Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders.

Neuroinflammation has been implicated in the pathophysiology of schizophrenia and obsessive-compulsive disorder (OCD) and deviations in brain structure and connectivity are seen in these disorders. Here, we explore the effects of a potent immunomodulatory treatment on neuroimaging. In a pilot study of rituximab treatment in schizophrenia and OCD, a subgroup (n = 13) underwent structural and functional magnetic resonance imaging before and 5 months after treatment, to study longitudinal changes in resting-state functional connectivity (rsFC) and voxel-based morphometry (VBM). A hypothesis-free exploratory whole-brain analysis was performed twice to assess changes in rsFC, using anterior cingulate cortex, anterior insula, posterior insula and nucleus accumbens as seed regions. There were significant interactions (diagnosis x time) in connectivity between right posterior insula and two clusters encompassing basal ganglia and anterior frontal pole, and between left anterior insula and a cluster in basal ganglia, where connectivity decreased in OCD and increased in schizophrenia. The increase of connectivity after rituximab, between left anterior insula and parts of cerebellum and lingual gyrus and between left posterior insula and parts of cerebellum, correlated with improved global psychosocial functioning according to the Personal and Social Performance Scale, especially in schizophrenia. VBM analysis identified two clusters with increased grey matter volumes (GMV) after rituximab, one in right insula overlapping one of the seed regions with significant rsFC changes. This pilot study implies that rituximab may influence both brain structure and connectivity and that GMV changes and rsFC changes are regionally associated.

Structural and functional whole brain changes in autism spectrum disorder at different age stages.

Autism spectrum disorder (ASD) is a developmental disorder involving regional changes and local neural disturbances. However, few studies have investigated the dysfunctional phenomenon across different age stages. This study explores the structural and functional brain changes across different developmental stages in individuals with ASD, focusing on childhood (6-12 years), adolescence (12-18 years), and adulthood (18 + years). Using a comprehensive set of neuroimaging metrics, including modulated and non-modulated voxel-based morphometry (VBM), regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF), we identified significant stage-specific alterations in both VBM and functional measurements. Our results reveal that ASD is associated with progressive and stage-specific abnormalities in brain structure and function, with distinct patterns emerging at each developmental stage. Specifically, we observed significant modulated VBM reductions in the precuneus, lentiform nucleus, and inferior parietal lobule, accompanied by increases in the midbrain and sub-gyral regions. Moreover, we observed unmodulated VBM increment in regions including lentiform nucleus and thalamus. Functionally, ReHo analyses demonstrated disrupted local synchronization in the medial frontal gyrus, while ALFF and fALFF metrics highlighted altered spontaneous brain activity in the sub-gyral and sub-lobar. Finally, correlation analyses revealed that stage-specific findings are closely linked to clinical social- and behavior-related scores, with VBM in the inferior parietal lobule and putamen as well as ReHo in supplemental motor area being significantly associated with restrictive repetitive behaviors in childhood. These findings underscore the importance of considering age-specific brain changes when studying ASD and suggest that targeted interventions may be necessary at different developmental stages.

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.

Correlations of gray matter volume with peripheral cytokines in Parkinson's disease.

