Gray Matter Volume Decrease Research Articles

Influence of dehydroepiandrosterone sulfate levels on the slower age-related decline in gray matter in younger women with polycystic ovary syndrome

Abstract Polycystic ovary syndrome (PCOS) is characterized by excess androgens, ovulatory disorders, and a higher prevalence of obesity and metabolic disturbances including type 2 diabetes, hyperlipidemia, and hypertension, some of which are risk factors for neurodegenerative disorders such as Alzheimer’s disease and brain atrophy. However, it is unclear whether brain aging occurs more rapidly in women with PCOS compared to those without PCOS. Except for the hypothalamic-pituitary-gonadal axis involved in the conventional ovulatory process, little is known regarding the role of the gray matter in the pathogenesis of PCOS, and limited existing studies examining brain structures in PCOS have shown inconsistent results. This case-control study aimed to investigate the age-related differences in total and regional brain gray matter volume and average cortical thickness in young women with and without PCOS by using brain magnetic resonance imaging (MRI) to understand whether women with PCOS exhibit distinctive patterns of brain aging, and their association with factors including obesity, hyperandrogenism, and metabolic disturbances. Seventy-six women diagnosed with PCOS and 68 age-matched women without PCOS (aged 20-35 years) underwent brain MRI to measure gray matter volume and cortical thickness. Anthropometric, hormonal, and metabolic measurements were conducted to assess their associations with the investigated brain structures. In women without PCOS, increasing age was significantly correlated with a decrease in global gray matter volume (r = -0.5598, P < 0.0001), while this association was not significant in women with PCOS (r = -0.1475, P = 0.204). The decline in gray matter volume with age differed significantly between the two groups regardless of obesity (body mass index exceeding 25 Kg/m2), especially in the frontal, parietal, occipital, and temporal regions. After adjusting for dehydroepiandrosterone sulfate (DHEAS) levels, the negative association between age and global gray matter volume became statistically significant in women with PCOS. Increasing age was also significantly associated with a decrease in global cortical thickness in women without PCOS, but not in women with PCOS. Such negative association between global cortical thickness and age was particularly stronger in women with obesity compared to those without. The negative association between age and global cortical thickness in women with PCOS became pronounced after adjusting for DHEAS levels. Women with PCOS experience a milder gray matter loss with age compared to women without PCOS. The neuroprotective effect of high DHEAS levels in women with PCOS may be implicated in this relationship.

Medial orbitofrontal cortex structure, function, and cognition associates with weight loss for laparoscopic sleeve gastrectomy.

The objective of this study was to investigate underlying mechanisms of long-term effective weight loss after laparoscopic sleeve gastrectomy (LSG) and effects on the medial orbitofrontal cortex (mOFC) and cognition. A total of 18 individuals with obesity (BMI ≥ 30 kg/m2) underwent LSG. Clinical data, cognitive scores, and brain magnetic resonance imaging scans were evaluated before LSG and 12 months after LSG. We employed voxel-based morphometry analysis and seed-based resting-state functional connectivity (RSFC) analysis to assess LSG-induced structural and functional changes in mOFC. Partial correlation analysis and univariate and multivariate linear regression models were used to explore associations among biochemical indexes, neuroimaging, cognition, and weight loss. No significant improvement in general cognition was found after LSG. Decreases in gray matter volume of the bilateral mOFC and increases in RSFC of the right mOFC were observed 12 months after LSG. Weight loss was associated with RSFC, general cognitive scores, and triglyceride changes. Multivariate linear regression model revealed gray matter volume of the left mOFC and working memory scores at baseline explained 55.2% of the variation in weight loss. These findings suggest that mOFC imaging and cognitive scores could serve as biomarkers for predicting persistent weight loss after LSG, which provides a solid foundation for a potential target for neuromodulation research.

Astrocyte proliferation in the hippocampal dentate gyrus is suppressed across the lifespan of dystrophin-deficient mdx mice.

