Group Differences In Cortical Thickness Research Articles

Cortical structure and subcortical volumes in conduct disorder: a coordinated analysis of 15 international cohorts from the ENIGMA-Antisocial Behavior Working Group

Conduct disorder is associated with the highest burden of any mental disorder in childhood, yet its neurobiology remains unclear. Inconsistent findings limit our understanding of the role of brain structure alterations in conduct disorder. This study aims to identify the most robust and replicable brain structural correlates of conduct disorder. The ENIGMA-Antisocial Behavior Working Group performed a coordinated analysis of structural MRI data from 15 international cohorts. Eligibility criteria were a mean sample age of 18 years or less, with data available on sex, age, and diagnosis of conduct disorder, and at least ten participants with conduct disorder and ten typically developing participants. 3D T1-weighted MRI brain scans of all participants were pre-processed using ENIGMA-standardised protocols. We assessed group differences in cortical thickness, surface area, and subcortical volumes using general linear models, adjusting for age, sex, and total intracranial volume. Group-by-sex and group-by-age interactions, and DSM-subtype comparisons (childhood-onset vs adolescent-onset, and low vs high levels of callous-unemotional traits) were investigated. People with lived experience of conduct disorder were not involved in this study. We collated individual participant data from 1185 young people with conduct disorder (339 [28·6%] female and 846 [71·4%] male) and 1253 typically developing young people (446 [35·6%] female and 807 [64·4%] male), with a mean age of 13·5 years (SD 3·0; range 7-21). Information on race and ethnicity was not available. Relative to typically developing young people, the conduct disorder group had lower surface area in 26 cortical regions and lower total surface area (Cohen's d 0·09-0·26). Cortical thickness differed in the caudal anterior cingulate cortex (d 0·16) and the banks of the superior temporal sulcus (d -0·13). The conduct disorder group also had smaller amygdala (d 0·13), nucleus accumbens (d 0·11), thalamus (d 0·14), and hippocampus (d 0·12) volumes. Most differences remained significant after adjusting for ADHD comorbidity or intelligence quotient. No group-by-sex or group-by-age interactions were detected. Few differences were found between DSM-defined conduct disorder subtypes. However, individuals with high callous-unemotional traits showed more widespread differences compared with controls than those with low callous-unemotional traits. Our findings provide robust evidence of subtle yet widespread brain structural alterations in conduct disorder across subtypes and sexes, mostly in surface area. These findings provide further evidence that brain alterations might contribute to conduct disorder. Greater consideration of this under-recognised disorder is needed in research and clinical practice. Academy of Medical Sciences and Economic and Social Research Council.

The impact of paramagnetic rim lesions on cortical thickness and gray to white matter contrast in relapsing-remitting multiple sclerosis.

Paramagnetic rim lesions (PRLs) on susceptibility magnetic resonance sequences have been suggested as an imaging marker of disease progression in multiple sclerosis. This retrospective cross-sectional study aimed to investigate the impact of PRLs on cortical thickness and gray matter (GM) to white matter (WM) contrast in relapsing-remitting multiple sclerosis (RRMS). A total of 82 RRMS patients (40 patients with at least 1 PRL and 42 patients without PRL) and 43 healthy controls (HC) were included in this study. The T1-weighted images (T1WI) were processed with the FreeSurfer pipeline. GM to WM signal intensity ratio (GWR) was obtained from T1WI by dividing the GM signal intensity by the WM signal intensity for each vertex. Group differences in cortical thickness and GWR were tested on reconstructed cortical surface. Compared to HC, patients with PRL had thinner mean cortical thickness (P<0.001), higher mean GWR (P=0.001), and lower brain structure volumes (cortex volume, P=0.001; WM volume, P<0.001; deep GM volume, P<0.001). Vertex-based analysis found significant cortical thinning in several regions and increased GWR in a wider range of regions in patients with PRL. The two types of clusters had both overlapping regions and independent regions. However, in patients without PRL, only a few regions showed significant cortical thickness changes. Correlation analysis found that in patients with PRL, only PRL volume showed a significant negative correlation with mean cortical thickness (P=0.048), and PRL volume and count, non-PRL count, and total lesion volume were significantly and positively correlated with mean GWR (P<0.05). There were significant changes in cortical thickness, GWR, and brain structure volume in RRMS patients with PRL that may contribute to further understanding of the pathological mechanisms underlying neurological tissue damage.

