Subcortical Gray Matter Volume Research Articles

P48. Sex Differences in Cortical Thickness in Cannabis Use Disorder

Sex differences exist in cannabis use characteristics and its neurobiological effects, but little is known of cannabis-related sexual dimorphism in brain structure. We investigated sex differences in cortical and subcortical gray matter volumes among adults with Cannabis Use Disorder (CUD) and examined whether these differences related to behavior.

Dynamic Effects of Immersive Bilingualism on Cortical and Subcortical Grey Matter Volumes.

Bilingualism has been shown to induce neuroplasticity in the brain, but conflicting evidence regarding its specific effects in grey matter continues to emerge, probably due to methodological differences between studies, as well as approaches that may miss the variability and dynamicity of bilingual experience. In our study, we devised a continuous score of bilingual experiences and we investigated their non-linear effects on regional GM volume in a sample of young healthy participants from an immersive and naturalistic bilingual environment. We focused our analyses on cortical and subcortical regions that had been previously proposed as part of the bilingual speech pipeline and language control network. Our results showed a non-linear relationship between bilingualism score and grey matter volume of the inferior frontal gyrus. We also found linear increases in volumes of putamen and cerebellum as a function of bilingualism score. These results go in line with predictions for immersive and naturalistic bilingual environments with increased intensity and diversity of language use and provide further evidence supporting the dynamicity of bilingualism’s effects on brain structure.

Association of Prenatal Exposure to Early-Life Adversity With Neonatal Brain Volumes at Birth

Exposure to early-life adversity alters the structural development of key brain regions underlying neurodevelopmental impairments. The association between prenatal exposure to adversity and brain structure at birth remains poorly understood. To examine whether prenatal exposure to maternal social disadvantage and psychosocial stress is associated with neonatal global and regional brain volumes and cortical folding. This prospective, longitudinal cohort study included 399 mother-infant dyads of sociodemographically diverse mothers recruited in the first or early second trimester of pregnancy and their infants, who underwent brain magnetic resonance imaging in the first weeks of life. Mothers were recruited from local obstetric clinics in St Louis, Missouri from September 1, 2017, to February 28, 2020. Maternal social disadvantage and psychosocial stress in pregnancy. Confirmatory factor analyses were used to create latent constructs of maternal social disadvantage (income-to-needs ratio, Area Deprivation Index, Healthy Eating Index, educational level, and insurance status) and psychosocial stress (Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Everyday Discrimination Scale, and Stress and Adversity Inventory). Neonatal cortical and subcortical gray matter, white matter, cerebellum, hippocampus, and amygdala volumes were generated using semiautomated, age-specific, segmentation pipelines. A total of 280 mothers (mean [SD] age, 29.1 [5.3] years; 170 [60.7%] Black or African American, 100 [35.7%] White, and 10 [3.6%] other race or ethnicity) and their healthy, term-born infants (149 [53.2%] male; mean [SD] infant gestational age, 38.6 [1.0] weeks) were included in the analysis. After covariate adjustment and multiple comparisons correction, greater social disadvantage was associated with reduced cortical gray matter (unstandardized β = -2.0; 95% CI, -3.5 to -0.5; P = .01), subcortical gray matter (unstandardized β = -0.4; 95% CI, -0.7 to -0.2; P = .003), and white matter (unstandardized β = -5.5; 95% CI, -7.8 to -3.3; P < .001) volumes and cortical folding (unstandardized β = -0.03; 95% CI, -0.04 to -0.01; P < .001). Psychosocial stress showed no association with brain metrics. Although social disadvantage accounted for an additional 2.3% of the variance of the left hippocampus (unstandardized β = -0.03; 95% CI, -0.05 to -0.01), 2.3% of the right hippocampus (unstandardized β = -0.03; 95% CI, -0.05 to -0.01), 3.1% of the left amygdala (unstandardized β = -0.02; 95% CI, -0.03 to -0.01), and 2.9% of the right amygdala (unstandardized β = -0.02; 95% CI, -0.03 to -0.01), no regional effects were found after accounting for total brain volume. In this baseline assessment of an ongoing cohort study, prenatal social disadvantage was associated with global reductions in brain volumes and cortical folding at birth. No regional specificity for the hippocampus or amygdala was detected. Results highlight that associations between poverty and brain development begin in utero and are evident early in life. These findings emphasize that preventive interventions that support fetal brain development should address parental socioeconomic hardships.