INTRODUCTION: Peripheral cytokine levels may affect specific brain volumes. Few studies have examined this possible relationship. OBJECTIVE: In a case-control study, we used magnetic resonance imaging (MRI) voxel-based morphological analysis techniques to examine the relationship between gray matter volume changes and cognitive, motor and emotional dysfunction as well as between gray matter volume changes and peripheral blood cytokine levels. METHOD: A total of 134 subjects, comprising 66 PD patients and 68 healthy controls, were recruited. Peripheral venous blood was collected to measure the concentrations of 12 cytokines, including IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-α, IFN-γ, and TNF-α. All the subjects also underwent MRI, where 3D-T1-weighted MR images were used for the analysis. In addition, the Montreal Cognitive Assessment (MoCA), Mini-Mental Status Examination (MMSE), Unified Parkinson's disease Rating Scale (UPDRS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) scores were assessed in PD patients. Statistical parameter mapping 12 software was used for the statistical analysis of the images. RESULT: Compared with control patients, PD patients presented decreased gray matter volume (GMV) in the bilateral frontal lobe, temporal lobe, parietal lobe, occipital lobe, insula, and right cerebellar lobule VIII. Regional GMV in the temporal lobe, parietal lobe, and cerebellum was correlated with MoCA, MMSE, UPDRS, HAMA, and HAMD scores in PDs. In addition, the regional GMV in PDs was correlated with the concentrations of cytokines, including IL-4, IL-6, IFN-γ, and TNF-α. The IL-6 concentration was negatively correlated with the UPDRS-IV score. CONCLUSION: PD patients exhibit gray matter atrophy in a wide range of brain regions, which are symmetrically distributed and mainly concentrated in the frontal and temporal lobes, and these changes may be linked to motor disorders and neuropsychiatric manifestations. Cytokine concentrations in peripheral blood are correlated with regional gray matter volume in PDs, and the IL-6 level affects gray matter volume in the left precentral gyrus and the manifestation of motor complications.

Altered Brain Structure in Hemifacial Spasm Patients: A Multimodal Brain Structure Study.

Objective: Hemifacial spasm (HFS) is a clinical neurosurgical disease, which brain structural alterations caused by HFS remain a topic of debate. We evaluated changes in brain microstructure associated with HFS and observed their relevance to clinical characteristics. Methods: We enrolled 72 participants. T1-weighted structural and diffusion tensor images were collected from all participants using 3.0T magnetic resonance equipment. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to identify changes in gray matter volume (GMV) and disruptions in white matter (WM) integrity. The severity of the spasms was graded using the Cohn scale. Results: VBM analysis revealed that the GMV was significantly reduced in the left Thalamus and increased GMV in the right Cerebellum IV-V of the HFS group. TBSS analysis showed that FA in the left superior longitudinal fasciculus (SLF) of the HFS group was significantly increased. GMV in the thalamus showed a negative correlation with disease duration and Cohn grade, while FA in the left SLF had a positive correlation with both the disease duration and Cohn grade. Conclusion: We identified regions with altered GMV in HFS patients. Additionally, we determined that FA in the left SLF might serve as a significant neural indicator of HFS.

Differences in Grey Matter Concentrations and Functional Connectivity between Young Carriers and Non-Carriers of the APOE ε4 Genotype.

Background: The pathophysiology of Alzheimer's disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE ε4 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE ε4 status is highly relevant. Objective: Examine potential differences in grey matter (GM) and functional connectivity (FC) in brains of cognitively healthy young APOE ε4 carriers and non-carriers, denoted here as ε4(+) and ε4(-), respectively. Methods: Three Tesla magnetic resonance imaging (MRI) brain scans were acquired from cognitively healthy young participants aged approximately 20 years (n = 151). Voxel-based morphometry (VBM) analysis was employed to identify potential structural differences in GM between ε4(+) and ε4(-). In a subsequent seed-based connectivity (SBC) analysis, brain regions that structurally differed in the VBM analysis were considered as seeds and correlated with all the remaining voxels across the brains to then measure the differences in FC between groups. Results: The VBM analysis suggested that ε4(+) (n = 28) had greater GM densities relative to ε4(-) (n = 123) in the left hippocampus and the left posterior insula (puncorr < 0.001). However, the effect did not survive the correction for multiple comparisons, suggesting minimal structural differences in this age range. In contrast, the SBC analysis indicated that ε4(+) exhibited significantly decreased FC between the left hippocampus and areas of the left middle temporal gyrus (n = 27) compared to ε4(-) (n = 102). These results remained significant after multiple comparisons (pFDR < 0.05). Lastly, no statistically significant differences in FC between groups were observed for the left insular seed (pFDR > 0.05). Discussion: These results suggest early structural and functional brain changes associated with the APOE ε4 genotype on young adults. Yet, they must be cautiously interpreted and contrasted with both older adults with genetic risk for AD and patients diagnosed with AD.

