Vertex-wise Analysis Research Articles

Neurostructural and neurocognitive correlates of APOE ε4 in youth bipolar disorder

Bipolar disorder (BD) is a clinical risk factor for Alzheimer's disease (AD). Apolipoprotein E ε4 (APOE ε4), a genetic risk factor for AD, has been associated with brain structure and neurocognition in healthy youth. We evaluated whether there was an association between APOE ε4 with neurostructure and neurocognition in youth with BD. Participants included 150 youth (78 BD:19 ε4-carriers, 72 controls:17 ε4-carriers). 3T-magnetic resonance imaging yielded measures of cortical thickness, surface area, and volume. Regions-of-interest (ROI) and vertex-wise analyses of the cortex were conducted. Neurocognitive tests of attention and working memory were examined. Vertex-wise analyses revealed clusters with a diagnosis-by-APOE ε4 interaction effect for surface area (p = 0.002) and volume (p = 0.046) in pars triangularis (BD ε4-carriers > BD noncarriers), and surface area (p = 0.03) in superior frontal gyrus (controls ε4-carriers > other groups). ROI analyses were not significant. A significant interaction effect for working memory (p = 0.001) appeared to be driven by nominally poorer performance in BD ε4-carriers but not control ε4-carriers; however, post hoc contrasts were not significant. APOE ε4 was associated with larger neurostructural metrics in BD and controls, however, the regional association of APOE ε4 with neurostructure differed between groups. The role of APOE ε4 on neurodevelopmental processes is a plausible explanation for the observed differences. Future studies should evaluate the association of APOE ε4 with pars triangularis and its neurofunctional implications among youth with BD.

White matter and gray matter changes related to cognition in community populations.

Further studies are needed to improve the understanding of the pathological process underlying cognitive impairments. The purpose of this study is to investigate the global and topographic changes of white matter integrity and cortical structure related to cognitive impairments in a community-based population. A cross-sectional analysis was performed based on 995 subjects (aged 56.8 ± 9.1 years, 34.8% males) from the Shunyi study, a community-dwelling cohort. Cognitive status was accessed by a series of neurocognitive tests including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), category Verbal Fluency Test (VFT), Digit Span Test (DST), and Trail Making Tests A and B (TMT-A and TMT-B). Structural and diffusional MRI data were acquired. White matter integrity was assessed using fractional anisotropy (FA), mean diffusivity (MD), and peak width of skeletonized mean diffusivity (PSMD). Cortical surface area, thickness, and volume were measured using Freesurfer. Probabilistic tractography was further conducted to track the white matter fibers connecting to the cortical regions related to cognition. General linear models were used to investigate the association between brain structure and cognition. Global mean FA and MD were significantly associated with performances in VFT (FA, β 0.119, p < 0.001; MD, β -0.128, p < 0.001). Global cortical surface area, thickness, and volume were not related to cognitive scores. In tract-based spatial statistics analysis, disruptive white matter integrity was related to cognition impairment, mainly in visuomotor processing speed, semantic memory, and executive function (TMT-A and VFT), rather than verbal short-term memory and working memory (DST). In the whole brain vertex-wise analysis, surface area in the left orbitofrontal cortex, right posterior-dorsal part of the cingulate gyrus, and left central sulcus were positively associated with MMSE and MoCA scores, and the association were independent of the connecting white matter tract. Disrupted white matter integrity and regional cortical surface area were related to cognition in community-dwelling populations. The associations of cortical surface area and cognition were independent of the connecting white matter tract.

Neuroimaging features of depression-frailty phenotype in older adults: a pilot study.

