Gray Matter Volume Decrease Research Articles

Progressive brain structural abnormality in cerebral small vessel disease assessed with MR imaging by using causal network analysis

AimsCerebral small vessel disease (CSVD) is a complex condition characterized by a combination of microcirculation disorders and neurodegenerative processes, CSVD is associated with structural abnormalities in multiple brain regions. However, the progressive pattern of structural changes remains unknown. MethodsIn order to detail the progressive structural changes in CSVD patients according to the degree of cognitive impairment, we recruited 121 CSVD patients and 104 healthy controls (HCs). Voxel-based morphometry was employed to measure the gray matter volume (GMV) of each participant. According to the VICCCS-2 diagnostic criteria, patients were initially divided into three stage groups, then we investigated the GMV changes in each stage and their causal relationships using causal structure covariance network (CaSCN) analysis. ResultsOverall, patients with CSVD presented stage-specific GMV alterations compared with HCs. With the worsening of cognitive impairment, the decrease in gray matter volume starts from the right hippocampus and gradually spreads to the cortical-subcortical brain regions. Importantly, the right hippocampus in CSVD patients plays a driving role in the directional network and forms both positive and negative causal effect networks with cortical-subcortical brain regions. ConclusionsThis study reveals the significance of the right hippocampus as an early pathological area in CSVD patients and its causal impact on brain GMV changes with disease progression, shedding light on structural brain damage hierarchy and compensatory mechanisms.

Changes in cortical grey matter volume with Cognitive Orientation to daily Occupational Performance intervention in children with developmental coordination disorder.

Cognitive Orientation to daily Occupational Performance (CO-OP) is a cognitive-based, task-specific intervention recommended for children with developmental coordination disorder (DCD). We recently showed structural and functional brain changes after CO-OP, including increased cerebellar grey matter. This study aimed to determine whether CO-OP intervention induced changes in cortical grey matter volume in children with DCD, and if these changes were associated with improvements in motor performance and movement quality. This study is part of a randomized waitlist-control trial (ClinicalTrials.gov ID: NCT02597751). Children with DCD (N = 78) were randomized to either a treatment or waitlist group and underwent three MRIs over 6 months. The treatment group received intervention (once weekly for 10 weeks) between the first and second scan; the waitlist group received intervention between the second and third scan. Cortical grey matter volume was measured using voxel-based morphometry (VBM). Behavioral outcome measures included the Performance Quality Rating Scale (PQRS) and Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2). Of the 78 children, 58 were excluded (mostly due to insufficient data quality), leaving a final N = 20 for analyses. Due to the small sample size, we combined both groups to examine treatment effects. Cortical grey matter volume differences were assessed using a repeated measures ANOVA, controlling for total intracranial volume. Regression analyses examined the relationship of grey matter volume changes to BOT-2 (motor performance) and PQRS (movement quality). After CO-OP, children had significantly decreased grey matter in the right superior frontal gyrus and middle/posterior cingulate gyri. We found no significant associations of grey matter volume changes with PQRS or BOT-2 scores. Decreased cortical grey matter volume generally reflects greater brain maturity. Decreases in grey matter volume after CO-OP intervention were in regions associated with self-regulation and motor control, consistent with our other studies. Decreased grey matter volume may be due to focal increases in synaptic pruning, perhaps as a result of strengthening networks in the brain via the repeated learning and actions in therapy. Findings from this study add to the growing body of literature demonstrating positive neuroplastic changes in the brain after CO-OP intervention.

Twelve weeks of physical exercise breaks with coordinative exercises at the workplace increase the sulcal depth and decrease gray matter volume in brain structures related to visuomotor processes

