP and disturbed radial migration of cortical neurons into cortical plate in Dmrt5-/- brains and demonstrated an increase in the proportion of multipolar cells in primary neuronal cultures from Dmrt5-/- embryonic brains. Dmrt5 affects cortical development with specific time sensitivity that we described in two conditional mice with slightly different deletion time. We only observed a transient SP phenotype at E15.5, but not by E18.5 after early (Dmrt5lox/lox;Emx1Cre), but not late (Dmrt5lox/lox;NestinCre) deletion of Dmrt5. SP was less disturbed in Dmrt5lox/lox;Emx1Cre and Dmrt3-/- brains than in Dmrt5-/- and affects dorsomedial cortex more than lateral and caudal cortex. Our study demonstrates a novel function of Dmrt5 in the regulation of early SP formation and radial cortical neuron migration. SUMMARY STATEMENT: Our study demonstrates a novel function of Dmrt5 in regulating marginal zone and subplate formation and migration of cortical neurons to cortical plate., SCOPUS: ar.j, info:eu-repo/semantics/published

Funder: Royal Children's Hospital Foundation; funder-id: http://dx.doi.org/10.13039/100014607, Funder: FP7 Ideas: European Research Council (); Grant(s): 319456, Interruption to gestation through preterm birth can significantly impact cortical development and have long-lasting adverse effects on neurodevelopmental outcome. We compared cortical morphology captured by high-resolution, multimodal magnetic resonance imaging (MRI) in n = 292 healthy newborn infants (mean age at birth = 39.9 weeks) with regional patterns of gene expression in the fetal cortex across gestation (n = 156 samples from 16 brains, aged 12 to 37 postconceptional weeks [pcw]). We tested the hypothesis that noninvasive measures of cortical structure at birth mirror areal differences in cortical gene expression across gestation, and in a cohort of n = 64 preterm infants (mean age at birth = 32.0 weeks), we tested whether cortical alterations observed after preterm birth were associated with altered gene expression in specific developmental cell populations. Neonatal cortical structure was aligned to differential patterns of cell-specific gene expression in the fetal cortex. Principal component analysis (PCA) of 6 measures of cortical morphology and microstructure showed that cortical regions were ordered along a principal axis, with primary cortex clearly separated from heteromodal cortex. This axis was correlated with estimated tissue maturity, indexed by differential expression of genes expressed by progenitor cells and neurons, and engaged in stem cell differentiation, neuron migration, and forebrain development. Preterm birth was associated with altered regional MRI metrics and patterns of differential gene expression in glial cell populations. The spatial patterning of gene expression in the developing cortex was thus mirrored by regional variation in cortical morphology and microstructure at term, and this was disrupted by preterm birth. This work provides a framework to link molecular mechanisms to noninvasive measures of cortical development in early life and highlights novel pathways to injury in neonatal populations at increased risk of neurodevelopmental disorder.

Structural grey matter covariance networks provide an individual quantification of morphological patterns in the brain. The network integrity is disrupted in sporadic Alzheimer’s disease, and network properties show associations with the level of amyloid pathology and cognitive decline. Therefore, these network properties might be disease progression markers. However, it remains unclear when and how grey matter network integrity changes with disease progression. We investigated these questions in autosomal dominant Alzheimer’s disease mutation carriers, whose conserved age at dementia onset allows individual staging based upon their estimated years to symptom onset. From the Dominantly Inherited Alzheimer Network observational cohort, we selected T1-weighted MRI scans from 269 mutation carriers and 170 non-carriers (mean age 38 ± 15 years, mean estimated years to symptom onset −9 ± 11), of whom 237 had longitudinal scans with a mean follow-up of 3.0 years. Single-subject grey matter networks were extracted, and we calculated for each individual the network properties which describe the network topology, including the size, clustering, path length and small worldness. We determined at which time point mutation carriers and non-carriers diverged for global and regional grey matter network metrics, both cross-sectionally and for rate of change over time. Based on cross-sectional data, the earliest difference was observed in normalized path length, which was decreased for mutation carriers in the precuneus area at 13 years and on a global level 12 years before estimated symptom onset. Based on longitudinal data, we found the earliest difference between groups on a global level 6 years before symptom onset, with a greater rate of decline of network size for mutation carriers. We further compared grey matter network small worldness with established biomarkers for Alzheimer disease (i.e. amyloid accumulation, cortical thickness, brain metabolism and cognitive function). We found that greater amyloid accumulation at baseline was associated with faster decline of small worldness over time, and decline in grey matter network measures over time was accompanied by decline in brain metabolism, cortical thinning and cognitive decline. In summary, network measures decline in autosomal dominant Alzheimer’s disease, which is alike sporadic Alzheimer’s disease, and the properties show decline over time prior to estimated symptom onset. These data suggest that single-subject networks properties obtained from structural MRI scans form an additional non-invasive tool for understanding the substrate of cognitive decline and measuring progression from preclinical to severe clinical stages of Alzheimer’s disease., Grey matter covariance networks are extracted from structural MRI. In the DIAN autosomal dominant Alzheimer’s disease family cohort, we demonstrate for the first time the trajectory of network properties in Alzheimer’s disease. These network properties related to other eurodegeneration markers and can form a non-invasive tool for studying Alzheimer’s disease progression., Graphical Abstract Graphical Abstract