Frailty and late-life depression (LLD) often coexist and share several structural brain changes. We aimed to study the joint effect LLD and frailty have on brain structure. Cross-sectional study. Academic Health Center. Thirty-one participants (14 LLD+Frail and 17 Never-depressed+Robust). LLD was diagnosed by a geriatric psychiatrist according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition for single episode or recurrent major depressive disorder without psychotic features. Frailty was assessed using the FRAIL scale (0-5), classifying subjects as robust (0), prefrail (1-2), and frail (3-5). Participants underwent T1-weighted magnetic resonance imaging in which covariance analysis of subcortical volumes and vertex-wise analysis of cortical thickness values were performed to access changes in grey matter. Participants also underwent diffusion tensor imaging in which tract-based spatial statistics was used with voxel-wise statistical analysis on fractional anisotropy and mean diffusion values to assess changes in white matter (WM). We found a significant difference in mean diffusion values (48,225 voxels; peak voxel: pFWER=0.005, MINI coord. (X,Y,Z) = -26,-11,27) between the LLD-Frail group and comparison group. The corresponding effect size (f=0.808) was large. We showed the LLD+Frailty group is associated with significant microstructural changes within WM tracts compared to Never-depressed+Robust individuals. Our findings indicate the possibility of a heightened neuroinflammatory burden as a potential mechanism underlying the co-occurrence of both conditions and the possibility of a depression-frailty phenotype in older adults.

Distinct Associations of Deprivation and Threat With Alterations in Brain Structure in Early Childhood

The dimensional model of adversity and psychopathology hypothesizes deprivation and threat impact distinct neurobiological pathways, such as brain structure. This hypothesis has not been examined longitudinally or in young children. This study tested longitudinal associations between threat and deprivation measured in preschool and brain structure in childhood. It was hypothesized that threat would be associated with amygdala and hippocampal subcortical volume and deprivation would be associated with cortical thickness in association cortex. The study included T1-weighted scans from 72 children (5-10 years old, 54.2% female participants). Threat was measured by the presence of domestic violence, sexual abuse, physical abuse, or neighborhood violence. Deprivation was measured by the presence of neglect. Associations of deprivation or threat with brain structure were examined controlling for other dimension (deprivation or threat) and nuisance covariates using whole-brain vertex-wise analyses. Subcortical volume was extracted, and the same associations were examined using multiple regression. Threat was associated with widespread decreases in cortical surface area across the prefrontal cortex and other regions. Threat was not associated with amygdala or hippocampal volume. Deprivation was associated with increased thickness in occipital cortex, insula, and cingulate. Results suggest distinct associations of deprivation and threat on brain structure in early childhood. Threat is associated with widespread differences in surface area, and deprivation is associated with differences in cortical thickness. These observations are consistent with work in adolescence and adulthood and reflect how dimensions of adversity differentially impact neural structure.

The intracortical myelin content of impulsive choices: results from T1- and T2-weighted MRI myelin mapping.

Delay discounting (DD) refers to a phenomenon that humans tend to choose small-sooner over large-later rewards during intertemporal choices. Steep discounting of delayed outcome is related to a variety of maladaptive behaviors and is considered as a transdiagnostic process across psychiatric disorders. Previous studies have investigated the association between brain structure (e.g. gray matter volume) and DD; however, it is unclear whether the intracortical myelin (ICM) influences DD. Here, based on a sample of 951 healthy young adults drawn from the Human Connectome Project, we examined the relationship between ICM, which was measured by the contrast of T1w and T2w images, and DD and further tested whether the identified associations were mediated by the regional homogeneity (ReHo) of brain spontaneous activity. Vertex-wise regression analyses revealed that steeper DD was significantly associated with lower ICM in the left temporoparietal junction (TPJ) and right middle-posterior cingulate cortex. Region-of-interest analysis revealed that the ReHo values in the left TPJ partially mediated the association of its myelin content with DD. Our findings provide the first evidence that cortical myelination is linked with individual differences in decision impulsivity and suggest that the myelin content affects cognitive performances partially through altered local brain synchrony.