Absence of the structural protein, dystrophin, results in the neuromuscular disorder Duchenne Muscular Dystrophy (DMD). In addition to progressive skeletal muscle dysfunction, this multisystemic disorder can also result in cognitive deficits and behavioural changes that are likely to be consequences of dystrophin loss from central neurons and astrocytes. Dystrophin-deficient mdx mice exhibit decreases in grey matter volume in the hippocampus, the brain region that encodes and consolidates memories, and this is exacerbated with ageing. To understand changes in cellular composition that might underpin these age-related developments, we have compared neurogenesis and the prevalence of immunofluorescently identified newly born and mature neurons, astrocytes and microglia in the dentate gyrus of mdx and wild-type mice at 2, 4, 8 and 16 months of age. The number of adult-born neurons was suppressed in the dentate gyrus subgranular zone of 2-month-old mdx mice. However, the numbers of granule cells and GABAA receptor, alpha 1-expressing cells were similar in wild-type and mdx mice at all ages. Strikingly, the numbers of astrocytes, particularly in the dentate gyrus molecular layer, were suppressed in mdx mice at all time points. Thus, dystrophin loss was associated with reduced hippocampal neurogenesis in early life but did not impact the prevalence of mature neurons across the lifespan of mdx mice. In contrast, normal age-related dentate gyrus astrocyte proliferation was suppressed in dystrophic mice. Astrocytes are the most abundant cell type in the brain and are crucial in supporting neuronal function, such that loss of these cells is likely to contribute to hippocampal dysfunction reported in mdx mice.

Co-methylation networks associated with cognition and structural brain development during adolescence.

Typical adolescent neurodevelopment is marked by decreases in grey matter (GM) volume, increases in myelination, measured by fractional anisotropy (FA), and improvement in cognitive performance. To understand how epigenetic changes, methylation (DNAm) in particular, may be involved during this phase of development, we studied cognitive assessments, DNAm from saliva, and neuroimaging data from a longitudinal cohort of normally developing adolescents, aged nine to fourteen. We extracted networks of methylation with patterns of correlated change using a weighted gene correlation network analysis (WCGNA). Modules from these analyses, consisting of co-methylation networks, were then used in multivariate analyses with GM, FA, and cognitive measures to assess the nature of their relationships with cognitive improvement and brain development in adolescence. This longitudinal exploration of co-methylated networks revealed an increase in correlated epigenetic changes as subjects progressed into adolescence. Co-methylation networks enriched for pathways involved in neuronal systems, potassium channels, neurexins and neuroligins were both conserved across time as well as associated with maturation patterns in GM, FA, and cognition. Our research shows that correlated changes in the DNAm of genes in neuronal processes involved in adolescent brain development that were both conserved across time and related to typical cognitive and brain maturation, revealing possible epigenetic mechanisms driving this stage of development.

Cortical and subcortical gray matter volume and cognitive impairment in Parkinson’s disease

Introduction This study investigated the cortical and subcortical gray matter volume (GMV) and cognitive impairment (CI) in patients with Parkinson’s disease (PD). Methods In this study, T1-weighted magnetic resonance imaging of the cortex and subcortex was conducted on 92 individuals diagnosed with PD and 92 healthy controls (HCs). PD patients were divided into three groups: PD with normal cognition (PD-NC, n = 21), PD with mild CI (PD-MCI, n = 43), and PD with severe CI (PD-SCI, n = 28). Differences in GMV were analyzed using voxel-based morphometry (VBM). Statistical analysis was conducted using SPSS 26. Results Compared to the HCs, the PD-NC group exhibited reduced GMV in the right middle frontal gyrus (RMFG), right precentral gyrus medial segment (RPGMS), left temporal pole, and right superior frontal gyrus medial segment (RSFGMS). In comparison to the HC and PD-NC groups, the PD-MCI and PD-SCI groups (respectively) demonstrated significant decreases in GMV in the right caudate, left hippocampus, left thalamus, RMFG, RPGMS, RSFGMS, and cerebellum (right crus I and left crus I). The regression analysis indicated that changes in the GMV of the frontal areas can predict cognitive test outcomes. Conclusion Compared to HCs, PD patients with CI presented significant volume reductions in the RC, LH, LT, RMFG, RPGMS, RSFGMS, and the right and left crus I regions. Consequently, as average GMV atrophy increased in the specified regions, PD patients exhibited more severe cognitive impairment than the HC group. This may be attributed to the initial pathological loss of frontal GMV (especially in the RMFG and RPGMS regions), which could subsequently lead to subcortical dysfunction.