Food-Approach Eating Behaviors and Brain Morphology: The Generation R Study.

Food-approach eating behaviors are associated with an increased risk of developing overweight/obesity and binge-eating disorder, while obesity and binge-eating disorder have also been linked with altered brain morphology in adults. To understand these associations, we examined the association of food-approach eating behaviors during childhood with adolescents' brain morphology. The sample included 1,781 adolescents with assessments of eating behaviors at ages 4 and 10 years and brain imaging data at 13 years from a large, population-based cohort. Food approach eating behaviors (enjoyment of food, emotional overeating, and food responsiveness) were assessed using the Child Eating Behavior Questionnaire. Additionally, we assessed binge eating symptoms using two items from the Development and Well-Being Assessment at 13 years of age. Adolescents participated in an MRI procedure and measures of brain morphology, including cerebral white, cerebral gray and subcortical gray matter volumes, were extracted from T1-weighted images processed using FreeSurfer. Enjoyment of food and food responsiveness at the age of 4 and 10 years were positively associated with cerebral white matter and subcortical gray matter volumes at age 13 years (e.g., enjoyment of food at 4 years and cerebral white matter: β = 2.73, 95% CI 0.51, 4.91). Enjoyment of food and food responsiveness at 4 years of age, but not at 10 years, were associated with a larger cerebral gray matter volume at 13 years of age (e.g., enjoyment of food at 4 years: β = 0.24, 95% CI 0.03, 0.45). No statistically significant associations were found for emotional overeating at both ages and brain measurements at 13 years of age. post-hoc analyses showed no associations of food-approach eating behaviors with amygdala or hippocampus. Lastly, we did not observe significant associations of binge-eating symptoms with global brain measurements and a priori-defined regions of interest, including the right frontal operculum, insular and orbitofrontal cortex. Our findings support an association between food-approach eating behaviors, especially enjoyment of food and food responsiveness, and brain morphology in adolescence. Our findings add important knowledge to previous studies that were mostly conducted in adults, by suggesting that the eating behavior-brain link may be visible earlier in life. Further research is needed to determine causality.

Comparing brain asymmetries independently of brain size

Studies examining cerebral asymmetries typically divide the l-R Measure (e.g., Left–Right Volume) by the L + R Measure to obtain an Asymmetry Index (AI). However, contrary to widespread belief, such a division fails to render the AI independent from the L + R Measure and/or from total brain size. As a result, variations in brain size may bias correlation estimates with the AI or group differences in AI. We investigated how to analyze brain asymmetries in to distinguish global from regional effects, and report unbiased group differences in cerebral asymmetries in the UK Biobank (N = 40, 028).We used 306 global and regional brain measures provided by the UK Biobank. Global gray and white matter volumes were taken from Freesurfer ASEG, subcortical gray matter volumes from Freesurfer ASEG and subsegmentation, cortical gray matter volumes, mean thicknesses, and surface areas from the Destrieux atlas applied on T1-and T2-weighted images, cerebellar gray matter volumes from FAST FSL, and regional white matter volumes from Freesurfer ASEG.We analyzed the extent to which the L + R Measure, Total Cerebral Measure (TCM, e.g., Total Brain Volume), and l-R TCM predict regional asymmetries. As a case study, we assessed the consequences of omitting each of these predictors on the magnitude and significance of sex differences in asymmetries.We found that the L + R Measure, the TCM, and the l-R TCM predicted the AI of more than 89% of regions and that their relationships were generally linear. Removing any of these predictors changed the significance of sex differences in 33% of regions and the magnitude of sex differences across 13–42% of regions. Although we generally report similar sex and age effects on cerebral asymmetries to those of previous large-scale studies, properly adjusting for regional and global brain size revealed additional sex and age effects on brain asymmetry.

