Abstracts

Intrinsic Cortical Structure of Neural Synchrony and Excitability During Transition from Wakefulness to Light Non-rapid Eye Movement and Implications for Focal Epilepsies

Abstract number : 3.162
Submission category : 3. Neurophysiology / 3D. MEG
Year : 2022
Submission ID : 2204072
Source : www.aesnet.org
Presentation date : 12/5/2022 12:00:00 PM
Published date : Nov 22, 2022, 05:23 AM

Authors :
Joline Fan, MD – UCSF; Kiwamu Kudo, PhD – UCSF; Parul Verma, PhD – UCSF; Kamalini Ranasinghe, MBBS, PhD – UCSF; Hirofumi Morise, PhD – UCSF; Anne Findlay, MS – UCSF; Heidi Kirsch, MD, MS – UCSF; Ashish Raj, PhD – UCSF; Andrew Krystal, MD – UCSF; Srikantan Nagarajan, PhD – UCSF

This abstract is a recipient of the Young Investigator Award
This abstract has been invited to present during the Neurophysiology platform session
This abstract has been invited to present during the Basic Science Poster Highlights poster session

Rationale: Sleep-wake states have long been identified to endogenously facilitate and suppress epileptic activity, yet the mechanisms guiding this complex relationship remain unclear. Non-rapid eye movement (NREM) sleep increases the frequency and spatial spread of interictal discharges and facilitates seizure initiation, as compared to wakefulness. This facilitation is location-dependent with frontal lobe localizations having the highest likelihood of occurrence during NREM. To better understand the cortical network mechanisms that influence the likelihood of epileptic activity and that may explain the clinical patterns of seizure occurrence with sleep-wake states, we examined cortical synchrony and excitability during transition from wakefulness to NREM in healthy individuals.

Methods: Fourteen healthy subjects underwent simultaneous EEG and magnetoencephalography (MEG) imaging. Sleep states were determined by scalp EEG. Eight 15s artifact-free epochs were selected to represent each behavioral state: N1, N2 and wake. Atlas-based source reconstructions were performed using adaptive beamforming methods. To approximate long-range synchrony, functional connectivity measures were computed using imaginary coherence, across regions of interests in multiple frequency bands. Regional cortical excitation-to-inhibition was then estimated by a biophysical neural mass model (NMM), which optimizes characteristic gain and time constants of local excitatory and inhibitory inputs based on the observed power spectra.

Results: Light NREM was identified to be encoded in spatially and temporally specific patterns of local and long-range neural synchrony (Figure 1 for example delta frequency band local and long-range synchrony). Global functional connectivity was highest during N1, as compared to N2 and wake in the delta and theta frequency bands. Biophysical NMM demonstrated spatially heterogeneous properties of cortical excitation-to-inhibition from wake to NREM. Cortical excitation-to-inhibition was highest over the bilateral frontal lobe regions during N1, while the bilateral parietal regions exhibited relatively increased cortical excitation-to-inhibition during wakefulness, as compared to NREM (Figure 2).

Conclusions: Our findings provide evidence for structured long-range, frequency-specific cortical interactions and spatially heterogenous properties of cortical excitation-to-inhibition upon transition from wake to NREM. The combination of long-range synchrony measures and location-specific excitation-to-inhibition model metrics follow the observational patterns of seizure likelihood with sleep onset (e.g., highest modulation in light NREM; frontal location predominance during light NREM), which may provide an underlying mechanism for the complex observational findings between sleep and focal epilepsies. Further investigation in patients with focal epilepsy will help further elucidate these proposed mechanisms.

Funding: Doris Duke Physician Scientist Fellowship, CTSI TL1 grant
Neurophysiology