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Abstract: While a large number of studies have examined brain volume differences associated with cocaine use, much less is known about structural differences related to amphetamine-type stimulant (ATS) use. What is known about cocaine may help to interpret emerging information on the interaction of brain volume with ATS consumption. To date, volumetric studies on the two types of stimulant have focused almost exclusively on brain differences associated with chronic use. There is considerable variability in the findings between studies which may be explained in part by the wide variety of methodologies employed. Despite this variability, seven recurrent themes are worth noting: (1) loci of lower cortical volume (approximately 10% on average) are consistently reported, (2) almost all studies indicate less volume in all or parts of the frontal cortex, (3) more specifically, a core group of studies implicate the ventromedial prefrontal cortex (including the medial portion of the orbital frontal cortex) and (4) the insula, (5) an enlarged striatal volume has been repeatedly observed, (6) reports on volume differences in the hippocampus and amygdala have been equivocal, (7) evidence supporting differential interaction of brain structure with cocaine vs. ATS is scant but the volume of all or parts of the temporal cortex appear lower in a majority of studies on cocaine but not ATS. Future research should include longitudinal designs on larger sample sizes and examine other stages of exposure to psychostimulants. [Copyright &y& Elsevier]

Abstract: Tinnitus is a heterogeneous disorder with respect to its etiology and phenotype. Thus, the identification of sub-types implicates high relevance for treatment recommendations. For this aim, we used cluster analysis of patients for which clinical data, positron-emission tomography (PET) data and voxel-based morphometry (VBM) data were available. 44 patients with chronic tinnitus were included in this analysis. On a phenotypical level, we used tinnitus distress, duration, and laterality for clustering. To correct PET and VBM data for age, gender, and hearing, we built up a design matrix including these variables as regressors and extracted the residuals. We applied Ward''s clustering method and forced cluster analysis to divide the data into two groups for both imaging and phenotypical data. On a phenotypical level the clustered groups differed only in tinnitus laterality (uni- vs. bilateral tinnitus), but not in tinnitus duration, distress, age, gender, and hearing. For grey matter volume, groups differed mainly in frontal, cingulate, temporal, and thalamic areas. For glucose metabolism, groups differed in temporal and parietal areas. The correspondence of classification was near chance level for the interrelationship of all three data set clusters. Thus, we showed that clustering according to imaging data is feasible and might depict a new approach for identifying tinnitus sub-types. However, it remains an open question to what extent the phenotypical and imaging levels may be interrelated. This article is part of a Special Issue entitled: Tinnitus Neuroscience. [Copyright &y& Elsevier]

The brain regions functionally engaged in motor sequence learning and performance are well established, but the structural characteristics of these regions and the fibre pathways involved have been less well studied. In addition, relatively few studies have combined multiple magnetic resonance imaging (MRI) measures with and behavioural performance measures in the same sample. Therefore, the current study used diffusion tensor imaging, probabilistic tractography, and voxel-based morphometry to determine the structural correlates of skilled motor performance. Further, we compared these findings with fMRI results in the same sample. We correlated final performance and rate of improvement measures on a temporal motor sequence task with skeletonised fractional anisotropy (FA) and whole brain grey matter (GM) volume. Final synchronisation performance was negatively correlated with FA in white -matter underlying bilateral sensorimotor cortex - an effect that was mediated by a positive correlation with radial diffusivity. Multi-fibre tractography indicated that this region contained crossing fibres from the corticospinal tract and superior longitudinal fasciculus (SLF). The traced identified SLF pathway linked parietal and auditory cortical regions that have been shown to be functionally engaged in this task. Thus, we hypothesise that enhanced synchronisation performance on this task may be related to greater fibre integrity of the SLF. Rate of improvement on synchronisation was positively correlated with GM volume in cerebellar lobules HVI and V - regions that showed training-related decreases in activity in the same sample. Taken together, our results link individual differences in brain structure and function to motor sequence learning and performance on the same task. Further, our study illustrates the utility of using multiple MR measures and analysis techniques to specify the interpretation of structural findings. [ABSTRACT FROM AUTHOR]

Abstract: Regional brain grey matter volume (GMV) reductions and abnormal cerebrospinal fluid (CSF) levels of τ and Aβ, extensively studied as biomarkers of Alzheimer''s disease (AD), have also been reported in Parkinson''s disease (PD) and related dementia (PDD). However, the relationship between these CSF and MRI biomarkers in PD and PDD remains unexplored. We studied these associations in 33 PD patients (18 with no dementia [PDND]; 15 fulfilling PDD criteria) and 12 neurologically unimpaired controls, with neuropsychological assessment, CSF ELISA studies, and voxel-based morphometry (VBM) analysis of high-field brain MRI. Neuropsychological assessment showed a gradation in cognitive performance from controls to PDND (significantly worse on visuospatial performance) and then to PDD (more impaired on memory, naming, fluency and visuospatial functions). No CSF-VBM correlations were found in controls or PDND patients. In contrast, in the analysis of both the PDD subgroup and the entire PD (PDND + PDD) sample, we found significant negative CSF-GMV correlations for τ and phospho-τ and significant positive CSF-GMV correlations for Aβ in mostly frontal and temporal structures. The correlations in the entire PD sample fitted with a linear model and were thus unlikely to have been driven solely by the PDD subgroup. Additionally, an association between both the CSF markers and the CSF-associated GMV reductions with several neuropsychological functions was found. We interpret that CSF markers of AD pathology are associated with VBM-measures of brain atrophy in PD-related dementia and within the PD cognitive continuum, and deserve further attention as putative biomarkers of cognitive impairment and dementia in PD. [Copyright &y& Elsevier]