Developmental trajectory of MEG resting-state oscillatory activity in children and adolescents: a longitudinal reliability study.

Neural oscillations may be sensitive to aspects of brain maturation such as myelination and synaptic density changes. Better characterization of developmental trajectories and reliability is necessary for understanding typical and atypical neurodevelopment. Here, we examined reliability in 110 typically developing children and adolescents (aged 9-17years) across 2.25years. From 10 min of magnetoencephalography resting-state data, normalized source spectral power and intraclass correlation coefficients were calculated. We found sex-specific differences in global normalized power, with males showing age-related decreases in delta and theta, along with age-related increases in beta and gamma. Females had fewer significant age-related changes. Structural magnetic resonance imaging revealed that males had more total gray, subcortical gray, and cortical white matter volume. There were significant age-related changes in total gray matter volume with sex-specific and frequency-specific correlations to normalized power. In males, increased total gray matter volume correlated with increased theta and alpha, along with decreased gamma. Split-half reliability was excellent in all frequency bands and source regions. Test-retest reliability ranged from good (alpha) to fair (theta) to poor (remaining bands). While resting-state neural oscillations can have fingerprint-like quality in adults, we show here that neural oscillations continue to evolve in children and adolescents due to brain maturation and neurodevelopmental change.

Gray matter volumetric correlates of dimensional impulsivity traits in children: Sex differences and heritability.

Previous research investigated the cerebral volumetric correlates of impulsivity largely in moderate‐sized samples and few have examined the distinct correlates of dimensions of impulsivity, sex differences, or heritability of the correlates. Here, we performed voxel‐based morphometry analysis of data (n = 11,474; 5,452 girls, 9–10 years) curated from the Adolescent Brain Cognition Development project. In a linear regression with all five UPPS‐P subscores as regressors and age in months, total intracranial volume, study site, and scanner model as covariates, higher levels of lack of premeditation, and sensation seeking were correlated with larger cortical and subcortical gray matter volumes (GMVs). In contrast, higher positive urgency was correlated with smaller GMVs in many of the same regions. The dimensional impulsivity traits also involved distinct volumetric correlates, with, for instance, sensation seeking and positive urgency specifically implicating bilateral caudate head/mid‐cingulate cortex and bilateral lateral orbitofrontal cortex/left precentral gyrus, respectively. Boys relative to girls scored higher in all impulsivity dimensions. Girls relative to boys showed significantly stronger positive and negative correlations between sensation seeking and insula, putamen, and inferior frontal gyrus (IFG) GMVs and between positive urgency and cingulate cortex, insula, and IFG GMVs, respectively. With a subsample of twins, the dimensional impulsivity traits were weakly to moderately heritable in both girls and boys, and the GMV correlates were highly heritable in girls and boys combined. These findings collectively suggest shared and nonshared as well as sex differences in the cerebral volumetric bases of dimensional impulsivity traits and may facilitate research of externalizing psychopathology in children.

Linking Vestibular Function and Subcortical Gray Matter Volume Changes in a Longitudinal Study of Aging Adults

