Structural Magnetic Resonance Imaging Scans Research Articles

Cortical and subcortical changes in patients with premenstrual syndrome

BackgroundPremenstrual syndrome (PMS) is characterized by a series of emotional, physical and behavioral symptoms. Although PMS is related to dysfunctions of the central nervous system, the neuropathological mechanism of PMS still has not been clearly established. The aim of this study is to evaluate potential differences in both cortical thickness and subcortical volumes in PMS patients compared to healthy controls (HCs). MethodsTwenty PMS patients and twenty HCs underwent a structural magnetic resonance imaging scan and clinical assessment. Cortical thickness and subcortical volumes were computed using the FreeSurfer image analysis suite. Relationships between cortical thickness/subcortical volumes and the daily rating of severity of problems (DRSP) score were then measured in patients. ResultsCompared to HCs, PMS patients exhibited reduced cortical thickness in the medial prefrontal cortex (MPFC), orbitofrontal cortex (OFC) and insula, and increased subcortical volumes of the amygdala, thalamus and pallidum. Furthermore, negative correlations were detected between the DRSP and cortical thickness in the anterior cingulate cortex and precuneus. LimitationsThe study is limited by a small sample size and narrow age range of participants. ConclusionsOur findings indicate that the abnormal morphological changes are mainly implicated in emotional regulation and visceral perception in PMS patients. We hope that our study may contribute to a better understanding of PMS.

S22. A TRANSDIAGNOSTIC NEUROANATOMICAL SIGNATURE OF PSYCHIATRIC ILLNESS

BackgroundDespite an increasing research and clinical focus on trans-diagnostic approaches to mental health, it remains unclear whether different diagnostic categories share a common neuronatomical basis. The current investigation sought to investigate whether a shared (trans-diagnostic) set of structural alterations characterized schizophrenia, depression, post-traumatic stress disorder and obsessive-compulsive disorder, and determine whether any such alterations reflected markers of psychiatric illness or pre-existing familial vulnerability.MethodsA total of 404 patients with a psychiatric diagnosis were recruited (psychosis, n=129; unipolar depression, n=92; post-traumatic stress disorder, n=91; obsessive compulsive disorder, n=92) alongside 201 healthy controls and 20 unaffected first-degree relatives. We collected structural Magnetic Resonance Imaging scans from each participant using the same 3.0 Tesla scanner and acquisition sequence, and tested for trans-diagnostic alterations using Voxel-Based Morphometry.ResultsWe report that the four psychiatric groups were all characterized by significantly greater gray matter volume in the bilateral putamen relative to healthy controls (right putamen: x=32 y=6 z=-2; z-score: 5.97; p-value<0.001 after FWE-correction; left putamen: x=-30 y=5 z=-7; z-score: 4.97; p-value=0.001 after FWE-correction). Furthermore, the volume of this region was positively correlated with severity of symptoms across groups, so that a higher gray matter volume in the putamen was associated with higher severity of symptoms (partial correlation: the results are age and gender corrected; right putamen: r=0.313, p<0.001; left putamen: =0.326, p<0.001). Bilateral putamen enlargement was also evident in unaffected relatives compared to healthy controls (right putamen: x=32 y=-6 z=2; t-value: 8.13, p-value<0.001 after FWE-correction; left putamen: x=-32 y=-8 z=2; z-score:9.39, p-value<0.001 after FWE-correction).DiscussionThese findings indicate that increased putamen volume may reflect a trans-diagnostic marker of underlying familial vulnerability to psychopathology. This raises the prospect that this region could be used to assess degree of familiar vulnerability to psychopathology above and beyond traditional diagnostic boundaries. Our investigation provides support to emerging conceptualisations of psychiatric illness, in which each disorder is best understood as a combination of diagnosis-specific features and a trans-diagnostic factor reflecting general psychopathology.

