Putamen Volume Research Articles

Cardiovascular health, infection burden and their interactive association with brain volumetric and white matter integrity outcomes in the UK Biobank

BackgroundCardiovascular health is associated with brain magnetic resonance imaging (MRI) markers of pathology and infections may modulate this association. MethodsUsing data from 38,803 adults (aged 40–70 years) and followed-up for 5–15 years, we tested associations of prevalent total (47.5%) and hospital-treated infection burden (9.7%) with brain structural and diffusion-weighted MRI (i.e., sMRI and dMRI, respectively) common in dementia phenome. Poor white matter tissue integrity was operationalized with lower global and tract-specific fractional anisotropy (FA) and higher mean diffusivity (MD). Volumetric sMRI outcomes included total, gray matter (GM), white matter (WM), frontal bilateral GM, white matter hyperintensity (WMH), and selected based on previous associations with dementia. Cardiovascular health was measured with Life’s Essential 8 score (LE8) converted to tertiles. Multiple linear regression models were used, adjusting for intracranial volumes (ICV) for subcortical structures, and for demographic, socio-economic, and the Alzheimer’s Disease polygenic risk score for all outcomes, among potential confounders. ResultsIn fully adjusted models, hospital-treated infections were inversely related to GM (β ± SE: −1042 ± 379, p = 0.006) and directly related to WMH as percent of ICV (Loge transformed) (β ± SE:+0.026 ± 0.007, p < 0.001). Both total and hospital-treated infections were associated with poor WMI, while the latter was inversely related to FA within the lowest LE8 tertile (β ± SE:-0.0011 ± 0.0003, p < 0.001, PLE8×IB < 0.05), a pattern detected for GM, Right Frontal GM, left accumbens and left hippocampus volumes. Within the uppermost LE8 tertile, total infection burden was linked to smaller right amygdala while being associated with larger left frontal GM and right putamen volumes, in the overall sample. Within that uppermost tertile of LE8, caudate volumes were also positively associated with hospital-treated infections. ConclusionsHospital-treated infections had more consistent deleterious effects on volumetric and white matter integrity brain neuroimaging outcomes compared with total infectious burden, particularly in poorer cardiovascular health groups. Further studies are needed in comparable populations, including longitudinal studies with multiple repeats on neuroimaging markers.

Characterizing gait and exploring neuro-morphometry in patients with PSP-Richardson's syndrome and vascular parkinsonism

Gait differentiation in progressive supranuclear palsy (PSP) and vascular parkinsonism (VaP) is sometimes difficult to detect with the naked eye. Here, we compared specific gait parameters, neuro-morphometric indices, and their associations between patients with PSP Richardson's syndrome (PSP-RS) and VaP. A total of 18 PSP-RS and 13 VaP patients were recruited. Spatio-temporal gait parameters (GAITRite®) and neuroanatomical morphometry (FreeSurfer pipeline) were assessed. The groups were compared using unpaired t-tests involving 10000 random permutations after statistically controlling for total UPDRS-III and H&Y scores. Statistically significant differences between the groups were decided at < 5% Benjamini-Hochberg False Discovery Rate (FDR) for multiple-comparison related corrections. Spearman's correlations were performed to assess the significant associations (p < 0.05) between the gait parameters and morphometry indices. Among all the spatio-temporal gait parameters, PSP-RS patients displayed greater stride time, step time, swing time, and stance time variabilities compared to VaP. Morphometric analyses showed that thalamus, and caudate volumes were significantly lower, but cerebellar cortex, hippocampus, amygdala, accumbens, and putamen volumes were higher in PSP-RS than VaP. Moreover, the bilateral insula was significantly thinner in VaP than in PSP-RS. Correlation analyses support the involvement of limbic structures besides cerebellum in postural control during self-paced walking of PSP-RS patients. Our findings underline the importance of examining individual brain regions to understand the association of cortical and subcortical morphometric estimates and gait variability parameters in PSP-RS and VaP. This study suggests the involvement of the limbic system in addition to the classical neural structures for motor control and gait.