Funder: Tampereen Yliopisto (University of Tampere); doi: https://doi.org/10.13039/501100004371, Funder: Tekes (Finnish Funding Agency for Innovation); doi: https://doi.org/10.13039/501100003406, Human pluripotent stem cell (hPSC)-derived neurons provide exciting opportunities for in vitro modeling of neurological diseases and for advancing drug development and neurotoxicological studies. However, generating electrophysiologically mature neuronal networks from hPSCs has been challenging. Here, we report the differentiation of functionally active hPSC-derived cortical networks on defined laminin-521 substrate. We apply microelectrode array (MEA) measurements to assess network events and compare the activity development of hPSC-derived networks to that of widely used rat embryonic cortical cultures. In both of these networks, activity developed through a similar sequence of stages and time frames; however, the hPSC-derived networks showed unique patterns of bursting activity. The hPSC-derived networks developed synchronous activity, which involved glutamatergic and GABAergic inputs, recapitulating the classical cortical activity also observed in rodent counterparts. Principal component analysis (PCA) based on spike rates, network synchronization and burst features revealed the segregation of hPSC-derived and rat network recordings into different clusters, reflecting the species-specific and maturation state differences between the two networks. Overall, hPSC-derived neural cultures produced with a defined protocol generate cortical type network activity, which validates their applicability as a human-specific model for pharmacological studies and modeling network dysfunctions.

We have previously identified 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid (ATPCA) as the most potent substrate-inhibitor of the betaine/GABA transporter 1 (BGT1) (IC50 2.5 mu M) reported to date. Herein, we characterize the binding mode of 20 novel analogs and propose the molecular determinants driving BGT1-selectivity. A series of N-1-, exocyclic-N-, and C-4-substituted analogs was synthesized and pharmacologically characterized in radioligand-based uptake assays at the four human GABA transporters (hGATs) recombinantly expressed in mammalian cells. Overall, the analogs retained subtype-selectivity for hBGT1, though with lower inhibitory activities (mid to high micromolar IC50 values) compared to ATPCA. Further characterization of five of these BGT1-active analogs in a fluorescence-based FMP assay revealed that the compounds are substrates for hBGT1, suggesting they interact with the orthosteric site of the transporter. In silico-guided mutagenesis experiments showed that the non-conserved residues Q299 and E52 in hBGT1 as well as the conformational flexibility of the compounds potentially contribute to the subtype-selectivity of ATPCA and its analogs. Overall, this study provides new insights into the molecular interactions governing the subtype-selectivity of BGT1 substrate-inhibitors. The findings may guide the rational design of BGT1-selective pharmacological tool compounds for future drug discovery.

Using ultra-high field fMRI, we explored the cortical depth-dependent stability of acoustic feature preference in human auditory cortex. We collected responses from human auditory cortex (subjects from either sex) to a large number of natural sounds at submillimeter spatial resolution, and observed that these responses were well explained by a model that assumes neuronal population tuning to frequency-specific spectrotemporal modulations. We observed a relatively stable (columnar) tuning to frequency and temporal modulations. However, spectral modulation tuning was variable throughout the cortical depth. This difference in columnar stability between feature maps could not be explained by a difference in map smoothness, as the preference along the cortical sheet varied in a similar manner for the different feature maps. Furthermore, tuning to all three features was more columnar in primary than nonprimary auditory cortex. The observed overall lack of overlapping columnar regions across acoustic feature maps suggests, especially for primary auditory cortex, a coding strategy in which across cortical depths tuning to some features is kept stable, whereas tuning to other features systematically varies. SIGNIFICANCE STATEMENT In the human auditory cortex, sound aspects are processed in large-scale maps. Invasive animal studies show that an additional processing organization may be implemented orthogonal to the cortical sheet (i.e., in the columnar direction), but it is unknown whether observed organizational principles apply to the human auditory cortex. Combining ultra-high field fMRI with natural sounds, we explore the columnar organization of various sound aspects. Our results suggest that the human auditory cortex contains a modular coding strategy, where, for each module, several sound aspects act as an anchor along which computations are performed while the processing of another sound aspect undergoes a transformation. This strategy may serve to optimally represent the content of our complex acoustic natural environment.

