These findings provide robust evidence that multiscale MRI profiling can identify FCD signatures and contribute to in-vivo subtyping and the novel use of myeloarchitecture profiling and contextualization with macro-scale brain gradients provides new avenues to understand intracortical alterations and the embedding of FCD lesions into broader organizational patterns.
Multi-site findings demonstrate marked thalamic circuit fragmentation in TLE, and robustly showed subdivision-specific effects, which point to both mesiotemporal co-lateralization as well as broader system-level involvement.
Rui Ding, K. Xie, Judy Chen et al.· bioRxiv· 0 citations
A hypometabolic gradient is identified in TLE, which covaries with cytoarchitectonic organization, microstructural changes, and hippocampal-neocortical interactions and provides a biologically grounded framework for precise surgical planning, emphasizing that targeting severe hypometabolism may optimize prognosis.
J. Mo, F. Fadaie, J. Lam et al.· medRxiv· 0 citations
BACKGROUND
Despite recent advances, the pathophysiology of functional neurological disorder (FND) remains incompletely understood. Structural neuroimaging studies have identified grey matter alterations in somatomotor, salience, limbic, and default mode network associated areas, although findings are inconsistent. Mega-analyses, which combine individual-level data across studies, can help clarify structural alterations.
METHODS
We conducted a mega-analysis of brain structural morphometrics derived from T1-weighed MRI scans from fifteen international research groups. After across-site harmonisation with ComBat, we compared 493 functional motor and seizure patients with 564 healthy controls. Euler numbers were included to account for head motion.
RESULTS
The FND cohort showed reduced cortical thickness in the bilateral superior frontal gyri (left d = 0.22, right d = 0.21) and sulci (d = 0.22 & 0.23), bilateral superior precentral sulcus (d = 0.22 & 0.26), right precentral gyrus (d = 0.25), right paracentral gyrus and sulcus (d = 0.23), right cuneus (d = 0.23), and right inferior opercular gyrus (d = 0.21); reduced left postcentral gyrus surface area (d = 0.25) and right hippocampal volume (d = 0.22). No regions were different in relative surface area. There were no associations between morphometrics and illness duration, or lifetime history of depression or anxiety. Differences between motor and seizure variants were not identified.
CONCLUSIONS
This large mega-analysis suggests subtle morphometric differences, particularly in prefrontal and motor regions. This may represent predisposing vulnerabilities, compensatory mechanisms, or FND-specific alterations. Improved neuropsychiatric characterisation of FND research cohorts will help further contextualise the biological relevance of structural alterations.
Matt Butler, M. Vignando, J. Allendorfer et al.· Biological Psychiatry· 0 citations
Background and Objectives Disease-causing variants in the syntaxin-binding protein 1 (STXBP1) gene are among the most common genetic causes of developmental and epileptic encephalopathies and are associated with a wide phenotypic spectrum. Qualitative neuroimaging studies are usually unrevealing or uncover variable MRI findings, including cortical atrophy, thin/dysmorphic corpus callosum (CC), hypo/delayed myelination, and focal cortical dysplasia (FCD). Methods We used quantitative MRI methods to estimate abnormal brain properties of the cortical mantle and volume of subcortical structures in patients with STXBP1 encephalopathy and age- and sex-matched controls. We performed a region-of-interest group statistical analysis between patients with STXBP1 encephalopathy and controls by multivariable linear regression models to identify morphometric patterns and to evaluate the effect of the group (patients/controls) on morphometric features. We conducted a longitudinal analysis to estimate the volumetric changes in 4 patients with serial MRI scans at different ages. We calculated the association between the structural alterations and the known STXBP1 expression levels and explored associations between morphometric and volumetric features and clinical findings (age at seizure onset, intellectual disability [ID]) and genetic variants. Results Our analysis included 24 patients and 48 controls and revealed widespread cortical thickening, reduced frontal and occipital surface area, and reduced white matter (left/right hemisphere pvalue = 0.005/0.022) and CC (pvalue < 0.050) volumes. The longitudinal analysis highlighted that brain growth trends were lower than the average trend in the control cohort. In patients with more severe ID, we observed a significantly increased volume of the lateral ventricles (left/right pvalue = 0.049/0.030) and CSF (pvalue = 0.019). Patients with missense variants exhibited more altered morphometric values and more severe reductions of white-matter volumes, possibly because of a dominant negative effect of variants. Two patients were operated for intractable focal seizures, and the histopathologic substrate was FCD-I. Discussion The altered cortical patterns and WM reductions we observed in STXBP1 encephalopathy might be the structural counterpart of the widespread impaired neurotransmitter release caused by a dysfunctional syntaxin-binding protein. The 2 histopathologic observations we describe, bring to 4 the number of reported patients with STXBP1 encephalopathy and FCD-I, suggesting cortical dyslamination as the architectural substrate for the abnormal morphometric parameters and reduced surface areas.