Differential association of endothelial function with brain structure in youth with versus without bipolar disorder

BackgroundMood symptoms and disorders are associated with impaired endothelial function, a marker of early atherosclerosis. Given the increased vascular burden and neurostructural differences among individuals with mood disorders, we investigated the endothelial function and brain structure interface in relation to youth bipolar disorder (BD). MethodsThis cross-sectional case-controlled study included 115 youth, ages 13–20 years (n = 66 BD; n = 49 controls [CG]). Cortical thickness and volume for regions of interest (ROI; insular cortex, ventrolateral prefrontal cortex [vlPFC], temporal lobe) were acquired from FreeSurfer processed T1-weighted MRI images. Endothelial function was assessed using pulse amplitude tonometry, yielding a reactive hyperemia index (RHI). ROI and vertex-wise analyses controlling for age, sex, obesity, and intracranial volume investigated for RHI-neurostructural associations, and RHI-by-diagnosis interactions. ResultsIn ROI analyses, higher RHI (i.e., better endothelial function) was associated with lower thickness in the insular cortex (β = −0.19, pFDR = 0.03), vlPFC (β = −0.30, pFDR = 0.003), and temporal lobe (β = −0.22, pFDR = 0.01); and lower temporal lobe volume (β = −0.16, pFDR = 0.01) in the overall sample. In vertex-wise analyses, higher RHI was associated with lower cortical thickness and volume in the insular cortex, prefrontal cortex (e.g., vlPFC), and temporal lobe. Additionally, higher RHI was associated with lower vlPFC and temporal lobe volume to a greater extent in youth with BD vs. CG. ConclusionsBetter endothelial function was associated with lower regional brain thickness and volume, contrasting the hypothesized associations. Additionally, we found evidence that this pattern was exaggerated in youth with BD. Future studies examining the direction of the observed associations and underlying mechanisms are warranted.

Regional shape alteration of left thalamus associated with late chronotype in young adults

ABSTRACT Chronotype reflects individual differences in circadian rhythms and influences individual psychology and behavior. Previous studies found altered subcortical structures are closely related to individual chronotypes. However, these studies have been conducted mainly using voxel-based morphometry and traditional volume measurement methods with certain limitations. This study aimed to investigate subcortical aberrant volume and shape patterns in late chronotypes (LC) young adults compared to early chronotypes (EC) young adults. Magnetic resonance imaging (MRI) scanning and chronotype assessment were performed once for all participants, including 49 LC young adults and 49 matched EC young adults. The morningness and eveningness preferences were assessed using the Chronotype Questionnaire. A vertex-wise shape analysis was conducted to analyze structural MRI data. There were no significant differences in brain tissue volume and subcortical structural volume between groups. LC young adults showed significant regional shape atrophy in the left ventral posterior thalamus compared to EC individuals. A significant correlation was found between the regional shape atrophy of left ventral posterior thalamus and the score of Chronotype Questionnaire in LC young adults. Regional shape alteration of left thalamus was closely related to the chronotype, and LC may be a potential risk factor for sleep-related behavioral and mental problems in young adults. However, the predominantly female sample and the failure to investigate the effect of chronotype on the subcortical structure-function network are limitations of this study. Further prospective studies are needed to investigate the temporal characteristics of thalamic shape changes and consequent behavioral and psychiatric problems in adults with LC.

Stress and the brain: Emotional support mediates the association between myelination in the right supramarginal gyrus and perceived chronic stress

Perceived stress, which refers to people's evaluation of a stressful event and their ability to cope with it, has emerged as a stable predictor for physical and mental health outcomes. Increasing evidence has suggested the buffering effect of social support on perceived stress. Although previous studies have investigated the brain structural features (e.g., gray matter volume) associated with perceived stress, less is known about the association between perceived chronic stress and intra-cortical myelin (ICM), which is an important microstructure of brain and is essential for healthy brain functions, and the role of social support in this association. Using a sample of 1076 healthy young adults drawn from the Human Connectome Project, we quantified the ICMby the contrast of T1w and T2w images and examined its association with perceived chronic stress during the last month and social support. Behavioral results showed that perceived chronic stress was negatively associated with both emotional support and instrumental support. Vertex-wise multiple regression analyses revealed that higher level of perceived chronic stress was significantly associated with lower ICM content of a cluster in the right supramarginal gyrus (rSMG). Interestingly, the emotional support, but not the instrumental support, significantly mediated the association of perceived chronic stress with ICM in the rSMG. Overall, the present study provides novel evidence for the cortical myelination of perceived chronic stress in humans and highlights the essential role of the rSMG in perceived chronic stress and emotional support.

