Cognitive function in severe progressive multiple sclerosis.

Cognitive impairment is common in multiple sclerosis and negatively impacts quality of life. Cognitive status has yet to be described in people with severe progressive multiple sclerosis, in whom conventional neuropsychological testing is exceptionally difficult. The objective for the study was to characterize cognitive performance in severe progressive multiple sclerosis and compare them with age-, sex- and disease duration-matched less disabled people with multiple sclerosis using a specifically developed auditory, non-motor test of attention/cognitive processing speed-Auditory Test of Processing Speed. Also, we aimed to determine the relationship between cognitive performance and MRI-based outcomes in these matched cohorts. The Comprehensive Assessment of Severely Affected Multiple Sclerosis study was carried out at the University at Buffalo and the Boston Home, a skilled nursing facility in Dorchester, MA. Inclusion criteria were age 30-80 years and expanded disability status scale 3.0-6.5 for community-dwelling and 7.0-9.5 for skilled nursing facility people with multiple sclerosis. The cognitive assessment was performed using the Brief International Cognitive Assessment for Multiple Sclerosis consisting of Symbol Digit Modalities Test, Brief Visuospatial Memory Test-Revised, California Verbal Learning Test-2nd edition along with Auditory Test of Processing Speed, Paced Auditory Serial Addition Test-3 second and Controlled Oral Word Association Test. MRI scans were retrospectively collected and analysed for lesion and volumetric brain measurements. The rate of completion and performance of the cognitive tests was compared between the groups, and the relationship with MRI measures was determined using sex, age and years of education-adjusted linear regression models. Significantly greater percentage of the severe multiple sclerosis group completed Auditory Test of Processing Speed when compared with the current gold standard of Symbol Digit Modalities Test (93.2% versus 65.9%). Severe progressive multiple sclerosis had worse cognitive performance in all cognitive domains with greatest differences for cognitive processing speed (Symbol Digit Modalities Test > Paced Auditory Serial Addition Test-3 second > Auditory Test of Processing Speed, Cohen's d < 2.13, P < 0.001), learning and memory (Cohen's d < 1.1, P < 0.001) and language (Controlled Oral Word Association Test with Cohen's d = 0.97, P < 0.001). Multiple cognitive domains were significantly associated with lower thalamic (standardized ß < 0.419, P < 0.006) and cortical (standardized ß < 0.26, P < 0.031) volumes. Specially designed (auditory) cognitive processing speed tests may provide more sensitive screening of cognitive function in severe progressive multiple sclerosis. The cognitive profile of severe multiple sclerosis is proportional to their physical outcomes and best explained by decreased grey matter volume.

Examining the neurostructural architecture of intelligence: The Lothian Birth Cohort 1936 study.

Examining underlying neurostructural correlates of specific cognitive abilities is practically and theoretically complicated by the existence of the positive manifold (all cognitive tests positively correlate): if a brain structure is associated with a cognitive task, how much of this is uniquely related to the cognitive domain, and how much is due to covariance with all other tests across domains (captured by general cognitive functioning, also known as general intelligence, or 'g')? We quantitatively address this question by examining associations between brain structural and diffusion MRI measures (global tissue volumes, white matter hyperintensities, global white matter diffusion fractional anisotropy and mean diffusivity, and FreeSurfer processed vertex-wise cortical volumes, smoothed at 20mm fwhm) with g and cognitive domains (processing speed, crystallised ability, memory, visuospatial ability). The cognitive domains were modelled using confirmatory factor analysis to derive both hierarchical and bifactor solutions using 13 cognitive tests in 697 participants from the Lothian Birth Cohort 1936 study (mean age 72.5 years; SD = .7). Associations between the extracted cognitive factor scores for each domain and g were computed for each brain measure covarying for age, sex and intracranial volume, and corrected for false discovery rate. There were a range of significant associations between cognitive domains and global MRI brain structural measures (r range .008 to .269, p < .05). Regions implicated by vertex-wise regional cortical volume included a widespread number of medial and lateral areas of the frontal, temporal and parietal lobes. However, at both global and regional level, much of the domain-MRI associations were shared (statistically accounted for by g). Removing g-related variance from cognitive domains attenuated association magnitudes with global brain MRI measures by 27.9-59.7% (M = 46.2%), with only processing speed retaining all significant associations. At the regional cortical level, g appeared to account for the majority (range 22.1-88.4%; M = 52.8% across cognitive domains) of regional domain-specific associations. Crystallised and memory domains had almost no unique cortical correlates, whereas processing speed and visuospatial ability retained limited cortical volumetric associations. The greatest spatial overlaps across cognitive domains (as denoted by g) were present in the medial and lateral temporal, lateral parietal and lateral frontal areas.