Physical exercise can evoke changes in the brain structure. Consequently, these can lead to positive impacts on brain health. However, physical exercise studies including coordinative exercises are rare. Therefore, in this study, we investigated how 12 weeks of physical exercise breaks (PEBs) with coordinative exercises, focusing mainly on juggling tasks, affected the brain structure. The participants were randomly allocated to an intervention group (IG, n = 16; 42.8 ± 10.2 years) and a control group (CG, n = 9; 44.2 ± 12.3 years). The IG performed the PEBs with coordinative exercises twice per week for 15–20 min per session. Before the intervention, after 6 weeks of the intervention, and after 12 weeks of the intervention, participants underwent a high-resolution 3T T1-weighted magnetic resonance imagining scan. Juggling performance was assessed by measuring the time taken to perform a three-ball cascade. A surface-based analysis revealed an increase in vertex-wise cortical depth in a cluster including the inferior parietal lobe after 6 and 12 weeks of training in the IG. After 12 weeks, the IG showed a decrease in gray matter (GM) volume in a cluster primarily involving the right insula and the right operculum. The changes in the GM volume were related to improvements in juggling performance. No significant changes were found for the CG. To conclude, the present study showed that regular engagement in PEBs with coordinative exercises led to changes in brain structures strongly implicated in visuomotor processes involving hand and arm movements.

Differential cortical gray matter changes in early- and late-onset patients with amyotrophic lateral sclerosis.

Age at onset may be an important feature associated with distinct subtypes of amyotrophic lateral sclerosis (ALS). Little is known about the neuropathological mechanism of early-onset ALS (EO-ALS) and late-onset ALS (LO-ALS). Ninety ALS patients were divided into EO-ALS and LO-ALS group, and 128 healthy controls were matched into young controls(YCs) and old controls (OCs). A voxel-based morphometry approach was employed to investigate differences in gray matter volume (GMV). Significant age at onset-by-diagnosis interactions were found in the left parietal operculum, left precentral gyrus, bilateral postcentral gyrus, right occipital gyrus, and right orbitofrontal cortex. Post hoc analysis revealed a significant decrease in GMV in all affected regions of EO-ALS patients compared with YCs, with increased GMV in 5 of the 6 brain regions, except for the right orbitofrontal cortex, in LO-ALS patients compared with OCs. LO-ALS patients had a significantly increased GMV than EO-ALS patients after removing the aging effect. Correspondingly, GMV of the left postcentral gyrus correlated with disease severity in the 2 ALS groups. Our findings suggested that the pathological mechanisms in ALS patients with different ages at onset might differ. These findings provide unique insight into the clinical and biological heterogeneity of the 2 ALS subtypes.

Brain structural change associated with Cognitive Behavioral Therapy in maltreated children

BackgroundSeverely maltreatment child is a harmful social factor that can disrupt normal neurodevelopment. Two commonly reported effects of maltreatment are post-traumatic stress disorder (PTSD) symptoms and brain structural and functional alteration. While Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) is effectively used to reduce PTSD symptoms in maltreated children, yet, its impact on brain structural alterations has not been fully explored. This study investigated whether TF-CBT can attenuate alterations in brain structures associated with PTSD in middle childhood. MethodsThe study evaluated the longitudinal effects of Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) on post-traumatic stress disorder (PTSD) symptoms and gray matter volume (GMV) in two groups of children under 12 years old: maltreated children (MC) and healthy non– maltreatmentd children (HC). Structural magnetic resonance images T1 were obtained before and after TF-CBT in the MC group, while the HC group was scanned twice within the same time interval. Voxel-based morphometry (VBM) was used to analyze GMV changes over time. ResultsAfter TF-CBT, maltreated children showed significantly reduced PTSD symptoms. Furthermore, a significant group-by-time interaction effect was observed in certain areas of the Left Temporal, Left Occipital, and bilateral Frontal Cortex, the Basal Ganglia and Cerebellum. These interaction effects were driven by a GMV decrease in the MC group compared to the HC group. GMV changes can be predicted with clinical improvement in the left Middle Temporal gyrus, left Precuneus, and Cerebellum. ConclusionsOur results suggest that TF-CBT intervention in very young maltreated children may have an effect on gray matter. This evidence demonstrates the importance of timely intervention when neuroplasticity mechanisms may be activated.