The Endophenotypic Effect of the SORL1 Variant rs2298813 on Regional Brain Volume in Patients with Alzheimer’s Disease

AbstractBackgroundTwo common variants of sortilin‐related receptor 1 gene (SORL1), rs2298813 and rs1784933, have been associated with late‐onset Alzheimer’s disease (AD) in the Han Chinese population in Taiwan. However, neuroimaging correlates of these two SORL1 variants remain unknown. We aimed to determine whether the two SORL1 polymorphisms were associated with any volumetric differences in brain regions in AD patients.MethodsWe recruited 200 patients with late‐onset AD from Taipei Veterans General Hospital. All patients received a structural magnetic resonance imaging brain scan and completed a battery of neurocognitive tests at enrollment. We followed up to assess changes in Mini‐Mental State Examination (MMSE) scores in 155 patients (77.5%) at an interval of 2 years. Volumetric measures and cortical thickness of various brain regions were performed using FreeSurfer. Regression analysis controlled for apolipoprotein E status. Multiple comparisons were corrected for using the false discovery rate.ResultThe rs2298813 and rs1783933 genotypes were not associated with cognitive test performance or clinical progression. The homozygous major allele of rs2298813 was associated with larger volumes in the right putamen (p = 0.0442) and right pallidum (p = 0.0346). There was no link of the rs1784933 genotypes with any of the imaging measures. In the rs2298813 homozygous major allele carriers, the right putaminal volume was associated with verbal fluency (p = 0.008) and clinical progression (p = 0.020). In the minor allele carriers, the right putaminal and right pallidal volumes were not significantly related to cognitive test scores or clinical progression.ConclusionThe major and minor alleles of rs2298813 had differential effects on the right lentiform nucleus volume and distinctively modulated the association between the regional volume and cognitive function.

0912 Striatal atrophy and clinical correlates in REM sleep behavior disorder

Abstract Introduction Idiopathic/isolated REM sleep behavior disorder (iRBD) is regarded as the most specific prodromal stage of ⍺-synucleinopathies including Parkinson’s disease (PD). Striatal dopamine dysfunction is a pathological hallmark in PD, which has been similarly reported in iRBD as a sensitive marker for detecting early ⍺-synucleinopathies. In contrary, although there is a broad consensus that patients with PD have striatal volumes reduction, studies in iRBD are relatively scarce and inconsistent. In this study, we aim to investigate the difference of striatal nuclei volumes between iRBD and controls and their correlation with clinical presentations. Methods Altogether 105 patients (mean age=68.19, male 76.2%) with polysomnography-confirmed iRBD and 85 age and sex comparable controls (mean age=66.74, male 64.7%) underwent 3-tesla MRI and clinical assessments. FreeSurfer automatic segmentation pipelines measured the size of bilateral striatal nuclei including caudate, putamen, pallidum and accumbens area. The comparisons of the volume of individual striatal nucleus were made between iRBD and controls with age, sex, handness, and total intracranial volume as covariates. Correlations were performed to investigate the association between striatal nuclei volume and clinical domains in motor (Unified Parkinson’s Disease Rating Scale, Part III), cognitive (Montreal Cognitive Assessment, MoCA), visual (pareidolia), autonomic function (Scales for Outcomes in Parkinson’s Disease - Autonomic Dysfunction, SCOPA-AUT) and mood symptoms (Hospital Anxiety and Depression Scale). Results There were smaller volumes in the bilateral putamen (t=-2.13/-2.32, p=0.03/0.02, left/right side respectively) and accumbens area (t=-2.58/-2.07, p=0.01/0.04, left/right side respectively) in iRBD comparing to controls. In addition, MoCA score was significantly positively correlated with the volumes of bilateral putamen (r=0.212/0.213, p=0.032/0.033), while pareidolia score was significantly negatively correlated with volumes of bilateral putamen (r=-0.205/-0.233, p=0.039/0.018,) and accumbens area (r=-0.249/-0.279, p=0.012/0.004, left/right respectively). The SCOPA-AUT score was significantly negatively correlated with volumes of the left putamen (r=-0.286, p=0.014) and the left accumbens area (r=-0.245, p=0.037). No other correlations with mood and motor features were found. Conclusion In this large case-control study, PD-like striatal atrophy was already present in patients with iRBD, which were significantly associated with worse cognitive performance, visual and autonomic dysfunction. Support (if any) This study was supported by Hong Kong Health and Medical Research Fund, 08191416.