Cocaine use disorder is associated with widespread surface-based alterations of the basal ganglia

Cocaine use is a major public health problem with significant negative consequences at the individual and societal levels. Cocaine use disorder (CUD) is closely associated with brain structure alterations, which are mainly analyzed using voxel-based morphometric and traditional volumetric methods with certain limitations. This study conducted vertex-wise shape analysis to examine the effects of cocaine use on surface-based alterations of the basal ganglia in CUD. A total of 68 CUD individuals and 52 matched healthy controls (HCs) were enrolled in the study and underwent MRI scans and clinical measures. There were no significant differences in the volume of brain tissues and subcortical structures between groups. Related to HCs, CUD individuals showed regional surface atrophy of the left medial anterior thalamus, right medial posterior thalamus, and right dorsal anterior caudate, which were found to exhibit more significant surface atrophy in CUD individuals with onset age of cocaine use below 18. Furthermore, surface-based alteration of the right dorsal anterior caudate was significantly associated with years of cocaine use and the onset age of cocaine use in CUD individuals. Furthermore, both CUD individuals with onset age of cocaine use below 18 and CUD individuals with onset age of cocaine use above 18 showed similar significant relationship patterns between regional surface alteration of right dorsal anterior caudate and the onset age of cocaine use. These findings shed light on the effect of cocaine use on basal ganglia, help us understand the neural basis of cocaine dependence, and further provide effective interventions for CUD.

Mapping Cholinergic Synaptic Loss in Parkinson's Disease: An [18F]FEOBV PET Case-Control Study.

Cholinergic degeneration is strongly associated with cognitive decline in patients with Parkinson's disease (PD) but may also cause motor symptoms and olfactory dysfunction. Regional differences are striking and may reflect different PD related symptoms and disease progression patterns. To map and quantify the regional cerebral cholinergic alterations in non-demented PD patients. We included 15 non-demented PD patients in early-moderate disease stage and 15 age- and sex-matched healthy controls for [18F]FEOBV positron emission tomography imaging. We quantitated regional variations using VOI-based analyses which were supported by a vertex-wise cluster analysis. Correlations between imaging data and clinical and neuropsychological data were explored. We found significantly decreased [18F]FEOBV uptake in global neocortex (38%, p = 0.0002). The most severe reductions were seen in occipital and posterior temporo-parietal regions (p < 0.0001). The vertex-wise cluster analysis corroborated these findings. All subcortical structures showed modest non-significant reductions. Motor symptoms (postural instability and gait difficulty) and cognition (executive function and composite z-score) correlated with regional [18F]FEOBV uptake (thalamus and cingulate cortex/insula/hippocampus, respectively), but the correlations were not statistically significant after multiple comparison correction. A strong correlation was found between interhemispheric [18F]FEOBV asymmetry, and motor symptom asymmetry of the extremities (r = 0.84, p = 0.0001). Cortical cholinergic degeneration is prominent in non-demented PD patients, but more subtle in subcortical structures. Regional differences suggest uneven involvement of cholinergic nuclei in the brain and may represent a window to follow disease progression. The correlation between asymmetric motor symptoms and neocortical [18F]FEOBV asymmetry indicates that unilateral cholinergic degeneration parallels ipsilateral dopaminergic degeneration.