Pathophysiological mechanisms of grey matter morphometry changes in preclinical Alzheimer’s disease

AbstractBackgroundThe biological mechanisms underlying structural brain changes in early Alzheimer’s disease (AD) are not well understood. Combining a wide selection of biomarkers of AD pathology, synaptic dysfunction, neuroaxonal injury, and neuroinflammation, and examining their effects on grey matter (GM) changes may provide a deeper understanding of the multifactorial nature of AD. We aimed to identify biological components of key fluid biomarkers predictive of longitudinal GM changes in cognitively unimpaired adults.MethodWe studied 322 cognitively unimpaired individuals from the ALFA+ cohort (Table1) with available longitudinal MRI and cerebrospinal fluid (CSF) biomarkers of β‐amyloid (Aβ42/40), phospho‐tau (p‐tau181), neurogranin, neurofilament light chain (NfL), total‐tau, α‐synuclein, glial fibrillary acidic protein (GFAP), chitinase‐3‐like protein‐1 (YKL‐40), soluble triggering receptor expressed on myeloid cells‐2 (sTREM2), S100 calcium‐binding protein B (S100B), and interleukin‐6 measured using the Roche NeuroToolKit immunoassays. Pairwise longitudinal registration analysis was performed using SPM12 to calculate Jacobian determinant maps. Next, we performed partial least‐squares analysis to determine the optimal number of CSF biomarker components and tested their association with GM volume changes by AT (Amyloid‐Tau) stage.ResultFour distinct biomarker components (C1‐4) were identified (Figure1). C1 was driven by moderate contributions from several biomarkers, particularly markers of core AD pathology and neurodegeneration, which were strongly associated with temporal lobe atrophy in A+T‐ individuals. C2 represented mainly Aβ pathology and, to a lesser extent, axonal damage and astrogliosis that contributed to a decrease in GM volume, especially in the hippocampus in A‐T‐ participants, while showing strong correlations with volume increases in medial frontal regions in A+T+ participants. C3 loading was associated with greater frontoparietal atrophy, especially in A+T+ individuals, and consisted of microglial activation together with Aβ pathology but in the absence of reactive astrogliosis. Lastly, C4, reflecting mostly microglial activation alone, was also strongly associated with frontoparietal atrophy, particularly in A+T+ participants.ConclusionOur results suggest important contributions of Aβ pathology, neuroaxonal damage, and microglial activation to GM morphometry changes in the earliest stages of the AD continuum. Atrophy patterns differed depending on the underlying pathological drivers and on A and T positivity, showing stronger correlations with increasing disease severity; however, volumetric increases were also observed.

Pathophysiological mechanisms of grey matter morphometry changes in preclinical Alzheimer’s disease

AbstractBackgroundThe biological mechanisms underlying structural brain changes in early Alzheimer’s disease (AD) are not well understood. Combining a wide selection of biomarkers of AD pathology, synaptic dysfunction, neuroaxonal injury, and neuroinflammation, and examining their effects on grey matter (GM) changes may provide a deeper understanding of the multifactorial nature of AD. We aimed to identify biological components of key fluid biomarkers predictive of longitudinal GM changes in cognitively unimpaired adults.MethodWe studied 322 cognitively unimpaired individuals from the ALFA+ cohort (Table1) with available longitudinal MRI and cerebrospinal fluid (CSF) biomarkers of ß‐amyloid (Aß42/40), phospho‐tau (p‐tau181), neurogranin, neurofilament light chain (NfL), total‐tau, a‐synuclein, glial fibrillary acidic protein (GFAP), chitinase‐3‐like protein‐1 (YKL‐40), soluble triggering receptor expressed on myeloid cells‐2 (sTREM2), S100 calcium‐binding protein B (S100B), and interleukin‐6 measured using the Roche NeuroToolKit immunoassays. Pairwise longitudinal registration analysis was performed using SPM12 to calculate Jacobian determinant maps. Next, we performed partial least‐squares analysis to determine the optimal number of CSF biomarker components and tested their association with GM volume changes by AT (Amyloid‐Tau) stage.ResultFour distinct biomarker components (C1‐4) were identified (Figure1). C1 was driven by moderate contributions from several biomarkers, particularly markers of core AD pathology and neurodegeneration, which were strongly associated with temporal lobe atrophy in A+T‐ individuals. C2 represented mainly Aß pathology and, to a lesser extent, axonal damage and astrogliosis that contributed to a decrease in GM volume, especially in the hippocampus in A‐T‐ participants, while showing strong correlations with volume increases in medial frontal regions in A+T+ participants. C3 loading was associated with greater frontoparietal atrophy, especially in A+T+ individuals, and consisted of microglial activation together with Aß pathology but in the absence of reactive astrogliosis. Lastly, C4, reflecting mostly microglial activation alone, was also strongly associated with frontoparietal atrophy, particularly in A+T+ participants.ConclusionOur results suggest important contributions of Aß pathology, neuroaxonal damage, and microglial activation to GM morphometry changes in the earliest stages of the AD continuum. Atrophy patterns differed depending on the underlying pathological drivers and on A and T positivity, showing stronger correlations with increasing disease severity; however, volumetric increases were also observed.

