Substantia nigra iron-related alterations, white matter disruption, and functional network dysconnectivity in temporal lobe epilepsy: a multimodal neuroimaging study
The authors' multimodal findings suggest subregion- and laterality-specific alterations in the SN of patients with TLE, with patterns differing between RTLE and LTLE.
Abstract
Although the substantia nigra (SN) has been implicated in temporal lobe epilepsy (TLE) pathophysiology, clinical studies remain scarce. This study aimed to characterize alterations in SN susceptibility, white matter (WM) microstructure, and functional connectivity (FC), as well as their associations with cognitive functions in TLE patients.
This study included 20 right-TLE (RTLE), 21 left-TLE (LTLE), and 23 healthy controls (HCs). Multimodal neuroimaging was used to assess the susceptibility, diffusion tensor imaging metrics, and FC of SN subregions. Group differences were examined by analysis of covariance. Exploratory correlation analyses were performed to evaluate associations between imaging metrics and cognitive performance.
RTLE patients showed higher susceptibility (post-hoc
P
= 0.015 vs. HCs;
P
= 0.002 vs. LTLE) and radial diffusivity (RD) (post-hoc
P
= 0.014 vs. HCs;
P
= 0.001 vs. LTLE) in the contralateral substantia nigra pars reticulata (SNr), alongside lower fractional anisotropy (FA) (post-hoc
P
= 0.009 vs. HCs;
P
= 0.006 vs. LTLE) in the contralateral substantia nigra pars compacta (SNc). LTLE patients exhibited decreased FA in the ipsilateral SNr (post-hoc
P
< 0.001 vs. HCs;
P
= 0.001 vs. RTLE) and reduced connectivity between the left SNc and the right superior parietal lobule (
P
= 0.026, cluster-level FDR corrected). Susceptibility and RD positively correlated in the contralateral SNr of RTLE cohorts (
r
= 0.564, uncorrected
P
= 0.010). Exploratory analyses suggested associations between SNr susceptibility, FA, and cognitive performance in TLE patients (all uncorrected
P
< 0.05).
Our multimodal findings suggest subregion- and laterality-specific alterations in the SN of patients with TLE, with patterns differing between RTLE and LTLE.
Different patterns of spontaneous brain activity associated with cognitive impairment in SCA3 are revealed, providing novel imaging evidence for the pathophysiological mechanisms underlying cognitive decline in these patients.
Background Primary insomnia is associated with cognitive impairment and subtle brain structural alterations; however, the relationship between white matter microstructural damage and glymphatic-related imaging changes remains unclear. This study investigated these alterations by jointly assessing peak width of skeletonized mean diffusivity (PSMD), diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), and enlarged perivascular spaces (EPVS). Methods This retrospective cross-sectional study included 64 right-handed adults, comprising 32 patients with primary insomnia and 32 healthy controls. All participants underwent standardized assessments of sleep, mood, and cognition, as well as 3.0-T magnetic resonance imaging, including diffusion tensor imaging and T2-weighted imaging. PSMD and the DTI-ALPS index were calculated from diffusion data, and EPVS in the basal ganglia and centrum semiovale were visually rated. Between-group differences were evaluated using independent-samples t-tests or Mann-Whitney U tests with false discovery rate correction. Ordinal logistic regression was used to adjust the basal ganglia EPVS comparison for demographic and vascular risk factors. Partial correlations were adjusted for age, sex, and education, with additional analyses further adjusted for depressive and anxiety symptoms. Results Patients with primary insomnia had higher PSMD values than healthy controls (P=0.047). Basal ganglia EPVS scores were higher in the unadjusted comparison (P=0.040), but this association was attenuated after adjustment for age, education, sex, diabetes, hypertension, smoking, and alcohol consumption (odds ratio =0.329, 95% confidence interval: 0.099–1.091; P=0.069). No significant between-group differences were found in the DTI-ALPS index (P=0.267) or centrum semiovale EPVS scores (false discovery rate-adjusted P=0.211). In the full sample, higher PSMD was associated with lower DTI-ALPS values (r=−0.331, adjusted P=0.019), higher basal ganglia EPVS scores (r=0.456, adjusted P=0.001), and lower Montreal Cognitive Assessment (r=−0.329, adjusted P=0.019) and Mini-Mental State Examination scores (r=−0.440, adjusted P=0.001). These associations remained significant after additional adjustment for depressive and anxiety symptoms. Conclusions Primary insomnia was associated with greater white matter microstructural heterogeneity, whereas evidence of glymphatic dysfunction was partial and indirect. Higher PSMD was related to glymphatic-related imaging markers and poorer cognitive performance; however, the small sample and cross-sectional design warrant cautious interpretation.