Emerging evidence suggests a relationship between impairments of the vestibular (inner ear balance) system and alterations in the function and the structure of the central nervous system (CNS) in older adults. However, it is unclear whether age-related vestibular loss is associated with volume loss in brain regions known to receive vestibular input. To address this gap, we investigated the association between vestibular function and the volumes of four structures that process vestibular information (the hippocampus, entorhinal cortex, thalamus, and basal ganglia) in a longitudinal study of 97 healthy, older participants from the Baltimore Longitudinal Study of Aging. Vestibular testing included cervical vestibular-evoked myogenic potentials (cVEMP) to measure saccular function, ocular VEMP (oVEMP) to measure utricular function, and video head impulse tests to measure the horizontal semicircular canal vestibulo-ocular reflex (VOR). Participants in the sample had vestibular and brain MRI data for a total of one (18.6%), two (49.5%), and three (32.0%) visits. Linear mixed-effects regression was used to model regional volume over time as a function of vestibular physiological function, correcting for age, sex, intracranial volume, and intersubject random variation in the baseline levels and rates of change of volume over time. We found that poorer saccular function, characterized by lower cVEMP amplitude, is associated with reduced bilateral volumes of the basal ganglia and thalamus at each time point, demonstrated by a 0.0714 cm3 ± 0.0344 (unadjusted p = 0.038; 95% CI: 0.00397–0.139) lower bilateral-mean volume of the basal ganglia and a 0.0440 cm3 ± 0.0221 (unadjusted p = 0.046; 95% CI: 0.000727–0.0873) lower bilateral-mean volume of the thalamus for each 1-unit lower cVEMP amplitude. We also found a relationship between a lower mean VOR gain and lower left hippocampal volume (β = 0.121, unadjusted p = 0.018, 95% CI: 0.0212–0.222). There were no significant associations between volume and oVEMP. These findings provide insight into the specific brain structures that undergo atrophy in the context of age-related loss of peripheral vestibular function.

Quantitative brain MRI morphology in severe and attenuated forms of mucopolysaccharidosis type I.

To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition. Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4-25years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls. Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC. Thicker cortex, lower white matter and corpus callosum volumes were already present at the youngest MPS I participants aged 4-5years. Age-related differences were observed in both MPS I groups, but most markedly in MPS IH, particularly in cortical gray matter metrics. IQ scores were inversely associated with ventricular volume in both MPS I groups and were positively associated with cortical thickness only in MPS IA. Quantitatively-derived MRI measures distinguished MPS I participants from HC as well as severe from attenuated forms. Age-related neurodevelopmental trajectories in both MPS I forms differed from HC. The extent to which brain structure is altered by disease, potentially spared by treatment, and how it relates to neurocognitive dysfunction needs further exploration.

Relationship Between Brain Volumes and Objective Balance and Gait Measures in Parkinson's Disease.

Instrumented measures of balance and gait measure more specific balance and gait impairments than clinical rating scales. No prior studies have used objective balance/gait measures to examine associations with ventricular and brain volumes in people with Parkinson's disease (PD). To test the hypothesis that larger ventricular and smaller cortical and subcortical volumes are associated with impaired balance and gait in people with PD. Regional volumes from structural brain images were included from 96 PD and 50 control subjects. Wearable inertial sensors quantified gait, anticipatory postural adjustments prior to step initiation (APAs), postural responses to a manual push, and standing postural sway on a foam surface. Multiple linear regression models assessed the relationship between brain volumes and balance/gait and their interactions in PD and controls, controlling for sex, age and corrected for multiple comparisons. Smaller brainstem and subcortical gray matter volumes were associated with larger sway area in people with PD, but not healthy controls. In contrast, larger ventricle volume was associated with smaller APAs in healthy controls, but not in people with PD. A sub-analysis in PD showed significant interactions between freezers and non-freezers, in several subcortical areas with stride time variability, gait speed and step initiation. Our models indicate that smaller subcortical and brainstem volumes may be indicators of standing balance dysfunction in people with PD whereas enlarged ventricles may be related to step initiation difficulties in healthy aging. Also, multiple subcortical region atrophy may be associated with freezing of gait in PD.

Predict initial subthalamic nucleus stimulation outcome in Parkinson's disease with brain morphology.

AimSubthalamic nucleus deep brain stimulation (STN‐DBS) has been reported to be effective in treating motor symptoms in Parkinson's disease (PD), which may be attributed to changes in the brain network. However, the association between brain morphology and initial STN‐DBS efficacy, as well as the performance of prediction using neuroimaging, has not been well illustrated. Therefore, we aim to investigate these issues.MethodsIn the present study, 94 PD patients underwent bilateral STN‐DBS, and the initial stimulation efficacy was evaluated. Brain morphology was examined by magnetic resonance imaging (MRI). The volume of tissue activated in the motor STN was measured with MRI and computed tomography. The prediction of stimulation efficacy was achieved with a support vector machine, using brain morphology and other features, after feature selection and hyperparameter optimization.ResultsA higher stimulation efficacy was correlated with a thicker right precentral cortex. No association with subcortical gray or white matter volumes was observed. These morphological features could estimate the individual stimulation response with an r value of 0.5678, an R 2 of 0.3224, and an average error of 11.4%. The permutation test suggested these predictions were not based on chance.ConclusionOur results indicate that changes in morphology are associated with the initial stimulation motor response and could be used to predict individual initial stimulation‐related motor responses.