Clinical Manifestations.

the vestibular system has neural connections from the vestibular nucleus to limbic and cortical areas, involved in both cognition and spatial orientation. The superior vestibular cortex consists of a network that interacts with other sensory systems, such as visual, sensorimotor, motor and cognition. Studies have found structural changes in the brain of patients with persistent perceptual postural dizziness (PPPD) when compared to controls, particularly in visual, vestibular and limbic areas, including a decrease in gray matter volume and turnover, a decrease in blood flow to the cortex region. cross-sectional, observational and analytical study. The sample consisted of 50 elderly people, of both sexes, aged between 60 and 86 years. Elderly individuals with vestibular dysfunction confirmed by Vestibular Evoked Myogenic Potential (VEMP) and Video Head Impulse Test (v-HIT) tests were included. Balance and the impact of dizziness on quality of life were evaluated through tests and vestibular scales. Cognition, functioning and depression were assessed in a quiet room using tests and scales. Univariate analysis was performed using the Spearman test. Variables that presented correlation ≤ 0.2 were selected for multivariate analysis by linear regression. A significance level of 5% was adopted (p< 0.05). there was a correlation between vestibular dysfunction and imbalance with the results of neuropsychological assessment (p = 0.000), depressive symptoms (p = 0.001) and functionality (p = 0.002). in this present study, a correlation was found between vestibular dysfunction and imbalance with the worst clinical and functional indices, worse functionality, depressive symptoms and in visuospatial function skills, executive functions and praxis.

Cognitive reserve in figural and verbal memory in healthy older adults – preliminary results

AbstractBackgroundCognitive reserve plays an important role in individual trajectories of age‐related memory decline, with education and semantic fluency representing cognitive reserve proxies (CRPs). Higher CR may attenuate well‐known effects of ageing on the brain, such as decreases in grey matter volume (GMV). We hypothesised that the known associations between age‐related GMV and cognition would be (differentially) attenuated by CRPs.MethodWe analysed 3‐Tesla T1‐weighted Multi‐Echo MPRAGE and cognitive data (Verbal Learning and Memory Test (VLMT), Rey Complex Figure Test (RCFT), and Regensburg Verbal Fluency Test (RWT)) from 51 cognitively normal adults (73.2±7.62 years, 31 male) in our new cohort established within the CRC1436 (https://sfb1436.de/). MRI data were pre‐processed and analysed using CAT12. We performed a whole‐brain linear regression to first assess age‐related reductions in GMV (covariates: sex, total intracranial volume (TIV), education), extracting mean betas for significant regions of interest (ROIs). We investigated the relationship between GMV in age‐vulnerable regions and memory using linear regressions in R (covariates: age, sex, TIV), and assessed CRPs as moderators on this relationship. Finally, we tested whether CRPs explained variance in memory performance over and above that of GMV and age. We accounted for multiple testing via Benjamini‐Hochberg‐correction.ResultWhole brain analyses identified bilateral hippocampal GMV as negatively associated with age (Fig.1). Linear regression analyses yielded a significant positive association between bilateral hippocampal GMV and figural memory (Fig.2). However, we observed no significant moderation by CRPs on this relationship. Finally, we observed weak evidence for cognitive reserve when adjusting for GMV and age, with higher variance explained by CRPs (Table 1). Semantic fluency positively predicted a figural memory composite when adjusting for right (p = 0.006) as well as left hippocampal GMV (p = 0.014). Education positively predicted verbal memory when adjusting for right (p&lt;0.001) as well as left hippocampal GMV (p&lt;0.001).ConclusionConsistent with operational definitions, our results provide weak evidence for semantic fluency and for education as CRPs in figural and verbal memory, respectively. However, our findings are preliminary, given the future addition of more participants. Nevertheless, these results provide important first insights into cognitive reserve in this developing cohort.

Clinical Manifestations.