T21. ALTERATIONS OF CRY2 AND PER3 GENE EXPRESSION ARE ASSOCIATED WITH GRAY MATTER ABNORMALITIES OF THALAMIC-LIMBIC NETWORK IN UNIPOLAR DEPRESSION AND BIPOLAR DEPRESSION

BackgroundThe current study aimed to identify shared and distinct brain structure abnormalities and their relationships with circadian gene expression in patients with bipolar depression and unipolar major depression.MethodsA total of 103 subjects participated in this study, including 32 patients with bipolar depression (BDP), 26 patients with unipolar depression (UDP) and age, sex-matched 35 healthy controls were conducted brain structural magnetic resonance imaging scans and then used optimized voxel-based morphometry to explore group differences in regional gray matter volume (GMV). Circadian gene mRNA expressions in peripheral blood were measured on a subset of 12 patients with BDP, 19 patients with UDP and 33 control subjects using reverse transcription quantitative real-time polymerase chain reaction.ResultsThe GMV of the thalamus-limbic pathways had significantly increased in BDP cases relative to comparison subjects, while in UDP the increased GMV focused on the thalamus. The circadian-related gene mRNA expressions have significantly decreased in the patients with BDP, however with higher expression levels in the UDP cases. In addition, the GMV of right thalamus in the UDP was positively associated mRNA level of CRY2 gene, while the GMV of right hippocampus in the UDP was negatively associated mRNA level of PER3 gene.DiscussionOur study identified the relationship between abnormalities of thalamic-limbic network and alterations of circadian gene pathway in BDP and UDP. The shared GMV abnormality was the right thalamus. PER3 might be critical to hippocampus dysfunction in UDP, and CRY2 might be critical to thalamus dysfunction at a right-hemisphere function in BDP.

S178. ALTERED GYRIFICATION IN THE SCHIZOPHRENIA SPECTRUM

BackgroundIncreased gyrification in diverse cortical areas has been reported in patients with schizophrenia, which is considered to reflect deviations in early neurodevelopment. Schizotypal personality disorder (SPD) is thought to be a prototypic disorder within the schizophrenia spectrum, which shares biological and psychological commonalities with schizophrenia as a neurobiological basis for vulnerability factors. However, to the best of our knowledge, no magnetic resonance imaging (MRI) studies have investigated the gyrification pattern in SPD.MethodsT1-weighted structural MRI scans were obtained by 1.5-T scanner from 101 patients with schizophrenia, 46 patients with SPD, and 77 age- and gender- matched healthy control subjects. Using FreeSurfer software (version 5.3.), the local gyrification indices (LGIs) of entire cortex were obtained with the method of Schaer and colleagues. Clinical symptoms of the patients were rated with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) at the time of scanning. A general linear model controlling for age, gender, medication dose, and duration of medication was used to compare the LGIs across the groups and to conduct vertex-by-vertex whole brain LGI correlation analyses with clinical variables. This study was approved by the Committee on the Medical Ethics of Toyama University based on the declaration of Helsinki. After a complete description of the study was provided, written informed consent was obtained from all subjects.ResultsCompared with the controls, the patients with schizophrenia showed significantly higher LGI in widespread cortical areas including the bilateral frontal, parietal, and occipital regions. The patients with SPD demonstrated significantly higher LGI in the bilateral frontal and left parietal regions compared with the controls. Compared with the patients with SPD, the patients with schizophrenia showed significantly higher LGI in the left occipital and right frontal regions. Both SAPS and SANS total scores were positively correlated with LGI in the bilateral temporal regions in patients with schizophrenia, and were negatively correlated with LGI in the bilateral occipital regions in patients with SPD.DiscussionIncreased LGI in the bilateral frontal regions may be the common morphological substrates for the schizophrenia spectrum, possibly representing vulnerability to schizophrenia. In addition, increased LGI in the left occipital and right frontal regions preferentially observed in schizophrenia may have a critical role in manifestation of florid psychotic symptoms.

F206. A TRANSLATIONAL STUDY OF BEHAVIOR, BRAIN STRUCTURE AND GENE PATHWAY IN ERBB4 KNOCKOUT MICE AND FIRST-EPISODE TREATMENT-NAïVE PATIENTS WITH SCHIZOPHRENIA

