Neuroimaging Abnormalities in Idiopathic Generalized Epilepsy Map to a Common Brain Network Related to Myelination
Abstract number :
1.252
Submission category :
5. Neuro Imaging / 5A. Structural Imaging
Year :
2022
Submission ID :
2204701
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Frederic Schaper, MD PhD – Brigham and Women's Hospital, HMS; Gong-Jun Ji, MD PhD – Anhui Medical University; Yingru Wang, MD PhD – Anhui Medical University; Yuanyuan Zhang, MD PhD – Anhui Medical University,; Jinmei Sun, MD PhD – Anhui Medical University; Yanghua Tian, MD PhD – Anhui Medical University; Panpan Hu, MD PhD – Anhui Medical University; Xingui Chen, MD PhD – Anhui Medical University; Yubao Jiang, MD PhD – Anhui Medical University; Jiao Li, MD PhD – University of Electronic Science and Technology of China; Wei Liao, MD PhD – University of Electronic Science and Technology of China; Chunyan Zhu, MD PhD – Anhui Medical University; Kai Wang, MD PhD – Anhui Medical University; Michael Fox, MD PhD – Brigham and Women's Hospital, HMS
This abstract is a recipient of the Young Investigator Award
This abstract has been invited to present during the Neuroimaging platform session
This abstract has been invited to present during the Basic Science Poster Highlights poster session
Rationale: Idiopathic generalized epilepsy (IGE) is a common type of epilepsy with a strong genetic basis. Identifying the network of IGE may lead to new and effective treatment targets. Patients with IGE have multiple neuroimaging abnormalities, such as brain atrophy and hyperactivity. However, it is unknown if these abnormalities occur within a common brain network and have a genetic basis. Here, we test whether neuroimaging abnormalities in IGE map to a common brain network and investigate its genetic basis.
Methods: We systematically reviewed the literature on neuroimaging abnormalities in patients with IGE. We retrieved all coordinates of brain atrophy or hyperactivity associated with IGE compared to healthy controls. Atrophy was assessed using voxel-based morphometry and hyperactivity using resting state functional MRI (fMRI). We then performed an activation likelihood estimation (ALE) meta-analysis to test for consistent abnormalities across studies. Using a novel technique termed coordinate-network mapping, we computed the functional connections of each coordinate using the human connectome (n = 652). We then tested whether (1) neuroimaging abnormalities in IGE map to a common brain network, (2) this network is specific to IGE, and (3) this network aligns with previous neuroimaging correlates of IGE. Finally, we investigated the genetic basis of this network using the human brain transcriptome (Allen Brain Atlas), IGE risk genes derived from genome-wide association studies, and enrichment analyses.
Results: We identified 20 studies, including 540 IGE patients and 778 healthy controls, reporting 127 coordinates of brain atrophy and fMRI hyperactivity associated with IGE. An ALE meta-analysis showed that across studies, brain atrophy in IGE consistently occurs within the bilateral thalamus and cerebellum, while fMRI hyperactivity consistently occurs within the left thalamus. There was no overlap between these regions. Yet, >90% of coordinates were functionally connected to the same regions in the posterior putamen and cerebellum crus 1. These connections were specific to IGE (P < 0.05) compared to networks derived from random coordinates (n = 127) or coordinates from neurodegenerative diseases (26 studies). An IGE network, defined by functional connectivity to the putamen and cerebellum, includes connections to the sensorimotor cortex, superior temporal gyrus, insula, thalamus, basal ganglia, and cerebellum. This IGE network aligned with independent and previously published coordinates of (inter)ictal hyperactivity in simultaneous EEG-fMRI studies (P < 0.01) and regions of atrophy in the ENIGMA-Epilepsy studies (P < 0.001). Finally, we identified a cluster of 637 genes that shares spatial similarity to this IGE network (R = 0.54, P < 0.001), overlaps with IGE risk genes (P < 0.05), and is enriched in ontology terms related to myelination (P < 0.001), the oligodendrocyte cell type (P < 0.001), but not any specific chromosome.
Neuro Imaging