Psychological characteristics and structural brain changes in women with endometriosis and endometriosis-independent chronic pelvic pain.

STUDY QUESTION: Are there neurobiological changes induced by endometriosis? SUMMARY ANSWER: Women with endometriosis demonstrate specific neurobiological changes distinct from those in patients with chronic pelvic pain (CPP) in the absence of endometriosis. WHAT IS KNOWN ALREADY: Endometriosis is a chronic disease affecting women of reproductive age that presents with pain and infertility often accompanied by comorbid mental disorders. Only one study with a number of limitations has investigated changes in gray matter volumes and functional connectivity in a small group of patients with endometriosis. STUDY DESIGN, SIZE, DURATION: This prospective study recruited 53 women undergoing a laparoscopy due to suspicion of symptomatic endometriosis and 25 healthy, pain-free women. Clinical and psychological characteristics, thermal pain perception, and voxel- and surface-based morphology were assessed in all study participants. Thereafter, the patients underwent a laparoscopy, where endometriosis was either histologically confirmed and removed, or ruled out. Correspondingly, patients were assigned into the group with endometriosis (n = 27) or with endometriosis-independent CPP (n = 26) and compared to the pain-free controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study groups were generally representative for the population of women with endometriosis. Sociodemographic, medical, clinical, and psychological characteristics were collected using various questionnaires and a structured clinical interview. Thermal pain perception and voxel- and surface-based morphometry were assessed using thermode and MRI, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Despite comparable pain intensity and burden of mental disorders, both patient groups demonstrated distinct neurobiological patterns. Women with endometriosis exhibited increased gray matter volume (GMV) in the left cerebellum, lingual gyrus and calcarine gyrus, compared to those with endometriosis-independent CPP. Patients with CPP had decreased GMV in the right cerebellum as compared to controls. Dysmenorrhoea severity correlated positively with GMV in the left inferior parietal lobule, whereas depressive symptoms were associated with decreased GMV in the right superior medial gyrus across patient groups. Dyspareunia correlated negatively with cortical thickness in the left inferior temporal gyrus and left middle temporal gyrus. LIMITATIONS, REASONS FOR CAUTION: The study groups differed in a few baseline-characteristics, including educational levels, smoking and BMI. While measuring pain perception thresholds, we did not attempt to mimic CPP by placement of the thermode on the abdominal wall. WIDER IMPLICATIONS OF THE FINDINGS: Changes in gray matter volume associated with endometriosis differ from those observed in women with endometriosis-independent CPP. Our results underline an involvement of the cerebellum in pain perception and the pathogenesis of pain associated with endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the START Program of the Faculty of Medicine, RWTH Aachen, Germany, and supported by the International Research Training Group (IRTG 2150) of the German Research Foundation (DFG)-269953372/GRK2150, Germany. S.T. was supported by postdoctoral fellowship of the Faculty of Medicine, RWTH Aachen, Germany. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: DRKS00021236.

Eight brain structures mediate the age-related alterations of the working memory: forward and backward digit span tasks.

Introduction: Working memory (WM) as one of the executive functions is an essential neurocognitive ability for daily life. Findings have suggested that aging is often associated with working memory and neural decline, but the brain structures and resting-state brain networks that mediate age-related differences in WM remain unclear. Methods: A sample consisting of 252 healthy participants in the age range of 20 to 70years was used. Several cognitive tasks, including the n-back task and the forward and backward digit span tests were used. Also, resting-state functional imaging, as well as structural imaging using a 3T MRI scanner, were performed, resulting in 85 gray matter volumes and five resting-state networks, namely the anterior and posterior default mode, the right and left executive control, and the salience networks. Also, mediation analyses were used to investigate the role of gray matter volumes and resting-state networks in the relationship between age and WM. Results: Behaviorally, aging was associated with decreased performance in the digit span task. Also, aging was associated with a decreased gray matter volume in 80 brain regions, and with a decreased activity in the anterior default mode network, executive control, and salience networks. Importantly, the path analysis showed that the GMV of the medial orbitofrontal, precentral, parieto-occipital, amygdala, middle occipital, posterior cingulate, and thalamus areas mediated the age-related differences in the forward digit span task, and the GMV of superior temporal gyrus mediated the age-related differences in the backward digit span task. Discussion: This study identified the brain structures mediating the relationship between age and working memory, and we hope that our research provides an opportunity for early detection of individuals at risk of age-related memory decline.