Intrauterine exposure to chorioamnionitis and neuroanatomical alterations at term-equivalent age in preterm infants.

Infants born to mothers with chorioamnionitis (CAM) are at increased risk of developing adverse neurodevelopmental disorders in later life. However, clinical magnetic resonance imaging (MRI) studies examining brain injuries and neuroanatomical alterations attributed to CAM have yielded inconsistent results. We aimed to determine whether exposure to histological CAM in utero leads to brain injuries and alterations in the neuroanatomy of preterm infants using 3.0- Tesla MRI at term-equivalent age. A total of 58 preterm infants born before 34weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible for this study (CAM group, n = 21; non-CAM group, n = 37). Brain injuries and abnormalities were assessed using the Kidokoro Global Brain Abnormality Scoring system. Gray matter, white matter, and subcortical gray matter (thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) volumes were evaluated using segmentation tools (SPM12 and Infant FreeSurfer). The Kidokoro scores for each category and severity in the CAM group were comparable to those observed in the non-CAM group. White matter volume was significantly smaller in the CAM group after adjusting for covariates (postmenstrual age at MRI, infant sex, and gestational age) (p = 0.007), whereas gray matter volume was not significantly different. Multiple linear regression analyses revealed significantly smaller volumes in the bilateral pallidums (right, p = 0.045; left, p = 0.038) and nucleus accumbens (right, p = 0.030; left, p = 0.004) after adjusting for covariates. Preterm infants born to mothers with histological CAM showed smaller volumes in white matter, pallidum, and nucleus accumbens at term-equivalent age.

Shared molecular genetic factors influence subcortical brain morphometry and Parkinson’s disease risk

Parkinson’s disease (PD) is a late-onset and genetically complex neurodegenerative disorder. Here we sought to identify genes and molecular pathways underlying the associations between PD and the volume of ten brain structures measured through magnetic resonance imaging (MRI) scans. We leveraged genome-wide genetic data from several cohorts, including the International Parkinson’s Disease Genomics Consortium (IPDG), the UK Biobank, the Adolescent Brain Cognitive Development (ABCD) study, the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the Enhancing Neuroimaging Genetics through Meta-Analyses (ENIGMA), and 23andMe. We observed significant positive genetic correlations between PD and intracranial and subcortical brain volumes. Genome-wide association studies (GWAS) - pairwise analyses identified 210 genomic segments with shared aetiology between PD and at least one of these brain structures. Pathway enrichment results highlight potential links with chronic inflammation, the hypothalamic-pituitary-adrenal pathway, mitophagy, disrupted vesicle-trafficking, calcium-dependent, and autophagic pathways. Investigations for putative causal genetic effects suggest that a larger putamen volume could influence PD risk, independently of the potential causal genetic effects of intracranial volume (ICV) on PD. Our findings suggest that genetic variants influencing larger intracranial and subcortical brain volumes, possibly during earlier stages of life, influence the risk of developing PD later in life.

Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model

Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pediatric disease, with symptom development leading to clinical diagnosis. Early diagnosis and effective tracking of disease progression are required for treatment. We hypothesize that brain volumetry is valuable in identifying CLN2 disease at an early stage and tracking disease progression in a genetically modified miniswine model. CLN2R208X/R208X miniswine and wild type controls were evaluated at 12- and 17-months of age, correlating to early and late stages of disease progression. Magnetic resonance imaging (MRI) T1- and T2-weighted data were acquired. Total intercranial, gray matter, cerebrospinal fluid, white matter, caudate, putamen, and ventricle volumes were calculated and expressed as proportions of the intracranial volume. The brain regions were compared between timepoints and cohorts using Gardner-Altman plots, mean differences, and confidence intervals. At an early stage of disease, the total intracranial volume (− 9.06 cm3), gray matter (− 4.37% 95 CI − 7.41; − 1.83), caudate (− 0.16%, 95 CI − 0.24; − 0.08) and putamen (− 0.11% 95 CI − 0.23; − 0.02) were all notably smaller in CLN2R208X/R208X miniswines versus WT, while cerebrospinal fluid was larger (+ 3.42%, 95 CI 2.54; 6.18). As the disease progressed to a later stage, the difference between the gray matter (− 8.27%, 95 CI − 10.1; − 5.56) and cerebrospinal fluid (+ 6.88%, 95 CI 4.31; 8.51) continued to become more pronounced, while others remained stable. MRI brain volumetry in this miniswine model of CLN2 disease is sensitive to early disease detection and longitudinal change monitoring, providing a valuable tool for pre-clinical treatment development and evaluation.

Sparring and the Brain: The Associations between Sparring and Regional Brain Volumes in Professional Mixed Martial Arts Fighters.

Mixed martial arts (MMA) fighters, due to exposure to repetitive head impacts, are at risk for brain atrophy and neurodegenerative sequelae. Simultaneously, motor skills training and cognition-rich activities have been linked with larger regional brain volumes. The majority of an MMA fighter's sporting activity occurs during practice (e.g., sparring) rather than formal competition. This study, therefore, aims to be the first to explore regional brain volumes associated with sparring in MMA fighters. Ninety-four active, professional MMA fighters from the Professional Fighters Brain Health Study met inclusion criteria for this cross-sectional analysis. Adjusted multivariable regression analyses were utilized to examine the relationship between the number of sparring practice rounds per week during typical training and a select number of regional brain volumes (i.e., caudate, thalamus, putamen, hippocampus, amygdala). A higher number of weekly sparring rounds during training was significantly associated with larger left (beta = 13.5µL/round, 95%CI 2.26-24.8) and right (beta = 14.9µL/round, 95%CI 3.64-26.2) caudate volumes. Sparring was not significantly associated with left or right thalamus, putamen, hippocampus, or amygdala volumes. More weekly rounds of sparring was not significantly associated with smaller volumes in any of the brain regions studied in active, professional MMA fighters. Sparring's significant association with larger caudate volume raises questions about whether fighters who spar more experience attenuated trauma-related decreases in caudate volume relative to fighters who spar less, whether fighters who spar more experience minimal or even positive changes to caudate volume, whether baseline differences in caudate size may have mediated results, or whether some other mechanism may be at play. Given limitations inherent to the cross-sectional study design, more research is needed to further explore the brain effects of sparring in MMA.

Maternal ART throughout gestation prevents caudate volume reductions in neonates who are HIV exposed but uninfected.