Abstract: Structural brain changes are amongst the most robust biological alterations in schizophrenia, and their investigation in unaffected relatives is important for an assessment of the contribution of genetic factors. In this cross-sectional morphometry study we investigated whether volume changes in SZ are linked with genetic vulnerability and whether these effects are separated from secondary illness effects. We compared density of grey and white matter using high-resolution 3D-anatomical MRI imaging data in 31 SZ patients, 29 first-degree relatives and 38 matched healthy controls, using Voxel-Based Morphometry (VBM) with SPM8. Volume of basal ganglia was also compared by manual segmentation. We found increased grey matter in the striatum, globus pallidus internus and thalamus and decreased grey matter in the parahippocampal and cingulate gyri both in SZ patients and relatives. Additionally, SZ patients had decreased volume of temporal, frontal and limbic grey and white matter in comparison with relatives and controls. Relatives showed intermediate values in many of these areas. Increased volume in the thalamus and parts of the basal ganglia and decreased volume of cortical areas and underlying white matter were thus associated with schizophrenia and its genetic vulnerability. These results suggest that brain morphological changes associated with SZ are in part determined by genetic risk factors and are not entirely explained by effects of medication or changes secondary to illness. [Copyright &y& Elsevier]

Abstract: Resting state networks such as the default mode network have been widely reported. Although a plethora of information on its functional relevance has been generated, little is known about lateralization or hemisphere asymmetry within the DMN. We used high-resolution resting state fMRI and T1 3D data to investigate such asymmetries in two groups of healthy subjects, one right-handed and one left-handed. Independent component analysis and the dual regression approach were carried out to identify functional asymmetries, while voxel-based morphometry was used to identify structural asymmetries in grey matter volume within the DMN. Greater leftward functional connectivity was observed in the posterior cingulate gyrus (PCG) for both groups. Leftward functional asymmetry was observed in the thalamus and rightward functional asymmetries were observed in the middle frontal and middle/superior temporal gyrus in the right-handed group. Rightward asymmetries in grey matter volume were observed in the posterior portion of the PCG for both groups. The right-handed group exhibited leftward structural asymmetries in the anterior portion of the PCG and in the middle frontal and posterior portion of the middle temporal gyrus, while rightward asymmetries were observed in the posterior portion of the PCG and anterior portions of temporal regions. These results suggest that functional connectivity and grey matter volume are not equally distributed between hemispheres within the DMN, and that functional asymmetries are not always reflected or determined by structural asymmetries. [Copyright &y& Elsevier]

Abstract: We examine normal aging from the perspective of topological patterns of structural brain networks constructed from two healthy age cohorts 20 years apart. Based on graph theory, we constructed structural brain networks using 90 cortical and subcortical regions as a set of nodes and the interregional correlations of grey matter volumes across individual brains as edges between nodes, and further analyzed the topological properties of the age-specific networks. We found that the brain structural networks of both cohorts had small-world architecture, and the older cohort (N = 374; mean age = 66.6 years, range 64–68) had lower global efficiency but higher local clustering in the brain structural networks compared with the younger cohort (N = 428; mean age = 46.7, range 44–48). The older cohort had reduced hemispheric asymmetry and lower centrality of certain brain regions, such as the bilateral hippocampus, bilateral insula, left posterior cingulated, and right Heschl gyrus, but that of the prefrontal cortex (PFC) was not different. These structural network differences may provide the basis for changes in functional connectivity and indeed cognitive function as we grow older. [Copyright &y& Elsevier]

Abstract: Computational neuroscience integrate-and-fire attractor network models can be used to understand the factors that alter the stability of cortical networks in the face of noise caused for example by neuronal spiking times. A reduction of the firing rates of cortical neurons caused for example by reduced NMDA receptor function (present in schizophrenia) can lead to instability of the high firing rate attractor states that normally implement short-term memory and attention, contributing to the cognitive and negative symptoms of schizophrenia. Reduced cortical inhibition caused by a reduction of GABA neurotransmission (present in schizophrenia) can lead to instability of the spontaneous firing states of cortical networks, leading to a noise-induced jump to a high firing rate attractor state even in the absence of external inputs, contributing to the positive symptoms of schizophrenia. We consider how effects occurring at the time of late adolescence including synaptic pruning, decreases in grey matter volume, and changes in GABA-mediated inhibition and dopamine may contribute to the onset in some individuals of schizophrenia at this time. [Copyright &y& Elsevier]

Summary: Objective: Several studies have established links between thyroid gland dysfunction and mood disorders, in particular major depressive disorder (MDD). Preliminary evidence also suggests that thyroid hormone gene variants influence grey matter (GM) volume, which is reportedly altered in patients with MDD. This study tested for associations of single nucleotide polymorphisms (SNPs) in two thyroid hormone transporter genes with regional GM volume differences in a large sample population of patients with recurrent MDD and healthy volunteers. Methods: High-resolution T1-weighted magnetic resonance images were acquired at the Max Planck Institute, Munich, Germany. After quality control procedures were applied to images and genotypes, data for 134 patients and 144 well-matched controls were included in a stringent voxel-based morphometry analysis using non-stationary cluster-based inference. We first tested for associations between 10 candidate SNPs and regional GM volume differences across the combined sample population. We then tested for group-by-genotype interactions (i.e., differential associations determined by group status). Results: No significant associations were found between SNPs and regional GM volume when testing across the combined sample population. However, group-by-genotype interactions for two highly correlated SNPs (rs496549 and rs479640) revealed co-localised association clusters in the left occipital cortex (P-values 0.002 and 0.004, respectively, after full correction for whole brain and multiple SNP testing). The effect magnitudes within the average modulated GM clusters were greater in the control group relative to the MDD group. This study provides supporting evidence to the existing literature that thyroid-related gene variants influence regional GM volume. We propose that future studies should consider neuroimaging phenotypes when investigating the effects of thyroid hormones on brain structure and function. [ABSTRACT FROM AUTHOR]

Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain structure including reduced gray matter (GM) volume and/or density in areas including frontal and cingulate cortices, thalamus, and insula. However, associations between brain structure and smoking cessation treatment outcomes have not been reported. In the present analysis we sought to identify associations between regional GM volume—as measured by voxel-based morphometry (VBM)—and a smoking cessation treatment outcome (point prevalence abstinence at 4 weeks). Adult smokers underwent high-resolution anatomical MRI scanning prior to an open label smoking cessation treatment trial. VBM was conducted in SPM5 using the DARTEL algorithm and relapser vs. quitter groups were compared using independent sample t tests ( p < 0.001, uncorrected). Analyses controlled for potentially confounding factors including years smoked, cigarettes per day, total intracranial volume (TIV), and sex. Of 18 smokers, 8 achieved a 4-week point prevalence abstinence, confirmed by CO level (≤8 ppm). After controlling for all covariates, compared to relapsers, quitters had significantly higher GM volume in the left putamen and right occipital lobe, while also significantly lower GM volume in bilateral hippocampus and right cuneus. These preliminary results suggest that maintaining smoking abstinence is associated with higher pre-quit brain volume in regions that subserve habit learning and visual processing, and lower brain volume in regions that subserve long-term memory processes and visual information processing. Future, large-scale studies can determine whether brain structure variables can serve as clinically useful predictors of smoking cessation treatment outcome. [ABSTRACT FROM AUTHOR]

Background: Converging animal findings suggest that higher peripheral levels of inflammation are associated with activation of central inflammatory mechanisms that result in hippocampal neurodegeneration and related impairment of memory function. We have recently shown, consistent with animal findings, an inverse association between peripheral levels of interleukin-6 (IL-6), a relatively stable marker of systemic inflammation, and memory function in mid-life adults. In the current study, we extend this work to test whether systemic inflammation is associated with reduced grey matter volume of the hippocampus. Methods: For this purpose, we used a computational structural neuroimaging method (optimized voxel-based morphometry) to evaluate the relationship between plasma IL-6 levels and hippocampal grey matter volume in a sample of 76 relatively healthy community volunteers ages 30–54. Results: Peripheral levels of IL-6 covaried inversely with hippocampal grey matter volume, and this relationship persisted after accounting for several possible confounders, including age, gender, race, years of education, percent body fat, blood pressure, smoking, physical activity, hours of sleep, alcohol use, and total grey matter volume. Conclusions: To our knowledge, this is the first report of a relationship between a peripheral marker of IL-6 and hippocampal grey matter volume, raising the possibility that low-grade systemic inflammation could plausibly presage subclinical cognitive decline in part via structural neural pathways. [Copyright &y& Elsevier]

Structural brain imaging is assumed to be a key method to elucidate the underlying neuropathology of bipolar disorder. However, magnetic resonance imaging studies using region of interest analysis and voxel-based morphometry (VBM) revealed quite inconsistent findings. Hence, there is no clear evidence so far for core regions of cortical or subcortical structural abnormalities in bipolar disorder. The aim of this study was to investigate grey and white matter volumes in a large sample of patients with bipolar I disorder. Thirty-five patients with bipolar I disorder and 32 healthy controls matched with respect to gender, handedness and education participated in the study. MRI scanning was performed and an optimized VBM analysis was conducted. We could not observe any significant differences of grey or white matter volumes between patients with bipolar disorder and healthy control subjects. Additional analyses did not reveal significant correlations between grey or white matter volume with number of manic or depressive episodes, duration of illness, existence of psychotic symptoms, and treatment with lithium or antipsychotics. With this VBM study we were not able to identify core regions of structural abnormalities in bipolar disorder. [ABSTRACT FROM AUTHOR]

Cognitive performance in type 1 diabetes may be compromised as a result of chronic hyperglycaemia. The aim of this study was to investigate the cognitive functioning of patients with type 1 diabetes (including a subgroup with a microvascular complication) and nondiabetic controls, and to assess the relationship between cognition and cerebral grey and white matter volumes. Twenty-five patients with type 1 diabetes (of whom ten had proliferative retinopathy) and nine nondiabetic controls (matched in terms of sex, age and education) underwent a neuropsychological examination and magnetic resonance imaging of the brain. Fractional brain tissue volumes (tissue volume relative to total intracranial volume) were obtained from each participant. Compared with nondiabetic controls, patients with diabetes performed worse on tests measuring speed of information processing and visuoconstruction; patients with microvascular disease performed worse on the former cognitive domain ( p = 0.03), whereas patients without complications performed worse on the latter domain ( p = 0.01). Patients with a microvascular complication had a significantly smaller white matter volume than nondiabetic controls ( p = 0.04), and smaller white matter volume was associated with worse performance on the domains of speed of information processing and attention and executive function. Patients with diabetes demonstrated several subtle neuropsychological deficits, which were found to be related to white matter volume. Since patients with diabetic retinopathy had a smaller white matter volume, this suggests that cognitive decline is at least partly mediated by microvascular disease. This needs to be addressed in future studies. [ABSTRACT FROM AUTHOR]