Plasma IL-6 levels and their association with brain health and dementia risk: A population-based cohort study.

BACKGROUND: Recent studies have associated immune abnormalities with dementia. IL-6 is a crucial cytokine in inflammatory responses, and recent evidence has linked elevated IL-6 levels to changes in brain structure and cognitive decline. However, the connection between IL-6 levels, cognition, brain volumes, and dementia risk requires exploration in large prospective cohorts. METHODS: This study utilized a longitudinal cohort from the UK Biobank to analyze the correlation between IL-6 expression levels, cognitive performance, and cortical and subcortical brain volumes through linear regression. Additionally, we assessed the association between IL-6 levels and long-term dementia risk using Cox regression analysis. We also used one-sample Mendelian randomization to analyze the impact of genetic predisposition of dementia on elevated IL-6 levels. RESULTS: A total of 50,864 participants were included in this study, with 1,391 new cases of all-cause dementia identified. Higher plasma IL-6 levels are associated with cortical and subcortical atrophy in regions such as the fusiform, thalamus proper, hippocampus, and larger ventricle volumes. IL-6 levels are negatively associated with cognitive performance in pair matching, numeric memory, prospective memory, and reaction time tests. Furthermore, elevated IL-6 levels are linked to a 23-35 % increased risk of all-cause dementia over an average follow-up period of 13.2 years. The one-sample Mendelian randomization analysis did not show associations between the genetic predisposition of dementia and elevated IL-6 levels. CONCLUSIONS: Increased IL-6 levels are associated with worse cognition, brain atrophy, and a heightened risk of all-cause dementia. Our study highlights the need to focus on the role of peripheral IL-6 levels in managing brain health and dementia risk.

Associations between behavioral and self-reported impulsivity, brain structure, and genetic influences in middle childhood.

Impulsivity undergoes a normative developmental trajectory from childhood to adulthood and is thought to be driven by maturation of brain structure. However, few large-scale studies have assessed associations between impulsivity, brain structure, and genetic susceptibility in children. In 9112 children ages 9-10 from the ABCD study, we explored relationships among impulsivity (UPPS-P impulsive behavior scale; delay discounting), brain structure (cortical thickness (CT), cortical volume (CV), and cortical area (CA)), and polygenic scores for externalizing behavior (PGSEXT). Both higher UPPS-P total scores and more severe delay-discounting had widespread, low-magnitude associations with smaller CA in frontal and temporal regions. No associations were seen between impulsivity and CV or CT. Additionally, higher PGSEXT was associated with both higher UPPS-P scores and with smaller CA and CV in frontal and temporal regions, but in non-overlapping cortical regions, underscoring the complex interplay between genetics and brain structure in influencing impulsivity. These findings indicate that, within large-scale population data, CA is significantly yet weakly associated with each of these impulsivity measures and with polygenic risk for externalizing behaviors, but in distinct brain regions. Future work should longitudinally assess these associations through adolescence, and examine associated functional outcomes, such as future substance use and psychopathology.

Negative association between neurovascular coupling and cortical gray matter volume during the lifespan.