The relationship between metabolic control and basal ganglia morphometry and function in individuals with early-treated phenylketonuria.

Abnormalities of the cortical white matter are the most prominent and widely-reported neurological findings in individuals with early-treated phenylketonuria (ETPKU). Much less is known regarding the effects of ETPKU on gray matter structures in the brain such as the basal ganglia. Previous findings on basal ganglia in ETPKU have been mixed. The current study was designed to further elucidate the effects of ETPKU and elevated phe levels on the morphometry of basal ganglia structures (i.e., putamen, caudate nucleus, nucleus accumbens, and globus pallidus). High resolution magnetic resonance imaging (MRI) data was collected from a sample of 37 adults with ETPKU and a demographically-matched comparison group of 33 individuals without PKU. No overall group differences (ETPKU vs. non-PKU) in basal ganglia volumes were observed. However, within the ETPKU group, poorer metabolic control (as reflected by higher blood phenylalanine levels) was associated with larger putamen volume. Vertex-wise shape analysis revealed that the volume increase was accompanied by shape changes in the middle left putamen. Consistent with this area's role in motor control, a significant correlation between left putamen volume and motor performance was also observed. Additional research is needed to fully understand the cellular level processes underlying this effect as well as to better understand the clinical impact of these morphometric changes and their potential relation to treatment response.

Intracortical myelin in individuals with alcohol use disorder: An initial proof-of-concept study.

IntroductionDisruption of cortical gray matter and white matter tracts are well‐established markers of alcohol use disorder (AUD), but less is known about whether similar differences are present in intracortical myelin (ICM, i.e., highly myelinated gray matter in deeper cortical layers). The goal of this study was to provide initial proof‐of‐concept for using an optimized structural magnetic resonance imaging (MRI) sequence to detect differences in ICM in individuals with AUD compared to control participants reporting drinking within recommended guidelines.MethodsThis study used an optimized 3T MRI sequence for high intracortical contrast to examine ICM‐related MRI signal in 30 individuals with AUD and 33 healthy social drinkers. Surface‐based analytic techniques were used to quantify ICM‐related MRI signal in 20 bilateral a priori regions of interest based on prior cortical thickness studies, and exploratory vertex‐wise analyses were examined using Cohen's d effect size.ResultsThe global distribution of ICM‐related signal was largely comparable between groups. Region of interest analysis indicated that AUD group exhibited greater ICM‐related MRI signal in precuneus, ventromedial prefrontal cortex, posterior cingulate, middle anterior cingulate, middle/posterior insula, and dorsolateral prefrontal cortex (Cohen's ds = 0.50–0.75). Four regions (right precuneus, ventromedial prefrontal cortex, posterior cingulate and left dorsolateral prefrontal cortex) remained significant (p < .05) after covarying for smoking status.ConclusionThese findings provide initial evidence of ICM differences in a moderately sized sample of individuals with AUD compared to controls, although the inflation of type 1 error rate necessitates caution in drawing conclusions. Robustly establishing these differences in larger samples is necessary. The cross‐sectional design cannot address whether the observed differences predate AUD or are consequences of heavy alcohol consumption.

Elastic shape analysis of brain structures for predictive modeling of PTSD.

It is well-known that morphological features in the brain undergo changes due to traumatic events and associated disorders such as post-traumatic stress disorder (PTSD). However, existing approaches typically offer group-level comparisons, and there are limited predictive approaches for modeling behavioral outcomes based on brain shape features that can account for heterogeneity in PTSD, which is of paramount interest. We propose a comprehensive shape analysis framework representing brain sub-structures, such as the hippocampus, amygdala, and putamen, as parameterized surfaces and quantifying their shape differences using an elastic shape metric. Under this metric, we compute shape summaries (mean, covariance, PCA) of brain sub-structures and represent individual brain shapes by their principal scores under a shape-PCA basis. These representations are rich enough to allow visualizations of full 3D structures and help understand localized changes. In order to validate the elastic shape analysis, we use the principal components (PCs) to reconstruct the brain structures and perform further evaluation by performing a regression analysis to model PTSD and trauma severity using the brain shapes represented via PCs and in conjunction with auxiliary exposure variables. We apply our method to data from the Grady Trauma Project (GTP), where the goal is to predict clinical measures of PTSD. The framework seamlessly integrates accurate morphological features and other clinical covariates to yield superior predictive performance when modeling PTSD outcomes. Compared to vertex-wise analysis and other widely applied shape analysis methods, the elastic shape analysis approach results in considerably higher reconstruction accuracy for the brain shape and reveals significantly greater predictive power. It also helps identify local deformations in brain shapes associated with PTSD severity.