Recently, an increasing interest in investigating interactions between brain regions using functional connectivity (FC) methods has shifted the initial focus of cognitive neuroimaging research from localizing functional circuits based on task activation to mapping brain networks based on intrinsic FC dynamics. Leveraging the advantages of the latter approach, it has been shown that despite primarily invariant intrinsic organization of the large-scale functional networks, interactions between and within these networks significantly differ between various behavioral and cognitive states. These differences presumably indicate transient reconfiguration of functional connections-an instantaneous process that flexibly mediates and calibrates human behavior according to momentary demands of the environment. Nevertheless, the specificity of these reconfigured FC patterns to the task at hand and their relevance to adaptive processes during learning remain elusive. To address this knowledge gap, we investigated (1) to what extent FC within the somatomotor network is reconfigured during motor skill practice, and (2) how these changes are related to learning. We applied a seed-driven FC approach to data collected during a continuous task-free condition, so-called resting state, and during a motor sequence learning task using functional magnetic resonance imaging. During the task, participants repeatedly performed a short five-element sequence with their non-dominant (left) hand. As predicted, such unimanual sequence production was associated with lateralized activation of the right somatomotor cortex (SMC). Using this "active" region as a seed, here we show that unimanual performance of the motor sequence relies on functional segregation between the two SMC and selective integration between the "active" SMC and supplementary motor area. Whereas, greater segregation between the two SMC was associated with gains in performance rate, greater segregation within the "active" SMC itself was associated with more consistent performance by the end of training. Nether the resting-state FC patterns within the somatomotor network nor their relative modulation by the task state predicted these behavioral benefits of learning. Our results suggest that task-induced FC changes reflect reconfiguration of the connectivity patterns within the somatomotor network rather than a simple amplification or silencing of its intrinsic dynamics. Such reconfiguration not only supports motor behavior but may also predict learning. ispartof: FRONTIERS IN NEUROLOGY vol:10 ispartof: location:Switzerland status: published

Resting-state fMRI is widely used to study brain function and connectivity. However, interpreting patterns of resting state (RS) fMRI activity remains challenging as they may arise from different neuronal mechanisms than those triggered by exogenous events. Currently, this limits the use of RS-fMRI for understanding cortical function in health and disease. Here, we examine the phase synchronization (PS) properties of blood-oxygen level dependent (BOLD) signals obtained during visual field mapping (VFM) and RS with 7T fMRI. This data-driven approach exploits spatiotemporal covariations in the phase of BOLD recordings to establish the presence of clusters of synchronized activity. We find that, in both VFM and RS data, selecting the most synchronized neighboring recording sites identifies spatially localized PS clusters that follow the topographic organization of the visual cortex. However, in activity obtained during VFM, PS is spatially more extensive than in RS activity, likely reflecting stimulus-driven interactions between local responses. Nevertheless, the similarity of the PS clusters obtained for RS and stimulus-driven fMRI suggest that they share a common neuroanatomical origin. Our finding justifies and facilitates direct comparison of RS and stimulus-evoked activity. (C) 2017 Elsevier Inc. All rights reserved.

Resting-state fMRI is widely used to study brain function and connectivity. However, interpreting patterns of resting state (RS) fMRI activity remains challenging as they may arise from different neuronal mechanisms than those triggered by exogenous events. Currently, this limits the use of RS-fMRI for understanding cortical function in health and disease. Here, we examine the phase synchronization (PS) properties of blood-oxygen level dependent (BOLD) signals obtained during visual field mapping (VFM) and RS with 7T fMRI. This data-driven approach exploits spatiotemporal covariations in the phase of BOLD recordings to establish the presence of clusters of synchronized activity. We find that, in both VFM and RS data, selecting the most synchronized neighboring recording sites identifies spatially localized PS clusters that follow the topographic organization of the visual cortex. However, in activity obtained during VFM, PS is spatially more extensive than in RS activity, likely reflecting stimulus-driven interactions between local responses. Nevertheless, the similarity of the PS clusters obtained for RS and stimulus-driven fMRI suggest that they share a common neuroanatomical origin. Our finding justifies and facilitates direct comparison of RS and stimulus-evoked activity. (C) 2017 Elsevier Inc. All rights reserved.