Recent studies have established the moment-to-moment turnover of the blood-oxygen-level-dependent signal (TBOLD) at resting state as a key measure of local cortical brain function. Here, we sought to extend that line of research by evaluating TBOLD in 70 cortical areas with respect to corresponding brain volume, age, and sex across the lifespan in 1,344 healthy participants including 633 from the Human Connectome Project (HCP)-Development cohort (294 males and 339 females, age range 8-21 yr) and 711 healthy participants from HCP-Aging cohort (316 males and 395 females, 36-90 yr old). In both groups, we found that 1) TBOLD increased with age, 2) volume decreased with age, and 3) TBOLD and volume were highly significantly negatively correlated, independent of age. The inverse association between TBOLD and volume was documented in nearly all 70 brain areas and for both sexes, with slightly stronger associations documented for males. The strong correspondence between TBOLD and volume across age and sex suggests a common influence such as chronic neuroinflammation contributing to reduced cortical volume and increased TBOLD across the lifespan.NEW & NOTEWORTHY We report a significant negative association between resting functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) signal turnover (TBOLD) and cortical gray matter volume across the lifespan, such that TBOLD increased whereas volume decreased. We attribute this association to a hypothesized chronic, low-grade neuroinflammation, probably induced by various neurotropic pathogens, including human herpes viruses known to be dormant in the brain in a latent state and reactivated by stress, fever, and various environmental exposures, such as ultraviolet light.

Cortical Gray Matter Thickness and Volume Changes and Their Association with Memory Functions in Hyperthyroid Patients.

INTRODUCTION: Hyperthyroidism, characterized by excessive thyroid hormone production, is a common endocrine disorder that affects various physiological processes, including brain function. Recent advancements in neuroimaging techniques have enabled researchers to investigate structural alterations in the brain associated with hyperthyroidism. This study aimed to examine regional cortical thickness and cortical volume differences across the brain between hyperthyroid patients and control subjects. METHODS: We examined localized cortical thicknesses and volumes in 34 hyperthyroid patients and 35 control subjects with high-resolution T1-weighted images using FreeSurfer software and assessed group differences with analysis of covariance (covariates: age, sex, education, and total intracranial volume). Spearman and partial correlations were performed between clinical variables and cortical thicknesses/volumes and between neuropsychological scores and cortical thicknesses/volumes, respectively. RESULTS: Hyperthyroid patients exhibited significantly increased cortical thickness in bilateral superior temporal and superior frontal gyri, along with higher cortical volumes in various regions, including the right superior temporal gyrus, right superior parietal gyrus, right rostral and caudal middle frontal gyrus, and left superior frontal gyrus. Notably, thyroid hormones (fT3, fT4) correlated positively with cortical thicknesses and volumes in the superior temporal gyrus and superior frontal gyrus. Additionally, recognition memory scores negatively correlated with the right superior temporal gyrus and right superior frontal gyrus cortical thickness. CONCLUSION: The observed cortical thickening and increased cortical volume in specific brain areas provide new insights into the pathophysiological mechanism associated with brain impairment in hyperthyroidism.

Hemispheric asymmetries in cortical grey matter of gyri and sulci in modern human populations from South America.

Structural asymmetries of brain regions associated with lateralised functions have been extensively studied. However, there are fewer morphometric analyses of asymmetries of the gyri and sulci of the entire cortex. The current study assessed cortical asymmetries in a sample of healthy adults (N = 175) from an admixed population from South America. Grey matter volume and surface area of 66 gyri and sulci were quantified on T1 magnetic resonance images. The departure from zero of the differences between left and right hemispheres (L-R), a measure of directional asymmetry (DA), the variance of L-R, and an index of fluctuating asymmetry (FA) were evaluated for each region. Significant departures from perfect symmetry were found for most cortical gyri and sulci. Regions showed leftward asymmetry at the population level in the frontal lobe and superior lateral parts of the parietal lobe. Rightward asymmetry was found in the inferior parietal, occipital, frontopolar, and orbital regions, and the cingulate (anterior, middle, and posterior-ventral). Despite this general pattern, several sulci showed the opposite DA compared to the neighbouring gyri, which remarks the need to consider the neurobiological differences in gyral and sulcal development in the study of structural asymmetries. The results also confirm the absence of DA in most parts of the inferior frontal gyrus and the precentral region. This study contributes with data on populations underrepresented in the databases used in neurosciences. Among its findings, there is agreement with previous results obtained in populations of different ancestry and some discrepancies in the middle frontal and medial parietal regions. A significant DA not reported previously was found for the volume of long and short insular gyri and the central sulcus of the insula, frontomarginal, transverse frontopolar, paracentral, and middle and posterior parts of the cingulate gyrus and sulcus, gyrus rectus, occipital pole, and olfactory sulcus, as well as for the volume and area of the transverse collateral sulcus and suborbital sulcus. Also, several parcels displayed significant variability in the left-right differences, which can be partially attributable to developmental instability, a source of FA. Moreover, a few gyri and sulci displayed ideal FA with non-significant departures from perfect symmetry, such as subcentral and posterior cingulate gyri and sulci, inferior frontal and fusiform gyri, and the calcarine, transverse collateral, precentral, and orbital sulci. Overall, these results show that asymmetries are ubiquitous in the cerebral cortex.