BackgroundThe current study was to explore how disruption of specific molecular circuits in the cerebral cortex may cause large-scale brain structure deficits and behavior changes via a translational study in conditional Erbb4 mutant mice and patients with schizophrenia.MethodsWe conducted prepulse inhibition (PPI) and brain structural and diffusion magnetic resonance imaging (MRI) scans in 27 mice with ErbB4 knockout in parvalbumin (PV) interneurons and 23 age, sex-matched controls. Real-time quantitative polymerase chain reaction was used to assess the levels of five GABA-related transcripts in brain regions. We also measured structural and diffusion MRI and cumulative contribution of risk alleles in the GABA pathway genes using polygenic risk scores (PRS) in first-episode treatment-naïve schizophrenic patients (N=117) and age, sex-matched healthy controls (N=86).ResultsErbB4 knockout mice displayed behavioral deficit of PPI, as well as gray and white matter impairment in right sensorimotor cortical-striatal networks. We found significant correlations between gray matter volumes (GMVs) of the somatosensory cortex and PPI as well as GAD1 mRNA expression in controls but not in knockout mice. These findings were confirmed in a human sample where we observed significantly decreased gray and white matter impairment in sensorimotor cortical-striatal networks in schizophrenics. The PRS of GABA-pathway genes also displayed a negative correlation with the GMVs of the somatosensory cortex in patients.DiscussionOur study identified ErbB4 ablation induced prepulse inhibition deficits and GABAergic dysregulation in sensorimotor cortical-lateral striatal networks. We propose that ErbB4 signaling participates in sensorimotor gating dysfunction in schizophrenia by getting involved in somatosensory cortex deficits and GABAergic dysfunction.

A New Measure for Neural Compensation Is Positively Correlated With Working Memory and Gait Speed.

Neuroimaging studies suggest that older adults may compensate for declines in brain function and cognition through reorganization of neural resources. A limitation of prior research is reliance on between-group comparisons of neural activation (e.g., younger vs. older), which cannot be used to assess compensatory ability quantitatively. It is also unclear about the relationship between compensatory ability with cognitive function or how other factors such as physical exercise modulates compensatory ability. Here, we proposed a data-driven method to semi-quantitatively measure neural compensation under a challenging cognitive task, and we then explored connections between neural compensation to cognitive engagement and cognitive reserve (CR). Functional and structural magnetic resonance imaging scans were acquired for 26 healthy older adults during a face-name memory task. Spatial independent component analysis (ICA) identified visual, attentional and left executive as core networks. Results show that the smaller the volumes of the gray matter (GM) structures within core networks, the more networks were needed to conduct the task (r = −0.408, p = 0.035). Therefore, the number of task-activated networks controlling for the GM volume within core networks was defined as a measure of neural compensatory ability. We found that compensatory ability correlated with working memory performance (r = 0.528, p = 0.035). Among subjects with good memory task performance, those with higher CR used fewer networks than subjects with lower CR. Among poor-performance subjects, those using more networks had higher CR. Our results indicated that using a high cognitive-demanding task to measure the number of activated neural networks could be a useful and sensitive measure of neural compensation in older adults.

Functional connectivity maps based on hippocampal and thalamic dynamics may account for the default-mode network.

The default-mode network (DMN) has been reported to comprise a set of inter-connected transmodal cortical areas, including the posterior cingulate cortex (PCC), medial prefrontal cortex, posterior inferior parietal lobule, lateral temporal region and others. However, the subcortical constituents of the DMN are still not clear. This study aimed to examine whether the correlation maps derived from subcortical structures may also account for neural pattern of the DMN. Structural magnetic resonance imaging (MRI) and resting-state functional MRI scans of 36 subjects were selected from the Rockland sample (Nathan Kline Institute). The hippocampus and thalamus were chosen as subcortical regions of interest (ROIs). Each ROI was partitioned into composite modules which in turn provided simplified and representative dynamics of blood-oxygen-level-dependent (BOLD) signals. PCC-seeded and ROI-based correlation maps were compared by conjunction analyses and paired t-tests (corrected P<0.05). Our results unveiled that the hippocampus-, thalamus- and PCC-centred correlation patterns actually overlapped to a substantial degree. Integrating the signals in the thalamus and hippocampus altogether fully explained the PCC-seeded DMN. Supplementary analyses based on the BOLD dynamics in several subcortical nuclei (caudate, putamen and globus pallidus) were dissimilar to the DMN. The DMN derived from the ROI/seed-based approach may represent combined limbic and region-specific informatics (and their closely interacting neural substrates). The possible causes for previous methods of task-induced deactivation and seed-based correlation that failed to depict the holistic limbic picture are discussed. The neocortical manifestation of DMN may reflect the limbic information in the transmodal brain regions.