Progressive brain atrophy and cortical reorganization related to surgery in temporal lobe epilepsy.

Epilepsy is associated with progressive cortical atrophy exceeding normal aging. We aimed to explore longitudinal cortical alterations in patients with temporal lobe epilepsy (TLE) and distinct surgery outcomes. We obtained longitudinal T1-weighted MRI data in a well-designed cohort, including 53 operative TLE patients, 23 nonoperative TLE patients, and 23 healthy controls. According to seizure outcomes at 24 months after surgery, operative patients were divided into seizure-free (SF) and nonseizure-free (NSF) group. Operative patients were scanned before and after surgery, while nonoperative patients and healthy controls were rescanned with similar interval times. We measured gray matter volume (GMV) in all participants and compared longitudinal cortical alterations among groups. In nonoperative group, statistically significant GMV decrease was observed in ipsilateral median cingulate and paracingulate gyri and cerebellum crus I when compared with healthy controls. In operative group, postoperative GMV increase was discovered in many regions involving bilateral hemispheres, especially in the frontal lobe, without differences between SF and NSF group. Postoperative GMV decrease was found in ipsilateral inferior frontal gyrus, putamen, thalamus, and insula. GMV decrease in ipsilateral inferior frontal gyrus, putamen, and insula was more significant in SF group. Progressive cortical atrophy existed in nonoperative TLE patients. Cortical remodeling indicated by postoperative GMV increase may arise mostly from the surgery itself, rather than postsurgical seizure outcomes. More significant GMV decrease in ipsilateral inferior frontal gyrus, putamen, and insula may imply their closer connections with resected regions in seizure-free patients.

MRI Assessment of Healthy Aging Trajectories in the Marmoset Brain

AbstractBackgroundThe common marmoset (Callithrix jacchus) is an important animal model in neuroscience and neurological diseases (e.g., Alzheimer’s disease ‐ AD), as they present primate‐specific evolutionary features such as an expanded frontal cortex. We established a new consortium with funding support from the National Institute on Aging to generate, characterize, and validate MArmosets as Research MOdels of AD (MARMO‐AD). This consortium develops and studies gene‐edited marmoset models carrying genetic risk for AD, comparing them against wild‐type aging marmosets from birth throughout their lifespan, using non‐invasive longitudinal assessments. Here, we aim to characterize healthy aging trajectories of regional brain volume in a population of marmosets.MethodsWe imaged a cohort of 59 marmosets (45 males, 14 females) across the lifespan (8 to 150 months) using a dedicated 9.4T 30cm bore MRI scanner (Bruker BioSpin Corp, Billerica). The animals were anesthetized under isoflurane and maintained under normal physiological conditions. High‐resolution (250 µm isotropic) T1‐, T2‐, and diffusion‐weighted structural MRI were acquired. The brain images were aligned and registered to the Marmoset Brain Mapping V3 template. The brain was segmented into cortical (CTX) and subcortical (SUB CTX) grey matter, white matter (WM), and cerebral spinal fluid (CSF), and voxel‐based‐morphometry was used to quantify regional brain volume in the left and right hemispheres.ResultsWe discovered a decrease in grey matter volume in both males and females with age (Figure 1), reflected by the reduction in several cortical and subcortical brain regions in both sexes. Overall, we discovered that age affects female marmoset brains (38 CTX and 5 SUB CTX regions) more than males (15 CTX and 2 SUB CTX regions). We found no significant age‐dependent changes in WM and CSF.ConclusionsOur work is the first to thoroughly describe the normal aging of the marmoset brain, a valuable model for age‐related neuropathologies (e.g., AD). This research will establish normative baselines for changes in regional marmoset brain volume with aging that will be used to evaluate our genetically engineered marmoset models of AD, which is the goal of the MARMO‐AD consortium.