Diffusion and structural MRI as potential biomarkers in people with Parkinson's disease and cognitive impairment.

OBJECTIVE: To explore the neuroimage change in Parkinson's disease (PD) patients with cognitive impairments, this study investigated the correlation between plasma biomarkers and morphological brain changes in patients with normal cognition and mild cognitive impairment. The objective was to identify the potential target deposition regions of the plasma biomarkers and to search for the relevant early neuroimaging biomarkers on the basis of different cognitive domains. METHODS: Structural brain MRI and diffusion weighted images were analyzed from 49 eligible PD participants (male/female: 27/22; mean age: 73.4 ± 8.5 years) from a retrospective analysis. Plasma levels of α-synuclein, amyloid beta peptide, and total tau were collected. A comprehensive neuropsychological assessment of the general and specific cognitive domains was performed. Difference between PD patients with normal cognition and impairment was examined. Regression analysis was performed to evaluate the correlation between image-derived index and plasma biomarkers or neuropsychological assessments. RESULTS: Significant correlation was found between plasma Aß-42 level and fractional anisotropy of the middle occipital, angular, and middle temporal gyri of the left brain, as well as plasma T-tau level and the surface area of the isthmus or the average thickness of the posterior part of right cingulate gyrus. Visuospatial and executive function is positively correlated with axial diffusivity in bilateral cingulate gyri. CONCLUSION: In nondemented PD patients, the target regions for plasma deposition might be located in the cingulate, middle occipital, angular, and middle temporal gyri. Changes from multiple brain regions can be correlated to the performance of different cognitive domains. CLINICAL RELEVANCE STATEMENT: Cognitive impairment in Parkinson's disease is primarily linked to biomarkers associated with Alzheimer's disease rather than those related to Parkinson's disease and resembles the frontal variant of Alzheimer's disease, which may guide management strategies for cognitive impairment in Parkinson's disease. KEY POINTS: • Fractional anisotropy, surface area, and thickness in the cingulate, middle occipital, angular, and middle temporal gyri can be significantly correlated with plasma Aß-42 and T-tau level. • Axial diffusivity in the cingulate gyri was correlated with visuospatial and executive function. • The pattern of cognitive impairment in Parkinson's disease can be similar to the frontal variant than typical Alzheimer's disease.

Association Between Wnt Target Genes and Cortical Volumes in Alzheimer's Disease.

The disproportionate cortical atrophy is an established biomarker for the pathophysiological process of Alzheimer's disease (AD). However, the genetic basis underlying the cortical atrophy remains poorly defined. Herein, we aim to illustrate the effect of the Wnt target genes on the cortical volumes of AD patients. 82 sporadic AD patients were recruited. All the subjects had history survey, blood biochemical examination, cognitive assessment, MRI morphometry and whole exome sequencing. This report focused on 84 common variants (minor allele frequency > 0.01) of 32 Wnt target genes, including the APC, DAAM1, DACT1, DISC1, LATS2, TLR2, WDR61, and the AXIN, DVL, FZD, LRP, TCF/LEF, WNT family genes. The Wnt target genes showed asymmetric effects on the cortical volumes of AD patients. The right temporal/parietal/occipital cortices were more affected than left temporal/parietal/occipital cortices. Nevertheless, the reverse applied to the frontal cortex. The DACT1 affected the cortical thickness most, followed by the TCF3 and APC. The DACT1 rs698025-GG genotype displayed greater right temporal pole and left medial orbito-frontal gyrus than rs698025-GA genotype (2.4 ± 0.4 vs. 2.0 ± 0.6, P = 0.005; 5.2 ± 0.6 vs. 5.0 ± 0.6, P = 0.001). The brain region most influenced by the Wnt target genes was the right calcarine cortex. In conclusion, the common variants of the Wnt target genes exert asymmetric effects on the cortical volumes of AD patients. The Wnt signaling pathway may play a role in the cortical atrophy of AD patients.