The Dorsolateral Prefrontal Cortex Presents Structural Variations Associated with Empathy and Emotion Regulation in Psychotherapists.

Empathic abilities have been shown to be linked with brain structural variations. Since psychotherapists constitute a population that tends to display greater empathic abilities, as shown in psychometric differences in cognitive empathy and emotional regulation, we aimed to identify cortical thickness (CT) differences between a group of professional psychotherapists and a control group. In line with the recently emphasized urge to employ more than a single workflow in cortical analyses, we utilized two cortical surface extraction and thickness estimation pipelines-CIVET and FreeSurfer. Eighteen psychotherapists and eighteen controls underwent MRI scanning and completed empathy-related psychometric assessments. We evaluated how CT measures differed between groups and if there was an association with individual empathy-related scores in a series of regions of interest (ROIs). Our analysis with CIVET shows that psychotherapists display a significantly greater CT at a ROI in the left dorsolateral prefrontal cortex (dlPFC; p < 0.05, FDR corrected). With FreeSurfer, a whole-brain vertex-wise analysis identified a statistically significant cluster in the left PFC that partially overlaps with the previous ROI. These results were reinforced by a structural covariance analysis revealing that, in psychotherapists, the left dlPFC ROI seemed to vary independently from the rest of the cortex. These findings are relevant because the dlPFC region importantly participates in the cognitive components of the empathic response, such as emotion regulation and perspective taking. Thus, our findings support the idea that empathic capacity is reflected by brain structural variations while also studying for the first time a sample of subjects for whom empathic responding is crucial in their profession.

Polygenic risk scores for antisocial behavior in relation to amygdala morphology across an attention deficit hyperactivity disorder case-control sample with and without disruptive behavior

Antisocial and aggressive behaviors show considerable heritability and are central to disruptive behavior disorders (DBDs), but are also frequently observed in attention deficit hyperactivity disorder (ADHD). While the amygdala is implicated as a key neural structure, it remains unclear whether common genetic variants underlie this brain-behavior association. We hypothesized that polygenic (risk) scores for antisocial and aggressive behaviors (ASB-PRS) would be related to amygdala morphology. Using the Broad Antisocial Behavior Consortium genome-wide association study (GWAS; mostly population based cohorts), we calculated ASB-PRS in the NeuroIMAGE I ADHD case-control sample with varying levels of DBD symptomatology (n=679 from 379 families, aged 7 – 29). We first investigated associations of several ASB-PRS p value thresholds with the presence of DBD symptoms and self-reported antisocial behavior (ASB) to determine the threshold for further analyses. This PRS was then related to amygdala volume and shape using regression and vertex-wise analyses. Our results showed associations of ASB-PRS with the presence of DBD symptoms, self-reported ASB, and left basolateral amygdala shape, independent of ADHD symptom severity and ADHD-PRS, with a relative outward displacement of the vertices. No associations of ASB-PRS, DBD symptoms or self-reported ASB with amygdala volume were found. Our results indicate that genetic risk for antisocial and aggressive behaviors is related to amygdala shape alterations, and point to genetic sharing across different DBD and ASB and aggression-related phenotypes as a spectrum of genetically related quantitative traits. Additionally, our findings support the utility of vertex-based shape analyses in genetic studies of ASB, aggression, and DBDs.