Successful programmes for prevention of vertical HIV transmission have reduced the risk of infant HIV infection in South Africa from 8% in 2008 to below 1% in 2018/2019, resulting in an increasing population of children exposed to HIV perinatally but who are uninfected (HEU). However, the long-term effects of HIV and antiretroviral treatment (ART) exposure on the developing brain are not well understood. Whereas children who are HEU perform better than their HIV-infected counterparts, they demonstrate greater neurodevelopmental delay than children who are HIV unexposed and uninfected (HUU), especially in resource-poor settings. Here we investigate subcortical volumetric differences related to HIV and ART exposure in neonates. We included 120 infants (59 girls; 79 HEU) born to healthy women with and without HIV infection in Cape Town, South Africa, where HIV sero-prevalence approaches 30%. Of the 79 HEU infants, 40 were exposed to ART throughout gestation (i.e., mothers initiated ART pre conception; HEU-pre), and 39 were exposed to ART for part of gestation (i.e., mothers initiated ART post conception; HEU-post). Post-conception mothers had a mean (± SD) gestational age (GA) of 15.4 (± 5.7) weeks at ART initiation. Mothers with HIV received standard care fixed drug combination ART (Tenofovir/Efavirenz/Emtricitabine). Infants were imaged unsedated on a 3T Skyra (Siemens, Erlangen, Germany) at mean GA equivalent of 41.5 (± 1.0) weeks. Selected regions (caudate, putamen, pallidum, thalamus, cerebellar hemispheres and vermis, and corpus callosum) were manually traced on T1-weighted images using Freeview. HEU neonates had smaller left putamen volumes than HUU [β (SE) = -90.3 (45.3), p = 0.05] and caudate volume reductions that depended on ART exposure duration in utero. While the HEU-pre group demonstrated no caudate volume reductions compared to HUU, the HEU-post group had smaller caudate volumes bilaterally [β (SE) = -145.5 (45.1), p = 0.002, and -135.7 (49.7), p = 0.008 for left and right caudate, respectively]. These findings from the first postnatal month suggest that maternal ART throughout gestation is protective to the caudate nuclei. In contrast, left putamens were smaller across all HEU newborns, despite maternal ART.

Effectiveness of ocrelizumab on clinical and MRI outcome measures in multiple sclerosis across black and white cohorts: A single-center retrospective study.

To examine differences in the therapeutic response to ocrelizumab in multiple sclerosis (MS) patients who self-identified as either White or Black, assessed longitudinally by expanded disability status scale (EDSS) progression and MRI brain volume loss. MS subjects treated with ocrelizumab were retrospectively identified. Clinical data were available for 229 subjects (White 146; Black 83) and MRI data from for 48 subjects (White 31; Black 17). Outcome measures were changes in the EDSS and brain volume over time. EDSS were analyzed as raw scores, ambulatory (EDSS <5.0) vs. ambulatory with assistance (5.5 ≤ EDSS ≤ 6.5) status, and EDSS severity (< 3.0, 3.0-5.0, and > 5.5 ≤ 6.5). General linear mixed model was used for statistical analysis. FreeSurfer was used for volumetric analysis. The Black cohort had overrepresentation of females (78% vs. 62%, p=0.013), lower age (median, 45 (IQR 39-51) vs. 49 (38-58), p=0.08), lower Vitamin D levels (33 (21-45) vs. 40 (29-52), p=0.002), and higher EDSS (4 (2-6) vs. 2.5 (1-6), p=0.019). There was no progression of EDSS scores over the 2-year observation period. The covariates with significant influence on the baseline EDSS scores were older age, race, longer disease duration, prior MS treatment, and lower vitamin D levels. No differences were observed between the racial groups over time in the cortical, thalamic, caudate, putamen, and brainstem gray matter volumes nor in the cortical thickness or total lesion volume. In this real-world clinical and radiological study, ocrelizumab treatment was highly effective in stabilizing clinical and MRI measures of disease progression in Blacks and Whites, despite higher baseline disability in the Black cohort.

Dynamic effects of bilingualism on brain structure map onto general principles of experience-based neuroplasticity

Bilingualism has been linked to structural adaptations of subcortical brain regions that are important for controlling multiple languages. However, research on the location and extent of these adaptations has yielded variable patterns, especially as far as the subcortical regions are concerned. Existing literature on bilingualism-induced brain restructuring has so far largely overseen evidence from other domains showing that experience-based structural neuroplasticity often triggers non-linear adaptations which follow expansion-renormalisation trajectories. Here we use generalised additive mixed models to investigate the non-linear effects of quantified bilingual experiences on the basal ganglia and the thalamus in a sample of bilinguals with a wide range of bilingual experiences. Our results revealed that volumes of the bilateral caudate nucleus and nucleus accumbens were significantly related to bilingual experiences. Importantly, these followed a non-linear pattern, with increases followed by plateauing in the most experienced bilinguals, suggesting that experience-based volumetric increases are only necessary up to a certain level of bilingual experience. Moreover, the volumes of putamen and thalamus were positively predicted by bilingual experiences. The results offer the first direct evidence that bilingualism, similarly to other cognitively demanding skills, leads to dynamic subcortical structural adaptations which can be nonlinear, in line with expansion-renormalisation models of experience-dependent neuroplasticity.