Long-Term Cerebellar Consequences of Post-traumatic Brain Injury Assessed by MRI With Diffusion Tensor Imaging

BACKGROUND AND OBJECTIVES: Post-traumatic brain injury (TBI) lesions, which combine brain atrophy and white matter injuries, can lead to progressive post-traumatic encephalopathy. However, the specific involvement of the cerebellum, which participates in cognitive, executive, and sensory functions, has been little studied. The aim of this work was to explore the long-term cerebellar consequences of severe TBI. METHODS: In this retrospective study, patients included were hospitalized for a severe TBI and reassessed after discharge with a clinical examination and a MRI with diffusion tensor imaging. Patients were compared with a population of healthy volunteers. For a subgroup of this cohort, we analyzed the evolution of late post-TBI lesions on MRI up to 10 years after TBI. RESULTS: Ninety-seven patients reassessed 5 [3; 6] years after the TBI were included. Volume loss was revealed in the whole cerebellum (P = .01) and especially in the anterior lobe (P < .005) with a decrease in grey matter volume (P = 6.10−3). The mean diffusivity was increased in 4 cerebellar areas which are the right lower, right upper, left lower, and left upper cerebellar peduncles while the fractional anisotropy was decreased in all studied areas (P < 10−3). The longitudinal analysis (n = 17 patients) showed no progression of MRI lesions beyond the acute phase. CONCLUSION: This work shows that even if direct cerebellar damage is rare, long-term post-TBI cerebellar lesions can be observed. Therefore, clinical correlates of cerebellar lesions should be considered more systematically.

Association of depression with longitudinal changes in brain structure across the lifespan: A mendelian randomization study.

Understanding the impact of depression on brain aging benefits the prognosis of this disease and of the risk that other age-related brain disorders will develop in the same population. The aim of the present study was to explore the genetic effect of depression on longitudinal changes in brain structure throughout the lifespan using a Mendelian randomization approach. Summary data from a genome-wide association study of 195,321 to 377,277 participants in the FinnGen consortium were used to predict depression, anxiety disorders, mood disorders, and antidepressant use genetically. Data from 15,640 participants in the ENIGMA consortium were included to predict changes in 15 brain structures throughout the lifespan. The causal relationship between these depressive traits and the brain structure parameters was assessed by two-sample Mendelian randomization (including inverse-variance weighted). Sensitivity analyses were conducted for quality control. Depression slowed the decrease of cortical gray matter volume significantly throughout the lifespan (p = 0.001). Depression, anxiety, and mood disorders nominally decreased the rates of change of volume in the cerebellum gray matter, lateral ventricles, and cortical gray matter throughout the lifespan (p = 0.048, p = 0.021, p = 0.038, respectively). Antidepressants did not affect these rates of change significantly (p > 0.05). Sensitivity analyses confirmed the reliability of this study. Depression and its main symptoms have a slight effect on longitudinal changes in a few brain structures throughout the lifespan at the genetic level. These findings do not support the notion that depression affects macro-aging in the brain crucially.