Decreased visual acuity is related to thinner cortex in cognitively normal adults: cross-sectional, single-center cohort study

BackgroundDecreased visual acuity (VA) is reported to be a risk factor for dementia. However, the association between VA and cortical thickness has not been established. We investigated the association between VA and cortical thickness in cognitively normal adults.MethodWe conducted a cross-sectional, single-center cohort study with cognitively normal adults (aged ≥ 45) who received medical screening examinations at the Health Promotion Center at Samsung Medical Center. Subjects were categorized as bad (VA ≤ 20/40), fair (20/40 < VA ≤ 20/25), and good (VA > 20/25) VA group by using corrected VA in the Snellen system. Using 3D volumetric brain MRI, cortical thickness was calculated using the Euclidean distance between the linked vertices of the inner and outer surfaces. We analyzed the association between VA and cortical thickness after controlling for age, sex, hypertension, diabetes, dyslipidemia, intracranial volume, and education level.ResultsA total of 2756 subjects were analyzed in this study. Compared to the good VA group, the bad VA group showed overall thinner cortex (p = 0.015), especially in the parietal (p = 0.018) and occipital (p = 0.011) lobes. Topographical color maps of vertex-wise analysis also showed that the bad VA group showed a thinner cortex in the parieto-temporo-occipital area. These results were more robust in younger adults (aged 45 to 65) as decreased VA was associated with thinner cortex in more widespread regions in the parieto-temporo-occipital area.ConclusionOur results suggest that a thinner cortex in the visual processing area of the brain is related to decreased visual stimuli.

Aberrant hippocampal shape development in young adults with heavy cannabis use: Evidence from a longitudinal study

Cannabis is one of the most commonly used illicit drugs globally. Mounting evidence indicates that cannabis use, particularly consumption during young adulthood, is related to adverse mental and behavioral outcomes and an increased risk of the onset and relapse of psychosis. However, the neuromechanism underpinnings of heavy cannabis use (HCU) in young adults remain largely unknown, and no study has yet investigated the development of hippocampal shape in young adults with HCU. Twenty young adults with HCU and 22 matched non-cannabis-use healthy controls (HCs) were enrolled. Neuroimaging scanning and clinical assessments for all participants were performed at baseline (BL) and 3-year follow-up (FU). The vertex-wise shape analysis was conducted to investigate aberrant hippocampal shape development in young adults with HCU. Aberrant shape development pattern of the hippocampus was observed in young adults with HCU. There was no significant difference in hippocampal shape between the groups at BL, but young adults with HCU at FU exhibited significant shape atrophy of the right dorsal anterior hippocampus related to HCs. In addition, there was a significantly lower growth rate of the right hippocampal shape. Furthermore, there were significant associations of heavy cannabis use, as indicated by the age at onset first and frequent cannabis use, with the growth rate of hippocampal shape in young adults with HCU. The aberrant hippocampal shape development may reflect the effect of heavy cannabis use on young adults and it may be a potential target for heavy cannabis use treatment for young adults.

Gray Matter Deficits of Cortical-striatal-limbic Circuit in Social Anxiety Disorder