Visual hallucinations (VH) phenomenology in Lewy Body Disease (LBD) is heterogenous, including minor phenomena (passage, presence, illusions) and complex hallucinations. Neural substrates and mechanisms involved are still unclear. Here we investigated grey matter (GM) alterations associated with minor (MVH) and complex VH (CVH). LBD patients (n = 28) with VH and Healthy controls (HC-n = 20) underwent MRI. We administered the North East Visual Hallucinations Interview (NEVHI), a semi-structured interview assessing the phenomenology of VH, their duration and frequency. VH were clustered in MVH and CVH and treated as a patient's trait. First we compared GM volume of LBD and HC. Then, multiple regressions were performed to disclose alterations associated with the duration, frequency and severity of MVH and CVH, including the opposite VH domain, total intracranial volume (TIV) and MMSE as nuisance regressors. We found a decreased GM volume in the bilateral fusiform gyrus (FG), in the left posterior cingulate and in the right inferior frontal gyrus in LBD compared to HC. We also found that CVH duration was negatively associated with GM volume in the left FG. We did not find any association with MVH phenomenology. LBD patients showed GM alterations in ventral-visual-stream, default-mode-network and inhibitory regions compared to HC. Although the LBD versus HC comparison is not specific to VH, the regions identified have been implicated in VH in previous studies suggesting they may represent structural hallmarks of functional alterations in networks contributing to VH. When the association with VH phenomenology was tested, we did not find GM alterations associated with MVH. It is likely that these phenomena might be not associated with structural alterations but with functional alterations within visual networks. CVH were instead associated with decreased GM in FG. The atrophy in the FG may lead to a spontaneous activation of this region that sustain CVH duration, accounting for VH content (D'Antonio et al., 2022). These alterations may represent the predisposing condition to VH in LBD. According to the hodotopic model, VH phenomenology may help identify brain regions implicated and might reveal the substrates for cortical region/network dysfunctions occurring during VH state (ffytche et al., 2008).

The Effect of Telomere Length on Gray Matter Volume Change and Cortical Thickness

AbstractBackgroundTelomeres are specific nucleotide repeats that play an important role in preventing DNA damage during cell division. Telomere length holds promise as a predictor for age‐related diseases. However, the relationship between leukocyte telomere length and structural changes in the brain is not well understood. The aim of this study is to evaluate the cross‐sectional and longitudinal relationship between telomere length, structural features of the brain, and to examine the interindividual differences in age‐related brain atrophy within the framework of biological age.MethodsA total of 202 individuals ≥50 years of age without any neurological complaints were included in the study. Telomere length measurements from the peripheral blood leukocytes and brain magnetic resonance imaging (MRI) were performed in all participants. Forty‐six of the individuals without any major health events during the follow‐up period were evaluated with a second structural brain MRI after an average of 4.7 years. The relationship between global gray matter volume change and telomere length was investigated with multivariate models. In addition, longitudinal surface‐based analysis was used to determine the relationship between telomere length and cortical thinning regionally.ResultsThe mean (standard deviation) age of the population was 65.9 (8.6) years; female gender constituted 60.9% of the cohort. The mean telomere length was 7.5 (2.0) kB. Telomere length was not significantly associated with brain volumes and cortical thickness. However, in the longitudinal phase of the study, we found a negative correlation between basal telomere length and the rate of total gray matter volume decrease over time (r = ‐0.370; p = 0.012). This significant relationship persisted after adjusting for age, gender, follow‐up time, and baseline total gray matter volume (Standardized β = ‐0.286, p = 0.05). Longitudinal surface‐based image analysis also revealed a negative association between telomere length and left superior parietal cortex thickness, which remained significant after cluster correction.ConclusionTelomere length might be a predictor of age‐dependent structural changes in the brain. The left superior parietal cortex, in particular, tended to possess a vulnerability in this interplay.

Low bone mineral density is associated with gray matter volume decrease in UK Biobank.