Machine learning based identification of structural brain alterations underlying suicide risk in adolescents.

Suicide is the third leading cause of death for individuals between 15 and 19 years of age. The high suicide mortality rate and limited prior success in identifying neuroimaging biomarkers indicate that it is crucial to improve the accuracy of clinical neural signatures underlying suicide risk. The current study implements machine-learning (ML) algorithms to examine structural brain alterations in adolescents that can discriminate individuals with suicide risk from typically developing (TD) adolescents at the individual level. Structural MRI data were collected from 79 adolescents who demonstrated clinical levels of suicide risk and 79 demographically matched TD adolescents. Region-specific cortical/subcortical volume (CV/SCV) was evaluated following whole-brain parcellation into 1000 cortical and 12 subcortical regions. CV/SCV parameters were used as inputs for feature selection and three ML algorithms (i.e., support vector machine [SVM], K-nearest neighbors, and ensemble) to classify adolescents at suicide risk from TD adolescents. The highest classification accuracy of 74.79% (with sensitivity = 75.90%, specificity = 74.07%, and area under the receiver operating characteristic curve = 87.18%) was obtained for CV/SCV data using the SVM classifier. Identified bilateral regions that contributed to the classification mainly included reduced CV within the frontal and temporal cortices but increased volume within the cuneus/precuneus for adolescents at suicide risk relative to TD adolescents. The current data demonstrate an unbiased region-specific ML framework to effectively assess the structural biomarkers of suicide risk. Future studies with larger sample sizes and the inclusion of clinical controls and independent validation data sets are needed to confirm our findings.

Non-abstinent recovery in alcohol use disorder is associated with greater regional cortical volumes than heavy drinking.

BACKGROUND: Harm-reduction (i.e., non-abstinent recovery) approaches to substance use treatment have garnered increasing attention. Reduced levels of alcohol consumption post-treatment have been associated with better psychosocial functioning and physical health, yet less is known regarding differences in brain structures associated with varying levels of alcohol consumption. This study investigated regional cortical volumes after alcohol use disorder (AUD) treatment among individuals who achieved complete abstinence and those who returned to lower and higher levels of consumption. METHODS: Data were collected from individuals with AUD (n = 68) approximately 8 months after the initiation of treatment. Using risk drinking levels defined by the World Health Organization, participants were classified as abstaining (AB) or relapsing with low (RL) or higher (RH) levels. Data were also obtained from 34 age-matched light/non-drinking controls (LN). All participants completed a 1.5 T magnetic resonance imaging session and volumes for 34 bilateral cortical regions of interest were quantitated with FreeSurfer. Generalized linear models were used to examine group differences in cortical volume. All group findings are significant at an FDR-corrected value of 0.018. RESULTS: Adjusting for age and intracranial volume, significant group differences were found in 13/34 cortical regions. AB showed greater volumes than RL in 2/13 regions and RH in 6/13 regions. RH demonstrated significantly smaller volumes than LN in 12/13 ROIs, whereas RL differed from LN in 9/13 regions. RH and RL differed in only two cortical regions. CONCLUSIONS: Individuals who consumed low-risk levels of alcohol post-treatment exhibited regional cortical volumes more similar to abstainers than individuals who returned to higher-risk levels. This suggests that low-risk levels of alcohol consumption are associated with brain integrity that is comparable to that seen with complete abstinence. Given the previously demonstrated improvement in psychosocial and physical health with reduced levels of alcohol consumption post-treatment, harm reduction may be a beneficial and more attainable goal for some individuals with AUD who are seeking treatment.

Modulation of associations between education years and cortical volume in Alzheimer's disease vulnerable brain regions by Aß deposition and APOE ε4 carrier status in cognitively normal older adults.