B - 01 Children with ADHD Demonstrate Cortical Thinning in Multiple Regions Compared to TD Controls.

Children with Attention-Deficit/Hyperactivity Disorder (ADHD) often demonstrate functional and volumetric differences compared to typically developing (TD) children. These regions are associated with the deficits commonly seen in ADHD. However, there is limited research on cortical thickness in ADHD, and what does exist is inconsistent in its findings. Thus, the objective of this study was to examine potential differences in cortical thickness between children with ADHD and TD controls. Participants included 73 children (aged 8-12years; 50.7% boys, 87.7% White) with ADHD and typically developing controls. It was a community sample. The children completed an MRI scan and a neuropsychological battery as part of a larger, grant-funded project (R03HD048752, R15HD065627). Group differences in cortical thickness were determined using CAT12 software. A t-test model was used for voxel-wise comparisons of cortical thickness between children with ADHD and TD controls. After aligning the MRI scans, the CAT12 software provides clusters of regions in which cortical thickness differs significantly between groups. Compared with TD controls, children with ADHD demonstrated reduced cortical thickness in three clusters in the left hemisphere and one large cluster in the right hemisphere (p < 0.05; FWE corrected). The clusters included several frontal and parietal regions, along with occipital and temporal regions. Results are consistent with findings from prior research comparing children with ADHD and TD controls using other neuroimaging methods, which displayed involvement of frontal-parietal and/or frontal-temporal networks. Furthermore, these regions are associated with cognitive and behavioral deficits commonly seen in ADHD, including various aspects of executive dysfunction.

Changed cortical thickness and sulcal depth in pediatric acute lymphoblastic leukemia survivors treated with chemotherapy only.

The purpose of this study is to observe the changes of cortical morphological characteristics and their potential contribution to cognitive function in ALL survivors by using surface-based morphometry (SBM). Using SBM analysis, we calculated and compared group differences in cortical thickness, sulcal depth, gyrification, and fractal dimension of the cerebral cortex between 18 pediatric ALL survivors treated on chemotherapy-only protocols and off treatment within 2years, and 18 healthy controls (HCs) with two-sample t-tests [P < 0.05, family-wise error (FWE) corrected]. Relationships between abnormal cortical characteristic values and cognitive function parameters were investigated with partial correlation analysis, taking age as a covariate. We found decreased cortical thickness mainly located in the prefrontal and temporal region, and increased sulcal depth in left rostral middle frontal cortex and left pars orbitalis in the ALL survivors compared to HCs. There were no statistically significant differences in the gyrification and fractal dimension between the two groups. In ALL survivors, cortical thickness and sulcal depth of above areas values revealed no significant correlation with the cognitive function parameters. In conclusion, pediatric ALL survivors show decreased cortical thickness in prefrontal and temporal regions, and increased sulcal depth in prefrontal region. These results suggest that SBM-based approach can be used to assess changes of cortical morphological characteristics in pediatric ALL survivors.

Hypogyrification in midlife women with surgical menopause, a population at risk for late life Alzheimer’s

AbstractBackgroundWomen with early ovarian hormone deprivation due to bilateral salpingo‐oophorectomy (BSO; ovarian and fallopian tube removal) are at risk for later life Alzheimer’s disease (AD), but estradiol therapy (ET) may be protective (Rocca et al., 2007). Working memory (WM), temporarily maintaining and manipulating information in mind, depends on structural integrity of fronto‐parietal brain regions (Burzynska et al., 2012). WM declines have been observed in midlife women with BSO not taking ET (Gervais et al., 2020), however, structural brain–WM relationships in this midlife population remain unexplored. This study aimed to: 1) Investigate fronto‐parietal cortical thickness and gyrification (folding) changes in younger women after early BSO and their relationship to WM, and 2) Explore whether ET ameliorates these changes.MethodWomen with early BSO taking ET (BSO+ET: M±SDage = 45±5.1; n = 26), or not taking ET (BSO: M±SDage = 46±5.0y; n = 26) were compared to premenopausal, age‐matched controls (AMC: M±SDage = 44±2.9y; n = 42) from Toronto and Montreal, Canada, and Linköping, Sweden. T1‐weighted scans were acquired on Siemens Prisma/Philips 3T scanners. WM was measured using Digit Span Backwards (Wechsler, 1945) maximum span and Digit Ordering Task (Petrides et al., 1993) errors. Average cortical thickness and gyrification of fronto‐parietal regions were calculated from CIVET (Ad‐Dab’bagh et al. 2005), adjusting for scanner and past cancer treatment.ResultLinear models showed no group differences in cortical thickness or WM. However, they showed BSO had significant hypogyrification (reduced cortical folding) in the supplementary motor area (SMA), part of the posterior prefrontal cortex, compared to AMC (adjusted for brain volume; FDR‐corrected p = 0.028). BSO+ET had intermediate SMA gyrification, and did not differ from either group. SMA gyrification was unrelated to WM, and gyrification–WM relationships did not differ by group.ConclusionWe found SMA hypogyrification in younger women with BSO compared to AMC and BSO+ET. The SMA supports WM manipulation and is an early area affected by age‐related gyrification declines (Madan, 2021). Moreover, hypogyrification may reflect reduced brain connectivity, and gyrification globally declines with AD severity (Liu et al., 2012). Although SMA hypogyrification in women with BSO was unrelated to WM, it may serve as an early sign of later life cognitive decline.