AB038. Establishing a reliable semi-automated segmentation method for assessing chemoradiotherapy effects on the non-tumoral brain.

BACKGROUND: Current voxel-based morphometry (VBM) studies of chemoradiotherapy effects on healthy tissues of the glioblastoma multiforme (GBM) brain face a challenge with neuroanatomical distortions (tumor, tumor edema, and resection cavities) and limited comparisons can be drawn across studies due to lack of a universally accepted software package. Our aim is to compare current semi-automated segmentation methods and optimize them for reliability in investigating the effects of chemoradiotherapy on GBM patients. METHODS: A publicly available dataset was used based on predefined inclusion and exclusion criteria. VBM pipelines CAT12 and FSL were tested and optimized to reduce the impact of neuroanatomical distortions. T1-weighted images were screened, and post-processed with FSL and CAT12. Gray matter (GM) and white matter (WM), and cerebrospinal fluid (CSF) volumes of whole brain, tumour-containing and non-tumor containing hemispheres, pre- and post-chemoradiotherapy were calculated and analyzed with Wilcoxon signed-rank tests. Agreement and consistency between FSL and CAT12 were assessed using Bland-Altman plots and intraclass correlation coefficients (ICCs). RESULTS: Post-chemoradiotherapy GM volumes were significantly reduced in whole brain with a compensatory significant increase in CSF volumes, while WM volumes had no significant changes. Similar trends were noted in tumor-containing and non-tumor-containing hemispheres. Bland-Altman plots showed good agreement between FSL and CAT12 processed GM and WM volumes of whole brain, tumor-containing, and non-tumor-containing hemispheres. ICC ≥0.70 was observed in GM [0.70 (0.53-0.82)] and WM [0.75 (0.60-0.85)] volumes of non-tumor-containing hemisphere, and WM [0.71 (0.55-0.83)] volumes of whole brain. GM volumes of tumor-containing hemisphere had good agreement but surprisingly, poor consistency [0.50 (0.25-0.68)]. CSF volumes in non-tumor-containing hemisphere had better agreement and consistency [0.55 (0.32-0.71)] than whole brain [0.49 (0.25-0.67)] and tumor-containing hemisphere CSF [0.36 (0.10-0.58)] volumes. Visual inspection revealed both CAT12 and FSL mis-segmented in the presence of neuroanatomical distortion although CAT12 was more susceptible in the presence of a hematoma. CONCLUSIONS: VBM studies of chemoradiotherapy effects on the brain post-tumor resection remain challenging due to neuroanatomical distortions. A reliable alternative is to use non-tumor-containing hemispheres with no anatomical distortion. Should tumor-containing brains be used, FSL is a more suitable choice, especially in the presence of hematoma distortion.

Atrophy in the supramarginal gyrus associated with impaired cognitive inhibition in grieving Chinese Shidu parents.