IntroductionThe extant findings have been of great heterogeneity due to partial volume effects in the investigation of cortical gray matter volume (GMV), high comorbidity with other psychiatric disorders, and concomitant therapy in the neuroimaging studies of social anxiety disorder (SAD).Objectives To identity gray matter deficits in cortical and subcortical structures in non-comorbid never-treated patients, so as to explore the “pure” SAD-specific pathophysiology and neurobiology.Methods Thirty-two non-comorbid free-of-treatment patients with SAD and 32 demography-matched healthy controls were recruited to undergo high-resolution 3.0-Tesla T1-weighted MRI. Cortical thickness (CT) and subcortical GMV were estimated using FreeSurfer; then the whole-brain vertex-wise analysis was performed to compare group differences in CT. Besides, differences in subcortical GMV of priori selected regions-of-interest: amygdala, hippocampus, putamen, and pallidum were compared by an analysis of covariance with age, gender, and total subcortical GMV as covariates.ResultsThe SAD patients demonstrated significantly decreased CT near-symmetrically in the bilateral prefrontal cortex (Monte Carlo simulations of P &lt; 0.05). Besides, smaller GMV in the left hippocampus and pallidum were also observed in the SAD cohort (two-sample t-test of P &lt; 0.05).ConclusionsFor the first time, the current study investigated the structural alterations of CT and subcortical GMV in non-comorbid never-treated patients with SAD. Our findings provide preliminary evidences that structural deficits in cortical-striatal-limbic circuit may contribute to the psychopathological basis of SAD, and offer more detailed structural substrates for the involvement of such aberrant circuit in the imbalance between defective bottom-up response and top-down control to external stimuli in SAD.DisclosureNo significant relationships.

Parsimonious model for mass-univariate vertexwise analysis.

Purpose: Covariance between gray-matter measurements can reflect structural or functional brain networks though it has also been shown to be influenced by confounding factors (e.g., age, head size, and scanner), which could lead to lower mapping precision (increased size of associated clusters) and create distal false positives associations in mass-univariate vertexwise analyses. Approach: We evaluated this concern by performing state-of-the-art mass-univariate analyses (general linear model, GLM) on traits simulated from real vertex-wise gray matter data (including cortical and subcortical thickness and surface area). We contrasted the results with those from linear mixed models (LMMs), which have been shown to overcome similar issues in omics association studies. Results: We showed that when performed on a large sample ( , UK Biobank), GLMs yielded greatly inflated false positive rate (cluster false discovery rate ). We showed that LMMs resulted in more parsimonious results: smaller clusters and reduced false positive rate but at a cost of increased computation. Next, we performed mass-univariate association analyses on five real UKB traits (age, sex, BMI, fluid intelligence, and smoking status) and LMM yielded fewer and more localized associations. We identified 19 significant clusters displaying small associations with age, sex, and BMI, which suggest a complex architecture of at least dozens of associated areas with those phenotypes. Conclusions: The published literature could contain a large proportion of redundant (possibly confounded) associations that are largely prevented using LMMs. The parsimony of LMMs results from controlling for the joint effect of all vertices, which prevents local and distal redundant associations from reaching significance.

Shape deformations of the basal ganglia in patients with classical trigeminal neuralgia: a cross-sectional evaluation.

Despite the involvement of subcortical brain structures in the pathogenesis of classic trigeminal neuralgia (CTN), the details of morphological abnormalities of basal ganglia to this disorder are still unknown. This study aimed to investigate potential changes in terms of volume and shape of subcortical regions in patients with CTN. Forty-eight patients with CTN and 46 matched healthy subjects were recruited in the study. The whole-brain T1 anatomical data was acquired at a 3.0 Tesla scanner using a fast spoiled gradient recalled sequence (FSPGR). Vertex-wise analysis was applied to detect the alterations of volume and shape in each subcortical region in the patients with CTN compared to healthy controls. The relationships of morphological abnormalities in subcortical structures to the severity of orofacial pain and the affective disturbance in the patient group were examined using the multiple linear regression model. No group difference was found about volumetric measurement in any of the subcortical regions. Vertex-wise analysis revealed areas of significant shape atrophy in bilateral putamen and bilateral pallidum in the patients with CTN compared to healthy controls. Besides, the patient group exhibited shape expansion in the head of the right caudate nucleus compared to healthy subjects. In addition, shape deformation in the head of the right caudate nucleus was positively associated with VAS score in CTN. The patients with CTN display shape alterations in the specific subregions of basal ganglia, which may contribute to the pathophysiology of this refractory disorder and may be useful for translational medicine.