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نمایش مقاله

Title:

Laterality-Specific Cortical Asymmetry Disruption in Drug-Resistant Focal Epilepsy: A Large-Scale Structural Neuroimaging Study

Subject:

Brain Mapping Applications in Epilepsy – Across Pediatric and Adult Populations

Presenter Author:
Name:	Amirhossein Moeini

Author:
Name 1:	Amirhossein Moeini - Presenter
Affiliation 1:	Student Research Committee, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Neuroscience & Neoplasia AI Research Group (NAIRG), Neurophysiology Research Center, Institute of Neuroscience and Cognition, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Name 2:	Mojgan Hamdami
Affiliation 2:	Neuroscience & Neoplasia AI Research Group (NAIRG), Neurophysiology Research Center, Institute of Neuroscience and Cognition, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Name 3:	Ali Fathi Jouzdani - Corresponding
Affiliation 3:	School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran Neuroscience & Neoplasia AI Research Group (NAIRG), Neurophysiology Research Center, Institute of Neuroscience and Cognition, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Abstract

Original Research

introduction :

Cortical lateralization is fundamental to normal brain organization. Drug-resistant focal epilepsy (DRFE) alters brain structure, but whether it disrupts hemispheric asymmetry remains unclear. To characterize cortical thickness asymmetry in a large DRFE cohort stratified by seizure laterality.

Methods:

We analyzed cortical thickness asymmetry indices (AI) from 442 patients with DRFE and 100 healthy control subjects, all with complete structural neuroimaging (aparc cortical thickness from Desikan-Killiany atlas, 34 bilateral regions). The DRFE cohort (n=442) comprised 238 females and 205 males with mean age at MRI scan 30–34 years (range 15–70 years). Seizure laterality: left-sided (L, n=235) and right-sided (R, n=208). Pathology distribution: hippocampal sclerosis (HS, 215 subjects, 48.5%), focal cortical dysplasia (FCD, 40), developmental nodular tuberous heterotopia (DNT, 52), cavernous malformation (CAV, 33), dual pathology (21), other lesions (74). Mean antiseizure medications: 2.5 (range 0–6). Operation types: temporal lobe resection (316 subjects), frontal resection (47), and selective resections (79). The control cohort (n=100) was age- and sex-matched to the DRFE sample with no history of seizures, neurological disorder, or brain pathology. Asymmetry Index (AI) was computed as: AI = 2×(LH−RH)/(LH+RH), where LH and RH denote left and right hemispheric cortical thickness. All AI regions were z-standardized prior to analysis. Linear regression models with HC3 robust standard errors were applied to four stratified comparisons: (1) complete DRFE cohort vs. controls; (2) right-hemisphere DRFE patients vs. controls; (3) left-hemisphere DRFE patients vs. controls; and (4) direct right versus left DRFE comparison . Group 1 covariates: age (binned), sex. Groups 2–3: age (binned), sex. Group 4: age at seizure onset (binned), sex, pathology category, number of ASMs, operation type. FDR-Benjamini-Hochberg correction applied; significance threshold p<0.05.

Results:

24 significant regions (FDR<0.05), with 17 showing reduced asymmetry (negative AI; loss of hemispheric dominance) and 7 showing increased asymmetry. Strongest reductions in right-hemispheric dominance: superior frontal cortex (β=−1.343, p_FDR=3.01×10⁻⁴¹), rostral middle frontal cortex (β=−1.267, p_FDR=3.57×10⁻²⁸), caudal middle frontal cortex (β=−0.994, p_FDR=1.79×10⁻²¹), and mean cortical thickness (β=−1.207, p_FDR=7.45×10⁻³⁵). Regions with increased asymmetry: lateral occipital cortex (β=1.076, p_FDR=2.18×10⁻²³), banks of superior temporal sulcus (β=0.832, p_FDR=9.49×10⁻¹¹), inferior temporal cortex (β=0.698, p_FDR=1.55×10⁻⁸). Right-hemisphere DRFE patients vs. controls: 24 significant regions—identical to the complete cohort—indicating right-sided seizure patients drive global asymmetry disruption. Strong frontal effects with preserved posterior positive effects. Left-hemisphere DRFE patients vs. controls: 11 significant regions, all showing reduced left-hemispheric asymmetry (100% negative effects). Complete loss of normal left-hemispheric structural advantage. Mean cortical thickness (β=−0.733, p_FDR=2.94×10⁻⁹), supramarginal cortex (β=−0.503, p_FDR=1.39×10⁻³), postcentral cortex (β=−0.478, p_FDR=4.13×10⁻⁴), superior temporal cortex (β=−0.472, p_FDR=1.18×10⁻³). Right vs. left DRFE: 18 significant regions (11 negative, 7 positive). Superior frontal cortex (β=−1.127, p_FDR=1.15×10⁻³⁸), rostral middle frontal cortex (β=−1.066, p_FDR=8.82×10⁻³⁴), lateral occipital cortex (β=+1.163, p_FDR=2.16×10⁻⁴⁰).

Conclusion:

In 442 DRFE patients with complete neuroimaging versus 100 healthy controls, we demonstrate systematic, laterality-dependent loss of normal cortical lateralization. The directional pattern of asymmetry disruption—determined by seizure laterality—establishes cortical asymmetry disruption as a hallmark of DRFE neurophysiology. Bilateral structural reorganization rather than focal pathology underlies the structural brain changes in drug-resistant focal epilepsy.

Keywords:

Drug Resistant Epilepsy Functional Laterality Cerebral Cortex Magnetic Resonance Imaging