Functional Networks Underlying Lesional Tonic Seizures Spatially Overlap with Networks of Generalized Paroxysmal Fast Activity in Lennox Gastaut Syndrome
Abstract number :
1.379
Submission category :
5. Neuro Imaging / 5B. Functional Imaging
Year :
2024
Submission ID :
1079
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Sem Kampman, BSc – Boston Children’s Hospital, Harvard Medical School
Aaron Warren, PhD – Brigham and Women's Hospital, Harvard Medical School
Gillian Miller, BA – Boston Children’s Hospital, Harvard Medical School
Matheus Soldatelli, MD PhD – Boston Children’s Hospital, Harvard Medical School
Krzysztof Sadowski, MD PhD – Boston Children’s Hospital, Harvard Medical School
Catharina Gout, MD – Boston Children’s Hospital, Harvard Medical School
Frederic Schaper, MD PhD – Brigham and Women's Hospital, Harvard Medical School
Alexander Cohen, MD PhD – Boston Children’s Hospital, Harvard Medical School
Michael Fox, MD PhD – Brigham and Women's Hospital, Harvard Medical School
John Rolston, MD, PhD – Brigham and Women's Hospital, Harvard Medical School
John Archer, MD PhD – The University of Melbourne
Linda Dalic, MD PhD – The University of Melbourne
Emma Macdonald-Laurs, MBChB, PhD – The Royal Children’s Hospital
Jurriaan Peters, MD PhD – Boston Children’s Hospital, Harvard Medical School
Rationale: Generalized paroxysmal fast activity (GPFA) on EEG has been proposed as an interictal or subclinical correlate of tonic seizures, the characteristic seizure type of Lennox-Gastaut syndrome (LGS), suggesting convergent mechanisms. We investigated the spatial overlap between (i) functional connectivity of cortical lesion locations associated with tonic seizures, and (ii) blood-oxygen-level-dependent (BOLD) activation seen during bursts of interictal GPFA studied using simultaneous EEG-functional MRI (EEG-fMRI) in patients with LGS.
Methods: Manually delineated sublobar-sized lesions of variable etiology in 37 children with tonic seizures were warped onto a common brain atlas and used as seeds in a normative fMRI connectome to explore shared patterns of connectivity (“lesion network mapping”). Using spin permutation testing (Alexander-Bloch et al. Neuroimage 2018;178:540-551), the map of common functional connectivity underlying cortical lesions causal for tonic seizures (i.e., the lesion network map) was spatially correlated with a statistical map of average BOLD signal changes during GPFA obtained from a previous EEG-fMRI study performed in 23 patients with LGS (Warren et al. Neurology 2019;93(3):e215-226).
Results: On a whole-brain level, the lesion network map of brain areas with common functional connectivity to cortical lesions associated with tonic seizures was positively correlated with areas of BOLD signal activation seen during interictal GPFA bursts (10,000 spins, Spearman’s rho=0.7, p=0.005, two-tailed) (Figures 1 and 2).
Maximal spatial overlap was seen in diffuse areas of frontal and parietal association cortex and the anterior and posterior cingulate cortex. Significant spatial overlap was also found in areas of sensorimotor and primary visual cortex.
Conclusions: We demonstrate spatial overlap between the network underlying tonic seizures of lesional etiology and the network underlying interictal GPFA. This suggests a shared pathogenesis between these key electroclinical entities of LGS and supports the proposed use of GPFA as a biomarker for tonic seizures. Additionally, these findings may (i) inform a risk map for progression towards LGS and (ii) refine targeting for neuromodulation therapies.
Funding: The MacPherson Fund.
Neuro Imaging