Apathy is associated with striatal atrophy and cognitive impairment in cerebral small vessel disease

BackgroundApathy has been considered a common neuropsychiatric symptom and an important contributor to cognitive impairment in cerebral small vessel disease (SVD). However, the mechanism leading to apathy in SVD and the process whereby apathy promotes cognitive impairments remain largely unknown. We aimed to explore the relationship between apathy, cognition, and structural changes of deep grey matter (DGM) in SVD patients. MethodsParticipants were screened for SVD, completed assessments of apathy cognition, underwent magnetic resonance imaging (MRI) scanning, and then stratified into apathy and non-apathy groups. We used region of interest (ROI)-based, voxel-based volume, and vertex-based shape analyses to compare DGM structures between study groups. Using linear regression analysis, we examined the association between apathy, structural changes, and cognition, followed by a mediation analysis of these factors. ResultsA total of sixty-four SVD participants were included, with thirty in the apathy group and thirty-four in the non-apathy group. Intergroup comparison showed significantly lower volumes in bilateral caudate, right putamen, and pallidum and smaller vertex-based shapes in the right caudate and pallidum in participants with apathy compared to those without apathy. Apathy was associated with the striatal atrophy (i.e., lower volumes and smaller shape) and independently contributed to cognitive impairments in SVD. However, the above structural differences did not mediate the association between apathy and cognitive impairments. ConclusionThese results highlight the important role of striatal atrophy in apathy in SVD and call for additional studies to explore the relationship between apathy, cognition, and DGM.

Altered gray matter volume and functional connectivity in adolescent borderline personality disorder with non-suicidal self-injury behavior.

Non-suicidal self-injury (NSSI) behavior is one of the characteristics of borderline personality disorder (BPD) in adolescents. Prior studies have shown that adolescents with BPD may have a unique pattern of brain alterations. The purpose of this study was to investigate the alterations in brain structure and function including gray matter volume and resting-state functional connectivity in adolescents with BPD, and to assess the association between NSSI behavior and brain changes on neuroimaging in adolescents with BPD. 53 adolescents with BPD aged 12-17years and 39 age-gender matched healthy controls (HCs) were enrolled into this study. Brain magnetic resonance imaging (MRI) was acquired with both 3D-T1 weighted structural imaging and resting-state functional imaging. Voxel-based morphometry (VBM) analysis for gray matter volume and seed-based functional connectivity (FC) analysis were performed for assessing gray matter volume and FC. Clinical assessment for NSSI, mood, and depression was also obtained. Correlative analysis of gray matter alterations with self-injury or mood scales were performed. There were reductions of gray matter volume in the limbic-cortical circuit and default mode network in adolescents with BPD as compared to HCs (FWE P < 0.05, cluster size ≥ 1000). The diminished gray matter volumes in the left putamen and left middle occipital gyrus were negatively correlated with NSSI in adolescents with BPD (r = -0.277 and P = 0.045, r = -0.422 and P = 0.002, respectively). Furthermore, there were alterations of FC in these two regions with diminished gray matter volumes (voxel P < 0.001, cluster P < 0.05, FWE corrected). Our results suggest that diminished gray matter volume of the limbic-cortical circuit and default mode network may be an important neural correlate in adolescent BPD. In addition, the reduced gray matter volume and the altered functional connectivity may be associated with NSSI behavior in adolescents with BPD.

Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

BackgroundTourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year. MethodsWe performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants. ResultsWe identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. ConclusionsOur work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.