Gray matter volumetric changes in tinnitus: The impact of hearing loss and severity

Tinnitus is a phantom auditory sensation that commonly co-occurs with hearing loss. Both tinnitus and hearing loss can impact the quality of life, emotional well-being, and cognitive functioning of the affected individuals. While previous studies have highlighted structural alterations in hearing loss and/or tinnitus, the fundamental neural mechanisms underpinning tinnitus severity remain poorly understood. In this study, we conducted a voxel-based morphometry to investigate gray matter (GM) volume differences among groups of participants with varying tinnitus severity and hearing status, and controls within a large sample. We observed reduced GM volume in the left anterior insula and right planum polare in participants with hearing loss, regardless of their tinnitus status, compared to normal hearing controls. We noted decreased GM volume in the bilateral anterior and posterior insula for those with tinnitus and normal hearing compared to a normal hearing control group. Further, the tinnitus with hearing loss group showed decreased GM volume in the left planum polare, left inferior temporal gyrus, bilateral anterior temporal gyri, and right superior frontal gyrus compared to the normal hearing control group, suggesting a combined effect of hearing loss and tinnitus. While tinnitus severity did not show a significant overall effect, there was a significant positive correlation between tinnitus distress and GM volume in bilateral planum polare. Our findings enhance the understanding of structural brain changes related to hearing loss and tinnitus, and advance the overall knowledge of tinnitus pathophysiology, which can contribute to the development of more effective treatments for tinnitus.

Baseline and Longitudinal MRI Markers Associated With 16-Year Mortality in Patients With Cerebral Small Vessel Disease.

Information on whether small vessel disease (SVD) reduces life expectancy is limited. Moreover, the excess mortality risk attributed specifically to SVD compared with controls from the general population has not been evaluated. This study aimed to investigate the baseline and progression of MRI markers of SVD associated with mortality in a 16-year follow-up cohort study and to determine the excess long-term mortality risk of patients with SVD. Participants with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) study (with MRI assessments in 2006, 2011, 2015, and 2020) were followed until their death or December 1, 2021. Adjusted Cox regression analyses and linear mixed-effect regression models were used to investigate the association between MRI markers of SVD and mortality. The excess mortality risk of SVD was calculated by comparing mortality data of the RUN DMC study with the general population matched by sex, age, and calendar year. 200 of 503 (39.9%) participants died during a follow-up period of 15.9 years. Cause of death was available for 182 (91%) participants. Baseline white matter hyperintensity volume (HR 1.3 per 1-SD increase [95% CI 1.1-1.5], p = 0.010), presence of lacunes (1.5 [95% CI 1.1-2.0], p = 0.008), mean diffusivity (HR 1.1 per 1-SD increase [95% CI 1.1-1.2], p = 0.001), and total brain volume (HR 1.5 per 1-SD decrease [95% CI 1.3-1.9], p < 0.001) were associated with all-cause mortality after adjusting for age, sex, and vascular risk factors. Total brain volume decrease over time was associated with all-cause mortality after adjusting for age, sex, and vascular risk factors (HR 1.3 per 1-SD decrease [95% CI 1.1-1.7], p = 0.035), and gray matter volume decrease remained significant after additionally adjusting for its baseline volume (1.3 per 1-SD decrease [1.1-1.6], p = 0.019). Participants with a Fazekas score of 3, presence of lacunes, or lower microstructural integrity had an excess long-term mortality risk (21.8, 15.7, 10.1 per 1,000 person-years, respectively) compared with the general population. Excess long-term mortality risk only exists in patients with severe SVD (Fazekas score of 3, presence of lacunes, or lower microstructural integrity). This could help in assisting clinicians to predict the clinical outcomes of patients with SVD by severity.

Neuroanatomical changes observed over the course of a human pregnancy

Pregnancy is a period of profound hormonal and physiological changes experienced by millions of women annually, yet the neural changes unfolding in the maternal brain throughout gestation are not well studied in humans. Leveraging precision imaging, we mapped neuroanatomical changes in an individual from preconception through 2 years postpartum. Pronounced decreases in gray matter volume and cortical thickness were evident across the brain, standing in contrast to increases in white matter microstructural integrity, ventricle volume and cerebrospinal fluid, with few regions untouched by the transition to motherhood. This dataset serves as a comprehensive map of the human brain across gestation, providing an open-access resource for the brain imaging community to further explore and understand the maternal brain.