Previous research has found an association of low bone mineral density (BMD) and regional gray matter (GM) volume loss in Alzheimer's disease (AD). We were interested whether BMD is associated with GM volume decrease in brains of a healthy elderly population from the UK Biobank. T1-weighted images from 5,518 women (MAge = 70.20, SD = 3.54; age range: 65-82 years) and 7,595 men (MAge = 70.84, SD = 3.68; age range: 65-82 years) without neurological or psychiatric impairments were included in voxel-based morphometry (VBM) analysis in CAT12 with threshold-free-cluster-enhancement (TFCE) across the whole brain. We found a significant decrease of GM volume in women in the superior frontal gyri, middle temporal gyri, fusiform gyri, temporal poles, cingulate gyri, precunei, right parahippocampal gyrus and right hippocampus, right ventral diencephalon, and right pre- and postcentral gyrus. Only small effects were found in men in subcallosal area, left basal forebrain and entorhinal area. BMD is associated with low GM volume in women but less in men in regions afflicted in the early-stages of AD even in a sample without neurodegenerative diseases.

Macrostructural Cerebellar Neuroplasticity Correlates With Motor Recovery After Stroke

Background Motor recovery varies across post-stroke individuals, some of whom require a better rehabilitation strategy. We hypothesized that macrostructural neuroplasticity of the motor control network including the cerebellum might underlie individual differences in motor recovery. Objectives. To gain insight into the macrostructural neuroplasticity after stroke, we examined 52 post-stroke individuals using both the Fugl-Meyer assessment and structural magnetic resonance imaging. Methods We performed voxel-based lesion symptom mapping and cross-sectional voxel-based morphometry to correlate the motor scores with the lesion location and the gray matter volume (GMV), respectively. Longitudinal data were available at ~8 and/or 15 weeks after admission from 43 individuals with supratentorial lesions. We performed a longitudinal VBM analysis followed by a multiple regression analysis to correlate between the changes of the motor assessment scores and those of GMV overtime. Results We found a cross-sectional correlation of residual motor functioning with GMV in the ipsilesional cerebellum and contralesional parietal cortex. Longitudinally, we found increases in GMV in the ipsilesional supplementary motor area, and the ipsilesional superior and inferior cerebellar zones, along with a GMV decrease in the ipsilesional thalamus. The motor recovery was correlated with the GMV changes in the superior and inferior cerebellar zones. The regaining of upper-limb motor functioning was correlated with the GMV changes of both superior and inferior cerebellum while that of lower-limb motor functioning with the GMV increase of the inferior cerebellum only. Conclusions The present findings support the hypothesis that macrostructural cerebellar neuroplasticity is correlated with individual differences in motor recovery after stroke.

Changes in Behavior and Neural Dynamics across Adolescent Development.

Adolescence is an important developmental period, during which substantial changes occur in brain function and behavior. Several aspects of executive function, including response inhibition, improve during this period. Correspondingly, structural imaging studies have documented consistent decreases in cortical and subcortical gray matter volume, and postmortem histologic studies have found substantial (∼40%) decreases in excitatory synapses in prefrontal cortex. Recent computational modeling work suggests that the change in synaptic density underlie improvements in task performance. These models also predict changes in neural dynamics related to the depth of attractor basins, where deeper basins can underlie better task performance. In this study, we analyzed task-related neural dynamics in a large cohort of longitudinally followed subjects (male and female) spanning early to late adolescence. We found that age correlated positively with behavioral performance in the Eriksen Flanker task. Older subjects were also characterized by deeper attractor basins around task related evoked EEG potentials during specific cognitive operations. Thus, consistent with computational models examining the effects of excitatory synaptic pruning, older adolescents showed stronger attractor dynamics during task performance.SIGNIFICANCE STATEMENT There are well-documented changes in brain and behavior during adolescent development. However, there are few mechanistic theories that link changes in the brain to changes in behavior. Here, we tested a hypothesis, put forward on the basis of computational modeling, that pruning of excitatory synapses in cortex during adolescence changes neural dynamics. We found, consistent with the hypothesis, that variability around event-related potentials shows faster decay dynamics in older adolescent subjects. The faster decay dynamics are consistent with the hypothesis that synaptic pruning during adolescent development leads to stronger attractor basins in task-related neural activity.

Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease

Increased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors. To estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes. This cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers-the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer's Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019). The main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH. Data from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = -3.1 [P = .002]; ADNI: t = -5.6 [P < .001]; HABS: t = -2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P < .001]; ADNI: t = 9.1 [P < .001]; HABS: t = 5.4 [P < .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P < .001). The findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.