The purpose of the study was to evaluate brain myelination by measuring the magnetization transfer ratio (MTR) and to measure grey (GMV) and white matter volume (WMV) in macrocephalic children with neurofibromatosis type 1 (NF1). Seven NF1 patients (aged 0.65-16.67 years) and seven age- and gender-matched controls were studied. A three-dimensional (3D) gradient echo sequence with and without magnetization transfer (MT) prepulse was used for MTR assessment. Volume measurements of GM and WM were performed by applying segmentation techniques on T2-weighted turbo spin echo images (T2WI). MTR of unidentified bright objects (UBOs) on T2WI in cerebellar white matter (52.8+/-3.3), cerebral peduncles (48.5+/-1.5), hippocampus (52.6+/-1.1), internal capsule (55.7+/-0.3), globus pallidus (52.7+/-3.9), and periventricular white matter (52.6+/-1.2) was lower than in the corresponding areas of controls (64.6+/-2.5, 60.8+/-1.3, 56.4+/-0.9, 64.7+/-1.9, 59.2+/-2.3, 63.6+/-1.7, respectively; p<0.05). MTR of normal-appearing brain tissue in patients was not significantly different than in controls. Surface area (mm(2)) of the corpus callosum (809.1+/-62.8), GMV (cm(3)) (850.7+/-42.9), and white matter volume (WMV) (cm(3)) (785.1+/-85.2) were greater in patients than in controls (652.5+/-52.6 mm(2), 611.2+/-92.1 cm(3), 622.5+/-108.7 cm(3), respectively; p<0.05). To conclude, macrocephaly in NF1 patients is related to increased GMV and WMV and corpus callosum enlargement. MTR of UBOs is lower than that of normal brain tissue. [ABSTRACT FROM AUTHOR]

Abstract: We have previously demonstrated that obese people have reduced grey matter (GM) in several brain areas, including regions implicated in the regulation of taste (i.e., inferior frontal operculum and postcentral gyrus), reward (i.e., putamen), and behavioural processing (i.e., middle frontal gyrus), compared with their lean counterparts. It is well established that the brain may serve as a direct target for adiposity signals, one of the most important being leptin. We investigated the relationships between fasting plasma leptin concentrations and brain tissue composition in a group of 32 young adult Caucasians (12M/20F, age 32±1 years, body fat 29±1%, mean±S.E.) with normal glucose tolerance by using voxel-based morphometry of magnetic resonance imaging scans. Fasting plasma leptin concentrations were positively correlated with GM volumes of the left cerebellum and left inferior temporal gyrus and negatively associated with GM volumes of the left inferior frontal operculum, left postcentral gyrus, and right putamen (P <0.001, uncorrected for multiple comparisons) after adjustment for sex, percent body fat, age, fasting plasma insulin concentrations (i.e., the major determinants of plasma leptin), and global GM volume (thus allowing for an assessment of regional effects only). This study showed an independent, negative correlation between fasting plasma leptin concentrations, which are increased in obesity, and the volumes of GM in brain areas where obese people have reduced GM compared to their lean counterparts. These relationships may explain some of the abnormalities in brain morphology recently found to be associated with excess body fatness. [Copyright &y& Elsevier]

Background: Grip strength is a widely used and well-validated measure of overall health that is increasingly understood to index risk for psychiatric illness and neurodegeneration in older adults. However, existing work has not examined how grip strength relates to a comprehensive set of mental health outcomes, which can detect early signs of cognitive decline. Furthermore, whether brain structure mediates associations between grip strength and cognition remains unknown., Methods: Based on cross-sectional and longitudinal data from over 40,000 participants in the UK Biobank, this study investigated the behavioral and neural correlates of handgrip strength using a linear mixed effect model and mediation analysis., Results: In cross-sectional analysis, we found that greater grip strength was associated with better cognitive functioning, higher life satisfaction, greater subjective well-being, and reduced depression and anxiety symptoms while controlling for numerous demographic, anthropometric, and socioeconomic confounders. Further, grip strength of females showed stronger associations with most behavioral outcomes than males. In longitudinal analysis, baseline grip strength was related to cognitive performance at ~9 years follow-up, while the reverse effect was much weaker. Further, baseline neuroticism, health, and financial satisfaction were longitudinally associated with subsequent grip strength. The results revealed widespread associations between stronger grip strength and increased grey matter volume, especially in subcortical regions and temporal cortices. Moreover, grey matter volume of these regions also correlated with better mental health and considerably mediated their relationship with grip strength., Conclusions: Overall, using the largest population-scale neuroimaging dataset currently available, our findings provide the most well-powered characterization of interplay between grip strength, mental health, and brain structure, which may facilitate the discovery of possible interventions to mitigate cognitive decline during aging., (© 2022. The Author(s).)

Schizophrenia which is an abnormally developmental disease has been widely reported to show abnormal brain structure and function. Enhanced functional integration is a predominant neural marker for brain mature. Abnormal development of structure and functional integration may be a biomarker for early diagnosis of schizophrenia. Fifty-five patients with early onset schizophrenia (EOS) and 79 healthy controls were enrolled in this study. Voxel-based morphometry (VBM) and functional connectivity density (FCD) were performed to explore gray matter volume (GMV) lesion, abnormal functional integration, and concurrent structural and functional abnormalities in the brain. Furthermore, the relationships between abnormalities structural and function and clinical characteristics were evaluated in EOS. Compared with healthy controls, EOS showed significantly decreased GMV in the bilateral OFC, frontal, temporal, occipital, parietal and limbic system. EOS also showed decreased FCD in precuneus and increased FCD in cerebellum. Moreover, we found concurrent changes of structure and function in left lateral orbitofrontal cortex (lOFC). Finally, correlation analyses did not find significant correlation between abnormal neural measurements and clinical characteristic in EOS. The results reveal disassociated and bound structural and functional abnormalities patterns in EOS suggesting structural and functional measurements play different roles in delineating the abnormal patterns of EOS. The concurrent structural and functional changes in lOFC may be a biomarker for early diagnosis of schizophrenia. Our findings will deepen our understanding of the pathophysiological mechanisms in EOS., (© 2022. The Author(s).)

