Subcortical Gray Matter Volume Research Articles

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.

Tackling clinical heterogeneity across the amyotrophic lateral sclerosis–frontotemporal dementia spectrum using a transdiagnostic approach

The disease syndromes of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) display considerable clinical, genetic and pathological overlap, yet mounting evidence indicates substantial differences in progression and survival. To date, there has been limited examination of how profiles of brain atrophy might differ between clinical phenotypes. Here, we address this longstanding gap in the literature by assessing cortical and subcortical grey and white matter volumes on structural MRI in a large cohort of 209 participants. Cognitive and behavioural changes were assessed using the Addenbrooke’s Cognitive Examination and the Cambridge Behavioural Inventory. Relative to 58 controls, behavioural variant FTD (n = 58) and ALS–FTD (n = 41) patients displayed extensive atrophy of frontoinsular, cingulate, temporal and motor cortices, with marked subcortical atrophy targeting the hippocampus, amygdala, thalamus and striatum, with atrophy further extended to the brainstem, pons and cerebellum in the latter group. At the other end of the spectrum, pure-ALS patients (n = 52) displayed considerable frontoparietal atrophy, including right insular and motor cortices and pons and brainstem regions. Subcortical regions included the bilateral pallidum and putamen, but to a lesser degree than in the ALS–FTD and behavioural variant FTD groups. Across the spectrum the most affected region in all three groups was the insula, and specifically the anterior part (76–90% lower than controls). Direct comparison of the patient groups revealed disproportionate temporal atrophy and widespread subcortical involvement in ALS–FTD relative to pure-ALS. In contrast, pure-ALS displayed significantly greater parietal atrophy. Both behavioural variant FTD and ALS–FTD were characterized by volume decrease in the frontal lobes relative to pure-ALS. The motor cortex and insula emerged as differentiating structures between clinical syndromes, with bilateral motor cortex atrophy more pronounced in ALS–FTD compared with pure-ALS, and greater left motor cortex and insula atrophy relative to behavioural variant FTD. Taking a transdiagnostic approach, we found significant associations between abnormal behaviour and volume loss in a predominantly frontoinsular network involving the amygdala, striatum and thalamus. Our findings demonstrate the presence of distinct atrophy profiles across the ALS–FTD spectrum, with key structures including the motor cortex and insula. Notably, our results point to subcortical involvement in the origin of behavioural disturbances, potentially accounting for the marked phenotypic variability typically observed across the spectrum.

The Association Between Perivascular Spaces and Cerebral Blood Flow, Brain Volume, and Cardiovascular Risk.

Background: Basal ganglia perivascular spaces are associated with cognitive decline and cardiovascular risk factors. There is a lack of studies on the cardiovascular risk burden of basal ganglia perivascular spaces (BG-PVS) and their relationship with gray matter volume (GMV) and GM cerebral blood flow (CBF) in the aging brain. Here, we investigated these two issues in a large sample of cognitively intact older adults.Methods: A total of 734 volunteers were recruited. MRI was performed with 3.0 T using a pseudo-continuous arterial spin labeling (pCASL) sequence and a sagittal isotropic T1-weighted sequence for CBF and GMV analysis. The images obtained from 406 participants were analyzed to investigate the relationship between the severity of BG-PVS and GMV/CBF. False discovery rate-corrected P-values (PFDR) of <0.05 were considered significant. The images obtained from 254 participants were used to study the relationship between the severity of BG-PVS and cardiovascular risk burden. BG-PVS were rated using a 5-grade score. The severity of BG-PVS was classified as mild (grade <3) and severe (grade ≥3). Cardiovascular risk burden was assessed with the Framingham General Cardiovascular Risk Score (FGCRS).Results: Severe basal ganglia perivascular spaces were associated with significantly smaller GMV and CBF in multiple cortical regions (PFDR <0.05), and were associated with significantly larger volume in the bilateral caudate nucleus, pallidum, and putamen (PFDR <0.05). The participants with severe BG-PVS were more likely to have a higher cardiovascular risk burden than the participants with mild BG-PVS (60.71% vs. 42.93%; P =0.02).Conclusion: In cognitively intact older adults, severe BG-PVS are associated with smaller cortical GMV and CBF, larger subcortical GMV, and higher cardiovascular risk burden.