Subcortical Volumes as Early Predictors of Fatigue in Multiple Sclerosis

Fatigue is a frequent and severe symptom in multiple sclerosis (MS), but its pathophysiological origin remains incompletely understood. We aimed to examine the predictive value of subcortical gray matter volumes for fatigue severity at disease onset and after 4 years by applying structural equation modeling (SEM). This multicenter cohort study included 601 treatment-naive patients with MS after the first demyelinating event. All patients underwent a standardized 3T magnetic resonance imaging (MRI) protocol. A subgroup of 230 patients with available clinical follow-up data after 4 years was also analyzed. Associations of subcortical volumes (included into SEM) with MS-related fatigue were studied regarding their predictive value. In addition, subcortical regions that have a central role in the brain network (hubs) were determined through structural covariance network (SCN) analysis. Predictive causal modeling identified volumes of the caudate (s [standardized path coefficient]=0.763, p= 0.003 [left]; s=0.755, p= 0.006 [right]), putamen (s=0.614, p= 0.002 [left]; s=0.606, p= 0.003 [right]) and pallidum (s=0.606, p= 0.012 [left]; s=0.606, p= 0.012 [right]) as prognostic factors for fatigue severity in the cross-sectional cohort. Moreover, the volume of the pons was additionally predictive for fatigue severity in the longitudinal cohort (s=0.605, p= 0.013). In the SCN analysis, network hubs in patients with fatigue worsening were detected in the putamen (p= 0.008 [left]; p= 0.007 [right]) and pons (p= 0.0001). We unveiled predictive associations of specific subcortical gray matter volumes with fatigue in an early and initially untreated MS cohort. The colocalization of these subcortical structures with network hubs suggests an early role of these brain regions in terms of fatigue evolution. ANN NEUROL 2022;91:192-202.

Cortical and subcortical grey matter atrophy in Amyotrophic Lateral Sclerosis correlates with measures of disease accumulation independent of disease aggressiveness

There is a growing demand for reliable biomarkers to monitor disease progression in Amyotrophic Lateral Sclerosis (ALS) that also take the heterogeneity of ALS into account.In this study, we explored the association between Magnetic Resonance Imaging (MRI)-derived measures of cortical thickness (CT) and subcortical grey matter (GM) volume with D50 model parameters.T1-weighted MRI images of 72 Healthy Controls (HC) and 100 patients with ALS were analyzed using Surface-based Morphometry for cortical structures and Voxel-based Morphometry for subcortical Region-Of-Interest analyses using the Computational Anatomy Toolbox (CAT12). In Inter-group contrasts, these parameters were compared between patients and HC. Further, the D50 model was used to conduct subgroup-analyses, dividing patients by a) Phase of disease covered at the time of MRI-scan and b) individual overall disease aggressiveness. Finally, correlations between GM and D50 model-derived parameters were examined.Inter-group analyses revealed ALS-related cortical thinning compared to HC located mainly in frontotemporal regions and a decrease in GM volume in the left hippocampus and amygdala. A comparison of patients in different phases showed further cortical and subcortical GM atrophy along with disease progression. Correspondingly, regression analyses identified negative correlations between cortical thickness and individual disease covered. However, there were no differences in CT and subcortical GM between patients with low and high disease aggressiveness.By application of the D50 model, we identified correlations between cortical and subcortical GM atrophy and ALS-related functional disability, but not with disease aggressiveness. This qualifies CT and subcortical GM volume as biomarkers representing individual disease covered to monitor therapeutic interventions in ALS.