Differential effects of parental socioeconomic status on cortical thickness in patients with schizophrenia spectrum disorders and healthy controls

ObjectivesWidespread changes in cortical thickness (CT) have been repeatedly reported in schizophrenia (SZ). The nature of the pathophysiologic process underlying such changes remains to be elucidated. The aims of the present study were to measure the CT; evaluate parent socioeconomic status (pSES), childhood trauma (ChT) and premorbid adjustment (PA) in patients with schizophrenia spectrum disorders (SSDs); and investigate group differences in CT (i.e., SSD vs. healthy controls (HCs)), pSES, PA, and/or ChT, as well as the interactions among these factors. Methods164 patients with SSD and 245 age-, sex- and education-matched healthy controls have participated. The pSES, ChT and PA were evaluated using Korean version of Polyenvironmental Risk Score, Early Trauma Inventory Self Report-Short Form and Premorbid Adjustment Scale, respectively. Vertex-wise measure of CT was estimated using the FreeSurfer. To investigate the main effects and interactions, multilevel regression was employed. ResultsWe found widespread cortical thinning in patients with SSDs compared to HCs. The cortical thinning was associated with ChT, symptom severity and chlorpromazine equivalent dose and duration of illness in patients. In multilevel regression, main effects of group and pSES and interaction between group and pSES were found whereas a significant interaction between ChT and CPZ equivalent was found in patients. ConclusionOur findings indicate that compared to HCs, patients with SSDs have cortical structural abnormalities, and that group and pSES interaction determines CT. Further studies are needed to explore the effects of psychosocial factors on brain structural and functional abnormalities in SZ.

Increased cortical surface area but not altered cortical thickness or gyrification in bipolar disorder following stabilisation from a first episode of mania

BackgroundDespite reports of altered brain morphology in established bipolar disorder (BD), there is limited understanding of when these morphological abnormalities emerge. Assessment of patients during the early course of illness can help to address this gap, but few studies have examined surface-based brain morphology in patients at this illness stage. MethodsWe completed a secondary analysis of baseline data from a randomised control trial of BD individuals stabilised after their first episode of mania (FEM). The magnetic resonance imaging scans of n = 35 FEM patients and n = 29 age-matched healthy controls were analysed. Group differences in cortical thickness, surface area and gyrification were assessed at each vertex of the cortical surface using general linear models. Significant results were identified at p < 0.05 using cluster-wise correction. ResultsThe FEM group did not differ from healthy controls with regards to cortical thickness or gyrification. However, there were two clusters of increased surface area in the left hemisphere of FEM patients, with peak coordinates falling within the lateral occipital cortex and pars triangularis. ConclusionsCortical thickness and gyrification appear to be intact in the aftermath of a first manic episode, whilst cortical surface area in the inferior/middle prefrontal and occipitoparietal cortex is increased compared to age-matched controls. It is possible that increased surface area in the FEM group is the outcome of abnormalities in a premorbidly occurring process. In contrast, the findings raise the hypothesis that cortical thickness reductions seen in past studies of individuals with more established BD may be more attributable to post-onset factors.