Background: The loss of an only child, known as Shidu in China, is a profoundly distressing experience, often leading to Prolonged Grief Disorder (PGD). Despite its impact, the structural brain alterations associated with PGD, potentially influencing cognitive impairments in Shidu parents, remain understudied.Objective: This study aims to identify brain structural abnormalities related to prolonged grief and their relation with cognitive inhibition in Shidu parents.Methods: The study included 40 Shidu parents and 42 non-bereaved participants. Prolonged grief was evaluated using the Prolonged Grief Questionnaire (PG-13). We employed voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to assess brain structural alterations and their correlation with cognitive inhibition, as measured by Stroop interference scores.Results: Findings suggest that greater prolonged grief intensity correlates with reduced grey matter volume in the right amygdala and the left supramarginal gyrus (SMG). Additionally, enhanced amygdala-to-whole-brain structural connectivity showed a marginal association with prolonged grief, particularly with emotional-related symptoms. Furthermore, a decrease in SMG volume was found to mediate the relation between prolonged grief and Stroop Time Inference (TI) score, indicating an indirect effect of prolonged grief on cognitive inhibition.Conclusions: The study provides insight into the neural correlates of prolonged grief in Shidu parents, highlighting the SMG's role in cognitive inhibition. These findings emphasise the need for comprehensive grief interventions to address the complex cognitive and emotional challenges faced by this unique bereaved population.

The Shidu parents had a delay in cognitive inhibition when performing the Stroop test, compared to the control group.Prolonged grief intensity was linked to decreased grey matter in the right amygdala and a potential increase in amygdala-to-whole-brain structural connectivity. These volumes were associated with prolonged grief symptoms related to emotions.A higher level of prolonged grief was also associated with reduced grey matter volume in the left supramarginal gyrus, mediating the relationship between prolonged grief and Stroop Time Inference score, which indicates cognitive inhibition.

Relationship between punishment sensitivity and risk-taking propensity.

Previous research has shown that, in both laboratory and real-world contexts, punishment sensitivity is associated with lower risk-taking propensity. The neural underpinnings of the association between punishment sensitivity and risk-taking, however, remain largely unknown. To address this issue, we implemented resting-state functional connectivity (RSFC) and voxel-based morphometry (VBM) methodologies to investigate the neural basis of their relationship in the current study (N=594). The behavioral results confirmed a negative association between punishment sensitivity and risk-taking propensity, which supports the hypothesis. The VBM results demonstrated a positive correlation between punishment sensitivity and gray matter volume in the right orbitofrontal cortex (ROFC). Furthermore, the results of the RSFC analysis revealed that the functional connectivity between ROFC and the right medial temporal gyrus (RMTG) was positively associated with punishment sensitivity. Notably, mediation analysis demonstrated that punishment sensitivity acted as a complete mediator in the influence of ROFC-RMTG functional connectivity on risk-taking. These findings suggest that ROFC-RMTG functional connectivity may be the neural basis underlying the effect of punishment sensitivity on risk-taking propensity, which provides a new perspective for understanding the relationship between punishment sensitivity and risk-taking propensity.

Progressive gray matter atrophy in parkinsonian variant of multiple system atrophy assessed by using causal structural covariance network.

INTRODUCTION: Multiple system atrophy (MSA), a rare neurodegenerative disease, is usually accompanied by brain morphological alterations. However, the causal relationships between progressive gray matter atrophy in MSA parkinsonian (MSA-P) subtype remain unknown. METHODS: In total, thirty-five MSA-P patients and thirty-five healthy controls (HC) underwent three-dimensional high-resolution T1-weighted structural imaging and voxel-based morphometry analysis. The causal structural covariance network (CaSCN) of gray matter was assessed to explore the causal relationships in MSA-P. RESULTS: With greater illness duration, the reduction of gray matter was originated from right cerebellum and progressed to bilateral cerebellum, fusiform gyrus, insula, putamen, caudate nucleus, frontal lobe, right angular gyrus, right precuneus, left middle occipital lobe and left inferior temporal lobe, then expanded to midbrain, bilateral para-hippocampus, thalamus, temporal lobe, inferior parietal lobule (IPL), precentral gyrus, postcentral gyrus and middle cingulate cortex. The right cerebellum was revealed to be the core node of the directional network and projected positive causal effects to bilateral cerebellum, caudate nucleus and left IPL. CONCLUSION: MSA-P patients showed progression of gray matter atrophy over time, with the right cerebellum probably as a primary hub. Furthermore, the early structural vulnerability of cerebellum in MSA-P may play a pivotal role in the modulation of motor and non-motor circuits at the structural level.