Early structural brain development in infants exposed to HIV and antiretroviral therapy in utero in a South African birth cohort.

IntroductionThere is a growing population of children who are HIV‐exposed and uninfected (HEU) with the successful expansion of antiretroviral therapy (ART) use in pregnancy. Children who are HEU are at risk of delayed neurodevelopment; however, there is limited research on early brain growth and maturation. We aimed to investigate the effects of in utero exposure to HIV/ART on brain structure of infants who are HEU compared to HIV‐unexposed (HU).MethodsMagnetic resonance imaging using a T2‐weighted sequence was undertaken in a subgroup of infants aged 2–6 weeks enrolled in the Drakenstein Child Health Study birth cohort, South Africa, between 2012 and 2015. Mother–child pairs received antenatal and postnatal HIV testing and ART per local guidelines. We compared subcortical and total grey matter volumes between HEU and HU groups using multivariable linear regression adjusting for infant age, sex, intracranial volume and socio‐economic variables. We further assessed associations between brain volumes with maternal CD4 cell count and ART exposure.ResultsOne hundred forty‐six infants (40 HEU; 106 HU) with high‐resolution images were included in this analysis (mean age 3 weeks; 50.7% male). All infants who were HEU were exposed to ART (88% maternal triple ART). Infants who were HEU had smaller caudate volumes bilaterally (5.4% reduction, p < 0.05) compared to HU infants. There were no group differences in other subcortical volumes (all p > 0.2). Total grey matter volume was also reduced in infants who were HEU (2.1% reduction, p < 0.05). Exploratory analyses showed that low maternal CD4 cell count (<350 cells/mm3) was associated with decreased infant grey matter volumes. There was no relationship between timing of ART exposure and grey matter volumes.ConclusionsLower caudate and total grey matter volumes were found in infants who were HEU compared to HU in the first weeks of life, and maternal immunosuppression was associated with reduced volumes. These findings suggest that antenatal HIV exposure may impact early structural brain development and improved antenatal HIV management may have the potential to optimize neurodevelopmental outcomes of children who are HEU.

Associations between neonatal hypoglycaemia and brain volumes, cortical thickness and white matter microstructure in mid-childhood: An MRI study

Neonatal hypoglycaemia is a common metabolic disorder that may cause brain damage, most visible in parieto-occipital regions on MRI in the acute phase. However, the long term effects of neonatal hypoglycaemia on the brain are not well understood. We investigated the association between neonatal hypoglycaemia and brain volumes, cortical thickness and white matter microstructure at 9–10 years.Children born at risk of neonatal hypoglycaemia at ≥ 36 weeks’ gestation who took part in a prospective cohort study underwent brain MRI at 9–10 years. Neonatal hypoglycaemia was defined as at least one hypoglycaemic episode (at least one consecutive blood glucose concentration < 2.6 mmol/L) or interstitial episode (at least 10 min of interstitial glucose concentrations < 2.6 mmol/L). Brain volumes and cortical thickness were computed using Freesurfer. White matter microstructure was assessed using tract-based spatial statistics.Children who had (n = 75) and had not (n = 26) experienced neonatal hypoglycaemia had similar combined parietal and occipital lobe volumes and no differences in white matter microstructure at nine years of age. However, those who had experienced neonatal hypoglycaemia had smaller caudate volumes (mean difference: −557 mm3, 95% confidence interval (CI), −933 to −182, p = 0.004) and smaller thalamus (−0.03%, 95%CI, −0.06 to 0.00; p = 0.05) and subcortical grey matter (−0.10%, 95%CI −0.20 to 0.00, p = 0.05) volumes as percentage of total brain volume, and thinner occipital lobe cortex (−0.05 mm, 95%CI −0.10 to 0.00, p = 0.05) than those who had not. The finding of smaller caudate volumes after neonatal hypoglycaemia was consistent across analyses of pre-specified severity groups, clinically detected hypoglycaemic episodes, and severity and frequency of hypoglycaemic events.Neonatal hypoglycaemia is associated with smaller deep grey matter brain regions and thinner occipital lobe cortex but not altered white matter microstructure in mid-childhood.