Stressful life events (SLEs) in adulthood are a risk factor for various disorders such as depression, cancer or infections. Part of this risk is mediated through pathways altering brain physiology and structure. There is a lack of longitudinal studies examining associations between SLEs and brain structural changes. High-resolution structural magnetic resonance imaging data of 212 healthy subjects were acquired at baseline and after 2 years. Voxel-based morphometry was used to identify associations between SLEs using the Life Events Questionnaire and grey matter volume (GMV) changes during the 2-year period in an ROI approach. Furthermore, we assessed adverse childhood experiences as a possible moderator of SLEs-GMV change associations. SLEs were negatively associated with GMV changes in the left medial prefrontal cortex. This association was stronger when subjects had experienced adverse childhood experiences. The medial prefrontal cortex has previously been associated with stress-related disorders. The present findings represent a potential neural basis of the diathesis-stress model of various disorders., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

• Small left hemisphere caudate grey matter volume at age 12 related to high subjective wellbeing. • Protective neurobiological factors may be identifiable early in adolescence. • Cross-sectional, baseline paper for longitudinal study of adolescents in Australia. It has been suggested that biological markers that define mental health are different to those that define mental illness. The basal ganglia changes dramatically over adolescence and has been linked to wellbeing and mental health disorders in young people. However, there remains a paucity of research on wellbeing and brain structure in early adolescence. This cross-sectional study examined relationships between grey matter volume (GMV) of basal ganglia regions (caudate, putamen, pallidum and nucleus accumbens) and self-reported wellbeing (COMPAS-W), in a sample of Australian adolescents aged 12 years (N = 49, M = 12.6, 46.9% female). Significant negative associations were found between left hemisphere caudate GMV and scores on 'total wellbeing', 'composure' and 'positivity'. The results of this study indicate that smaller caudate GMV at age 12 is linked to increased subjective wellbeing. While seemingly counter-intuitive, our finding is consistent with previous research of decreased GMV in the pons and increased COMPAS-W scores in adults. Our results suggest that protective neurobiological factors may be identifiable early in adolescence and be linked to specific types of wellbeing (such as positive affect and optimism). This has implications for interventions targeted at building resilience against mental health disorders in young people. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between baseline alterations in grey matter volume (GMV) and clinical and functional outcomes in people at clinical high risk (CHR) for psychosis., Methods: 265 CHR individuals and 92 healthy controls were recruited as part of a prospective multi-center study. After a baseline assessment using magnetic resonance imaging (MRI), participants were followed for at least two years to determine clinical and functional outcomes, including transition to psychosis (according to the Comprehensive Assessment of an At Risk Mental State, CAARMS), level of functioning (according to the Global Assessment of Functioning), and symptomatic remission (according to the CAARMS). GMV was measured in selected cortical and subcortical regions of interest (ROI) based on previous studies (ie orbitofrontal gyrus, cingulate gyrus, gyrus rectus, inferior temporal gyrus, parahippocampal gyrus, striatum, and hippocampus). Using voxel-based morphometry, we analysed the relationship between GMV and clinical and functional outcomes., Results: Within the CHR sample, a poor functional outcome (GAF < 65) was associated with relatively lower GMV in the right striatum at baseline ( P < .047 after Family Wise Error correction). There were no significant associations between baseline GMV and either subsequent remission or transition to psychosis., Conclusions: In CHR individuals, lower striatal GMV was associated with a poor level of overall functioning at follow-up. This finding was not related to effects of antipsychotic or antidepressant medication. The failure to replicate previous associations between GMV and later psychosis onset, despite studying a relatively large sample, is consistent with the findings of recent large-scale multi-center studies., (© The Author(s) 2022. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Need for closure (NFC) reflects stable individual differences in the desire for a quick, definite, and stable answer to a question. A large body of research has documented the association between NFC and various cognitive, emotional and social processes. Despite considerable interest in psychology, little effort has been made to uncover the neural substrates of individual variations in NFC. Herein, we took a data-driven approach to predict NFC trait combining machine learning framework and the whole-brain grey matter volume (GMV) features, which represent a reliable brain imaging measure and have been commonly employed to explore neural basis underlying individual differences of cognition and behaviors. Brain regions contributing to the prediction were then subjected to functional connectivity and decoding analyses for a quantitative inference on their psychophysiological functions. Our results indicated that multivariate patterns of GMV derived from multiple regions across distributed brain systems predicted NFC at individual level. The contributing regions are distributed across the emotional processing network (e.g., striatum), cognitive control network (e.g., lateral prefrontal cortex), social cognition network (e.g., temporoparietal junction) and perceptual processing network (e.g., occipital cortex). The current study provided the first evidence that dispositional NFC is embodied in multiple large-scale brain networks, helping to delineate a more complete picture about the neuropsychological processes that support individual differences in NFC. Beyond these findings, the current interdisciplinary approach to constructing and interpreting neuroimaging-based prediction model of personality traits would be informative to a wide range of future studies on personality., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The understanding of brain structural abnormalities across different clinical forms of dystonia and their contribution to clinical characteristics remains unclear. The objective of this study is to investigate shared and specific gray matter volume (GMV) abnormalities in various forms of isolated idiopathic dystonia. We collected imaging data from 73 isolated idiopathic dystonia patients and matched them with healthy controls to explore the GMV alterations in patients and their correlations with clinical characteristics using the voxel-based morphometry (VBM) technique. In addition, we conducted an activation likelihood estimation (ALE) meta-analysis of previous VBM studies. Our study demonstrated widespread morphometry alterations in patients with idiopathic dystonia. Multiple systems were affected, which mainly included basal ganglia, sensorimotor, executive control, and visual networks. As the result of the ALE meta-analysis, a convergent cluster with increased GMV was found in the left globus pallidus. In subgroup VBM analyses, decreased putamen GMV was observed in all clinic forms, while the increased GMV was observed in parahippocampal, lingual, and temporal gyrus. GD demonstrated the most extensive GMV abnormalities in cortical regions, and the aberrant GMV of the posterior cerebellar lobe was prominent in CD. Moreover, trends of increased GMV regions of the left precuneus and right superior frontal gyrus were demonstrated in the moderate-outcome group compared with the superior-outcome group. Results of our study indicated shared pathophysiology of the disease-centered on the dysfunction of the basal ganglia-thalamo-cortical circuit, impairing sensorimotor integration, high-level motor execution, and cognition of patients. Dysfunction of the cerebello-thalamo-cortical circuit could also be involved in CD especially. Finally, the frontal-parietal pathway may act as a potential marker for predicting treatment outcomes such as deep brain stimulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Zhang, Li, Feng, Zhang, Li, Wang, Zhang, Jin, Zhang, Zhang, Li, Wu, Wei and Sun.)