Background: Education years, as a measure of cognitive reserve, have been shown to affect the progression of Alzheimer's disease (AD), both pathologically and clinically. However, inconsistent results have been reported regarding the association between years of education and intermediate structural changes in AD-vulnerable brain regions, particularly when AD risk factors were not considered during the preclinical phase. Objective: This study aimed to examine how Aß deposition and APOE ε4 carrier status moderate the relationship between years of education and cortical volume in AD-vulnerable regions among cognitively normal older adults. Methods: A total of 121 participants underwent structural MRI, [18F] flutemetamol PET-CT imaging, and neuropsychological battery assessment. Multiple regression analysis was conducted to examine the interaction between years of education and the effects of potential modifiers on cortical volume. The associations between cortical volume and neuropsychological performance were further explored in subgroups categorized based on AD risk factors. Results: The cortical volume of the left lateral occipital cortex and bilateral fusiform gyrus demonstrated a significant differential association with years of education, depending on the presence of Aß deposition and APOE ε4 carrier status. Furthermore, a significant relationship between the cortical volume of the bilateral fusiform gyrus and AD-nonspecific cognitive function was predominantly observed in individuals without AD risk factors. Conclusion: AD risk factors exerted varying influences on the association between years of education and cortical volume during the preclinical phase. Further investigations into the long-term implications of these findings would enhance our understanding of cognitive reserves in the preclinical stages of AD.

Identification of structural brain alterations in adolescents with depressive symptomatology.

INTRODUCTION: Depressive symptoms can emerge as early as childhood and may lead to adverse situations in adulthood. Studies have examined structural brain alternations in individuals with depressive symptoms, but findings remain inconclusive. Furthermore, previous studies have focused on adults or used a categorical approach to assess depression. The current study looks to identify grey matter volumes (GMV) that predict depressive symptomatology across a clinically concerning sample of adolescents. METHODS: Structural MRI data were collected from 338 clinically concerning adolescents (mean age = 15.30 SD=2.07; mean IQ = 101.01 SD=12.43; 132 F). Depression symptoms were indexed via the Mood and Feelings Questionnaire (MFQ). Freesurfer was used to parcellate the brain into 68 cortical regions and 14 subcortical regions. GMV was extracted from all 82 brain areas. Multiple linear regression was used to look at the relationship between MFQ scores and region-specific GMV parameter. Follow up regressions were conducted to look at potential effects of psychiatric diagnoses and medication intake. RESULTS: Our regression analysis produced a significant model (R2 = 0.446, F(86, 251) = 2.348, p < 0.001). Specifically, there was a negative association between GMV of the left parahippocampal (B = -0.203, p = 0.005), right rostral anterior cingulate (B = -0.162, p = 0.049), and right frontal pole (B = -0.147, p = 0.039) and a positive association between GMV of the left bank of the superior temporal sulcus (B = 0.173, p = 0.029). Follow up analyses produced results proximal to the main analysis. CONCLUSIONS: Altered regional brain volumes may serve as biomarkers for the development of depressive symptoms during adolescence. These findings suggest a homogeneity of altered cortical structures in adolescents with depressive symptoms.

Structural neuroimaging phenotypes and associated molecular and genomic underpinnings in autism: a review.

Autism has been associated with differences in the developmental trajectories of multiple neuroanatomical features, including cortical thickness, surface area, cortical volume, measures of gyrification, and the gray-white matter tissue contrast. These neuroimaging features have been proposed as intermediate phenotypes on the gradient from genomic variation to behavioral symptoms. Hence, examining what these proxy markers represent, i.e., disentangling their associated molecular and genomic underpinnings, could provide crucial insights into the etiology and pathophysiology of autism. In line with this, an increasing number of studies are exploring the association between neuroanatomical, cellular/molecular, and (epi)genetic variation in autism, both indirectly and directly in vivo and across age. In this review, we aim to summarize the existing literature in autism (and neurotypicals) to chart a putative pathway from (i) imaging-derived neuroanatomical cortical phenotypes to (ii) underlying (neuropathological) biological processes, and (iii) associated genomic variation.

Cortical grey matter changes, behavior and cognition in children with sleep disordered breathing.