Quantitative evaluation of cortical thickness in 3T in Behçet’s patients without neurological involvement and parenchymal neuro-Behçet’s disease

PurposeTo evaluate the spatial distribution of cortical damage in Behcet’s Disease (BD) with or without neurological involvement using a cortical thickness measurement approach using three-dimensional T1-weighted imaging. Material and methodsFifty-eight BD patients without neurological involvement, twenty-two Parenchymal Neuro-Behçets disease (PNBD) patients, and fifty healthy controls were included in the prospective study. Anatomical 3D T1 images were obtained from all participants using 3T MRI. Using a computational anatomy toolbox (CAT12), we calculated and compared group differences in cortical thickness. ResultsPatients with BD without neurological involvement showed cortical thickness reduction in bilateral frontal, bilateral parietal, and right precuneus compared with the healthy controls (HCs) (p < 0.05 FWE corrected [FWEc]). PNBD patients showed frontoparietal cortical thickness reduction when compared with BD patients without neurological involvement (p < 0.05 FWEc). The PNBD patients showed widespread cortical thickness reduction compared with the HC patients (p < 0.05 FWEc). Disease duration was correlated with cortical thickness in the right pericalcarine (p = 0.012 false discovery rate [FDR], r = −0.40), left pericalcarine (p = 0.013 FDR, r = −0.44), and left transverse temporal (p = 0.007 FDR, r = −0.41) regions. ConclusionThere is a decrease in cortical thickness in BD patients without neurological involvement. Cortical thickness reduction is more prominent in parenchymal neurobehçet's patients. Cortical thickness shows a negative correlation with disease duration in some regions.

Brain morphometric abnormalities and their associations with affective symptoms in males with methamphetamine use disorder during abstinence.

BackgroundMethamphetamine (METH) use induces neurotoxic effects in brain structures and affective symptoms that persist during abstinence. However, the brain morphometry of individuals with METH use disorder (MUD) remains unclear, as well as their associations with affective symptoms during abstinence.MethodsForty-eight abstinent males with MUD and 66 age-, sex-, and education-matched healthy controls (HCs) underwent high-resolution T1-weighted magnetic resonance imaging. Cortical thickness, surface area, volume, local gyrification index (LGI), and subcortical volume were obtained with FreeSurfer software. Brain morphometry differences between groups and their associations with affective symptoms and drug abuse history within the males with MUD were examined, with intracranial volume, age, and years of education as covariates.ResultsCompared with the HCs, the individuals with MUD showed a significantly higher LGI in the right cuneus gyrus, left lingual gyrus, bilateral supramarginal gyrus, right inferior parietal gyrus (IPG), and right dorsal anterior cingulate cortex (clusterwise p < 0.05, Monte Carlo-corrected), as well as a smaller volume of the left nucleus accumbens (NAcc) (p < 0.05, FDR-corrected). However, there were no significant group differences in cortical thickness, area or volume. In addition, the LGI in the right IPG was positively associatedwith the severity of depression and anxiety symptoms in MUDs (p < 0.05, FDR-corrected).ConclusionBrain morphometric abnormalities in abstinent males with MUD were characterized by hypergyrification across multiple mid-posterior brain regions anda smaller volume of the left NAcc.Gyrification of the right IPG may be a potential neural substrate underlying the affective symptoms experienced by MUDs during abstinence.

Abnormal cortical morphology in children and adolescents with intermittent exotropia.

PurposeTo investigate cortical differences, age-related cortical differences, and structural covariance differences between children with intermittent exotropia (IXT) and healthy controls (HCs) using high-resolution magnetic resonance imaging (MRI).MethodsSixteen IXT patients and 16 HCs underwent MRI using a 3-T MR scanner. FreeSurfer software was used to obtain measures of cortical volume, thickness, and surface area. Group differences in cortical thickness, volume and surface area were examined using a general linear model with intracranial volume (ICV), age and sex as covariates. Then, the age-related cortical differences between the two groups and structural covariance in abnormal morphometric changes were examined.ResultsCompared to HCs, IXT patients demonstrated significantly decreased surface area in the left primary visual cortex (PVC), and increased surface area in the left inferior temporal cortex (ITC). We also found increased cortical thickness in the left orbitofrontal cortex (OFC), right middle temporal cortex (MT), and right inferior frontal cortex (IFC). No significant differences were found in cortical volume between the two groups. There were several negative correlations between neuroanatomic measurements and age in the HC group that were not observed in the IXT group. In addition, we identified altered patterns of structural correlations across brain regions in patients with IXT.ConclusionTo our knowledge, this study is the first to characterize the cortical morphometry of the children and adolescents with IXT. Based on our results, children and adolescents with IXT exhibited significant alterations in the PVC and association cortices, different cortical morphometric development patterns, and disrupted structural covariance across brain regions.