Protective Effect of Human Leukocyte Antigen (HLA) Allele DRB1*13:02 on Age-Related Brain Gray Matter Volume Reduction in Healthy Women

BackgroundReduction of brain volume (brain atrophy) during healthy brain aging is well documented and dependent on genetic, lifestyle and environmental factors. Here we investigated the possible dependence of brain gray matter volume reduction in the absence of the Human Leukocyte Antigen (HLA) allele DRB1*13:02 which prevents brain atrophy in Gulf War Illness (James et al., 2017). MethodsSeventy-one cognitively healthy women (32–69years old) underwent a structural Magnetic Resonance Imaging (sMRI) scan to measure the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter. Participants were assigned to two groups, depending on whether they lacked the DRB1*13:02 allele (No DRB1*13:02 group, N=60) or carried the DRB1*13:02 allele (N=11). We assessed the change of brain gray matter volume with age in each group by performing a linear regression where the brain volume (adjusted for total intracranial volume) was the dependent variable and age was the independent variable. FindingsIn the No DRB1*13:02 group, the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter were reduced highly significantly. In contrast, none of these volumes showed a statistically significant reduction with age in the DRB1*13:02 group. InterpretationThese findings document the protective effect of DRB1*13:02 on age-dependent reduction of brain gray matter in healthy individuals. Since the role of this allele is to connect to matching epitopes of external antigens for the subsequent production of antibodies and elimination of the offending antigen, we hypothesize that its protective effect may be due to the successful elimination of such antigens to which we are exposed during the lifespan, antigens that otherwise would persist causing gradual brain atrophy. In addition, we consider a possible beneficial role of DRB1*13:02 attributed to its binding to cathepsin S, a known harmful substance in brain aging (Wendt et al., 2008). Of course, other factors covarying with the presence of DRB1*13:02 could be involved.

Do 2-year changes in superior frontal gyrus and global brain atrophy affect cognition?

IntroductionMetabolic alterations to the superior frontal gyrus (SFG) have been linked to cognitive decline. Whether these indicate structural atrophy, which could be screened for at a larger scale using noninvasive structural imaging, is unknown. MethodsWe assessed annual structural magnetic resonance imaging scans and cognitive data from 3 consecutive years from 204 participants from the AD Neuroimaging Initiative database (mean age 72.24 [8.175] years). We evaluated associations between brain structural changes and performance in the Montreal Cognitive Assessment, Everyday Cognition Visuospatial subtest (ECog Visuospatial), and Functional Assessment Questionnaire. ResultsChanges in the surface area of the SFG were associated with changes in the outcome of the ECog Visuospatial test (P < .05), but an inconsistent pattern of association was found between the 2-year global brain atrophy progression and changes in the outcome from the three cognitive tests selected. DiscussionThe extent into which (and if) changes in the SFG influence cognition warrant further evaluation in a larger period in more heterogeneous population.

Low-dose CT for the spatial normalization of PET images: A validation procedure for amyloid-PET semi-quantification.

The reference standard for spatial normalization of brain positron emission tomography (PET) images involves structural Magnetic Resonance Imaging (MRI) data. However, the lack of such structural information is fairly common in clinical settings. This might lead to lack of proper image quantification and to evaluation based only on visual ratings, which does not allow research studies or clinical trials based on quantification.PET/CT systems are widely available and CT normalization procedures need to be explored. Here we describe and validate a procedure for the spatial normalization of PET images based on the low-dose Computed Tomography (CT) images contextually acquired for attenuation correction in PET/CT systems. We included N = 34 subjects, spanning from cognitively normal to mild cognitive impairment and dementia, who underwent amyloid-PET/CT (18F-Florbetaben) and structural MRI scans. The proposed pipeline is based on the SPM12 unified segmentation algorithm applied to low-dose CT images. The validation of the normalization pipeline focused on 1) statistical comparisons between regional and global 18F-Florbetaben-PET/CT standardized uptake value ratios (SUVrs) estimated from both CT-based and MRI-based normalized PET images (SUVrCT, SUVrMRI) and 2) estimation of the degrees of overlap between warped gray matter (GM) segmented maps derived from CT- and MRI-based spatial transformations.We found negligible deviations between regional and global SUVrs in the two CT and MRI-based methods. SUVrCT and SUVrMRI global uptake scores showed negligible differences (mean ± sd 0.01 ± 0.03). Notably, the CT- and MRI-based warped GM maps showed excellent overlap (90% within 1 mm).The proposed analysis pipeline, based on low-dose CT images, allows accurate spatial normalization and subsequent PET image quantification. A CT-based analytical pipeline could benefit both research and clinical practice, allowing the recruitment of larger samples and favoring clinical routine analysis.

