OBJECTIVE: Drug-resistant epilepsy, a severe and diagnostically challenging neurological condition often linked to focal cortical dysplasia (FCD), represents a significant social and healthcare burden. While the thalamus is notably altered in this disorder, it remains unclear whether these changes result from epilepsy manifestation or participate in its pathophysiology. This study aimed to characterize volumetric and microstructural changes in the thalamus and thalamocortical pathways in epilepsy patients with FCD. METHODS: We prospectively enrolled 24 patients with drug-resistant epilepsy caused by FCD and 16 age-matched healthy controls. Diffusion MRI data and quantitative T1 were acquired, and advanced diffusion techniques - Diffusion Kurtosis Imaging (DKI), Neurite Orientation Dispersion and Density Imaging (NODDI), and Fixel-Based Analysis (FBA) - were employed. RESULTS: Volumetric analysis revealed a significant reduction in thalamic volume ipsilateral to the epileptic lesion. Microstructural analysis identified bilateral alterations in thalamocortical tracts, including changes in both DKI and NODDI diffusion metrics, indicating tissue disorganization and axonal integrity loss. However, no significant microstructural differences were observed between ipsilateral and contralateral thalami, suggesting that thalamic changes may be a consequence of epilepsy rather than its cause. SIGNIFICANCE: This study investigates widespread structural and microstructural disruptions in the thalamus and thalamocortical networks in drug-resistant epilepsy due to FCD, providing valuable insights into its complex pathophysiology and laying the groundwork for future research utilizing advanced diffusion imaging and analysis techniques. PLAIN LANGUAGE SUMMARY: This study used advanced MRI techniques to examine the thalamus - a deep brain structure that relays signals and helps coordinate brain activity - in people with focal epilepsy caused by abnormal development of the cerebral cortex, the part of the brain responsible for thinking, movement, and sensory processing, and where seizures often begin. Researchers found subtle structural changes in the thalamus and its connections to the cortex, even beyond the area directly affected by the lesion. These results provide new insight into how epilepsy can disrupt brain networks and offer a foundation for future studies using modern neuroimaging techniques.

Department of Clinical Psychology Motol University Hospital Prague Czech Republic

Department of Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Pathophysiology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Pediatric Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Psychology Faculty of Arts Charles University Prague Czech Republic

Department of Radiology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

EpiReC Epilepsy Research Center Prague Prague Czech Republic

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