Surface-based brain morphometry in schizophrenia vs. cannabis-induced psychosis: A controlled comparison

Background & aimWe examined group differences in cortical thickness and surface-parameters among age and handedness--matched persons with cannabis-induced psychosis (CIP), schizophrenia with heavy cannabis use (SZC), and healthy controls (HC). MethodsWe recruited 31 men with SZC, 28 with CIP, and 30 with HC. We used the Psychiatric Research Interview for Substance and Mental Disorders to differentiate between CIP and SZC. We processed and analyzed T1 MR images using the Surface-based Brain Morphometry (SBM) pipeline of the CAT-12 toolbox within the statistical parametric mapping. After pre-processing, volumes were segmented using surface and thickness estimation for the analysis of the region of interest. We used the projection-based thickness method to assess the cortical thickness and Desikan-Killiany atlas for cortical parcellation. ResultsWe observed the lowest cortical thickness, depth, and gyrification in the SZC, followed by CIP and the control groups. The differences were predominantly seen in frontal cortices, with limited parietal and temporal regions involvement. After False Discovery Rate (FDR) corrections and post-hoc analysis, SZC had reduced cortical thickness than HC in the middle and inferior frontal, right entorhinal, and left postcentral regions. Cortical thickness of SZC was also significantly lower than CIP in bilateral postcentral and right middle frontal regions. We found negative correlations (after FDR corrections) between the duration of cannabis use and cortical thickness in loci of parietal and occipital cortices. ConclusionOur study suggested cortical structural abnormalities in schizophrenia, in reference to healthy controls and cannabis-induced psychosis, indicating different pathophysiology of SZC and CIP.

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.

Multimodal MRI reveals alterations of the anterior insula and posterior cingulate cortex in bipolar II disorders: A surface-based approach

BackgroundBipolar disorder (BD) is a mental disorder with severe implications for those affected and their families. Previous studies detected brain structural and functional alterations in BD patients. However, very few studies conducted a multimodal MRI fusion analysis, and little is known about the role of common anomalies in the connectivity of BD. MethodsWe collected sMRI, rs-fMRI, and DTI data from 56 patients with unmedicated BD-II depression and 72 age-, sex- and handedness-matched healthy controls. We applied data-driven approaches to analyze multimodal MRI data and detected brain areas with significant group differences in cortical thickness (CT), amplitude of low frequency fluctuations (ALFF), and fractional anisotropy (FA) of the superficial white matter. We observed the common abnormal areas and took these areas as seeds to analyze the resting-state functional connectivity (RSFC) patterns in BD patients by overlapping these abnormal areas. ResultsThe BD patients showed two common abnormal areas: (1) the left anterior insula (AI) with abnormal CT and FA, and (2) the left posterior cingulate cortex (PCC) with abnormal CT and ALFF. Seed-based analyses showed RSFC between the left AI and left occipital sensory cortex, the left AI and left superior and inferior parietal cortex, and the left PCC and right medial prefrontal cortex were uniformly lower in the BD patients than controls. Correlation analyses showed negative correction between AI's FA and disease episodes and between AI's FA and disease duration in depressed BD-II patients. ConclusionsWe observed abnormal brain structural and functional properties in the left AI and left PCC in BD patients. The abnormal RSFC patterns may suggest sensory and cognitive dysfunction in BD.

Neural Correlates of Traumatic Brain Injury in Women Survivors of Intimate Partner Violence: A Structural and Functional Connectivity Neuroimaging Study.

