Human GABRG2 generalized epilepsy : Increased somatosensory and striato-thalamic connectivity

Journal article


Pedersen, Mangor, Kowalczyk, Magdalena, Omidvarnia, Amir, Perucca, Piero, Gooley, Samuel, Petrou, Steven, Scheffer, Ingrid E., Berkovic, Samuel F. and Jackson, Graeme D.. (2019). Human GABRG2 generalized epilepsy : Increased somatosensory and striato-thalamic connectivity. Neurology Genetics. 5(4), p. e340. https://doi.org/10.1212/NXG.0000000000000340
AuthorsPedersen, Mangor, Kowalczyk, Magdalena, Omidvarnia, Amir, Perucca, Piero, Gooley, Samuel, Petrou, Steven, Scheffer, Ingrid E., Berkovic, Samuel F. and Jackson, Graeme D.
Abstract

Objective To map functional MRI (fMRI) connectivity within and between the somatosensory cortex, putamen, and ventral thalamus in individuals from a family with a GABAergic deficit segregating with febrile seizures and genetic generalized epilepsy.

Methods We studied 5 adults from a family with early-onset absence epilepsy and/or febrile seizures and a GABAA receptor subunit gamma2 pathogenic variant (GABRG2[R43Q]) vs 5 age-matched controls. We infer differences between participants with the GABRG2 pathogenic variant and controls in resting-state fMRI connectivity within and between the somatosensory cortex, putamen, and ventral thalamus.

Results We observed increased fMRI connectivity within the somatosensory cortex and between the putamen and ventral thalamus in all individuals with the GABRG2 pathogenic variant compared with controls. Post hoc analysis showed less pronounced changes in fMRI connectivity within and between the primary visual cortex and precuneus.

Conclusions Although our sample size was small, this preliminary study suggests that individuals with a GABRG2 pathogenic variant, raising risk of febrile seizures and generalized epilepsy, display underlying increased functional connectivity both within the somatosensory cortex and in striatothalamic networks. This human network model aligns with rodent research and should be further validated in larger cohorts, including other individuals with generalized epilepsy with and without known GABA pathogenic variants.

Keywordsall epilepsy/seizures; all genetics; fMRI; functional neuroimaging; absence seizures
Year2019
JournalNeurology Genetics
Journal citation5 (4), p. e340
PublisherWolters Kluwer Health
ISSN2376-7839
Digital Object Identifier (DOI)https://doi.org/10.1212/NXG.0000000000000340
Scopus EID2-s2.0-85073782711
Open accessPublished as ‘gold’ (paid) open access
Research or scholarlyResearch
Page range1-7
FunderNational Health and Medical Research Council (NHMRC)
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online07 Jun 2019
Publication process dates
Accepted29 Apr 2019
Deposited11 Jul 2021
Grant IDNHMRC/628952
NHMRC/1060312
NHMRC/1091593
Permalink -

https://acuresearchbank.acu.edu.au/item/8w581/human-gabrg2-generalized-epilepsy-increased-somatosensory-and-striato-thalamic-connectivity

Download files


Publisher's version
  • 87
    total views
  • 27
    total downloads
  • 1
    views this month
  • 1
    downloads this month
These values are for the period from 19th October 2020, when this repository was created.