Early Childhood Socioeconomic Status and Cognitive and Adaptive Outcomes at the Transition to Adulthood: The Mediating Role of Gray Matter Development Across Five Scan Waves

BackgroundEarly low socioeconomic status (SES) is associated with poor outcomes in childhood, many of which endure into adulthood. It is critical to determine how early low SES relates to trajectories of brain development and whether these mediate relationships to poor outcomes. We use data from a unique 17-year longitudinal study with five waves of structural brain imaging to prospectively examine relationships between preschool SES and cognitive, social, academic, and psychiatric outcomes in early adulthood. MethodsChildren (n = 216, 50% female, 47.2% non-White) were recruited from a study of early onset depression and followed approximately annually. Family income-to-needs ratios (SES) were assessed when children were ages 3 to 5 years. Volumes of cortical gray and white matter and subcortical gray matter collected across five scan waves were processed using the FreeSurfer Longitudinal pipeline. When youth were ages 16+ years, cognitive function was assessed using the NIH Toolbox, and psychiatric diagnoses, high-risk behaviors, educational function, and social function were assessed using clinician administered and parent/youth report measures. ResultsLower preschool SES related to worse cognitive, high-risk, educational, and social outcomes (|standardized B| = 0.20–0.31, p values < .003). Lower SES was associated with overall lower cortical (standardized B = 0.12, p < .0001) and subcortical gray matter (standardized B = 0.17, p < .0001) volumes, as well as a shallower slope of subcortical gray matter growth over time (standardized B = 0.04, p = .012). Subcortical gray matter mediated the relationship of preschool SES to cognition and high-risk behaviors. ConclusionsThese novel longitudinal data underscore the key role of brain development in understanding the long-lasting relations of early low SES to outcomes in children.

Childhood Adversity and the Brain: Harnessing the Power of Neuroplasticity

In the current issue of Biological Psychiatry, Gehred et al. ( 1 Gehred M.Z. Knodt A.R. Ambler A. Bourassa K.J. Danese A. Elliott M.L. et al. Long-term neural embedding of childhood adversity in a population-representative birth cohort followed for 5 decades. Biol Psychiatry. 2021; 90: 182-193 Abstract Full Text Full Text PDF Scopus (6) Google Scholar ) showcase unique new data and a novel window on the long-term impact of childhood adversity on structural changes in the brain. This report uses data from a by now well-known birth cohort in Dunedin, New Zealand, creatively harnessed over many decades by Moffitt and Caspi. It is a testament to these scholars that they have continuously added to the measurement armamentarium of this project as new relevant measures and technologies have been developed. When the Dunedin study was first launched, neuroimaging did not exist. With the newly added neuroimaging measures along with the measurement of different aspects of development as the sample matured, this birth cohort offers a goldmine of rich data that have so effectively been explored over the years by Moffitt and Caspi and their colleagues. Gehred et al. ( 1 Gehred M.Z. Knodt A.R. Ambler A. Bourassa K.J. Danese A. Elliott M.L. et al. Long-term neural embedding of childhood adversity in a population-representative birth cohort followed for 5 decades. Biol Psychiatry. 2021; 90: 182-193 Abstract Full Text Full Text PDF Scopus (6) Google Scholar ) report that both prospectively ascertained and retrospective measures of childhood adversity were associated with smaller total cortical surface area, average cortical thickness, and smaller subcortical gray matter volume in a birth cohort of 861 participants. The imaging data were acquired when the participants were 45 years of age, with 94% of the original sample participating. Gehred et al. ( 1 Gehred M.Z. Knodt A.R. Ambler A. Bourassa K.J. Danese A. Elliott M.L. et al. Long-term neural embedding of childhood adversity in a population-representative birth cohort followed for 5 decades. Biol Psychiatry. 2021; 90: 182-193 Abstract Full Text Full Text PDF Scopus (6) Google Scholar ) also reported that associations with prospectively ascertained measures of adversity were consistently stronger than those with retrospectively reported adversity. Finally, the findings revealed widely distributed effects throughout the brain with virtually no regional specificity. SEE CORRESPONDING ARTICLE ON PAGE 182 SEE CORRESPONDING ARTICLE ON PAGE 182 Long-term Neural Embedding of Childhood Adversity in a Population-Representative Birth Cohort Followed for 5 DecadesBiological PsychiatryVol. 90Issue 3PreviewChildhood adversity has been previously associated with alterations in brain structure, but heterogeneous designs, methods, and measures have contributed to mixed results and have impeded progress in mapping the biological embedding of childhood adversity. We sought to identify long-term differences in structural brain integrity associated with childhood adversity. Full-Text PDF Open Access

Elevated body weight modulates subcortical volume change and associated clinical response following electroconvulsive therapy.

