Atypical Large-Scale Functional Network Organisation in Newly Diagnosed Focal Epilepsy Shows Brain-wide Patterns of Gene Expression Implicated in Epilepsy
Abstract number :
2.17
Submission category :
5. Neuro Imaging / 5B. Functional Imaging
Year :
2021
Submission ID :
1825638
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Christophe de Bézenac, PhD - University of Liverpool; Lorenzo Caciagli, MD, PhD - University of Pennsylvania; Batil Alonazi, PhD - Prince Sattam Bin Abdulaziz University; Boris Bernhardt, PhD - McGill University; Anthony Marson, MD, PhD - University of Liverpool; Simon Keller, PhD - University of Liverpool
Rationale: Neuroimaging research has provided insights into epilepsy as a disorder of brain connectivity which may have an identifiable underlying genetic component. Impairments have been observed in varied domains ranging from sensory and motor functioning to higher-order cognitive processing often from early stages of the disorder. We used gradient mapping of resting-sate fMRI (rs-fMRI) to examine whether this impairment pattern can be accounted for by imbalance in a large-scale connectome gradient spanning from unimodal to transmodal networks and explored associations of such alterations to patterns of cortical gene expression.
Methods: We compared cortical maps of gradient scores in patients with newly diagnosed focal epilepsy (NDfE, n = 27) with minimal exposure to antiepileptic medication to a group of age- and sex-matched controls (HC, n = 36). Differences between persistent seizure (PS, n = 10) and seizure free (SF, n = 17) patients at 12-months follow-up were also investigated.
Results: We found increased functional separation between unimodal and transmodal networks in NDfE which was particularly pronounced in the PS group. Differences corresponded to gradient score reductions in the visual network and increases in limbic and default mode systems associated with higher-level cognition. The cortical map of NDfE–control differences was significantly correlated with the distribution of gene expression across the brain as defined by the Allen Human Brain Atlas (AHBA). A disease enrichment and pathway analysis revealed that genes most strongly associated with NDfE–control (but not PS-SF) differences along the cortex were part of a network of genes previously implicated in seizure-related disorders including focal epilepsy.
Conclusions: In conclusion, we propose that large-scale functional hierarchy has the potential to contribute to a more parsimonious account of wide-ranging impairments associated with focal epilepsy. Combining functional neuroimaging and transcriptional data analysis particularly in patients with minimal exposure to antiepileptic medication can provide mechanistic insight into how gene processes may drive alterations in large-scale features of brain dynamics mediating the genetic risk of epilepsy.
Funding: Please list any funding that was received in support of this abstract.: Medical Research Council (grant number MR/S00355X/1).
Neuro Imaging