Purpose of Review: With the voxel-based morphometry (VBM), structural imaging studies turned into new directions aiming to explore neurological disorders differently. This approach helps identify possible pathophysiological correlations between neuroanatomical grey matter (GM) structures in patients with sleep dysfunction. This article reviews recent findings on GM structure in various sleep disorders and possible causes of disturbed sleep and discusses the future perspectives., Recent Findings: At present, research on the effect of GM volume changes in specific brain areas on the pathogenesis of sleep disturbances is incomplete. It remains unknown if the GM thickness reduction in patients with REM sleep behaviour disorder, obstructive sleep apnea, restless legs syndrome, and insomnia is due to complex disease presentation or direct response to disturbed sleep. Additionally, many VBM studies have yielded inconsistent results showing either reduction or increase in GM. The spatiotemporal complexity of whole-brain networks and state transitions during sleep and the role of GM changes increase new debates. Having multimodal data from large sample studies can help model sleep network dynamics in different disorders and provide novel data for possible therapeutic interventions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Post-traumatic stress disorder (PTSD) is a chronic disease caused by traumatic incidents. Numerous studies have revealed grey matter volume differences in affected individuals. The nature of the disease renders it difficult to distinguish between a priori versus a posteriori changes. To overcome this difficulty, we studied the consequences of a traumatic event on brain morphology in mice before and 4 weeks after exposure to brief foot shocks (or sham treatment), and correlated morphology with symptoms of hyperarousal. In the latter context, we assessed hyperarousal upon confrontation with acoustic, visual, or composite (acoustic/visual/tactile) threats and integrated the individual readouts into a single Hyperarousal Score using logistic regression analysis. MRI scans with subsequent whole-brain deformation-based morphometry (DBM) analysis revealed a volume decrease of the dorsal hippocampus and an increase of the reticular nucleus in shocked mice when compared to non-shocked controls. Using the Hyperarousal Score as regressor for the post-exposure MRI measurement, we observed negative correlations with several brain structures including the dorsal hippocampus. If the development of changes with respect to the basal MRI was considered, reduction in globus pallidus volume reflected hyperarousal severity. Our findings demonstrate that a brief traumatic incident can cause volume changes in defined brain structures and suggest the globus pallidus as an important hub for the control of fear responses to threatening stimuli of different sensory modalities. • We studied changes in brain volume associated with a traumatic experience in mice using repeated in vivo MRI scans. • To correlate morphology with symptoms , we assessed hyperarousal upon confrontation with different threatening stimuli. • The individual behavioral readouts were integrated into a single Hyperarousal Score using logistic regression analysis. • We observed negative correlations of the Hyperarousal Score with several brain structures 4 weeks aftertrauma. • Reduction in globus pallidus volume from baseline to post-trauma conditions reflected hyperarousal severity. [ABSTRACT FROM AUTHOR]