This paper investigated cortical thickness and volumetric changes in children to better understand the impact of obstructive sleep disordered breathing (SDB) on the neurodevelopment of specific regions of the brain. We also aimed to investigate how these changes were related to the behavioral and cognitive deficits observed in the condition. Neuroimaging, behavioral, and sleep data were obtained from 30 children (15 non-snoring controls, 15 referred for assessment of SDB) aged 7 to 17 years. Gyral-based regions of interest were identified using the Desikan-Killiany atlas. Student's t-tests were used to compare regions of interest between the controls and SDB groups. We found that the cortical thickness was significantly greater in the right caudal anterior cingulate and right cuneus regions and there were volumetric increases in the left caudal middle frontal, bilateral rostral anterior cingulate, left, right, and bilateral caudate brain regions in children with SDB compared with controls. Neither cortical thickness nor volumetric changes were associated with behavioral or cognitive measures. The findings of this study indicate disruptions to neural developmental processes occurring in structural regions of the brain; however, these changes appear unrelated to behavioural or cognitive outcomes.

Multi-modal MRI measures reveal sensory abnormalities in major depressive disorder patients: A surface-based study.

BACKGROUND: Multi-modal magnetic resonance imaging (MRI) measures are supposed to be able to capture different brain neurobiological aspects of major depressive disorder (MDD). A fusion analysis of structural and functional modalities may better reveal the disease biomarker specific to the MDD disease. METHODS: We recruited 30 MDD patients and 30 matched healthy controls (HC). For each subject, we acquired high-resolution brain structural images and resting-state fMRI (rs-fMRI) data using a 3 T MRI scanner. We first extracted the brain morphometric measures, including the cortical volume (CV), cortical thickness (CT), and surface area (SA), for each subject from the structural images, and then detected the structural clusters showing significant between-group differences in each measure using the surface-based morphology (SBM) analysis. By taking the identified structural clusters as seeds, we performed seed-based functional connectivity (FC) analyses to determine the regions with abnormal FC in the patients. Based on a logistic regression model, we performed a classification analysis by selecting these structural and functional cluster-wise measures as features to distinguish the MDD patients from the HC. RESULTS: The MDD patients showed significantly lower CV in a cluster involving the right superior temporal gyrus (STG) and middle temporal gyrus (MTG), and lower SA in three clusters involving the bilateral STG, temporal pole gyrus, and entorhinal cortex, and the left inferior temporal gyrus, and fusiform gyrus, than the controls. No significant difference in CT was detected between the two groups. By taking the above-detected clusters as seeds to perform the seed-based FC analysis, we found that the MDD patients showed significantly lower FC between STG/MTG (CV's cluster) and two clusters located in the bilateral visual cortices than the controls. The logistic regression model based on the structural and functional features reached a classification accuracy of 86.7% (p < 0.001) between MDD and controls. CONCLUSION: The present study showed sensory abnormalities in MDD patients using the multi-modal MRI analysis. This finding may act as a disease biomarker distinguishing MDD patients from healthy individuals.

The neuroanatomical hallmarks of chronic tinnitus in comorbidity with pure-tone hearing loss.

Tinnitus is one of the main hearing impairments often associated with pure-tone hearing loss, and typically manifested in the perception of phantom sounds. Nevertheless, tinnitus has traditionally been studied in isolation without necessarily considering auditory ghosting and hearing loss as part of the same syndrome. Hence, in the present neuroanatomical study, we attempted to pave the way toward a better understanding of the tinnitus syndrome, and compared two groups of almost perfectly matched individuals with (TIHL) and without (NTHL) pure-tone tinnitus, but both characterized by pure-tone hearing loss. The two groups were homogenized in terms of sample size, age, gender, handedness, education, and hearing loss. Furthermore, since the assessment of pure-tone hearing thresholds alone is not sufficient to describe the full spectrum of hearing abilities, the two groups were also harmonized for supra-threshold hearing estimates which were collected using temporal compression, frequency selectivity und speech-in-noise tasks. Regions-of-interest (ROI) analyses based on key brain structures identified in previous neuroimaging studies showed that the TIHL group exhibited increased cortical volume (CV) and surface area (CSA) of the right supramarginal gyrus and posterior planum temporale (PT) as well as CSA of the left middle-anterior part of the superior temporal sulcus (STS). The TIHL group also demonstrated larger volumes of the left amygdala and of the left head and body of the hippocampus. Notably, vertex-wise multiple linear regression analyses additionally brought to light that CSA of a specific cluster, which was located in the left middle-anterior part of the STS and overlapped with the one found to be significant in the between-group analyses, was positively associated with tinnitus distress level. Furthermore, distress also positively correlated with CSA of gray matter vertices in the right dorsal prefrontal cortex and the right posterior STS, whereas tinnitus duration was positively associated with CSA and CV of the right angular gyrus (AG) and posterior part of the STS. These results provide new insights into the critical gray matter architecture of the tinnitus syndrome matrix responsible for the emergence, maintenance and distress of auditory phantom sensations.