Association of open skill exercise and long-chain polyunsaturated fatty acid intake with brain volume changes among older community-dwelling Japanese individuals

Considering that a multifactorial lifestyle approach may prove more effective than a single factor approach to improve or maintain brain health, we evaluated the association of exercise (open skill exercise [OSE] or closed skill exercise [CSE]) combined with long-chain polyunsaturated fatty acid (LCPUFAs) (docosahexaenoic acid [C22:6n-3, DHA], eicosapentaenoic acid [C20:5n-3, EPA], and arachidonic acid [C20:4n-6, ARA]) intake with brain atrophy among older Japanese individuals (n = 795, aged 60–88 years) without a self-reported history of dementia based on the datasets of a two-year longitudinal study. Brain volumes were measured using three-dimensional T1-weighted brain magnetic resonance imaging for follow-up periods of two years. The associations between multivariate-adjusted changes in brain volumes and OSE or CSE frequency (≥ once/month and < once/month) along with LCPUFA intake (≥ median and < median) at the baseline were assessed using a general linear model. Subgroup analysis was performed by restricting DHA and EPA intakes (n = 263; median, 323 mg/d), which represented levels similar to those in countries with low fish consumption. Higher OSE frequencies, ARA intakes, and their combination were inversely associated with decreases in total gray matter and frontal cortex volumes. In subgroup analysis, a combination of higher OSE frequencies and DHA intakes was also associated with a smaller decrease in total gray matter volume. Overall, our findings suggest that regular OSE engagement and appropriate LCPUFA intake may contribute to preventing brain volume decreases in older individuals.

Behavioral and brain morphological changes before and after hemispherotomy.

Hemispherotomy is an effective surgery for treating refractory epilepsy from diffuse unihemispheric lesions. To date, postsurgery neuroplastic changes supporting behavioral recovery after left or right hemispherotomy remain unclear. In the present study, we systematically investigated changes in gray matter volume (GMV) before and after surgery and further analyzed their relationships with behavioral scores in two large groups of pediatric patients with left and right hemispherotomy (29 left and 28 right). To control for the dramatic developmental effect during this stage, age-adjusted GMV within unaffected brain regions was derived voxel by voxel using a normative modeling approach with an age-matched reference cohort of 2115 healthy children. Widespread GMV increases in the contralateral cerebrum and ipsilateral cerebellum and GMV decreases in the contralateral cerebellum were consistently observed in both patient groups, but only the left hemispherotomy patients showed GMV decreases in the contralateral cingulate gyrus. Intriguingly, the GMV decrease in the contralateral cerebellum was significantly correlated with improvement in behavioral scores in the right but not the left hemispherotomy patients. Importantly, the preoperative voxelwise GMV features can be used to significantly predict postoperative behavioral scores in both patient groups. These findings indicate an important role of the contralateral cerebellum in the behavioral recovery following right hemispherotomy and highlight the predictive potential of preoperative imaging features in postoperative behavioral performance.

Gray matter volume of limbic brain structures during the development of chronic back pain: a longitudinal cohort study.

This study set out to investigate in a population-based longitudinal cohort, whether chronification of back pain (BP) is related to structural gray matter changes in corticolimbic brain structures. Gray matter volume (GMV) was measured in participants with chronic BP (CBP, n = 168) and controls without chronic pain (n = 323) at 2 time points with an interval of 7 years (baseline t1, follow-up t2). Over this time period, participants with CBP showed an increase of GMV in the left ventral striatum, whereas controls showed a decrease. By contrast, participants with CBP had a GMV decrease in the left parahippocampal gyrus. Within the CBP group, pain duration was negatively associated with GMV in the left caudate. Those with emerging CBP had less GMV in the right entorhinal area, right amygdala, and left medial frontal cortex. Additional variables differing between those who had BP at t1 and later developed CBP or not were pain intensity, body mass index, and depression score. In sum, these findings are in accordance with the notion that limbic brain properties are both predisposing risk factors and drivers of brain reorganization during the development of CBP.

