Search Results (153)

Background/Objectives: Alzheimer’s disease is one of the most prevalent forms of dementia and is accompanied by progressive anatomical changes within the brain. However, large-scale analyses that compare global and local anatomical differences across age, sex, diagnosis, and repeated scans remain limited. Methods: We constructed a cohort of 1385 total participants, with 3593 scans, who were diagnosed as cognitively normal or with Alzheimer’s at entry into the study. Global and medial temporal brain volumes from 3T MRI scans were normalized to intracranial volume, and we used a linear mixed-effects model to analyze the association between participants’ age, sex, and diagnosis while also accounting for multiple follow-up scans. Diagnosis-dependent relationships between global and medial temporal structures, brain parenchymal and hippocampal fractions, and body mass index were also calculated. Results: Older age was associated with a decrease in normalized brain volume across each region of interest. In general, AD participants had significantly lower volumes than cognitively normal individuals, with a greater degree of difference in medial temporal regions. Global measures did have different degrees of separation, with gray matter showing greater separation than white matter. Exponential model equations showed that the AD group generally had a greater age-associated percentage decrease across-ROI/ICV association. BMI nor BMI x diagnosis was significantly associated with brain volumes within the model, while the exploratory pooled pTau217 analysis showed it was 4.6 times higher in AD and negatively associated with most morphometric areas. Conclusions: This large, integrated analysis supports the use of MRI morphometry as a valuable tool to directly compare AD-associated differences across global and medial temporal areas and also evaluate diagnosis-dependent relationships across anatomically related structures. Findings indicate that medial temporal measures provide a greater AD vs. CN separation than global measures, with GM being more sensitive than WM. Plasma pTau217 also gives biological context, which helps suggest that MRI results should be interpreted with multiple clinical and biological factors. Full article

Alzheimer’s disease (AD) is the leading cause of dementia and disproportionately affects women, who experience a higher lifetime risk and more rapid structural brain changes than men. Reliable imaging biomarkers are essential for detecting these changes, although their estimation may be influenced by voxel geometry, image resolution, and segmentation methodology. In this study, magnetic resonance imaging (MRI) scans from 40 female participants with AD obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were analyzed using the Computational Anatomy Toolbox 12 (CAT12), implemented within Statistical Parametric Mapping 12 (SPM12), and Materialise Mimics to identify structural biomarkers associated with neurodegeneration. Cortical thickness, gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and total intracranial volume (TIV) were quantified, while Brain Parenchymal Volume (BPV) and Brain Parenchymal Fraction (BPF) were calculated to assess global brain tissue preservation. The analyses demonstrated characteristic AD-related changes, including cortical thinning, GM loss, ventricular enlargement, and increased CSF volume. Significant correlations among cortical thickness, tissue volumes, BPV, and BPF further supported their complementary role in characterizing disease-related structural changes. Overall, these findings suggest that MRI-derived measures of cortical thickness, tissue volumes, BPV, and BPF provide useful structural biomarkers of AD and emphasize the importance of considering voxel geometry and segmentation methodology when evaluating neuroimaging biomarkers. Full article

Background. Bipolar disorder (BD) is characterized by circadian rhythm disruptions, contributing to mood instability and recurrence. These rhythms are regulated by clock genes in the suprachiasmatic nucleus, including the CLOCK 3111T/C (rs1801260) polymorphism that has been linked to delayed sleep phase, insomnia, and altered circadian expression. Both circadian disruption and adverse childhood experiences (ACEs) correlate with white matter (WM) abnormalities. We hypothesized that rs1801260 moderates ACE effects on WM microstructure in BD. Methods. We enrolled 137 BD patients in depressive episodes. Participants underwent 3T MRI, rs1801260 genotyping and completed the Childhood Trauma Questionnaire. Moderation (PROCESS) tested genotype–ACE interactions on whole-brain fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) values; voxel-wise TBSS (FSL Randomize) localized effects, with sex-stratified and GLZ analyses for genotype–sex interactions. Results. Significant rs1801260 × ACE interactions emerged for FA and RD across physical abuse, physical neglect, and emotional neglect. Higher ACEs were associated with lower FA/higher RD only in CLOCK rs1801260*C carriers, mainly females. TBSS showed physical abuse × rs1801260 interaction in the corpus callosum, internal capsule and corona radiata. A GLZ model with separate slopes confirmed physical abuse × sex × rs1801260 interactions on FA/RD, with effects specific to female CLOCK rs1801260*C carriers but genotype-independent in males. Conclusions. rs1801260 moderates the impact of early-life stress on WM integrity in BD, particularly in emotion-regulation tracts, with CLOCK rs1801260*C carriers showing greater vulnerability. Effects are genotype-specific in females but genotype-independent in males, possibly reflecting sex-dimorphic neurodevelopment driven by estrogen–androgen modulation of clock genes, HPA axis, and myelination. Full article

