Larivière S, Royer J, Rodríguez-Cruces R, Paquola C, Caligiuri ME, Gambardella A, Concha L, Keller SS, Cendes F, Yasuda CL, Bonilha L, Gleichgerrcht E, Focke NK, Domin M, von Podewills F, Langner S, Rummel C, Wiest R, Martin P, Kotikalapudi R, O'Brien TJ, Sinclair B, Vivash L, Desmond PM, Lui E, Vaudano AE, Meletti S, Tondelli M, Alhusaini S, Doherty CP, Cavalleri GL, Delanty N, Kälviäinen R, Jackson GD, Kowalczyk M, Mascalchi M, Semmelroch M, Thomas RH, Soltanian-Zadeh H, Davoodi-Bojd E, Zhang J, Winston GP, Griffin A, Singh A, Tiwari VK, Kreilkamp BAK, Lenge M, Guerrini R, Hamandi K, Foley S, Rüber T, Weber B, Depondt C, Absil J, Carr SJA, Abela E, Richardson MP, Devinsky O, Severino M, Striano P, Tortora D, Kaestner E, Hatton SN, Vos SB, Caciagli L, Duncan JS, Whelan CD, Thompson PM, Sisodiya SM, Bernasconi A, Labate A, McDonald CR, Bernasconi N, and Bernhardt BC. Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression. Nat Commun 2022; 13(1):4320.
Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.
Medical Subject Headings
Adult; Connectome; Epilepsy; Epilepsy, Generalized; Epilepsy, Temporal Lobe; Gene Expression; Humans; Immunoglobulin E; Magnetic Resonance Imaging; Nerve Net