Impact of growth hormone-secreting pituitary adenoma on limbic system and its correlation with cognitive impairment

PurposeTo assess the quantitative gray matter volume of the limbic system in growth hormone-secreting pituitary adenoma (GHPAs) patients and its correlation to cognitive function. Method91 right-handed patients with pituitary adenomas were retrospectively included from the First Affiliated Hospital of Sun Yat-sen University −48 with GHPAs and 43 with non-functioning pituitary adenomas (NFPAs). Participants underwent serum hormone assessment, regular sellar MRI scanning with T1WI-MPRAGE. Cognitive function was gauged using MoCA and MMSE. Brain region auto-segmentation and gray matter volume calculation were conducted on the Brainsite platform. ResultsCompared to NFPAs patients, GHPAs patients had higher gray matter volume (758,285 vs 674,610 mm³, p < 0.001). No significant volumetric differences in both sides of limbic system gray matter while there were evident differences in the relative volumes of limbic system gray matter between groups. GHPAs patients scored lower on MOCA (24.0 (2.18) vs 25.1 (2.28), p < 0.031), with no difference in MMSE. We observed a significant correlation between the relative limbic volume and MOCA scales, while no evident correlation was found between relative limbic volume and serum hormone or tumor aggressiveness. Univariate and multivariate Logistic regression showed that hippocampus and limbic cortex (parahippocampal gyrus and internal olfactory area) of advantageous hemisphere correlated significantly with occurrence of mild cognitive impairment with the C-statistic reaching 0.90. ConclusionPatients with GHPAs show a relative decrease in limbic gray matter volume, especially in the hippocampus and limbic cortex of the dominant hemisphere, which is associated with mild cognitive impairment.

Investigating grey matter volumetric trajectories through the lifespan at the individual level

Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14–23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV). Group 1 show continuously decreasing GMV associated with higher neurocognitive performances than the other two groups during adolescence. Group 2 exhibit a slower rate of GMV decrease and lower neurocognitive performances compared with Group 1, which was associated with epigenetic differences and greater environmental burden. Group 3 show increasing GMV and lower baseline neurocognitive performances due to a genetic variation. Using the UK Biobank, we show these differences may be attenuated in mid-to-late adulthood. Our study reveals clusters of adolescent neurodevelopment based on GMV and the potential long-term impact.

Neuroprotective Effects of Inhaled Xenon Gas on Brain Structural Gray Matter Changes After Out-of-Hospital Cardiac Arrest Evaluated by Morphometric Analysis: A Substudy of the Randomized Xe-Hypotheca Trial.

We have earlier reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). A predefined secondary objective was to assess the effect of inhaled xenon on the structural changes in gray matter in comatose survivors after OHCA. Patients were randomly assigned to receive either inhaled xenon combined with target temperature management (33°C) for 24h (n = 55, xenon group) or target temperature management alone (n = 55, control group). A change of brain gray matter volume was assessed with a voxel-based morphometry evaluation of high-resolution structural brain magnetic resonance imaging (MRI) data with Statistical Parametric Mapping. Patients were scheduled to undergo the first MRI between 36 and 52h and a second MRI 10days after OHCA. Of the 110 randomly assigned patients in the Xe-Hypotheca trial, 66 patients completed both MRI scans. After all imaging-based exclusions, 21 patients in the control group and 24 patients in the xenon group had both scan 1 and scan 2 available for analyses with scans that fulfilled the quality criteria. Compared with the xenon group, the control group had a significant decrease in brain gray matter volume in several clusters in the second scan compared with the first. In a between-group analysis, significant reductions were found in the right amygdala/entorhinal cortex (p = 0.025), left amygdala (p = 0.043), left middle temporal gyrus (p = 0.042), left inferior temporal gyrus (p = 0.008), left parahippocampal gyrus (p = 0.042), left temporal pole (p = 0.042), and left cerebellar cortex (p = 0.005). In the remaining gray matter areas, there were no significant changes between the groups. In comatose survivors of OHCA, inhaled xenon combined with targeted temperature management preserved gray matter better than hypothermia alone. ClinicalTrials.gov: NCT00879892.