Whole-brain gray matter maturation trajectories associated with autistic traits from adolescence to early adulthood.

A growing number of evidence supports a continued distribution of autistic traits in the general population. However, brain maturation trajectories of autistic traits as well as the influence of sex on these trajectories remain largely unknown. We investigated the association of autistic traits in the general population, with longitudinal gray matter (GM) maturation trajectories during the critical period of adolescence. We assessed 709 community-based adolescents (54.7% women) at age 14 and 22. After testing the effect of sex, we used whole-brain voxel-based morphometry to measure longitudinal GM volumes changes associated with autistic traits measured by the Social Responsiveness Scale (SRS) total and sub-scores. In women, we observed that the SRS was associated with slower GM volume decrease globally and in the left parahippocampus and middle temporal gyrus. The social communication sub-score correlated with slower GM volume decrease in the left parahippocampal, superior temporal gyrus, and pallidum; and the social cognition sub-score correlated with slower GM volume decrease in the left middle temporal gyrus, the right ventromedial prefrontal and orbitofrontal cortex. No longitudinal association was found in men. Autistic traits in young women were found to be associated with specific brain trajectories in regions of the social brain and the reward circuit known to be involved in Autism Spectrum Disorder. These findings support both the hypothesis of an earlier GM maturation associated with autistic traits in adolescence and of protective mechanisms in women. They advocate for further studies on brain trajectories associated with autistic traits in women.

P11.27.A RADIOTHERAPY-INDUCED CHANGES IN THE BRAIN: A LONGITUDINAL STUDY IN PATIENTS WITH LOW-GRADE GLIOMAS

Abstract BACKGROUND Low-grade gliomas (LGG) are brain tumors with a comparably moderate malignancy grade and slow progression. Most patients are young to middle-aged adults with a relatively good prognosis given the advancement of multimodal treatment METHODS . Radiotherapy (RT) is an integral component of this treatment. During RT, protons or photons are used to eradicate the tumor while minimizing the damage to surrounding areas. However, healthy brain tissue is inevitably exposed to radiation, which can have adverse effects with a severe impact on the cognition and quality of life of survivors. With the improved survival of patients, understanding RT-induced changes and their consequences becomes more and more important. Here, we investigate the volumetric changes in LGG patients 2.5 years after treatment to gain insights into the neuronal long-term effects of RT. MATERIAL AND METHODS To quantify the volumetric changes in the brain of LGG patients over time, LGG patients (N= 17) were scanned before and 2.5 years after proton RT. For both time points, volume parameters per brain structure were extracted using T1w MRI scans and cNeuro® software. The volumes of the structures in the tumor-contralateral hemispheres before RT were compared with the measures 2.5 years after RT using paired samples t-tests or nonparametric alternatives. RESULTS Analysis of the total grey matter of the contralateral hemisphere indicated a statistically significant volumetric reduction in our cohort 2.5 years after RT. An analysis targeting volumetric changes in the contralateral hippocampus also indicated a statistically significant decrease. In the following steps, additional structures will be analyzed. CONCLUSION Preliminary results suggest a potential RT-induced decrease in the tumor-contralateral grey matter and hippocampal volume 2.5 years after treatment. Volumetric changes will be compared with the received radiation dose per structure using radiation dose distribution maps.

Functional Alterations of the Basal Ganglia Are Associated with Voluntary Activation of the Core Stabilizing Muscles in Patients with Chronic Low Back Pain: A Cross-Sectional Study.

Deficits in voluntary activation of the core stabilizing muscles are consistently observed in patients with chronic low back pain (CLBP); however, the underlying neural mechanism remains unclear. This cross-sectional study aimed at testing the hypothesis that the impaired voluntary activation of core stabilizing muscles is associated with structural and functional alterations in the basal ganglia, thalamus, and cortex in patients with CLBP. We obtained structural and resting-state functional magnetic resonance imaging (rs-fMRI) data from 53 patients with CLBP and 67 healthy controls and estimated the alterations in grey matter volume (GMV) and functional and effective connectivity (EC) of regions with altered GMV via whole brain analysis. The voluntary activation of the multifidus (MF) and transversus abdominis (TrA) was evaluated by ultrasound imaging in these patients. Compared with the HCs, they displayed a significant decrease in GMV in the bilateral thalamus and caudate nucleus, a significant increase in GMV in the left middle frontal gyrus, and increased resting-state functional connectivity between the right caudate nucleus and the bilateral precuneus (voxel-level p < 0.005, Gaussian random field-corrected p < 0.05). The patients also showed increased EC from the right caudate nucleus to the bilateral precuneus, which was significantly correlated with voluntary activation of the bilateral MF and TrA (all p < 0.050). Grey matter alterations may be confined to regions responsible for perception, motor control, and emotion regulation in patients with CLBP. The interrupted EC from the basal ganglia to the default mode network might be involved in the impairment of voluntary activation of the core stabilizing muscles.