Export as

Related outputs

Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence
Lorenzetti, Valentina, Gaillard, Alexandra, Beyer, Emillie, Kowalczyk, Magdalena, Kamboj, Sunjeev K., Manning, Victoria and Gleeson, John Francis Martin. (2023). Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence. BMC Psychiatry. 23(1), p. Article 407. https://doi.org/10.1186/s12888-023-04789-7
Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression
Larivière, Sara, Royer, Jessica, Rodríguez-Cruces, Raúl, Paquola, Casey, Caligiuri, Maria Eugenia, Gambardella, Antonio, Concha, Luis, Keller, Simon S., Cendes, Fernando, Yasuda, Clarissa L., Bonilha, Leonardo, Gleichgerrcht, Ezequiel, Focke, Niels K., Domin, Martin, von Podewills, Felix, Langner, Soenke, Rummel, Christian, Wiest, Roland, Martin, Pascal, ... Bernhardt, Boris 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), p. Article 4320. https://doi.org/10.1038/s41467-022-31730-5
Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy
Park, Bo-yong, Larivière, Sara, Rodríguez-Cruces, Raul, Royer, Jessica, Tavakol, Shahin, Wang, Yezhou, Caciagli, Lorenzo, Caligiuri, Maria Eugenia, Gambardella, Antonio, Concha, Luis, Keller, Simon S, Cendes, Fernando, Alvim, Marina K M, Yasuda, Clarissa, Bonilha, Leonardo, Gleichgerrcht, Ezequiel, Focke, Niels K, Kreilkamp, Barbara A K, Domin, Martin, ... Bernhardt, Boris C. (2022). Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy. Brain. 145(4), pp. 1285-1298. https://doi.org/10.1093/brain/awab417
Brain anatomical alterations in young cannabis users : Is it all hype? A meta-analysis of structural neuroimaging studies
Lorenzetti, Valentina, Kowalczyk, Magdalena, Duehlmeyer, Leonie, Greenwood, Lisa-Marie, Chye, Yann, Yücel, Murat, Whittle, Sarah and Roberts, Carl A.. (2022). Brain anatomical alterations in young cannabis users : Is it all hype? A meta-analysis of structural neuroimaging studies. Cannabis and Cannabinoid Research. 8(1), pp. 184-196. https://doi.org/10.1089/can.2021.0099
A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies
Altmann, Andre, Ryten, Mina, Di Nunzio, Martina, Ravizza, Teresa, Tolomeo, Daniele, Reynolds, Regina H., Somani, Alyma, Bacigaluppi, Marco, Iori, Valentina, Micotti, Edoardo, Di Sapia, Rossella, Cerovic, Milica, Palma, Eleonora, Ruffolo, Gabriele, Botía, Juan A., Absil, Julie, Alhusaini, Saud, Alvim, Marina K. M., Auvinen, Pia, ... Sisodiya, Sanjay M.. (2022). A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies. Neuropathology and Applied Neurobiology. 48(1), p. Article e12758. https://doi.org/10.1111/nan.12758
Patterns of brain function associated with cannabis cue-reactivity in regular cannabis users : A systematic review of fMRI studies
Sehl, Hannah, Terrett, Gill, Greenwood, Lisa-Marie, Kowalczyk, Magdalena, Thomson, Hannah, Poudel, Govinda, Manning, Victoria and Lorenzetti, Valentina. (2021). Patterns of brain function associated with cannabis cue-reactivity in regular cannabis users : A systematic review of fMRI studies. Psychopharmacology. 238(10), pp. 2709-2728. https://doi.org/10.1007/s00213-021-05973-x
Do comorbid personality disorders in cocaine dependence exacerbate neuroanatomical alterations? A structural neuroimaging study
Roberts, Carl A., Lorenzetti, Valentina, Albein-Urios, Natalia, Kowalczyk, Magdalena A., Martinez-Gonzalez, Jose M. and Verdejo-Garcia, Antonio. (2021). Do comorbid personality disorders in cocaine dependence exacerbate neuroanatomical alterations? A structural neuroimaging study. Progress in Neuropsychopharmacology and Biological Psychiatry. 110, p. 110298. https://doi.org/10.1016/j.pnpbp.2021.110298
Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study
Larivière, Sara, Rodríguez-Cruces, Raúl, Royer, Jessica, Caligiuri, Maria Eugenia, Gambardella, Antonio, Concha, Luis, Keller, Simon S., Cendes, Fernando, Yasuda, Clarissa, Bonilha, Leonardo, Gleichgerrcht, Ezequiel, Focke, Niels K., Domin, Martin, von Podewills, Felix, Langner, Soenke, Rummel, Christian, Wiest, Roland, Martin, Pascal, Kotikalapudi, Raviteja, ... Bernhardt, Boris C.. (2020). Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study. Science Advances. 6(47), p. eabc6457. https://doi.org/10.1126/sciadv.abc6457
Dynamic analysis of fMRI activation during epileptic spikes can help identify the seizure origin
Kowalczyk, Magdalena A., Omidvarnia, Amir, Dhollander, Thijs and Jackson, Graeme D.. (2020). Dynamic analysis of fMRI activation during epileptic spikes can help identify the seizure origin. Epilepsia. 61(11), pp. 2558-2571. https://doi.org/10.1111/epi.16695
Towards fast and reliable simultaneous EEG-fMRI analysis of epilepsy with automatic spike detection
Omidvarnia, Amir, Kowalczyk, Magdalena A., Pedersen, Mangor and Jackson, Graeme D.. (2019). Towards fast and reliable simultaneous EEG-fMRI analysis of epilepsy with automatic spike detection. Clinical Neurophysiology. 130(3), pp. 368-378. https://doi.org/10.1016/j.clinph.2018.11.024
Normal cerebral cortical thickness in first-degree relatives of temporal lobe epilepsy patients
Alhusaini, Saud, Kowalczyk, Magdalena A., Yasuda, Clarissa L., Semmelroch, Mira K., Katsurayama, Marilise, Zabin, Matheus, Zanão, Tamires, Nogueira, Mateus H., Alvim, Marina K. M., Ferraz, Victória R., Tsai, Meng-Han, Fitzsimons, Mary, Lopes-Cendes, Iscia, Doherty, Colin P., Cavalleri, Gianpiero L., Cendes, Fernando, Jackson, Graeme D. and Delanty, Norman. (2019). Normal cerebral cortical thickness in first-degree relatives of temporal lobe epilepsy patients. Neurology. 92(4), pp. e351-e358. https://doi.org/10.1212/WNL.0000000000006834
Clinical benefit of presurgical EEG-fMRI in difficult-to-localize focal epilepsy : A single-institution retrospective review.
Kowalczyk, Magdalena A., Omidvarnia, Amir, Abbott, David F., Tailby, Chris, Vaughan, David N. and Jackson, Graeme D.. (2019). Clinical benefit of presurgical EEG-fMRI in difficult-to-localize focal epilepsy : A single-institution retrospective review. Epilepsia. 61(1), pp. 49-60. https://doi.org/10.1111/epi.16399
Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study
Whelan, Christopher D., Altmann, Andre, Botía, Juan A., Jahanshad, Neda, Hibar, Derrek P., Absil, Julie, Alhusaini, Saud, Alvim, Marina K. M., Auvinen, Pia, Bartolini, Emanuele, Bergo, Felipe P. G., Bernardes, Tauana, Blackmon, Karen, Braga, Barbara, Caligiuri, Maria Eugenia, Calvo, Anna, Carr, Sarah J., Chen, Jian, Chen, Shuai, ... Sisodiya, Sanjay M.. (2018). Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain: a journal of neurology. 141(2), pp. 391-408. https://doi.org/10.1093/brain/awx341
Cognitive impairment in epilepsy : The role of reduced network flexibility
Tailby, Chris, Kowalczyk, Magdalena A. and Jackson, Graeme D.. (2018). Cognitive impairment in epilepsy : The role of reduced network flexibility. Annals of Clinical and Translational Neurology. 5(1), pp. 29-40. https://doi.org/10.1002/acn3.503
Mapping the verbal semantic memory network before anterior temporal lobectomy using a combination of rTMS and fMRI
Sethi, M., Carney, P., Kowalczyk, M., Pedersen, M., Tailby, C. and Jackosn, G.. (2001). Mapping the verbal semantic memory network before anterior temporal lobectomy using a combination of rTMS and fMRI. Epilepsia. 58(Suppl. 5), p. S182. https://doi.org/10.1111/epi.13944