Deep gray matter substructure volumes and depressive symptoms in a large multiple sclerosis cohort

Background Consistent findings on underlying brain features or specific structural atrophy patterns contributing to depression in multiple sclerosis (MS) are limited. Objective To investigate how deep gray matter (DGM) features predict depressive symptom trajectories in MS patients. Methods We used data from the MS Partners Advancing Technology and Health Solutions (MS PATHS) network in which standardized patient information and outcomes are collected. We performed whole-brain segmentation using SLANT-CRUISE. We assessed if DGM structures were associated with elevated depressive symptoms over follow-up and with depressive symptom phenotypes. Results We included 3844 participants (average age: 46.05 ± 11.83 years; 72.7% female) of whom 1905 (49.5%) experienced ⩾1 periods of elevated depressive symptoms over 2.6 ± 0.9 years mean follow-up. Higher caudate, putamen, accumbens, ventral diencephalon, thalamus, and amygdala volumes were associated with lower odds of elevated depressive symptoms over follow-up (odds ratio (OR) range per 1 SD (standard deviation) increase in volume: 0.88–0.94). For example, a 1 SD increase in accumbens or caudate volume was associated with 12% or 10% respective lower odds of having a period of elevated depressive symptoms over follow-up (for accumbens: OR: 0.88; 95% confidence interval (CI): 0.83–0.93; p < 0.001; for caudate: OR: 0.90; 95% CI: 0.85–0.96; p = 0.003). Conclusion Lower DGM volumes were associated with depressive symptom trajectories in MS.

Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group.

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.

Transdiagnostic brain correlates of self-reported trait impulsivity: A dimensional structure-symptom investigation

Impulsivity transcends psychiatric diagnoses and is often related to anhedonia. This ad hoc cross-sectional investigation explored 1) whether self-reported trait impulsivity mapped onto a common structural brain substrate across healthy controls (HCs) and psychiatric patients, and 2) in a more exploratory fashion, whether impulsivity and anhedonia were related to each other and shared overlapping brain correlates. Structural magnetic resonance imaging (sMRI) datasets from 234 participants including HCs (n = 109) and patients with opioid use disorder (OUD, n = 22), cocaine use disorder (CUD, n = 43), borderline personality disorder (BPD, n = 45) and schizophrenia (SZ, n = 15) were included. Trait impulsivity was measured with the Barratt Impulsiveness Scale (BIS-11) and anhedonia with a subscore of the Beck Depression Inventory (BDI). BIS-11 global score data were available for the entire sample, while data on the BIS-11 2nd order factors attentional, motor and non-planning were additionally in hand for a subsample consisting of HCs, OUD and BPD patients (n = 116). Voxel-based morphometry analyses were conducted for identifying dimensional associations between grey matter volume and impulsivity/anhedonia. Partial correlations were further performed to exploratory test the relationships between impulsivity and anhedonia and their corresponding volumetric brain substrates. Volume of the left opercular part of the inferior frontal gyrus (IFG) was negatively related to global impulsivity across the entire sample and specifically to motor impulsivity in the subsample of HCs, OUD and BPD patients. Across patients anhedonia expression was negatively correlated with left putamen volume. Although there was no relationship between global impulsivity and anhedonia across all patients, only across OUD and BPD patients anhedonia was positively associated with attentional impulsivity. Finally, also across OUD and BPD patients, motor impulsivity associated left IFG volume was positively linked with anhedonia-associated volume in the left putamen. Our findings suggest a critical role of left IFG volume in self-reported global impulsivity across healthy participants and patients with substance use disorder, BPD and SZ. Preliminary findings in OUD and BPD patients further suggests associations between impulsivity and anhedonia that are related to grey matter reductions in the left IFG and putamen.

Subcortical volumes in cerebral amyloid angiopathy compared with Alzheimer's disease and controls.

