Epilepsy Disrupts Hippocampal Phase Resetting and Impairs Working Memory
Abstract number :
3.075
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2021
Submission ID :
1825725
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:50 AM
Authors :
Olivia Arski, HBSc - Hospital for Sick Children; Simeon Wong, MHSc - Hospital for Sick Children; Nebras Warsi, MD, CM - Hospital for Sick Children; Elizabeth Kerr, PhD - Hospital for Sick Children; Mary Lou Smith, PhD - Hospital for Sick Children; Ayako Ochi, MD, PhD - Hospital for Sick Chldren; Hiroshi Otsubo, MD, PhD - Hospital for Sick Children; Elizabeth Donner, MD, PhD - Hospital for Sick Children; George Ibrahim, MD, PhD - Hospital for Sick Children
Rationale: Working memory (WM) deficits are commonly reported in children with epilepsy and are associated with significant morbidity and decreased quality of life. Although the neural mechanisms underpinning these deficits remain unclear, it is thought that transient focal epileptic activity may contribute to WM deficits by disrupting the WM network. In the WM network, phase resetting of neural oscillations in the hippocampus is thought to underly WM processing. Here, we leverage stereotactically-implanted electrodes in the hippocampus and suspected epileptogenic lesion to elucidate the specific mechanism by which transient focal epileptic activity disrupts the neural mechanisms subserving WM function in children with epilepsy.
Methods: Twelve children with epilepsy undergoing invasive monitoring with stereotactically-implanted electrodes in the hippocampus and suspected epileptogenic lesion completed a 1-back visual WM task concurrent with intracranial recordings. Instantaneous phase of the canonical frequency bands was determined at the time of stimulus presentation using the Hilbert transform. The occurrence of transient focal epileptic activity, including pathological high frequency oscillations (HFOs) and spikes, was determined using validated detectors.
Results: Significant phase resetting in the delta and theta frequency bands occurred in response to the WM stimuli. The precision of this phase resetting was associated with optimal WM processing, as indexed by faster reaction times. Furthermore, enhancement of delta and theta synchrony between the hippocampus and WM-related networks was evident during task performance. Conversely, trials coinciding with transient focal epileptic activity were associated with prolonged reaction time, attenuated delta and theta phase resetting, and altered delta and theta connectivity between the hippocampus and WM-related networks.
Conclusions: We present a rare and unique dataset demonstrating epileptogenic activity interference with hippocampal oscillatory activity. These findings further elucidate the neural mechanisms underpinning WM deficits in children with epilepsy and may guide the development of future treatments aimed at rescuing memory function.
Funding: Please list any funding that was received in support of this abstract.: N/A.
Translational Research