Brain morphometric changes in children born as small for gestational age without catch up growth.

Introduction: Most infants born as small for gestational age (SGA) demonstrate catch up growth by 2-4 years, but some fail to do so. This failure is associated with several health risks, including neuropsychological development issues. However, data on the morphological characteristics of the brains of infants born as SGA without achieving catch up growth are lacking. This study aims to determine the structural aspects of the brains of children born as SGA without catch up growth. Methods: We conducted voxel- and surface-based morphometric analyses of 1.5-T T1-weighted brain images scanned from eight infants born as SGA who could not achieve catch up growth by 3 years and sixteen individuals with idiopathic short stature (ISS) to exclude body size effects. Growth hormone (GH) secretion stimulation tests were used to rule out GH deficiency in all SGA and ISS cases. The magnetic resonance imaging data were assessed using Levene's test for equality of variances and a two-tailed unpaired t-test for equality of means. The Benjamini-Hochberg procedure was used to apply discovery rate correction for multiple comparisons. Results: Morphometric analyses of both t-statical map and surface-based analyses using general linear multiple analysis determined decreased left insula thickness and volume in SGA without catch up growth compared with ISS. Conclusion: The brain scans of patients with SGA who lack catch up growth indicated distinct morphological disparities when compared to those with ISS. The discernible features of brain morphology observed in patients born as SGA without catch up growth may improve understanding of the association of SGA without catch up growth with both intellectual and psychological outcomes.

Neural basis of false recognition in Alzheimer's disease and dementia with lewy bodies.

In Alzheimer's disease (AD), reports on the association between false recognition and brain structure have been inconsistent. In dementia with Lewy bodies (DLB), no such association has been reported. This study aimed to identify brain regions associated with false recognition in AD and DLB by analyzing regional gray matter volume (rGMV). We included 184 patients with AD and 60 patients with DLB. The number of false recognitions was assessed using the Alzheimer's Disease Assessment Scale' word recognition task. Brain regions associated with the number of false recognitions were examined by voxel-based morphometry analysis. The number of false recognitions significantly negatively correlated with rGMV in the bilateral hippocampus, left parahippocampal gyrus, bilateral amygdala, and bilateral entorhinal cortex in patients with AD (p < 0.05, family-wise error [FEW] corrected) and in the bilateral hippocampus, left parahippocampal gyrus, right inferior frontal gyrus, right middle frontal gyrus, right basal forebrain, right insula, left medial and lateral orbital gyri, and left fusiform in those with DLB (p < 0.05, FWE corrected). Bilateral hippocampus and left parahippocampal gyrus were associated with false recognition in both diseases. However, we found there were regions where the association between false recognition and rGMV differed from disease to disease.

Meta-analysis of structural and functional brain abnormalities in early-onset schizophrenia.

Background: Previous studies based on resting-state functional magnetic resonance imaging(rs-fMRI) and voxel-based morphometry (VBM) have demonstrated significant abnormalities in brain structure and resting-state functional brain activity in patients with early-onset schizophrenia (EOS), compared with healthy controls (HCs), and these alterations were closely related to the pathogenesis of EOS. However, previous studies suffer from the limitations of small sample sizes and high heterogeneity of results. Therefore, the present study aimed to effectively integrate previous studies to identify common and specific brain functional and structural abnormalities in patients with EOS. Methods: The PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases were systematically searched to identify publications on abnormalities in resting-state regional functional brain activity and gray matter volume (GMV) in patients with EOS. Then, we utilized the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software to conduct a whole-brain voxel meta-analysis of VBM and rs-fMRI studies, respectively, and followed by multimodal overlapping on this basis to comprehensively identify brain structural and functional abnormalities in patients with EOS. Results: A total of 27 original studies (28 datasets) were included in the present meta-analysis, including 12 studies (13 datasets) related to resting-state functional brain activity (496 EOS patients, 395 HCs) and 15 studies (15 datasets) related to GMV (458 EOS patients, 531 HCs). Overall, in the functional meta-analysis, patients with EOS showed significantly increased resting-state functional brain activity in the left middle frontal gyrus (extending to the triangular part of the left inferior frontal gyrus) and the right caudate nucleus. On the other hand, in the structural meta-analysis, patients with EOS showed significantly decreased GMV in the right superior temporal gyrus (extending to the right rolandic operculum), the right middle temporal gyrus, and the temporal pole (superior temporal gyrus). Conclusion: This meta-analysis revealed that some regions in the EOS exhibited significant structural or functional abnormalities, such as the temporal gyri, prefrontal cortex, and striatum. These findings may help deepen our understanding of the underlying pathophysiological mechanisms of EOS and provide potential biomarkers for the diagnosis or treatment of EOS.