Background/Objectives: Normal-appearing white (WM) and gray (GM) matter outside focal demyelinating lesions (WMH) has been found impaired in many diseases and normal aging. The present study aimed to compare global GM and WM alterations in patients with multiple sclerosis (MS), Parkinson’s disease, long COVID (LC) and normal aging. Methods: The study population comprised 196 participants including patients with MS (n = 42), PD (n = 16), LC (n = 75), and healthy volunteers (n = 63). All participants underwent MR scanning using the fast macromolecular fraction (MPF) mapping protocol and routine clinical sequences. MPF in global normal-appearing WM, GM, and mixed WM-GM was measured after exclusion of segmented focal lesions. To eliminate the influence of gender, age, and brain atrophy on the results, the corresponding covariates were included in the analysis. Results: Significant WMH volume increase and MPF decrease in global WM, WM-GM, and GM were found both in normal aging (75–85 years) and MS, PD, and LC patients (except for WM and WMH volume in LC patients). The greatest MPF decrease was observed in MS patients. The youngest (18–24 years) controls had a significant MPF decrease in global WM, WM-GM, and GM compared to middle-aged (35–44 years) participants. Among LC patients, the greatest global MPF reduction was found in patients with depression and insomnia as COVID-19 complications. In healthy controls, the peak age of myelination was estimated as 42.2 years for WM, 46.5 years for WM-GM, and 45.4 years for GM. Significant correlations were found between MPF and EDSS in MS patients (r = −0.71 in GM, r = −0.58 in WM-GM, r = −0.44 in WM) and stage of PD in PD patients (r = −0.58 in GM, r = −0.55 in WM-GM, r = −0.52 in WM). Conclusions: MPF mapping showed high sensitivity to age-related and disease-related differences in brain myelination, particularly in GM. Our results confirm the feasibility of using MPF mapping in large-scale clinical studies. Full article

Background and Objectives: Ocrelizumab significantly reduces inflammatory activity in relapsing-remitting multiple sclerosis (RRMS), but treatment-induced brain volume change and the specific contributions of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) compartments to global atrophy and pseudoatrophy remain unclear. We aim to characterize the longitudinal and infusion-related dynamics of brain compartments in ocrelizumab-treated RRMS patients and identify the clinical and time-dependent predictors of these changes. Methods: Fifty-one RRMS patients were enrolled in a four-year prospective study. Brain volumes, including WM, GM, peripheral GM (pGRAY), CSF, ventricular CSF (vCSF), total brain volume (TBV) and their respective fractions (WMF, GMF, BPF) were evaluated by absolute time points (baseline to 4 years) and infusion-based intervals (baseline to 8th infusion), before and after each ocrelizumab cycle. Correlations between brain volume measures and the Expanded Disability Status Scale (EDSS), as well as time-dependent variables such as age, age at onset and disease duration (DD) were examined. Results: Mean age was 41.62 ± 9.76 years, mean age at onset 28.17 ± 7.85, mean DD 12.89 ± 8.55 years and mean EDSS 3.26 ± 1.5, indicating moderate disability. During the study, vCSF and CSF significantly increased, whereas WM, WMF, TBV and BPF significantly decreased. Notably, these measures exhibited marked, non-linear, and transient changes during the first year of ocrelizumab treatment, consistent with pseudoatrophy, likely reflecting early resolution of inflammation rather than irreversible tissue loss. GM and pGRAY remained relatively stable, with minor early increases. Correlation analyses revealed that higher EDSS scores, older age, later age at onset and longer DD were associated with lower GM, pGRAY and TBV, emphasizing the interplay between disease progression and development of brain volumetric patterns. Conclusions: Ocrelizumab-induced pseudoatrophy is predominantly WM-driven and age-dependent, with WM shrinkage being the main contributor to parenchymal loss and secondary widening of CSF spaces. Age remains a powerful predictor of brain atrophy and neurological impairment. These findings provide mechanistic insights into the biological basis of this modulation in RRMS. Full article

