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
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