Neuropsychology and neuroimaging profiles of amyloid-positive versus amyloid-negative amnestic mild cognitive impairment patients

IntroductionPatients with amnestic mild cognitive impairment (aMCI) are heterogeneous as regard to their amyloid status. The present study aimed at highlighting the neuropsychological, brain atrophy, and hypometabolism profiles of amyloid-positive (Aβpos) versus amyloid-negative (Aβneg) aMCI patients. MethodsForty-four aMCI patients and 24 Aβneg healthy controls underwent neuropsychological, structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography scans. Data were compared between groups in specific regions of interest and voxelwise with statistical parametric mapping. ResultsWhen directly comparing Aβpos to Aβneg aMCI, the former had lower performances in episodic memory tests (P = .02 to P < .001) while the latter had worse scores in working memory (P = .01) and language (P < .005). Compared to Aβneg healthy controls, both aMCI subgroups showed similar profiles of atrophy and hypometabolism, with no difference between both aMCI subgroups. ConclusionIn a sample of aMCI patients recruited and scanned in the same center, the main difference at baseline between Aβpos and Aβneg aMCI concerned the neuropsychological profile, but not the structural magnetic resonance imaging or 18F-fluorodeoxyglucose positron emission tomography profiles of brain alterations.

Grey matter density in the right caudate nucleus predicts aphasic patients’ response to speech comprehension therapy

Grey matter density in the right caudate nucleus predicts aphasic patients’ response to speech comprehension therapy

Cerebral changes and disrupted gray matter cortical networks in asymptomatic older adults at risk for Alzheimer's disease

The diagnostic value of cerebrospinal fluid (CSF) biomarkers is well established in Alzheimer's disease, but our current knowledge about how abnormal CSF levels affect cerebral integrity, at local and network levels, is incomplete in asymptomatic older adults. Here, we have collected CSF samples and performed structural magnetic resonance imaging scans in cognitively normal elderly as part of a cross-sectional multicenter study (SIGNAL project). To identify group differences in cortical thickness, white matter volume, and properties of structural networks, participants were split into controls (N = 20), positive amyloid-β (Aβ1–42+) (N = 19), and positive phosphorylated tau (N = 18). The Aβ1–42+ group exhibited thickening of middle temporal regions, while positive phosphorylated tau individuals showed thinning in the superior parietal and orbitofrontal cortices. Subjects with abnormal CSF biomarkers further showed regional white matter atrophy and more segregated cortical networks, the Aβ1–42+ group showing heightened isolation of cingulate and temporal cortices. Collectively, these findings highlight the relevance of combining structural brain imaging and connectomics for in vivo tracking of Alzheimer's disease lesions in asymptomatic stages.

Cerebral gray matter volume in patients with chronic migraine: correlations with clinical features

BackgroundTo date, few MRI studies have been performed in patients affected by chronic migraine (CM), especially in those without medication overuse. Here, we performed magnetic resonance imaging (MRI) voxel-based morphometry (VBM) analyses to investigate the gray matter (GM) volume of the whole brain in patients affected by CM. Our aim was to investigate whether fluctuations in the GM volumes were related to the clinical features of CM.MethodsTwenty untreated patients with CM without a past medical history of medication overuse underwent 3-Tesla MRI scans and were compared to a group of 20 healthy controls (HCs). We used SPM12 and the CAT12 toolbox to process the MRI data and to perform VBM analyses of the structural T1-weighted MRI scans. The GM volume of patients was compared to that of HCs with various corrected and uncorrected thresholds. To check for possible correlations, patients’ clinical features and GM maps were regressed.ResultsInitially, we did not find significant differences in the GM volume between patients with CM and HCs (p < 0.05 corrected for multiple comparisons). However, using more-liberal uncorrected statistical thresholds, we noted that compared to HCs, patients with CM exhibited clusters of regions with lower GM volumes including the cerebellum, left middle temporal gyrus, left temporal pole/amygdala/hippocampus/pallidum/orbitofrontal cortex, and left occipital areas (Brodmann areas 17/18). The GM volume of the cerebellar hemispheres was negatively correlated with the disease duration and positively correlated with the number of tablets taken per month.ConclusionNo gross morphometric changes were observed in patients with CM when compared with HCs. However, using more-liberal uncorrected statistical thresholds, we observed that CM is associated with subtle GM volume changes in several brain areas known to be involved in nociception/antinociception, multisensory integration, and analgesic dependence. We speculate that these slight morphometric impairments could lead, at least in a subgroup of patients, to the development and continuation of maladaptive acute medication usage.