Background/Objectives: White matter (WM) tract detection is critical in the presurgical planning of tumor resection. However, standard-of-care imaging techniques including T₁-weighted, T₂-weighted, and Diffusion Tensor Imaging (DTI) often fail to identify WM tracts within edematous regions. In T₁/T₂-weighted imaging, edema increases extracellular water and reduces tissue contrast, and in diffusion-weighted imaging, edema elevates isotropic diffusion, reducing sensitivity to anisotropic diffusion along WM tracts. Advanced biophysical diffusion modeling techniques such as Neurite Orientation Dispersion and Density Imaging (NODDI) and the Standard Model (SM) address this limitation by compartmentalizing the diffusion signal into free-water, intra-neurite, and extra-neurite contributions. Here, we test if biophysical multi-compartment models can robustly identify WM tracts and recover tractography streamlines within edematous regions. Methods: In this study, we use multi-shell diffusion-weighted MRI data obtained from patients with meningiomas—a pathology allowing for isolation of the effects of edema without the confounding effects of tumor cell invasion. We compared FA from standard and free-water-corrected DTI, the orientation dispersion index (ODI) from NODDI, and P₂ (a scalar descriptor of fiber orientation coherence) from the SM fODF in edematous and unaffected contralateral WM regions. As a proof of concept, we visually evaluated the tractography performance across models. Results: Our results show that (1 − ODI) and P₂ values in edema remained close to within-subject contralateral measurements, contrasting with substantial reductions in FA and FW-FA. (1 − ODI) showed a small but statistically significant increase in edema (~8%, p = 0.02), while P₂ was unchanged. Conclusions: These results highlight the potential of biophysical diffusion models for preoperative mapping in edema. Full article

Background/Objectives: Preservation of critical white matter (WM) pathways is essential for maximizing surgical safety in neuro-oncology and functional neurosurgery. Constrained spherical deconvolution (CSD) offers superior modeling of complex fiber architecture compared to diffusion tensor imaging (DTI). This case series evaluates the clinical utility of CSD in surgical planning and intraoperative navigation. Methods: A retrospective review of 20 patients (15 brain tumors, 5 functional disorders) treated between September 2022, and September 2024 was performed. All patients underwent preoperative MRI with CSD-based reconstruction of eloquent WM tracts. Clinical presentation, tract involvement, surgical strategy, and postoperative outcomes were analyzed. Results: CSD reliably reconstructed CST, AF, IFOF, OT, and DRTT depending on tumor location or DBS target. Compared with standard DTI, CSD provided improved delineation of tract extent and tumor–tract interfaces. Gross total resection (GTR) was achieved in all tumor patients without new neurological deficits. DBS cases showed precise correlation between stimulation thresholds, side effects, and CSD-predicted distances to critical WM tracts. DRTT targeting resulted in marked clinical improvement in Holmes tremor. Conclusions: CSD enhances anatomical accuracy in WM tract visualization, supporting safer resections in eloquent areas and improving DBS targeting. Its integration into routine workflow may optimize neurosurgical outcomes. Full article