Characterization of gray matter volume changes from one week to 6 months after termination of electroconvulsive therapy in depressed patients

BackgroundIncreased gray matter volume (GMV) following electroconvulsive therapy (ECT) has been well-documented, with limited studies reporting a subsequent decrease in GMV afterwards. ObjectiveThis study characterized the reversion pattern of GMV after ECT and its association with clinical depression outcome, using multi-site triple time-point data from the Global ECT-MRI Research Collaboration (GEMRIC). Methods86 subjects from the GEMRIC database were included, and GMV in 84 regions-of-interest (ROI) was obtained from automatic segmentation of T1 MRI images at three timepoints: pre-ECT (T0), within one-week post-ECT (T1), and one to six months post-ECT (T2). RM-ANOVAs were used to assess longitudinal changes and LMM analyses explored associations between GMV changes and demographical and clinical characteristics. Results63 of the 84 ROIs showed a significant increase-and-decrease pattern (RM-ANOVA, Bonferroni corrected p < 0.00059). Post hoc tests indicated a consistent pattern in each of these 63 ROIs: significant increase from T0 to T1inGMV, followed by significant decrease from T1 to T2 and no difference between T0 and T2, except for both amygdalae, right hippocampus and pars triangularis, which showed the same increase and decrease but GMV at T2 remained higher compared to T0. No consistent relationship was found between GMV change pattern and clinical status. ConclusionThe GEMRIC cohort confirmed a rapid increase of GMV after ECT followed by reversion of GMV one to six months thereafter. The lack of association between the GMV change pattern and depression outcome scores implies a transient neurobiological effect of ECT unrelated to clinical improvement.

Gray matter alterations in Huntington's disease: A meta-analysis of VBM neuroimaging studies.

Increasing neuroimaging studies have attempted to identify biomarkers of Huntington's disease (HD) progression. Here, we conducted voxel-based meta-analyses of voxel-based morphometry (VBM) studies on HD to investigate the evolution of gray matter volume (GMV) alterations and explore the effects of genetic and clinical features on GMV changes. A systematic review was performed to identify the relevant studies. Meta-analyses of whole-brain VBM studies were performed to assess the regional GMV changes in all HD mutation carriers, in presymptomatic HD (pre-HD), and in symptomatic HD (sym-HD). A quantitative comparison was performed between pre-HD and sym-HD. Meta-regression analyses were used to explore the effects of genetic and clinical features on GMV changes. Twenty-eight studies were included, comparing a total of 1811 HD mutation carriers [including 1150 pre-HD and 560 sym-HD] and 969 healthy controls (HCs). Pre-HD showed decreased GMV in the bilateral caudate nuclei, putamen, insula, anterior cingulate/paracingulate gyri, middle temporal gyri, and left dorsolateral superior frontal gyrus compared with HCs. Compared with pre-HD, GMV decrease in sym-HD extended to the bilateral median cingulate/paracingulate gyri, Rolandic operculum and middle occipital gyri, left amygdala, and superior temporal gyrus. Meta-regression analyses found that age, mean lengths of CAG repeats, and disease burden were negatively associated with GMV atrophy of the bilateral caudate and right insula in all HD mutation carriers. This meta-analysis revealed the pattern of GMV changes from pre-HD to sym-HD, prompting the understanding of HD progression. The pattern of GMV changes may be biomarkers for disease progression in HD.