Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

Sara Larivière; Jessica Royer; Raúl Rodríguez-Cruces; Casey Paquola; Maria Eugenia Caligiuri; Antonio Gambardella; Luis Concha; Simon S. Keller; Fernando Cendes; Clarissa L. Yasuda; Leonardo Bonilha; Ezequiel Gleichgerrcht; Niels K. Focke; Martin Domin; Felix von Podewills; Soenke Langner; Christian Rummel; Roland Wiest; Pascal Martin; Raviteja Kotikalapudi; Terence J. O’Brien; Benjamin Sinclair; Lucy Vivash; Patricia M. Desmond; Elaine Lui; Anna Elisabetta Vaudano; Stefano Meletti; Manuela Tondelli; Saud Alhusaini; Colin P. Doherty; Gianpiero L. Cavalleri; Norman Delanty; Reetta Kälviäinen; Graeme D. Jackson; Magdalena Kowalczyk; Mario Mascalchi; Mira Semmelroch; Rhys H. Thomas; Hamid Soltanian-Zadeh; Esmaeil Davoodi-Bojd; Junsong Zhang; Gavin P. Winston; Aoife Griffin; Aditi Singh; Vijay K. Tiwari; Barbara A.K. Kreilkamp; Matteo Lenge; Renzo Guerrini; Khalid Hamandi; Sonya Foley; Theodor Rüber; Bernd Weber; Chantal Depondt; Julie Absil; Sarah J.A. Carr; Eugenio Abela; Mark P. Richardson; Orrin Devinsky; Mariasavina Severino; Pasquale Striano; Domenico Tortora; Erik Kaestner; Sean N. Hatton; Sjoerd B. Vos; Lorenzo Caciagli; John S. Duncan; Christopher D. Whelan; Paul M. Thompson; Sanjay M. Sisodiya; Andrea Bernasconi; Angelo Labate; Carrie R. McDonald; Neda Bernasconi; Boris C. Bernhardt

doi:10.1038/s41467-022-31730-5

Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

Sara Larivière^*, Jessica Royer, Raúl Rodríguez-Cruces, Casey Paquola, Maria Eugenia Caligiuri, Antonio Gambardella, Luis Concha, Simon S. Keller, Fernando Cendes, Clarissa L. Yasuda, Leonardo Bonilha, Ezequiel Gleichgerrcht, Niels K. Focke, Martin Domin, Felix von Podewills, Soenke Langner, Christian Rummel, Roland Wiest, Pascal Martin, Raviteja KotikalapudiTerence J. O’Brien, Benjamin Sinclair, Lucy Vivash, Patricia M. Desmond, Elaine Lui, Anna Elisabetta Vaudano, Stefano Meletti, Manuela Tondelli, Saud Alhusaini, Colin P. Doherty, Gianpiero L. Cavalleri, Norman Delanty, Reetta Kälviäinen, Graeme D. Jackson, Magdalena Kowalczyk, Mario Mascalchi, Mira Semmelroch, Rhys H. Thomas, Hamid Soltanian-Zadeh, Esmaeil Davoodi-Bojd, Junsong Zhang, Gavin P. Winston, Aoife Griffin, Aditi Singh, Vijay K. Tiwari, Barbara A.K. Kreilkamp, Matteo Lenge, Renzo Guerrini, Khalid Hamandi, Sonya Foley, Theodor Rüber, Bernd Weber, Chantal Depondt, Julie Absil, Sarah J.A. Carr, Eugenio Abela, Mark P. Richardson, Orrin Devinsky, Mariasavina Severino, Pasquale Striano, Domenico Tortora, Erik Kaestner, Sean N. Hatton, Sjoerd B. Vos, Lorenzo Caciagli, John S. Duncan, Christopher D. Whelan, Paul M. Thompson, Sanjay M. Sisodiya, Andrea Bernasconi, Angelo Labate, Carrie R. McDonald, Neda Bernasconi, Boris C. Bernhardt^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

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.

Original language	English
Article number	4320
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-31730-5
Publication status	Published - Dec 2022
Externally published	Yes

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Publisher Copyright:
© 2022, The Author(s).

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Larivière, S., Royer, J., Rodríguez-Cruces, R., Paquola, C., Caligiuri, M. E., Gambardella, A., Concha, L., Keller, S. S., Cendes, F., Yasuda, C. L., Bonilha, L., Gleichgerrcht, E., Focke, N. K., Domin, M., von Podewills, F., Langner, S., Rummel, C., Wiest, R., Martin, P., ... Bernhardt, B. C. (2022). Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression. Nature Communications, 13(1), Article 4320. https://doi.org/10.1038/s41467-022-31730-5