Relationship of Neural Correlates of Gait Characteristics and Cognitive Dysfunction in Patients with Mild Cognitive Impairment.

Background: Some patients with mild cognitive impairment (MCI) experience gait disturbances. However, there are few reports on the relationship between gait disturbance and cognitive function in patients with MCI. Therefore, we investigated the neural correlates of gait characteristics related to cognitive dysfunction. Methods: Eighty patients diagnosed with MCI from three dementia centers in Gangwon-do, Korea, were recruited for this study. We defined MCI as a Clinical Dementia Rating global score of 0.5 or higher, with a memory domain score of 0.5 or greater. The patients were classified as having either higher or lower MMSE and the groups were based on their Mini Mental Status Examination z-scores. Multiple logistic regression analysis was performed to examine the association between the gait characteristics and cognitive impairment. Analyses included variables such as age, sex, years of education, number of comorbidities, body mass index, and height. Results: Gait velocity, step count, step length, heel-to-heel base support, swing and stance phase duration, and support time were associated with cognitive function. A decrease in gray matter volume in the right pericalcarine area was associated with gait characteristics related to cognitive dysfunction. An increase in the curvature of gray matter in the right entorhinal, right lateral orbitofrontal, right cuneus, and right and left pars opercularis areas was also associated with gait characteristics related to cognitive dysfunction. Conclusion: Since gait impairment is an important factor in determining activities of daily living in patients with mild cognitive impairment, the evaluation of gait and cognitive functions in patients with mild cognitive impairment is important.

Gray matter alterations in tremor-dominant Parkinson's disease after MRgFUS thalamotomy are correlated with tremor improvement: a pilot study.

Regional differences in gray matter volume (GMV) have been reported to be a reliable marker for diagnosing Parkinson's disease (PD). This study aimed to explore the clinical value of GMV to assess magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy as a treatment for tremor-dominant PD (TDPD). Nine TDPD patients with MRgFUS thalamotomy were recruited for structural magnetic resonance image (MRI) scanning and clinical score evaluation. GMV was calculated. To investigate changes after treatment, voxel- and region of interest (ROI)-wise GMV analyses were performed. Then, GMV with significant differences was extracted from patients to investigate its dynamic alterations by one-way repeated-measures analysis of variance (ANOVA). The nonparametric Spearman rank correlation analysis was used to evaluate the relationship between GMV alterations and tremor improvement after thalamotomy. Tremors were significantly relieved after MRgFUS thalamotomy in nine patients (P<0.05). The treated hand tremor scores improved 74.82% on average in patients from pre-operation to 12 months post-operation. Voxel-wise analysis at the cluster level showed a significant decrease in GMV in the left middle occipital gyrus (MOG) [t=11.81, voxel-level P<0.001, cluster-level Pfamily-wise error (FWE) <0.05] and an increase in GMV in the left precentral gyrus (PreCG) (t=7.99, voxel-level P<0.001, cluster-level PFWE <0.05) in TDPD patients from preoperative to 12 months post-operation, which was significantly correlated with tremor scores (rho =0.346-0.439, P<0.05). ROI-wise analysis showed that GMV related to MRgFUS thalamotomy was associated with long-term structural alterations (P<0.05 with Bonferroni correction), including specific basal ganglia and related nuclei and cerebellum subregions. GMV can be used to reflect tremor improvement after MRgFUS thalamotomy and be helpful to better understand the distant effect of MRgFUS thalamotomy and the involvement of GMV in tremor control in TDPD. ClinicalTrials.gov identifier: NCT04570046.