The relationship between adolescents' externalizing and internalizing symptoms and brain development over a period of three years

BackgroundAdolescence is a crucial period for both brain maturation and the emergence of mental health disorders. Associations between brain morphology and internalizing/externalizing symptomatology have been identified in clinical or at-risk samples, but age-related developmental differences were rarely considered. The current study investigated the longitudinal relationship between internalizing/externalizing symptoms and brain development in the absence of psychiatric disorders during early and late adolescence. Methods98 healthy adolescents within two cohorts (younger: 9 years, older: 12 years) participated in annual assessments for three years; a clinical assessment measuring their externalizing and internalizing symptoms (SDQ) and an MRI assessment measuring their brain volume and white matter microstructure, including fractional anisotropy (FA), mean diffusivity (MD) and average path length. ResultsLinear mixed effect models and cross-lagged panel models showed that larger subcortical gray matter volume predicted more externalizing symptoms in older adolescents whereas decreases of subcortical gray matter volume predicted more externalizing symptoms for younger adolescents. Additionally, longer average white matter path length predicted more externalizing symptoms for older adolescents, while decreases in cerebral white matter volume were predictive of more externalizing symptoms for younger adolescents. There were no predictive effects for internalizing symptoms, FA or MD. ConclusionsDelays in subcortical brain maturation, in both early and late adolescence, are associated with increases in externalizing behavior which indicates a higher risk for psychopathology and warrants further investigations.

A multidimensional examination of psychopathy traits and gray matter volume in adults.

Uncovering the neurobiological abnormalities that may contribute to the manifestation of psychopathic traits is an important step toward understanding the etiology of this disorder. Although many studies have examined gray matter volume (GMV) in relation to psychopathy, few have examined how dimensions of psychopathic traits interactively relate to GMV, an approach that holds promise for parsing heterogeneity in neurobiological risk factors for this disorder. The aim of this study was to investigate the affective-interpersonal (Factor 1) and impulsive-antisocial (Factor 2) dimensions of psychopathy in relation to cortical surface and subcortical GMV in a mixed-gender, high-risk community sample with significant justice-system involvement (N = 156, 50.0% men). Cortex-wide analysis indicated that (i) the Factor 1 traits correlated negatively with GMV in two cortical clusters, one in the right rostral middle frontal region and one in the occipital lobe, and (ii) the interaction of the affective-interpersonal and impulsive-antisocial traits was negatively associated with GMV bilaterally in the parietal lobe, such that individuals high on both trait dimensions evidenced reduced GMV relative to individuals high on only one psychopathy factor. An interactive effect also emerged for bilateral amygdalar and hippocampal GMV, such that Factor 1 psychopathic traits were significantly negatively associated with GMV only at high (but not low) levels of Factor 2 traits. Results extend prior research by demonstrating the neurobiological correlates of psychopathy differ based on the presentation of Factor 1 and 2 traits.

Contributions of chronic tobacco smoking to HIV-associated brain atrophy and cognitive deficits.

Tobacco smoking is linked to cognitive deficits and greater white matter (WM) abnormalities in people with HIV disease (PWH). Whether tobacco smoking additionally contributes to brain atrophy in PWH is unknown and was evaluated in this study. We used a 2 × 2 design that included 83 PWH (43 nonsmokers, 40 smokers) and 171 HIV-seronegative (SN, 106 nonsmokers, 65 smokers) participants and assessed their brain structure and cognitive function. Selected subcortical volumes, voxel-wise cortical volumes and thickness, and total WM volume were analyzed using FreeSurfer. Independent and interactive effects of HIV and smoking were evaluated with two-way analysis of covariance on cognitive domain Z-scores and morphometric measures on T1-weighted MRI. Regardless of smoking status, relative to SN, PWH had smaller brain volumes [basal ganglia, thalami, hippocampi, subcortical gray matter (GM) and cerebral WM volumes (P = 0.002-0.042)], steeper age-related declines in the right superior-parietal (interaction: P < 0.001) volumes, and poorer attention/working memory and learning (P = 0.016-0.027). Regardless of HIV serostatus, smokers tended to have smaller hippocampi than nonsmokers (-0.6%, P = 0.055). PWH smokers had the smallest total and regional subcortical GM and cortical WM volume and poorest cognitive performance. Tobacco smoking additionally contributed to brain atrophy and cognitive deficits in PWH. The greater brain atrophy in PWH smokers may be due to greater neuronal damage or myelin loss in various brain regions, leading to their poor cognitive performance. Therefore, tobacco smoking may exacerbate or increase the risk for HIV-associated neurocognitive disorders.