Background/Objectives: Western and Mediterranean diets have divergent effects on the brain. The gut microbiome may mediate diet effects, and specific microbes may be particularly significant contributors to these processes. Oscillospira, a genus of gut-dwelling bacteria, has been implicated as a key microbial target. Other peripheral contributors may include short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), insulin resistance, and microbial translocation. Methods: We determined the effects of long-term (31 months, ~9 human years) consumption of a Mediterranean or Western-type diet on Oscillospira abundance, fecal SCFAs, plasma BCAAs, soluble CD14 (sCD14), and insulin responses in a randomized trial of 38 middle-aged female cynomolgus macaques (Macaca fascicularis). We determined diet effects and associations between dependent variables. For variables that were affected by diet composition and significantly associated with Oscillospira, we tested whether Oscillospira abundance mediated the effects of diet. Results: The Mediterranean diet resulted in higher Oscillospira (p = 0.004) and SCFAs (acetate p = 0.002; propionate p = 0.049) and lower BCAAs (isoleucine p = 0.035; leucine p = 0.007; valine p < 0.001). The Western diet increased insulin resistance (p = 0.040) and WM loss (p = 0.011). Oscillospira abundance was negatively associated with BCAAs (leucine p = 0.007; valine p = 0.005) and insulin resistance (insulin AUC: p = 0.024; increase in insulin AUC from pretreatment: p = 0.020), with trends for isoleucine (p = 0.066) and sCD14 (p = 0.103). Oscillospira abundance was positively associated with acetate (p = 0.032) and WM volume changes (p = 0.012). Oscillospira abundance significantly mediated the effects of diet on white matter volume changes (p = 0.020) and on insulin resistance (insulin AUC: p = 0.012 at study end; increase in insulin AUC during study: p = 0.020), presenting potential pathways through which diet may influence the brain. Conclusions: These findings suggest that diet-driven differences in Oscillospira are linked to metabolic regulation and white matter integrity, and Oscillospira may mediate the relationships. The results highlight a potential role for diet–microbiome interactions in shaping metabolic and brain aging trajectories. Full article

With the increasing prevalence of neurodegenerative diseases driven by population aging, imaging-based biomarkers are needed to quantify brain aging at an early stage. Brain age, which estimates structural brain aging relative to chronological age, has emerged as a useful indicator. Prior work has mainly used T1-weighted MRI with deep learning models such as convolutional neural networks (CNNs) or transformers; however, many approaches insufficiently capture three-dimensional structural continuity and localized anatomical patterns, and tissue-specific aging in gray matter (GM) and white matter (WM) is often treated as auxiliary. To address these limitations, we propose a 3D Global–Patch Transformer framework for brain age prediction that directly processes volumetric data while jointly learning global brain structure and local anatomical features. Our model runs global and patch pathways in parallel and explicitly incorporates GM and WM structural maps alongside T1-weighted MRI to encode tissue-specific aging signals. Experiments on multiple public datasets, including IXI and OASIS, show that the proposed method reduces mean absolute error (MAE) by approximately 10–15% compared with CNN-based and single-input transformer baselines, with notably improved performance in older populations, highlighting the value of tissue-level structural information for brain age estimation. Full article

Background/Objectives: Osmotic demyelination syndrome (ODS) causes marked myelin loss with relative axonal preservation. We used diffusion tensor imaging (DTI) to longitudinally assess white matter (WM) changes, hypothesizing that radial diffusivity (RD) would show dynamic recovery alongside clinical improvement. Methods: A 40-year-old woman with ODS and five age-matched female controls underwent DTI at 7 weeks and 6 months post-onset. Metrics were extracted from 27 WM tract categories using atlas-based regions of interest. Lesions were defined by directional dual thresholds (RD_d ≥ 2.0, axial diffusivity [AD] ≤ −2.0, or fractional anisotropy [FA] ≤ −2.0) and confirmed using the Crawford–Howell test with Benjamini–Hochberg FDR correction (q ≤ 0.05). Longitudinal percent change (Δ%) was compared using the Friedman test with Bonferroni-corrected Wilcoxon post hoc tests (α = 0.017). Results: Serum sodium increased from 126 to 138 mmol/L within 24 h, followed by a severe neurological deficit; near-complete recovery by 6 months. At 7 weeks, RD-defined lesions were detected in 10/27 tracts (37.0%)—1/6 brainstem-related and 9/21 non-brainstem—indicating widespread myelin-predominant injury. No AD- or FA-based lesions met criteria, although AD increase in the cingulate gyrus was significant. From 7 weeks to 6 months, the mean Δ% was −0.40 ± 9.38% (AD), −4.73 ± 9.73% (RD), and +7.94 ± 7.53% (FA). Changes differed across metrics (χ²(2) = 24.07, p = 5.92 × 10⁻⁶), with greater RD and FA changes than AD. Conclusions: Early RD-predominant abnormalities preceded RD reduction and FA increase during recovery, consistent with restoration of myelin-related microstructure. Larger studies are warranted. Full article