Heavy cannabis use (HCU) is frequently associated with a plethora of cognitive, psychopathological and sensorimotor phenomena. Although HCU is frequent, specific patterns of abnormal brain structure and function underlying HCU in individuals presenting without cannabis-use disorder or other current and life-time major mental disorders are unclear at present. This multimodal magnetic resonance imaging (MRI) study examined resting-state functional MRI (rs-fMRI) and structural MRI (sMRI) data from 24 persons with HCU and 16 controls. Parallel independent component analysis (p-ICA) was used to examine covarying components among grey matter volume (GMV) maps computed from sMRI and intrinsic neural activity (INA), as derived from amplitude of low-frequency fluctuations (ALFF) maps computed from rs-fMRI data. Further, we used JuSpace toolbox for cross-modal correlations between MRI-based modalities with nuclear imaging derived estimates, to examine specific neurotransmitter system changes underlying HCU. We identified two transmodal components, which significantly differed between the HCU and controls (GMV: p = 0.01, ALFF p = 0.03, respectively). The GMV component comprised predominantly cerebello-temporo-thalamic regions, whereas the INA component included fronto-parietal regions. Across HCU, loading parameters of both components were significantly associated with distinct HCU behavior. Finally, significant associations between GMV and the serotonergic system as well as between INA and the serotonergic, dopaminergic and μ-opioid receptor system were detected. This study provides novel multimodal neuromechanistic insights into HCU suggesting co-altered structure/function-interactions in neural systems subserving cognitive and sensorimotor functions., (© 2021 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Nowadays, increasing evidence has found transdiagnostic neuroimaging biomarkers across major psychiatric disorders (MPDs). However, it remains to be known whether this transdiagnostic pattern of abnormalities could also be seen in individuals at familial high-risk for MPDs (FHR). We aimed to examine shared neuroanatomical endophenotypes and protective biomarkers for MPDs., Methods: This study examined brain grey matter volume (GMV) of individuals by voxel-based morphometry method. A total of 287 individuals were included, involving 100 first-episode medication-naive MPDs, 87 FHR, and 110 healthy controls (HC). They all underwent high-resolution structural magnetic resonance imaging (MRI)., Results: At the group level, we found MPDs were characterized by decreased GMV in the right fusiform gyrus, the right inferior occipital gyrus, and the left anterior and middle cingulate gyri compared to HC and FHR. Of note, the GMV of the left superior temporal gyrus was increased in FHR relative to MPDs and HC. At the subgroup level, the comparisons within the FHR group did not return any significant difference, and we found GMV difference among subgroups within the MPDs group only in the opercular part of the right inferior frontal gyrus., Conclusion: Together, our findings uncover common structural disturbances across MPDs and substantial changes in grey matter that may relate to high hereditary risk across FHR, potentially underscoring the importance of a transdiagnostic way to explore the neurobiological mechanisms of major psychiatric disorders., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Bipolar spectrum disorders (BSDs) are associated with reward hypersensitivity, impulsivity, and structural abnormalities within the brain's reward system. Using a behavioral high-risk study design based on reward sensitivity, this paper had two primary objectives: 1) investigate whether elevated positive urgency, the tendency to act rashly when experiencing extreme positive affect, is a risk for or correlate of BSDs, and 2) examine the nature of the relationship between positive urgency and grey matter volume in fronto-striatal reward regions, among individuals at differential risk for BSD. Young adults (ages 18-28) screened to be moderately reward sensitive (MReward; N = 42), highly reward sensitive (HReward; N = 48), or highly reward sensitive with a lifetime BSD (HReward + BSD; N = 32) completed a structural MRI scan and the positive urgency subscale of the UPPS-P scale. Positive urgency scores varied with BSD risk (MReward < HReward < HReward + BSD; ps≤0.05), and positive urgency interacted with BSD risk group in predicting lateral OFC volume (p <.001). Specifically, the MReward group showed a negative relationship between positive urgency and lateral OFC volume. By contrast, there was no relationship between positive urgency and lateral OFC grey matter volume among the HReward and HReward + BSD groups. The results suggest that heightened trait positive urgency is a pre-existing vulnerability for BSD that worsens with illness onset, and there is a distinct relationship between positive urgency and lateral OFC volume among individuals at high versus low risk for BSD. These findings have implications for understanding the expression and development of impulsivity in BSDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Cross-sectional studies have reported lower brain grey matter volumes (GMV) and white matter volumes (WMV) in preterm (PT) born individuals. While large MRI studies in the normative population have led to a better understanding of brain growth trajectories across the lifespan, such results remain elusive for PT born individuals since large, aggregated datasets of PT born individuals do not exist. To close this gap, we investigated GMV and WMV in PT born individuals as reported in the literature and contrasted it against individual volumetric data and trajectories from the general population. Systematic database search of PubMed and Web of Science in March 2021, and extraction of outcome measures were conducted by two independent reviewers. Individual data on full-term (FT) controls was extracted from freely available databases. Mean GMV, WMV, total intracranial volume (TIV), and mean age at scan were the main outcome measures. Of 532 identified records, nine studies were included with 538 PT born subjects between 1.1 and 28.5 years of age. Reference data was generated from 880 FT controls between 1 and 30 years of age. GMV was consistently lower in PT born individuals from infancy to early adulthood with no evidence for catch-up growth. While GMV changes followed a similar trajectory as FT controls, WMV was particularly low in adolescence after PT birth. Results demonstrate altered brain volumes after PT birth across the first half of lifespan. Future studies should address this issue in large aggregated datasets of PT born individuals. [ABSTRACT FROM AUTHOR]

Increased severity of neurological soft signs (NSS) in schizophrenia have been associated with abnormal brain morphology in cerebello-thalamo-cortical structures, but it is unclear whether similar structures underlie NSS prior to the onset of psychosis. The present study investigated the relationship between severity of NSS and grey matter volume (GMV) in individuals at ultra-high risk for psychosis (UHR) stratified for later conversion to psychosis. Structural T1-weighted MRI scans were obtained from 56 antipsychotic-naïve UHR individuals and 35 healthy controls (HC). The UHR individuals had follow-up data (mean follow-up: 5.2 years) to ascertain clinical outcome. Using whole-brain voxel-based morphometry, the relationship between NSS and GMV at baseline was assessed in UHR, HC, as well as individuals who later transitioned (UHR-P, n = 25) and did not transition (UHR-NP, n = 31) to psychosis. NSS total and subscale scores except motor coordination were significantly higher in UHR compared to HC. Higher signs were also found in UHR-P, but not UHR-NP. Total NSS was not associated with GMV in the whole sample or in each group. However, in UHR-P individuals, greater deficits in sensory integration was associated with lower GMV in the left cerebellum, right insula, and right middle frontal gyrus. In conclusion, NSS are present in UHR individuals, particularly those who later transitioned to a psychotic disorder. While these signs show little overall variation with GMV, the association of sensory integration deficits with lower GMV in UHR-P suggests that certain brain areas may be implicated in the development of specific neurological abnormalities in the psychosis prodrome., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The deficits in sensory pathways caused by peripheral edema, pain, and inflammation of the damaged ligaments may induce maladaptive changes within the central nervous system. The purpose of this study was to determine whether patients with lateral ankle instability (LAI) exhibit morphological differences of brain grey matter when compared with healthy controls, and then assess the relationships between the observed differences and the characteristics of patients., Design: Cross-sectional., Methods: Thirty patients with LAI and 32 healthy controls without LAI underwent MRI scans using anatomical T1 sequences. A voxel-wise general linear model was used to compare the grey matter volume throughout the whole brain between patients and controls. Linear regression analyses were performed for the grey matter volume within the significant clusters to assess their relationship with age, sex, the existence of acute injury, pain level, sports activity level, and the duration of LAI within the patient group., Results: The grey matter volume of a cluster within the cerebellar vermis (Vermis&#95;4&#95;5 in automated anatomical labeling template) was significantly reduced in patients with LAI (Gaussian Random Field corrections with two-tailed p-cluster < 0.05 and p-voxel < 0.001). Multivariate linear regression analysis revealed that the duration of LAI tended to be passively associated with the grey matter volume of this LAI-related vermal cluster (p = 0.092)., Conclusions: Participants with LAI exhibited a reduced grey matter volume of a cluster within the cerebellar vermis compared with participants without LAI, and the degree of volume reduction tended to be positively associated with the duration of LAI., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Depression and low mood are leading contributors to disability worldwide. Research indicates that clinical depression may be associated with low creatine concentrations in the brain and low prefrontal grey matter volume. Because subclinical depression also contributes to difficulties in day-to-day life, understanding the neural mechanisms of depressive symptoms in all individuals, even at a subclinical level, may aid public health., Methods: Eighty-four young adult participants completed the Depression, Anxiety and Stress Scale (DASS) to quantify severity of depression, anxiety and stress, and underwent 1 H-Magnetic Resonance Spectroscopy of the medial prefrontal cortex and structural magnetic resonance imaging (MRI) to determine whole-brain grey matter volume., Results/outcomes: DASS depression scores were negatively associated (a) with concentrations of creatine (but not other metabolites) in the prefrontal cortex and (b) with grey matter volume in the right superior medial frontal gyrus. Medial prefrontal creatine concentrations and right superior medial frontal grey matter volume were positively correlated. DASS anxiety and DASS stress scores were not related to prefrontal metabolite concentrations or whole-brain grey matter volume., Conclusions/interpretations: This study provides preliminary evidence from a representative group of individuals who exhibit a range of depression levels that prefrontal creatine and grey matter volume are negatively associated with depression. While future research is needed to fully understand this relationship, these results provide support for previous findings, which indicate that increasing creatine concentrations in the prefrontal cortex may improve mood and well-being.