Previous reports have suggested that patients with cerebral amyloid angiopathy (CAA) may harbor smaller white matter, basal ganglia, and cerebellar volumes compared to age-matched healthy controls (HC) or patients with Alzheimer's disease (AD). We investigated whether CAA is associated with subcortical atrophy. The study was based on the multi-site Functional Assessment of Vascular Reactivity cohort and included 78 probable CAA (diagnosed according to the Boston criteria v2.0), 33 AD, and 70 HC. Cerebral and cerebellar volumes were extracted from brain 3D T1-weighted MRI using FreeSurfer (v6.0). Subcortical volumes, including total white matter, thalamus, basal ganglia, and cerebellum were reported as proportion (%) of estimated total intracranial volume. White matter integrity was quantified by the peak width of skeletonized mean diffusivity. Participants in the CAA group were older (74.0 ± 7.0, female 44%) than the AD (69.7 ± 7.5, female 42%) and HC (68.8 ± 7.8, female 69%) groups. CAA participants had the highest white matter hyperintensity volume and worse white matter integrity of the three groups. After adjusting for age, sex, and study site, CAA participants had smaller putamen volumes (mean differences, -0.024% of intracranial volume; 95% confidence intervals, -0.041% to -0.006%; p = 0.005) than the HCs but not AD participants (-0.003%; -0.024 to 0.018%; p = 0.94). Other subcortical volumes including subcortical white matter, thalamus, caudate, globus pallidus, cerebellar cortex or cerebellar white matter were comparable between all three groups. In contrast to prior studies, we did not find substantial atrophy of subcortical volumes in CAA compared to AD or HCs, except for the putamen. Differences between studies may reflect heterogeneity in CAA presenting syndromes or severity.

Family income buffers the relationship between childhood adverse experiences and putamen volume.

Adverse experiences and family income in childhood have been associated with altered brain development. While there is a large body of research examining these associations, it has primarily used cross-sectional data sources and studied adverse experiences and family income in isolation. However, it is possible that low family income and adverse experiences represent dissociable and potentially interacting profiles of risk. To address this gap in the literature, we examined brain structure as a function of adverse experiences in childhood and family income in 158 youths with up to five waves of MRI data. Specifically, we assessed the interactive effect of these two risk factors on six regions of interest: hippocampus, putamen, amygdala, nucleus accumbens, caudate, and thalamus. Adverse experiences and family income interacted to predict putamen volume (B = 0.086, p = 0.011) but only in participants with family income one standard deviation below the mean (slope estimate = -0.11, p = 0.03). These results suggest that adverse experiences in childhood result in distinct patterns of brain development across the socioeconomic gradient. Given previous findings implicating the role of the putamen in psychopathology-related behaviors, these results emphasize the importance of considering life events and socioeconomic context when evaluating markers of risk. Future research should include interactive effects of environmental exposures and family income to better characterize risk for psychopathology in diverse samples.

Local striatal volume and motor reserve in drug-naïve Parkinson’s disease

Motor reserve (MR) may explain why individuals with similar pathological changes show marked differences in motor deficits in Parkinson’s disease (PD). In this study, we investigated whether estimated individual MR was linked to local striatal volume (LSV) in PD. We analyzed data obtained from 333 patients with drug naïve PD who underwent dopamine transporter scans and high-resolution 3-tesla T1-weighted structural magnetic resonance images. Using a residual model, we estimated individual MRs on the basis of initial UPDRS-III score and striatal dopamine depletion. We performed a correlation analysis between MR estimates and LSV. Furthermore, we assessed the effect of LSV, which is correlated with MR estimates, on the longitudinal increase in the levodopa-equivalent dose (LED) during the 4-year follow-up period using a linear mixed model. After controlling for intracranial volume, there was a significant positive correlation between LSV and MR estimates in the bilateral caudate, anterior putamen, and ventro-posterior putamen. The linear mixed model showed that the large local volume of anterior and ventro-posterior putamen was associated with the low requirement of LED initially and accelerated LED increment thereafter. The present study demonstrated that LSV is crucial to MR in early-stage PD, suggesting LSV as a neural correlate of MR in PD.