Impact of Apolipoprotein E ε4 in Alzheimer's Disease: A Meta-Analysis of Voxel-Based Morphometry Studies.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is the most-prevalent form of dementia and imposes substantial burdens at the personal and societal levels. The apolipoprotein E (APOE) ε4 allele is a genetic factor known to increase AD risk and exacerbate brain atrophy and its symptoms. We aimed to provide a comprehensive review of the impacts of APOE ε4 on brain atrophy in AD as well as in mild cognitive impairment (MCI) as a transitional stage of AD. METHODS: We performed a coordinate-based meta-analysis of voxel-based morphometry studies to compare gray-matter atrophy patterns between carriers and noncarriers of APOE ε4. We obtained coordinate-based structural magnetic resonance imaging data from 1,135 individuals who met our inclusion criteria among 12 studies reported in PubMed and Google Scholar. RESULTS: We found that atrophy of the hippocampus and parahippocampus was significantly greater in APOE ε4 carriers than in noncarriers, especially among those with AD and MCI, while there was no significant atrophy in these regions in healthy controls who were also carriers. CONCLUSIONS: The present meta-analysis has highlighted the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, which emphasizes the critical influence of the allele on neurodegeneration, especially in the hippocampus. These findings improve the understanding of AD pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals at risk of AD who carry the APOE ε4 allele.

Gray Matter Volumes Mediate the Relationship Between Disease Duration and Balance Control Performance in Chronic Ankle Instability.

The relationship between structural changes in the cerebral gray matter and diminished balance control performance in patients with chronic ankle instability (CAI) has remained unclear. This paper aimed to assess the difference in gray matter volume (GMV) between participants with CAI and healthy controls (HC) and to characterize the role of GMV in the relationship between disease duration and balance performance in CAI. 42 participants with CAI and 33 HC completed the structural brain MRI scans, one-legged standing test, and Y-balance test. Regional GMV was measured by applying voxel-based morphometry methods. The result showed that, compared with HC, participants with CAI exhibited lower GMV in multiple brain regions (familywise error [FWE] corrected p < 0.021). Within CAI only, but not in HC, lower GMV in the thalamus (ß = -0.53, p = 0.003) and hippocampus (ß = -0.57, p = 0.001) was associated with faster sway velocity of the center of pressure (CoP) in eyes closed condition (i.e., worse balance control performance). The GMV in the thalamus (percentage mediated [PM] = 32.02%; indirect effect ß = 0.119, 95% CI = 0.003 to 0.282) and hippocampus (PM = 33.71%; indirect effect ß = 0.122, 95% CI = 0.005 to 0.278) significantly mediated the association between the disease duration and balance performance. These findings suggest that the structural characteristics of the supraspinal elements is critical to the maintenance of balance control performance in individuals suffering from CAI, which deserve careful consideration in the management and rehabilitation programs in this population.

Physical activity and hippocampal volume in young adults.