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title = "Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression",

abstract = "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.",

author = "Sara Larivi{\`e}re and Jessica Royer and Ra{\'u}l Rodr{\'i}guez-Cruces and Casey Paquola and Caligiuri, {Maria Eugenia} and Antonio Gambardella and Luis Concha and Keller, {Simon S.} and Fernando Cendes and Yasuda, {Clarissa L.} and Leonardo Bonilha and Ezequiel Gleichgerrcht and Focke, {Niels K.} and Martin Domin and {von Podewills}, Felix and Soenke Langner and Christian Rummel and Roland Wiest and Pascal Martin and Raviteja Kotikalapudi and O{\textquoteright}Brien, {Terence J.} and Benjamin Sinclair and Lucy Vivash and Desmond, {Patricia M.} and Elaine Lui and Vaudano, {Anna Elisabetta} and Stefano Meletti and Manuela Tondelli and Saud Alhusaini and Doherty, {Colin P.} and Cavalleri, {Gianpiero L.} and Norman Delanty and Reetta K{\"a}lvi{\"a}inen and Jackson, {Graeme D.} and Magdalena Kowalczyk and Mario Mascalchi and Mira Semmelroch and Thomas, {Rhys H.} and Hamid Soltanian-Zadeh and Esmaeil Davoodi-Bojd and Junsong Zhang and Winston, {Gavin P.} and Aoife Griffin and Aditi Singh and Tiwari, {Vijay K.} and Kreilkamp, {Barbara A.K.} and Matteo Lenge and Renzo Guerrini and Khalid Hamandi and Sonya Foley and Theodor R{\"u}ber and Bernd Weber and Chantal Depondt and Julie Absil and Carr, {Sarah J.A.} and Eugenio Abela and Richardson, {Mark P.} and Orrin Devinsky and Mariasavina Severino and Pasquale Striano and Domenico Tortora and Erik Kaestner and Hatton, {Sean N.} and Vos, {Sjoerd B.} and Lorenzo Caciagli and Duncan, {John S.} and Whelan, {Christopher D.} and Thompson, {Paul M.} and Sisodiya, {Sanjay M.} and Andrea Bernasconi and Angelo Labate and McDonald, {Carrie R.} and Neda Bernasconi and Bernhardt, {Boris C.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-31730-5",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

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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 & Bernhardt, BC 2022, 'Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression', Nature Communications, vol. 13, no. 1, 4320. https://doi.org/10.1038/s41467-022-31730-5

TY - JOUR

T1 - Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

AU - Larivière, Sara

AU - Royer, Jessica

AU - Rodríguez-Cruces, Raúl

AU - Paquola, Casey

AU - Caligiuri, Maria Eugenia

AU - Gambardella, Antonio

AU - Concha, Luis

AU - Keller, Simon S.

AU - Cendes, Fernando

AU - Yasuda, Clarissa L.

AU - Bonilha, Leonardo

AU - Gleichgerrcht, Ezequiel

AU - Focke, Niels K.

AU - Domin, Martin

AU - von Podewills, Felix

AU - Langner, Soenke

AU - Rummel, Christian

AU - Wiest, Roland

AU - Martin, Pascal

AU - Kotikalapudi, Raviteja

AU - O’Brien, Terence J.

AU - Sinclair, Benjamin

AU - Vivash, Lucy

AU - Desmond, Patricia M.

AU - Lui, Elaine

AU - Vaudano, Anna Elisabetta

AU - Meletti, Stefano

AU - Tondelli, Manuela

AU - Alhusaini, Saud

AU - Doherty, Colin P.

AU - Cavalleri, Gianpiero L.

AU - Delanty, Norman

AU - Kälviäinen, Reetta

AU - Jackson, Graeme D.

AU - Kowalczyk, Magdalena

AU - Mascalchi, Mario

AU - Semmelroch, Mira

AU - Thomas, Rhys H.

AU - Soltanian-Zadeh, Hamid

AU - Davoodi-Bojd, Esmaeil

AU - Zhang, Junsong

AU - Winston, Gavin P.

AU - Griffin, Aoife

AU - Singh, Aditi

AU - Tiwari, Vijay K.

AU - Kreilkamp, Barbara A.K.

AU - Lenge, Matteo

AU - Guerrini, Renzo

AU - Hamandi, Khalid

AU - Foley, Sonya

AU - Rüber, Theodor

AU - Weber, Bernd

AU - Depondt, Chantal

AU - Absil, Julie

AU - Carr, Sarah J.A.

AU - Abela, Eugenio

AU - Richardson, Mark P.

AU - Devinsky, Orrin

AU - Severino, Mariasavina

AU - Striano, Pasquale

AU - Tortora, Domenico

AU - Kaestner, Erik

AU - Hatton, Sean N.

AU - Vos, Sjoerd B.

AU - Caciagli, Lorenzo

AU - Duncan, John S.

AU - Whelan, Christopher D.

AU - Thompson, Paul M.

AU - Sisodiya, Sanjay M.

AU - Bernasconi, Andrea

AU - Labate, Angelo

AU - McDonald, Carrie R.

AU - Bernasconi, Neda

AU - Bernhardt, Boris C.

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-022-31730-5

DO - 10.1038/s41467-022-31730-5

M3 - Article

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AN - SCOPUS:85134892469

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

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M1 - 4320

ER -

Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

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