Atypical connectome topography and signal flow in temporal lobe epilepsy

Ke Xie; Jessica Royer; Sara Larivière; Raul Rodriguez-Cruces; Stefan Frässle; Donna Gift Cabalo; Alexander Ngo; Jordan DeKraker; Hans Auer; Shahin Tavakol; Yifei Weng; Chifaou Abdallah; Thaera Arafat; Linda Horwood; Birgit Frauscher; Lorenzo Caciagli; Andrea Bernasconi; Neda Bernasconi; Zhiqiang Zhang; Luis Concha; Boris C Bernhardt

doi:10.1016/j.pneurobio.2024.102604

Atypical connectome topography and signal flow in temporal lobe epilepsy

Prog Neurobiol. 2024 Apr 10:236:102604. doi: 10.1016/j.pneurobio.2024.102604. Online ahead of print.

Authors

Ke Xie¹, Jessica Royer², Sara Larivière¹, Raul Rodriguez-Cruces¹, Stefan Frässle³, Donna Gift Cabalo¹, Alexander Ngo¹, Jordan DeKraker¹, Hans Auer¹, Shahin Tavakol¹, Yifei Weng⁴, Chifaou Abdallah⁵, Thaera Arafat¹, Linda Horwood², Birgit Frauscher⁶, Lorenzo Caciagli⁷, Andrea Bernasconi⁸, Neda Bernasconi⁸, Zhiqiang Zhang⁴, Luis Concha⁹, Boris C Bernhardt¹⁰

Affiliations

¹ Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
² Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada; Analytical Neurophysiology Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
³ Translational Neuromodeling Unit (TNU), Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland.
⁴ Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
⁵ Analytical Neurophysiology Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
⁶ Analytical Neurophysiology Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada; Department of Neurology, Duke University School of Medicine and Department of Biomedical Engineering, Duke University Pratt School of Engineering, Durham, NC 27705, USA.
⁷ Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Neurology, Inselspital, Sleep-Wake-Epilepsy-Center, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London WC1N 3 BG, United Kingdom.
⁸ Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada.
⁹ Institute of Neurobiology, Universidad Nacional Autónoma de Mexico (UNAM), Queretaro, Mexico.
¹⁰ Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC H3A 2B4, Canada. Electronic address: boris.bernhardt@mcgill.ca.

PMID: 38604584
DOI: 10.1016/j.pneurobio.2024.102604

Abstract

Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment.

Keywords: Effectivity connectivity; Gradient; Memory; Multi-site; Multimodal; Temporal lobe epilepsy.