Global State-dependent Network Disruption Implicating Thalamic Dysfunction in Non-lesional Focal Epilepsy
Abstract number :
2.148
Submission category :
3. Neurophysiology / 3D. MEG
Year :
2024
Submission ID :
1252
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Joline Fan, MD – University of California, San Francisco
Ehsan Taydon, MD – University of California, San Francisco
Kiwamu Kudo, PhD – UCSF
Kamalini Ranasinghe, MBBS, PhD – University of California, San Francisco
Anne Findlay, MA – University of California San Francisco (UCSF)
Heidi E. Kirsch, MD, MS – University of California San Francisco (UCSF)
Robert Knowlton, MD – Weill Institute for Neurosciences, School of Medicine, University of California San Francisco (UCSF), San Francisco, California, U.S.A.
Andrew Krystal, MD – UCSF
Srikantan Nagarajan, PhD – University of California San Francisco (UCSF)
Rationale: Sleep and epilepsy have long been known to have an intricate bidirectional relationship. While sleep states endogenously facilitate and suppress epileptic activity, epilepsy is known to disrupt sleep architecture. The characterization and extent of disruption that epilepsy has on the whole-brain network organization during sleep remains unresolved. Identifying network disturbance across sleep-wake states may add to the conceptual understanding of epilepsy as a state-dependent network disorder.
Methods: We evaluated 71 patients (n=45 temporal lobe epilepsy; n=26 extratemporal lobe epilepsy) with focal epilepsy and age-matched 18 healthy normative controls undergoing magnetoencephalography (MEG) and simultaneous scalp EEG during resting-state and light non-rapid eye movement (NREM) sleep. Sixty seconds of artifact free recordings were selected for each subject and state: wake and N2. Atlas-based source reconstructions were performed using adaptive beamforming methods. To approximate local and long-range synchrony, power spectral density and functional connectivity measures, i.e. imaginary coherence, were computed respectively across regions of interest in multiple frequency bands. T-score maps were computed comparing epilepsy versus normative control cohorts for each brain region and assessed across sleep-wake states and seizure onset location. Finally, to link network dysfunction with contributions from deep subcortical regions, T-score maps were correlated to normative fMRI connectivity maps.
Results: When compared to normative maps, spectral power in focal epilepsy was largely decreased over the temporal-parietal regions in the alpha frequency during sleep. Long-range synchrony was reduced in all frequency bands across the entire brain network. Strikingly, network disruption was spatially correlated between extratemporal and temporal lobe seizure onset localizations in both wakefulness (local synchrony, r=0.669-0.831; long-range synchrony, 0.577-0.732 across all frequencies) and N2 (local, r=0.623-0.777; long-range, r=0.500-0.745). In addition, global network disturbances comparing sleep and wake states were correlated across all frequency bands (local, r=0.257-0.867; long-range, r=-0.152-0.338), except in the theta frequency band (local, r=-0.181; long-range, r=0.119). The state-dependent, systemic network disturbances were hypothesized to originate from a central mediator, e.g. thalamus. Association analysis between the T-score maps and normative connectivity maps of the thalamus revealed a correlation to the anterior nucleus of the thalamus and pulvinar nucleus within the delta and beta frequencies, as well as the dorsomedial thalamus within the theta frequency.
Conclusions: Our findings reveal global network disturbances that pervade both sleep and wake states in non-lesional focal epilepsy. Intriguingly, these network disruptions are largely independent of seizure onset zone and occur in a spatial pattern that correlates with functional connectivity maps of specific thalamic nuclei. These findings suggest that the global, state-dependent network dysfunction may be partly mediated by dysfunction of the thalamus.
Funding: K23NS125123
Neurophysiology