MRI markers of accelerated brain aging and misappraisal of sleep depth

AbstractBackgroundSlow‐wave sleep (SWS) is the deepest sleep stage, and has been linked to many important physiological functions, including the cerebral metabolic clearance of toxins associated with Alzheimer’s disease. SWS loss might correlate with accelerated brain aging. However, older individuals and people with cognitive impairment have an impaired ability to appraise their sleep, suggesting that accelerated brain aging might affect how sleep depth is perceived. The purpose of this study was to evaluate whether misappraisal of sleep depth was associated with MRI markers of accelerated brain aging.MethodWe studied 242 participants (mean: 62.0±8.7 years) participants in the Framingham Heart Study Offspring Cohort that were evaluated with an overnight in‐home polysomnography and an MRI 3.4 years later on average. Self‐reported sleep depth (whether sleep was light or deep) on the night of the polysomnography was compared to objective SWS (percent of total sleep spent in SWS, separated by the median). Four groups were created: 36% of the sample had consistent appraisal of deep sleep; 12% of the sample had consistent appraisal of light sleep; 36% misappraised their light sleep as deep; and 16% misappraised their deep sleep as light. We evaluated total brain volume, cortical gray matter volume, and subcortical gray matter volume on MRI. A first set of models were adjusted for age, sex, time between MRI and neuropsychology; a second set of models were additionally adjusted for APOE4 allele status, body mass index, sleeping pills, depression, and stroke risk.ResultParticipants who misappraised light sleep, i.e., reported deep sleep but had lower SWS, had lower cortical gray matter volume (model 1: β±SE=‐0.62±0.26, p=0.018; model 2: ‐0.56±0.27, p=0.036) compared to those that reported deep sleep with higher SWS. We also observed a trend for lower subcortical gray matter volume in the same group (model 1:β±SE=‐0.09±0.05, p=0.084). No other between‐group differences were observed.ConclusionParticipants with lower SWS that reported their sleep as deep displayed lower cortical volume. Accelerated brain aging might affect the ability to appropriately perceived sleep depth, which could be occurring in preclinical stages of dementia. Relying on self‐report sleep depth may introduce systematic misclassification.

Late chronotype is linked to greater cortical thickness in the left fusiform and entorhinal gyri

ABSTRACT Humans can be classified as early, intermediate and late chronotypes based on their preferred sleep and wakefulness patterns. Eveningness is associated with increased risk of developing several psychiatric conditions, such as major depressive and addictive disorders, however, the anatomical basis of chronotype distinctions, which might predispose to the above conditions, remains largely unexplored. Using magnetic resonance imaging data from 113 healthy young adults (71 females), we aimed to correlate individual chronotype scores with cortical thickness, as well as subcortical and cerebellar grey matter volume. The results revealed one cluster located in the left fusiform and entorhinal gyri showing increased cortical thickness with increasing preference for eveningness. These structures are well positioned to mediate well-established chronotype differences in affective processing, i.e. increased negative affect in late chronotypes. Furthermore, in line with the earlier findings, we found no differences in subcortical and cerebellar grey matter volume. Thus, our study confirms that circadian preference is associated with specific structural cortical substrates and provides a potential anatomical basis for differential affective functioning in morning- and evening-oriented individuals, bridging the gap between brain structure and function.