Background:Obesity is a frequent somatic comorbidity of major depression, and it has been associated with worse clinical outcomes and brain structural abnormalities. Converging evidence suggests that electroconvulsive therapy (ECT) induces both clinical improvements and increased subcortical grey matter volume in patients with depression. However, it remains unknown whether increased body weight modulates the clinical response and structural neuroplasticity that occur with ECT.Methods:To address this question, we conducted a longitudinal investigation of structural MRI data from the Global ECT-MRI Research Collaboration (GEMRIC) in 223 patients who were experiencing a major depressive episode (10 scanning sites). Structural MRI data were acquired before and after ECT, and we assessed change in subcortical grey matter volume using FreeSurfer and Quarc.Results:Higher body mass index (BMI) was associated with a significantly lower increase in subcortical grey matter volume following ECT. We observed significant negative associations between BMI and change in subcortical grey matter volume, with pronounced effects in the thalamus and putamen, where obese participants showed increases in grey matter volume that were 43.3% and 49.6%, respectively, of the increases found in participants with normal weight. As well, BMI significantly moderated the association between subcortical grey matter volume change and clinical response to ECT. We observed no significant association between BMI and clinical response to ECT.Limitations:Because only baseline BMI values were available, we were unable to study BMI changes during ECT and their potential association with clinical and grey matter volume change.Conclusion:Future studies should take into account the relevance of body weight as a modulator of structural neuroplasticity during ECT treatment and aim to further explore the functional relevance of this novel finding.

Childhood trauma is associated with reduced frontal gray matter volume: a large transdiagnostic structural MRI study.

Childhood trauma increases risk for psychopathology and cognitive impairment. Prior research mainly focused on the hippocampus and amygdala in single diagnostic categories. However, other brain regions may be impacted by trauma as well, and effects may be independent of diagnosis. This cross-sectional study investigated cortical and subcortical gray matter volume in relation to childhood trauma severity. We included 554 participants: 250 bipolar-I patients, 84 schizophrenia-spectrum patients and 220 healthy individuals without a psychiatric history. Participants filled in the Childhood Trauma Questionnaire. Anatomical T1 MRI scans were acquired at 3T, regional brain morphology was assessed using Freesurfer. In the total sample, trauma-related gray matter reductions were found in the frontal lobe (β = -0.049, p = 0.008; q = 0.048), this effect was driven by the right medial orbitofrontal, paracentral, superior frontal regions and the left precentral region. No trauma-related volume reductions were observed in any other (sub)cortical lobes nor the hippocampus or amygdala, trauma-by-group (i.e. both patient groups and healthy subjects) interaction effects were absent. A categorical approach confirmed a pattern of more pronounced frontal gray matter reductions in individuals reporting multiple forms of trauma and across quartiles of cumulative trauma scores. Similar dose-response patterns were revealed within the bipolar and healthy subgroups, but did not reach significance in schizophrenia-spectrum patients. Findings show that childhood trauma is linked to frontal gray matter reductions, independent of psychiatric morbidity. Our results indicate that childhood trauma importantly contributes to the neurobiological changes commonly observed across psychiatric disorders. Frontal volume alterations may underpin affective and cognitive disturbances observed in trauma-exposed individuals.

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.

Maternal depression during pregnancy alters infant subcortical and midbrain volumes.

BackgroundMaternal depression in pregnancy increases the risk for adverse neurodevelopmental outcomes in the offspring. The reason for this is unknown, however, one plausible mechanism may include the impact of maternal antenatal depression on infant brain. Nevertheless, relatively few studies have examined the brain anatomy of infants born to clinically diagnosed mothers. MethodsA legacy magnetic resonance imaging (MRI) dataset was used to compare regional brain volumes in 3-to-6-month-old infants born to women with a clinically confirmed diagnosis of major depressive disorder (MDD) during pregnancy (n = 31) and a reference sample of infants born to women without a current or past psychiatric diagnosis (n = 33). A method designed for analysis of low-resolution scans enabled examination of subcortical and midbrain regions previously found to be sensitive to the parent-child environment. ResultsCompared with infants of non-depressed mothers, infants exposed to maternal antenatal depression had significantly larger subcortical grey matter volumes and smaller midbrain volumes. There was no association between gestational medication exposure and the infant regional brain volumes examined in our sample. LimitationsOur scanning approach did not allow for an examination of fine-grained structural differences, and without repeated measures of brain volume, it is unknown whether the direction of reported associations are dependent on developmental stage. ConclusionsMaternal antenatal depression is associated with an alteration in infant brain anatomy in early postnatal life; and that this is not accounted for by medication exposure. However, our study cannot address whether anatomical differences impact on future outcomes of the offspring.