Human Leukocyte Antigen (HLA) and Gulf War Illness (GWI): HLA-DRB1*13:02 Spares Subcortical Atrophy in Gulf War Veterans

BackgroundGulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990–91 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. We reported previously on the protective role of six Human Leukocyte Antigen (HLA) alleles in GWI (Georgopoulos et al., 2016) and their association with regional brain function (James et al., 2016). More recently, we reported on the presence of subcortical brain atrophy in GWI (Christova et al., 2017) and discussed its possible relation to immune mechanisms. Here we focused on one of the six HLA GWI-protective HLA alleles, DRB1*13:02, which has been found to have a protective role in a broad range of autoimmune diseases (Furukawa et al., 2017), and tested its effects on brain volumes. MethodsSeventy-six Gulf War veterans (55 with GWI and 21 healthy controls) underwent a structural Magnetic Resonance Imaging (sMRI) scan to measure the volumes of 9 subcortical brain regions to assess differences between participants with (N=11) and without (N=65) HLA class II allele DRB1*13:02. FindingsWe found that DRB1*13:02 spared subcortical brain atrophy in Gulf War veterans; overall subcortical volume was 6.6% higher in carriers of DRB1*13:02 (P=0.007). The strongest effect was observed in the volume of cerebellar gray matter which was 9.6% higher (P=0.007) in carriers of DRB1*13:02 than in non-carriers. By contrast, DRB1*13:01 had no effect. InterpretationThese findings document the protective effect of DRB1*13:02 on brain atrophy in Gulf War veterans and are in keeping with recent results documenting sharing of brain mechanisms between GWI and other immune-related diseases (Georgopoulos et al., 2017). We hypothesize that the protective role of DRB1*13:02 is due to its successful elimination of external antigens to which Gulf War veterans were exposed, antigens that otherwise would persist causing low-grade inflammation and possibly leading to autoimmunity. Funding sourceU.S. Department of Defense (W81XWH-15-1-0520), Department of Veterans Affairs, American Legion Brain Sciences Chair, and University of Minnesota.

Morphology of subcortical brain nuclei is associated with autonomic function in healthy humans.

The autonomic nervous system (ANS) is a brain body interface which serves to maintain homeostasis by influencing a plethora of physiological processes, including metabolism, cardiorespiratory regulation and nociception. Accumulating evidence suggests that ANS function is disturbed in numerous prevalent clinical disorders, including irritable bowel syndrome and fibromyalgia. While the brain is a central hub for regulating autonomic function, the association between resting autonomic activity and subcortical morphology has not been comprehensively studied and thus was our aim. In 27 healthy subjects [14 male and 13 female; mean age 30 years (range 22-53 years)], we quantified resting ANS function using validated indices of cardiac sympathetic index (CSI) and parasympathetic cardiac vagal tone (CVT). High resolution structural magnetic resonance imaging scans were acquired, and differences in subcortical nuclei shape, that is, 'deformation', contingent on resting ANS activity were investigated. CSI positively correlated with outward deformation of the brainstem, right nucleus accumbens, right amygdala and bilateral pallidum (all thresholded to corrected P < 0.05). In contrast, parasympathetic CVT negatively correlated with inward deformation of the right amygdala and pallidum (all thresholded to corrected P < 0.05). Left and right putamen volume positively correlated with CVT (r = 0.62, P = 0.0047 and r = 0.59, P = 0.008, respectively), as did the brainstem (r = 0.46, P = 0.049). These data provide novel evidence that resting autonomic state is associated with differences in the shape and volume of subcortical nuclei. Thus, subcortical morphological brain differences in various disorders may partly be attributable to perturbation in autonomic function. Further work is warranted to investigate these findings in clinical populations. Hum Brain Mapp 39:381-392, 2018. © 2017 Wiley Periodicals, Inc.