Qi Pan, Sai-Jie Zhu, Yu-Ning Lin et al.· Quantitative Imaging in Medi...· 0 citations
Background: Disrupted brain connectivity is central to understanding the neurobiological basis of autism spectrum disorder (ASD). Diffusion tensor imaging (DTI) has been extensively used to study brain microstructure in ASD, often revealing reduced fractional anisotropy (FA) and increased mean diffusivity (MD) in white matter. Methods: We conducted a multivariate random-effects meta-analysis with a multilevel structure to evaluate the extent to which FA and MD measures of white matter microstructure are altered in individuals with ASD compared to typically developing (TD) individuals, as well as how publication year, participant characteristics (age, sex, IQ), and laterality moderate the magnitude of the estimated differences. Our analysis included 881 effect sizes from 66 studies (NASD = 2231, NTD = 1856; Mage = 2–50 years) across 12 white matter tracts. Results: We found a significant moderate summary effect size for FA in nine tracts (corpus callosum, corticospinal tract, thalamic radiation, arcuate fasciculus, inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF], uncinate fasciculus, cingulum; Hedges’ g = −0.30 to −0.50), suggesting that individuals with ASD have lower FA compared to TD controls. Additionally, we found a significant moderate-to-large summary effect size for MD in eight tracts (corpus callosum, corona radiata, corticospinal tract, arcuate fasciculus, IFOF, ILF, SLF, uncinate fasciculus; Hedges’ g = 0.29 to 0.97), suggesting that individuals with ASD have higher MD compared to TD controls. Furthermore, moderators demonstrated tract- and metric-specific effects. Conclusions: Our findings highlight the complex, multidimensional nature of white matter microstructure alterations observed in ASD.
Christy D Yoon, Andrew L. Alexander, B. Travers et al.· Biological Psychiatry: Cogni...· 0 citations
The cholinergic basal forebrain and subcortical gray matter have previously been implicated in Parkinson’s disease (PD), but the relationship between the symptomology of PD, including cognitive impairment, and specific patterns of damage remains unclear. Additionally, understanding the impact of fitness, including motor skills, on brain structure remains a knowledge gap. In this study, we examine a longitudinal cohort of PD patients using advanced microstructural analysis derived from diffusion MRI, alongside volumetric and connectivity components. These imaging metrics are compared to comprehensive cognitive and motor skill fitness metrics. Although the volumetric components well characterize change across the longitudinal timescale, the microstructural analysis was related to a number of composite cognitive scores, including attention, executive function, cognition, language, and the level of motor skill fitness. We further assess the connectivity of the cholinergic basal forebrain, particularly the nucleus basalis of Meynert in area 4 (CH4), and find that connectivity between CH4 and the thalamus is associated with motor skill fitness. The pattern of microstructural results suggests that increased cellularity may support reduced cognitive decline in individuals with PD and greater motor skill fitness.
B. Newman, R. Foreman, E. Donahue et al.· Frontiers in Neurology· 0 citations
Background Presbycusis is characterized by progressive age-related hearing loss and is often associated with cognitive decline and mental health disorders. Objective This study aimed to investigate gray matter volume (GMV) alterations and structural covariance network (SCN) reorganization in presbycusis patients via magnetic resonance imaging (MRI) and graph theory analysis. Methods A total of 129 presbycusis patients and 121 age-matched healthy controls (HCs) underwent neuropsychological assessments and high-resolution T1-weighted MRI. The voxel-based morphometry (VBM) method at the region of interest (ROI) level and the graph theory analysis method of the SCN based on GMV were used to study the impact of presbycusis on brain structure. Results Patients presented altered nodal topological properties in multiple brain regions, including the right insula, left hippocampus, bilateral superior frontal gyrus, and occipital cortices. Significant differences were observed in the characteristic path length (Lp) and normalized characteristic path length (λ) between the groups (p < 0.05). Cognitive assessments revealed impairments in executive function, memory, and visual-spatial abilities (p < 0.05). Conclusion Presbycusis is associated with GMV reduction and SCN reorganization across sensory, cognitive, and emotional brain networks. Compensatory neural mechanisms, such as enhanced visual processing, may alleviate the adverse impacts of auditory deprivation. These findings elucidate the neuroanatomical basis of cognitive decline in presbycusis and highlight the necessity of early clinical intervention.
Qi Yan, Ying Wang, Li Xu et al.· Frontiers in Aging Neuroscie...· 0 citations
Background: Neuroimaging studies implicate network alterations in functional motor disorder (FND-motor), yet white matter remains poorly characterized. Objectives: To characterize white matter microstructure in FND-motor relative to healthy (HCs) and psychiatric (PCs) controls and examine symptom associations. Methods: Fifty individuals with FND-motor, 50 age- and sex-matched HCs, and 50 PCs matched on age, sex, depression, anxiety, and post-traumatic stress disorder severity underwent multi-shell diffusion MRI. Voxel-based analyses examined whole-brain white matter using diffusion tensor imaging (fractional anisotropy [FA], mean diffusivity [MD]) and neurite orientation dispersion and density imaging (NODDI) (neurite density index [NDI], orientation dispersion index, and free water fraction [FWF]) metrics. Cross-metric convergence was characterized using atlas-based tract overlap analyses and probabilistic tractography. Associations with FND symptoms and transdiagnostic physical symptoms were also evaluated. Results: Compared with HCs, FND-motor showed higher FA/NDI and lower MD/FWF, predominantly in the middle cerebellar peduncle. Compared with PCs, differences were limited to lower MD/FWF, involving the corpus callosum, middle cerebellar peduncle, and left inferior longitudinal fasciculus. Greater FND symptom severity was associated with a lower FA/NDI and higher MD/FWF in the corpus callosum and right-lateralized association and projection pathways, whereas greater transdiagnostic physical symptom burden across FND-motor and PCs was associated with higher FA and lower MD/FWF in the middle cerebellar peduncle. Conclusions: This study provides a comprehensive multi-metric diffusion-weighted characterization of white matter microstructure in FND-motor relative to both HCs and PCs - highlighting cortico-cerebellar connections via the middle cerebellar peduncle as distinct in FND-motor and associated transdiagnostically with physical symptom burden.
C. Westlin, C. Bleier, A. Guthrie et al.· medRxiv· 0 citations
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