Background: Childhood trauma confers risk for psychosis and is associated with increased 'schizotypy' (a multi-dimensional construct reflecting risk for psychosis in the general population). Structural brain alterations are associated with both childhood trauma and schizotypy, but the potential role of trauma exposure in moderating associations between schizotypy and brain morphology has yet to be determined., Methods: Participants were 160 healthy individuals (mean age: 40.08 years, SD = 13.64, range 18-64; 52.5% female). Childhood trauma exposure was assessed using the Childhood Adversity Questionnaire, and schizotypy was assessed using the Schizotypal Personality Questionnaire. Univariate voxel-based morphometry and multivariate analyses of grey matter volume covariation (GMC; derived from independent component analysis) were performed to determine the main effects of schizotypy, trauma exposure and their interaction on these indices of grey matter volume. Moderation analyses were performed following significant interaction., Results: Levels of schizotypy, in particular the Cognitive-Perceptual and Interpersonal dimensions, were negatively associated with GMC in the striatum, the hippocampus/parahippocampal gyrus, thalamus and insulae. Trauma exposure was negatively associated with GMC of the middle frontal gyrus and parietal lobule, while negatively associated with GMC in the cerebellum. Levels of schizotypy (total scores, and the cognitive-perceptual dimension) were negatively associated with striatal GMC in individuals not exposed to trauma, but not in those exposed to trauma., Conclusions: Schizotypy and childhood trauma were independently associated with changes of grey matter in brain regions critical for cognition and social cognition. In individuals not exposed to trauma, increased schizotypy was associated with decreased striatal and limbic grey matter., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: To identify the reliable and consistent grey matter volume (GMV) abnormalities associated with major depressive disorder (MDD), we excluded the influence of confounding clinical characteristics, comorbidities and brain degeneration on brain morphological abnormalities by inclusion of non-comorbid and non-geriatric drug-naïve MDD individuals experiencing first episode depressive., Methods: The PubMed, Scopus, Web of Science, Science Direct and Google scholar databases were searched for papers published in English up to April 2020., Results: A total of 21 voxel based morphometric (VBM) studies comparing 845 individuals in the first depressive episode and medication-naïve with 940 healthy control subjects were included. The results showed a grey matter volumes reductions in the orbitofrontal cortex (OFC), prefrontal cortex (PFC), frontal and temporal gyri, temporal pole, insular lobe, thalamus, basal ganglia, cerebellum, hippocampus, cingulate cortex, and amygdala. In addition, increased grey matter volumes in the postcentral gyrus, superior frontal gyrus, insula, basal ganglia, thalamus, amygdala, cuneus, and precuneus differentiated the first depressive episode in medication-naïve individuals from healthy subjects., Conclusion: The present systematic review provided additional support for the involvement of grey matter structural abnormalities in limbic-cortical circuits as possibly specific structural abnormalities in the early stage of MDD.Key pointsDistinct brain regions in MDD patients might be associated with the early stages of illness, and thus it is critical to study the causal relationship between brain structures and the onset of the disease to improve the evaluation in clinic.Grey matter alterations in the fronto-limbic networks in the first episode, medication-naïve MDD might suggest that these abnormalities may play an important role in the neuropathophysiology of MDD at its onset.First episode, medically naïve depressive patients show grey matter volume alterations in brain regions mainly associated with emotion regulation including parietal-temporal regions, PFC, insular lobe, thalamus, basal ganglia, cerebellum and limbic structures that may be specific changes in early stage of MDD.Genotype-diagnosis interaction effects on brain morphology in the cortico-limbic-striatal circuits, including the PFC, amygdala, hippocampus and striatum that might be implicated in the dysfunctional regulation of emotion in first-episode MDD patients.Future longitudinal and prospective studies should be conducted to identify the core structural brain changes in people at-risk for MDD and explore the association of their brain volumes with symptom onset.