More than one-third of women in the United States experience intimate partner violence (IPV) in their lifetime, increasing their risk for traumatic brain injury (TBI). Despite the prevalence of TBI among IPV survivors, research is sparse in comparison with parallel populations (eg, military, accidents, sports). This pilot study aimed to provide a preliminary investigation of the effect of TBI on brain morphometry and resting-state functional connectivity in women who experience IPV. A total of 45 community-dwelling women survivors of IPV who screened positive for posttraumatic stress disorder (PTSD). Participants completed comprehensive assessments of trauma exposure, PTSD, TBI history, and brain neurological health. Twenty-three participants (51.1%) met diagnostic criteria for lifetime TBI. Of these, 15 participants experienced 1 or more TBIs resulting from IPV. The remaining participants experienced TBI from non-IPV exposures (eg, sports/motor vehicle accident). Surface-based neuroimaging analyses were performed to examine group differences in cortical thickness and in functional connectivity of amygdala and isthmus cingulate seeds to examine emotion regulation and the default mode network, respectively. Boston Assessment of Traumatic Brain Injury-Lifetime for Intimate Partner Violence (BAT-L/IPV); Clinician Administered PTSD Scale (CAPS); structural and functional neuroimaging. History of lifetime TBI in women IPV survivors was associated with differences in cortical thickness as well as functional connectivity between the isthmus cingulate seed and a variety of regions, including superior parietal and frontal cortices. Individuals with IPV-related TBI showed lower cortical thickness in the right paracentral gyrus than individuals with TBI from other non-IPV etiologies. Significant differences in brain structure and connectivity were observed in individuals with IPV and TBI. A lower mean cortical thickness of the paracentral gyrus was associated with TBI due to IPV than TBI from other etiologies. Although preliminary, findings from this pilot study present a step toward identifying potential mechanisms by which IPV and TBI secondary to IPV impact brain health in women.

Fronto-temporal functional disconnection precedes hippocampal atrophy in clinically confirmed multi-domain amnestic Mild Cognitive Impairment.

Mild Cognitive Impairment (MCI) is fraught with high false positive diagnostic errors. The high rate of false positive diagnosis hampers attempts to identify reliable and valid biomarkers for MCI. Recent research suggests that aberrant functional neurocircuitries emerge prior to significant cognitive deficits. The aim of the present study was to examine this in clinically confirmed multi-domain amnestic-MCI (mdaMCI) using an established, multi-time point, methodology for minimizing false positive diagnosis. Structural and resting-state functional MRI data were acquired in healthy controls (HC, n=24), clinically-confirmed multi-domain amnestic-MCI (mdaMCI, n=14) and mild Alzheimer's Dementia (mAD, n=6). Group differences in cortical thickness, hippocampal volume and functional connectivity were investigated. Hippocampal subvolumes differentiated mAD from HC and mdaMCI. Functional decoupling of fronto-temporal networks implicated in memory and executive function differentiated HC and mdaMCI. Decreased functional connectivity in these networks was associated with poorer cognitive performance scores. Preliminary findings suggest the large-scale decoupling of fronto-temporal networks associated with cognitive decline precedes measurable structural neurodegeneration in clinically confirmed MCI and may represent a potential biomarker for disease progression.

Cortical thickness, gyrification and sulcal depth in trigeminal neuralgia

Neuroimaging studies have documented brain structural alterations induced by chronic pain, particularly in gray matter volume. However, the effects of trigeminal neuralgia (TN), a severe paroxysmal pain disorder, on cortical morphology are not yet known. In this study, we recruited 30 TN patients and 30 age-, and gender-matched healthy controls (HCs). Using Computational Anatomy Toolbox (CAT12), we calculated and compared group differences in cortical thickness, gyrification, and sulcal depth with two-sample t tests (p < 0.05, multiple comparison corrected). Relationships between altered cortical characteristics and pain intensity were investigated with correlation analysis. Compared to HCs, TN patients exhibited significantly decreased cortical thickness in the left inferior frontal, and left medial orbitofrontal cortex; decreased gyrification in the left superior frontal cortex; and decreased sulcal depth in the bilateral superior frontal (extending to anterior cingulate) cortex. In addition, we found significantly negative correlations between the mean cortical thickness in left medial orbitofrontal cortex and pain intensity, and between the mean gyrification in left superior frontal cortex and pain intensity. Chronic pain may be associated with abnormal cortical thickness, gyrification and sulcal depth in trigeminal neuralgia. These morphological changes might contribute to understand the underlying neurobiological mechanism of trigeminal neuralgia.