Evidence from previous studies suggests that physical activity (PA) may contribute to functional and structural changes in the hippocampus throughout the lifespan. However, there is limited evidence available regarding the young adult population. Additionally, the personality traits that may influence this association remain unclear. With a sample of 84 young adults (43 women; age 22.7 ± 2.8y; range 18-29), the main aim of the current study was to analyze the association between objective and self-reported measures of daily PA and hippocampus subfield gray matter volumes, and to examine the role of the personality trait of punishment sensitivity in this association. Our results showed that only moderate to vigorous levels of objectively measured PA were positively associated with the hippocampal CA2/CA3 volume. Moreover, punishment sensitivity correlated negatively with the objective measure of sedentarism and with self-reported measures of PA. However, regression analyses did not find any interaction between punishment sensitivity and PA in explaining individual differences in hippocampal volumes. Thus, our data suggest that intense PA may contribute to enhancing the hippocampal CA2/CA3 volume in young adults.

Associations between brain structures, cognition and dual-task performance in patients with mild cognitive impairment: A study based on voxel-based morphology.

BACKGROUND: This study aimed to explore the associations between brain structures, cognition, and motor control in participants with mild cognitive impairment (MCI), with a focus on dual-task performance. METHODS: Thirty MCI patients and thirty healthy controls were enrolled. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Structural magnetic resonance imaging data were analyzed using voxel-based morphometry (VBM) to calculate brain parenchyma volume and gray matter volume (GMV). Participants performed single- and dual-task Timed Up and Go (TUG) tests, and the correlations between significant GMV differences and task execution time was analyzed. RESULTS: MCI patients showed significantly lower MoCA scores, particularly in visuospatial/executive, attention, and delayed recall domains (p < 0.05). Dual-task TUG execution time was significantly increased in MCI patients (p < 0.05). The GMV in the right anterior lobe of the cerebellum and both insulae was positively correlated with visuospatial/executive scores (FDR-corrected, p < 0.05). The GMV of the right cerebellar anterior lobe and insula were significantly reduced in MCI patients (p < 0.05). The GMV of the right cerebellar anterior lobe was negatively correlated with dual-task execution time (r = -0.32, p = 0.012). CONCLUSION: Smaller GMV in the right anterior lobe of the cerebellum was associated with impaired dual-task performance, which may provide more evidence for the neural mechanisms of cognitive and motor function impairments in MCI.

Male-female spatio-temporal differences of age-related bone changes show faster bone deterioration in older women at femoral regions associated with incident hip fracture.

A better understanding of how age-related bone loss affects the fracture-prone regions of the proximal femur could lead to more informed fracture-prevention strategies. Therefore, the aim of this work was to assess the spatio-temporal distribution of bone deterioration in older men and women with aging. A subset of 305 men (74.87 ± 4.76 years; mean ± SD) and 371 age-matched women (74.84 ± 4.71 years) with no history of fracture was randomly selected from the Age, Gene/Environment Susceptibility-Reykjavik study. Quantitative computed tomography (QCT) scans of the left proximal femur obtained at baseline and at 5.2 ± 0.4 years follow-up were processed to assess local changes in volumetric bone mineral density (vBMD), cortical bone thickness (Ct.Th), and internal bone structure using voxel-based morphometry (VBM), surface-based statistical parametric mapping (surf-SPM), and tensor-based morphometry (TBM). Local parametric changes within each sex and sex differences in these changes were statistically assessed using linear mixed effects models allowing for baseline and time-varying covariates, yielding Student's t-test and p-value statistical maps of the proximal femur. The statistical maps indicated regions with significant parametric changes in each sex and with significant different parametric changes between older men and older women with aging. Older women manifested significantly larger losses in vBMD, (Ct.Th), and structure than older men, and they did so in regions where deficiency in these parameters has been associated with incident hip fracture. Using longitudinal QCT scans of the proximal femur and Computational Anatomy, we provided new insights into the higher fracture rates of the proximal femur in older women compared with men of similar age providing new information on the pathophysiology of osteoporosis.