Background/Objectives: Emerging evidence suggests that enlarged perivascular spaces (EPVS), which play a significant role in brain fluid exchange and waste removal, may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). In this study, we aimed to explore the shared genetic link and causal effect between EPVS and ALS. Methods: This study used publicly available summary data from the largest and most recent genome-wide association studies (GWAS) on EPVS (n = 40,095) and ALS (n = 138,086) in European populations. EPVS were assessed in the hippocampus (EPVS-HIP), basal ganglia (EPVS-BG), and white matter (EPVS-WM). We used linkage disequilibrium score regression (LDSC) to investigate the genetic correlation. Multi-trait analysis of GWAS (MTAG), Cross-Phenotype Association (CPASSOC) analysis, and genetic colocalization analysis were performed to identify shared risk loci. Bidirectional Mendelian randomization analysis was used to investigate the causal relationship. Results: A negative genetic correlation was observed between EPVS-WM and ALS after Bonferroni correction (rg = −0.24, p < 0.01). No significant correlations were observed between ALS and EPVS-HIP (rg = −0.03, p = 0.79) or EPVS-BG (rg = 0.01, p = 0.91). Four significant loci including rs113247976 in KIF5A and rs118082508 in SDR9C7 were identified as potential pleiotropic loci of the relationship. None of these loci demonstrated evidence of genetic colocalization. Furthermore, Mendelian randomization analysis revealed no causative effect in either direction. Conclusions: EPVS-WM and ALS may share part of their genetic architecture, but no evidence for a causal relationship was observed. Future research is needed to further refine these relationships. Full article

Background: During the first 2 years of life, human white matter (WM) undergoes rapid development, establishing a structural foundation for later neurodevelopment. Methods: We conducted a mixed-model analysis for repeated measures to investigate the developmental trajectories of functionally distinct 26 WM pathways between preterm and full-term groups during the first 2 years of life using diffusion tensor imaging (total scans = 174; preterm = 58; full-term = 23). Results: We observed significant differences between the preterm and full-term groups in the developmental trajectories associated with motor function (left corticospinal tract and left pre-primary motor cortex connection tracts), visual processing (bilateral pathway between the V1/V2 and V4, PV-MT, pathway connecting the V1/V2 and V5/MT, and optic radiation), and cognition (genu, body, and splenium of the corpus callosum). Furthermore, inter-regional correlation matrix analysis revealed stronger connectivity, specifically within motor- and visual-related pathways, in the preterm group than that for the full-term group, suggesting an adaptive mechanism that supports circuit-level resilience following preterm birth. Moreover, in the model investigating the associations between the WM individual rate of change and long-term neurodevelopmental outcomes, the middle cerebellar peduncle (MCP) tract showed the strongest associations with motor scores, suggesting that faster maturation of the MCP tract may enhance motor functions as a key compensatory mechanism following preterm birth. Conclusions: Delineating the longitudinal change rates of specific WM pathways not only deepens our understanding of the neurodevelopmental sequelae of prematurity but also highlights their potential as early biomarkers to guide timely interventions. Full article