Abstract 54: Bilateral Developmental Alterations in Cortical Morphology in Children With Perinatal Stroke

Perinatal stroke (PS) causes hemiparetic cerebral palsy (CP) and lifelong disability. Compensatory changes in the nonlesioned hemisphere may mediate residual function and represent targets for neuromodulation. Region-based approaches may reveal relationships between cortical thickness of nonlesioned primary motor/sensory cortices and motor function. This study uses surface-based morphometry to explore cortical alterations in the nonlesioned hemisphere in children after perinatal stroke. Children aged 6-19 with MRI-confirmed unilateral perinatal stroke and CP underwent T1-weighted anatomical imaging. Participants were classified as arterial ischemic stroke (AIS; n=36), periventricular venous infarction (PVI; n=38), or typically developing controls (TDC; n=53). Group differences in cortical thickness (distance between grey/white matter boundary and pial surface), grey matter volume, gyrification and sulcal depth and relationships between these morphology metrics and validated measures of motor/executive function were explored. Group comparisons revealed less cortical thickness, greater gyrification, and greater surface area in the nonlesioned hemisphere in both AIS and PVI as compared to TDC. Greater volume and sulcal depth were observed in the nonlesioned hemisphere for AIS. The PVI group showed greater volume in the cingulate cortex and less volume in the precuneus relative to TDC. The AIS group showed more widespread differences than the PVI group in volume and other cortical surface parameters when compared with TDC. Only modest correlations were observed between morphometric changes and clinical function. We suggest that broad differences in structural developmental plasticity occur in the nonlesioned hemisphere after perinatal stroke, particularly the larger lesions seen with AIS, and may represent novel targets for therapeutic neuromodulation.

The relevance of multiple sclerosis cortical lesions on cortical thinning and their clinical impact as assessed by 7.0-T MRI.

This study aimed to investigate at 7.0-T MRI a) the role of multiple sclerosis (MS) cortical lesions in cortical tissue loss b) their relation to neurological disability. In 76 relapsing remitting and 26 secondary progressive MS patients (N = 102) and 56 healthy subjects 7.0-T T2*-weighted images were acquired for lesion segmentation; 3.0-T T1-weighted structural scans for cortical surface reconstruction/cortical thickness estimation. Patients were dichotomized based on the median cortical lesion volume in low and high cortical lesion load groups that differed by age, MS phenotype and degree of neurological disability. Group differences in cortical thickness were tested on reconstructed cortical surface. Patients were evaluated clinically by means of the Expanded Disability Status Scale (EDSS). Cortical lesions were detected in 96% of patients. White matter lesion load was greater in the high than in the low cortical lesion load MS group (p = 0.01). Both MS groups disclosed clusters (prevalently parietal) of cortical thinning relative to healthy subjects, though these regions did not show the highest cortical lesion density, which predominantly involved frontal regions. Cortical thickness decreased on average by 0.37mm, (p = 0.002) in MS patients for each unit standard deviation change in white matter lesion volume. The odds of having a higher EDSS were associated with cortical lesion volume (1.78, p = 0.01) and disease duration (1.15, p < 0.001). Cortical thinning in MS is not directly related to cortical lesion load but rather with white matter lesion volume. Neurological disability in MS is better explained by cortical lesion volume assessment.

Cerebral cortical thickness and surface area in adolescent anorexia nervosa: Separate and joint analyses with a permutation-based nonparametric method.

Reduction in cerebral volume is often found in underweight patients with anorexia nervosa (AN), but few studies have investigated other morphological measures. Cortical thickness (CTh) and surface area (CSA), often used to produce the measure of cortical volume, are developmentally distinct measures that may be differentially affected in AN, particularly in the developing brain. In the present study, we investigated CTh and CSA both separately and jointly to gain further insight into structural alterations in adolescent AN patients. Thirty female AN inpatients 12-18 years of age, and 27 age-matched healthy controls (HC) underwent structural magnetic resonance imaging. Group differences in CTh and CSA were investigated separately and jointly with a permutation-based nonparametric combination method (NPC) which may be more sensitive in detecting group differences compared to traditional volumetric methods. Results showed significant reduction in in both CTh and CSA in several cortical regions in AN compared to HC and the reduction was related to BMI. Different results for the two morphological measures were found in a small number of cortical regions. The joint NPC analyses showed significant group differences across most of the cortical mantle. Results from this study give novel insight to areal reduction in adolescent AN patients and indicate that both CTh and CSA reduction is related to BMI. The study is the first to use the NPC method to reveal large structural alterations covering most of the brain in adolescent AN.

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

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