Sex differences in structural covariance network based on MRI cortical morphometry: effects on episodic memory.

Sex differences in episodic memory (EM), remembering past events based on when and where they occurred, have been reported, but the neural mechanisms are unclear. T1-weighted images of 111 females and 61 males were acquired from the Dallas Lifespan Brain Study. Using surface-based morphometry and structural covariance (SC) analysis, we constructed structural covariance networks (SCN) based on cortical volume, and the global efficiency (Eglob) was computed to characterize network integration. The relationship between SCN and EM was examined by SC analysis among the top-n brain regions that were most relevant to EM performance. The number of SC connections (females: 3306; males: 437, P = 0.0212) and Eglob (females: 0.1845; males: 0.0417, P = 0.0408) of SCN in females were higher than those in males. The top-n brain regions with the strongest SC in females were located in auditory network, cingulo-opercular network (CON), and default mode network (DMN), and in males, they were located in frontoparietal network, CON, and DMN. These results confirmed that the Eglob of SCN in females was higher than males, sex differences in EM performance might be related to the differences in network-level integration. Our study highlights the importance of sex as a research variable in brain science.

Functional hyperconnectivity between corticocerebellar networks and altered decision making in young adult cannabis users: Evidence from 7T and multivariate pattern analysis.

Decision-making (DM) impairments are important predictors of cannabis initiation and continued use. In cannabis users, how decision-making abnormalities related to structural and functional connectivity in the brain are not fully understood. We employed a three-method multimodal image analysis and multivariate pattern analysis (MVPA) on high dimensional 7 tesla MRI images examining functional connectivity, white matter microstructure and gray matter volume in a group of cannabis users and non-users. Neuroimaging and cognitive analyses were performed on 92 CU and 92 age- matched NU from a total of 187 7T scans. CU were selected on the basis of their scores on the Semi-Structured Assessment for the Genetics of Alcoholism. The groups were first compared on a decision-making test and then on ICA based functional connectivity between corticocerebellar networks. An MVPA was done as a confirmatory analysis. The anatomy of these networks was then assessed using Diffusion Tensor imaging (DTI) and cortical volume analyses. Cannabis Users had significantly higher scores on the Iowa Gambling task (IGT) [Gambling task Percentage larger] and significantly lower scores on the [Gambling task reward Percentage smaller]. Left accumbens (L NAc) volume was significantly larger in cannabis users. DTI analysis between the groups yielded no significant (FWE corrected) differences. Resting state FC analysis of the left Cerebellum region 9 showed enhanced functional connectivity with the right nucleus accumbens and left pallidum and left putamen in CU. In addition, posterior cerebellum showed enhanced functional connectivity (FWE corrected) with 2 nodes of the DMN and left and right paracingulate (sub genual ACC) and the sub callosal cortex in CU. IGT percentage larger scores correlated with posterior cerebellar functional connectivity in non-user women. A multivariate pattern analysis confirmed this cerebellar hyperconnectivity in both groups. Our results demonstrate for the first time that deficits in DM observed in cannabis users are mirrored in hyper connectivity in corticocerebellar networks. Cortical volumes of some of the nodes of these networks showed increases in users. However, the underlying white matter was largely intact in CU. The observed DM deficits and hyper connectivity in resting networks may contribute to difficulties in quitting and/or facilitating relapse.

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

BACKGROUND: Mood 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). METHODS: This 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. RESULTS: In ROI analyses, higher RHI (i.e., better endothelial function) was associated with lower thickness in the insular cortex (ß = -0.19, pFDR = 0.03), vlPFC (ß = -0.30, pFDR = 0.003), and temporal lobe (ß = -0.22, pFDR = 0.01); and lower temporal lobe volume (ß = -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. CONCLUSIONS: Better 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.