Perinatal asphyxia (PA) remains a common cause of neonatal death and long-term disability, with an incidence of 20 per 1000 live births. Even mild PA, without significant neurological distress at birth, is linked to neurodevelopmental disorders. Premature babies are at high risk for both PA and long-term neurobehavioral deficits. The use of peripherally inserted central venous catheters in neonatal intensive care units has reduced mortality and morbidity in preterms. Given their prevalent use and associated complications, such as thrombosis, the present study aimed to investigate the effects of hypoxia associated with the ligation of the external jugular vein (JH model) in 5-day-old mice, whose central nervous system development shares similarities with that of human preterms. Diffuse white matter (WM) injury is associated with later neurodisabilities following very premature birth before 32 weeks of gestation. The present study aimed to investigate whether the murine JH model replicates a key phenotype of non-cystic WM injury, namely permanent hypomyelination and sensorimotor deficits. The second aim was to determine whether sodium phenylbutyrate (PBA), which is already prescribed in neonates for another indication, could prevent these disabilities. JH induced lasting dysmyelination in males, not prevented by PBA, contrary to the discrete JH-induced neurobehavioral deficits observed in both sexes in the short and long term. Full article

Purpose: Focal cortical dysplasia (FCD) is a common developmental malformation disease of the cerebral cortex. Although mounting evidence has suggested that FCD lesions have variable locations and topographies throughout the cortex, few studies have explored consistencies in structural connectivity among different lesion types. In this study, we analyzed microscopic structural changes via lesion analysis and explored structural changes in nonlesion regions across the brain. Methods: Diffusion tensor imaging (DTI) and magnetization transfer imaging were used to compare FCD lesions and contralateral normal appearing gray/white matter (cNAG/WM). Voxel-based morphometry was calculated for 28 children with FCD and 34 sex- and age-matched healthy participants. DTI indices of the FCD and healthy control groups were analyzed via the tract-based spatial statistic method to evaluate the microstructure abnormalities of WM fiber tracts in individuals with FCD. Results: In terms of FCD lesions, compared with those of the cNAG, the fractional anisotropy (FA) values were decreased, and the mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were increased; the magnetization transfer ratios were also decreased. In terms of whole-brain changes due to FCD, compared with the healthy control group, the FCD group showed a decrease in the volume of the right hippocampus and left anterior cingulate cortex. FCD patients had lower FA values, higher MD values, lower AD values, and mainly increased RD values in relation to WM microstructure. Conclusions: Microstructural abnormalities outside lesion regions may be related to injury to the epileptic network, and the identification of such abnormalities may complement diagnoses of FCD in pediatric patients. Full article

Background: Mindfulness and mind wandering are cognitive traits central to attentional control and psychological well-being, yet their neural underpinnings are yet to be elucidated. This study aimed to identify structural brain networks comprising gray matter (GM) and white matter (WM) that predict individual differences in mindfulness and distinct mind wandering tendencies (deliberate and spontaneous). Methods: Using structural MRI data and self-report measures from 76 participants, we applied an unsupervised data-fusion machine learning technique (parallel independent component analysis) to identify GM and WM networks associated with mindfulness and mind wandering traits. Results: Our analysis revealed several distinct brain networks linked to these cognitive constructs. Specifically, one GM network involving subcortical regions, including the caudate and thalamus, positively predicted mindfulness and deliberate mind wandering, while negatively influencing spontaneous mind wandering through the mediating role of the mindfulness facet “acting with awareness.” In addition, two separate WM networks, predominantly involving frontoparietal and temporal regions, were directly associated with reduced spontaneous mind wandering. Conclusions: These findings advance our current knowledge by demonstrating that specific GM and WM structures are involved in mindfulness and different forms of mind wandering. Our results also show that the “acting with awareness” facet has a mediating effect on spontaneous mind wandering, which provides supporting evidence for attentional and executive control models. These new insights into the neuroanatomical correlates of mindfulness and mind wandering have implications for ongoing research in the growing topic of mindfulness and mind wandering, mindfulness-based interventions, and other clinical applications. Full article