M. Lenge, Alice Dainelli, S. Balestrini et al.· Neurology: Genetics· 0 citations
Background This study aimed to investigate cortical and subcortical changes in GBA-related Parkinson’s disease (GBA-PD) patients and evaluate the ability of these structural changes to identify patients with GBA-PD. Methods T1-weighted magnetic resonance imaging images were obtained for 86 participants, including 19 GBA-PD, 42 idiopathic PD (iPD) cases, and 25 healthy controls (HCs). Cortical thickness, cortical volume, and subcortical volume (including amygdala volume) were calculated to identify cortical and subcortical morphological alterations and correlated with cognitive function. To reduce overfitting, classification was performed using least absolute shrinkage and selection operator (LASSO)-penalized logistic regression with nested stratified 5-fold cross-validation. Results Compared with iPD patients, GBA-PD patients had reduced cortical thickness in the left superior temporal sulcus (STS.L) and left superior occipital gyrus (SOG.L) as well as reduced cortical volume in the SOG.L and right amygdala subregion, including the basal nucleus, accessory basal nucleus, cortico-amygdaloid transition area, and paralaminar nucleus. Cortical thickness and cortical volume in the SOG.L, right basal nucleus, and right paralaminar nucleus were negatively correlated with memory and visuospatial function, respectively. After internal cross-validation, the exploratory LASSO-based model combining age, sex, and significant cortical and subcortical morphometric features showed moderate discrimination between GBA-PD and iPD, with an area under the curve of 0.821, sensitivity of 56.3%, and specificity of 88.1%. Conclusion GBA-PD patients showed distinct patterns of cortical thickness and volume thinning, as well as amygdala subregional atrophy. These cortical and subcortical changes may contribute to future exploratory phenotypic characterization or patient stratification, but validation in larger independent cohorts is required.
Jingru Ren, Yi Xing, Hao Zhou et al.· Frontiers in Aging Neuroscie...· 0 citations
The aim of this study was to quantitatively characterize MRI signal-intensity (SI) abnormalities in focal cortical dysplasia (FCD) and to compare expert visual lesion delineation with objective SI metrics across conventional structural MRI sequences and quantitative T1 mapping (qT1). Thirteen pediatric patients with histologically confirmed FCD type I or II underwent presurgical MRI including 3D T1-weighted, T2-weighted, FLAIR, and qT1 sequences. Two expert-defined lesion masks were generated: a conservative feature-focused mask (L1) and a broader contextual mask reflecting overall radiological judgement (L2). Signal-intensity values were extracted from lesions, perilesional zones, and contralateral homologous regions, and spatial correspondence with the resection cavity was evaluated using the Dice score. L2 delineations were substantially larger and showed markedly higher overlap with resected tissue than L1, suggesting that expert contextual assessment captures clinically relevant but quantitatively subtle abnormalities. In contrast, L1 showed stronger and more consistent SI abnormalities, particularly on T2-weighted and FLAIR images, indicating that expert visual judgement and quantitative SI metrics do not fully converge. Perilesional tissue closely resembled healthy brain, with only minimal SI gradients beyond the lesion border. Quantitative T1 mapping provided limited additional value over conventional T1-weighted imaging for the detection of white-matter abnormalities. These findings indicate that expert assessment and quantitative MRI capture complementary but non-identical aspects of FCD pathology, and suggest that future automated detection models should combine quantitative features with multiple layers of radiological expertise. Key words Focal cortical dysplasia " Signal intensity " Structural MRI " Pediatric " Quantitative T1.
Z. Holubová, D. Kala, V. Čapek et al.· Physiological Research· 0 citations