The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project

BackgroundSchizophrenia has a large genetic component, and the pathways from genes to illness manifestation are beginning to be identified. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) Consortium aims to clarify the role of genetic variation in brain abnormalities underlying schizophrenia. This article describes the GENUS Consortium sample collection. MethodsWe identified existing samples collected for schizophrenia studies consisting of patients, controls, and/or individuals at familial high-risk (FHR) for schizophrenia. Samples had single nucleotide polymorphism (SNP) array data or genomic DNA, clinical and demographic data, and neuropsychological and/or brain magnetic resonance imaging (MRI) data. Data were subjected to quality control procedures at a central site. ResultsSixteen research groups contributed data from 5199 psychosis patients, 4877 controls, and 725 FHR individuals. All participants have relevant demographic data and all patients have relevant clinical data. The sex ratio is 56.5% male and 43.5% female. Significant differences exist between diagnostic groups for premorbid and current IQ (both p<1×10−10). Data from a diversity of neuropsychological tests are available for 92% of participants, and 30% have structural MRI scans (half also have diffusion-weighted MRI scans). SNP data are available for 76% of participants. The ancestry composition is 70% European, 20% East Asian, 7% African, and 3% other. ConclusionsThe Consortium is investigating the genetic contribution to brain phenotypes in a schizophrenia sample collection of >10,000 participants. The breadth of data across clinical, genetic, neuropsychological, and MRI modalities provides an important opportunity for elucidating the genetic basis of neural processes underlying schizophrenia.

Cerebellar anatomical alterations and attention to eyes in autism

The cerebellum is implicated in social cognition and is likely to be involved in the pathophysiology of autism spectrum disorder (ASD). The goal of our study was to explore cerebellar morphology in adults with ASD and its relationship to eye contact, as measured by fixation time allocated on the eye region using an eye-tracking device. Two-hundred ninety-four subjects with ASD and controls were included in our study and underwent a structural magnetic resonance imaging scan. Global segmentation and cortical parcellation of the cerebellum were performed. A sub-sample of 59 subjects underwent an eye tracking protocol in order to measure the fixation time allocated to the eye region. We did not observe any difference in global cerebellar volumes between ASD patients and controls; however, regional analyses found a decrease of the volume of the right anterior cerebellum in subjects with ASD compared to controls. There were significant correlations between fixation time on eyes and the volumes of the vermis and Crus I. Our results suggest that cerebellar morphology may be related to eye avoidance and reduced social attention. Eye tracking may be a promising neuro-anatomically based stratifying biomarker of ASD.

Gray matter volumes of early sensory regions are associated with individual differences in sensory processing.

Sensory processing (i.e., the manner in which the nervous system receives, modulates, integrates, and organizes sensory stimuli) is critical when humans are deciding how to react to environmental demands. Although behavioral studies have shown that there are stable individual differences in sensory processing, the neural substrates that implement such differences remain unknown. To investigate this issue, structural magnetic resonance imaging scans were acquired from 51 healthy adults and individual differences in sensory processing were assessed using the Sensory Profile questionnaire (Brown et al.: Am J Occup Ther 55 (2001) 75-82). There were positive relationships between the Sensory Profile modality-specific subscales and gray matter volumes in the primary or secondary sensory areas for the visual, auditory, touch, and taste/smell modalities. Thus, the present results suggest that individual differences in sensory processing are implemented by the early sensory regions. Hum Brain Mapp 38:6206-6217, 2017. © 2017 Wiley Periodicals, Inc.

A structural MRI study of excoriation (skin-picking) disorder and its relationship to clinical severity

Excoriation (skin-picking) disorder (SPD) shares symptomology with other obsessive-compulsive and related disorders. Few studies, however, have examined the neurological profile of patients with SPD. This study examined differences in cortical thickness and basal ganglia structural volumes between 20 individuals with SPD and 16 healthy controls using magnetic resonance imaging (MRI). There were no significant differences in demographic variables (age, gender, education and race) between groups. All subjects completed a structural MRI scan and completed a battery of clinical assessments focusing on SPD symptom severity, depression and anxiety symptoms, and quality of life. No statistically significant differences in basal ganglia (caudate, putamen, and nucleus accumbens) structural volumes were found between groups. In individuals with SPD, increasing impulsiveness correlated positively with increased cortical thickness in the left insula, and skin picking severity correlated negatively with cortical thickness in the left supramarginal gyrus and a region encompassing the right inferior parietal, right temporal and right supramarginal gyrus. This study suggests similarities and differences exist in symptomology between SPD and the other obsessive-compulsive and related disorders. Additional neuroimaging research is needed to better delineate the underlying neurobiology of SPD.