Unveiling Thalamo-cortical Interactions in Rolandic Epilepsy: Neuromodulation of the Motor Thalamus for Seizure Suppression
Abstract number :
3.182
Submission category :
3. Neurophysiology / 3E. Brain Stimulation
Year :
2022
Submission ID :
2204828
Source :
www.aesnet.org
Presentation date :
12/5/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Arianna Damiani, MSc – University of Pittsburgh; Erinn Grigsby, PhD – Physical Medicine and Rehabilitation – University of Pittsburgh; Jonathan Ho, BS – School of Medicine – University of Pittsburgh; Lucy Liang, MS – Bioengineering – University of Pittsburgh; Simon Borgognon, PhD – Bioengineering – University of Pittsburgh; Emily Oby, PhD – Bioengineering – University of Pittsburgh; Aaron Batista, PhD – Bioengineering – University of Pittsburgh; Marco Capogrosso, PhD – Neurological Surgery – University of Pittsburgh; Elvira Pirondini, PhD – Physical Medicine and Rehabilitation – University of Pittsburgh; Jorge Gonzalez-Martinez, Phd,MD – Neurological Surgery – University of Pittsburgh
Rationale: The current standard of care for medically refractory epilepsy (MRE) relies on the focal resection of the epileptogenic zone if the cortical area is amenable for safe removal. In patients with focal epilepsy involving highly eloquent cortical areas such as the motor cortex, the risk of devastating neurological consequences such as motor deficits, minimizes resection options. Here, neuromodulation is an alternative. Previous studies have provided evidence of the involvement of subcortical structures, namely the thalamus, in the organization of epileptiform activity (Penfield W, 1952). However, our understanding of specific changes in thalamocortical communication during focal motor seizures is currently inadequate. Here, we aim to characterize the dynamic relation between thalamic nuclei and seizure activity in the motor cortex, with the goal of identifying potentially effective targets of thalamic deep brain stimulation (DBS) for rolandic MRE. We hypothesize that electrical stimulation of the motor thalamus will result in cortical activity desynchronization and epileptiform activity decrement in rolandic cortical areas.
Methods: We performed experiments in acute preparations of anesthetized nonhuman primates (n=2) where we simultaneously stimulated the thalamus and recorded from motor cortex (M1). We used a multichannel depth electrode implanted in the ventro-oralis posterior (Vop) to stimulate the thalamus at frequencies varying from 1 to 200 Hz. Importantly, the second animal expressed chronic spontaneous epilepsy characterized by focal clonic motor seizures in the right forelimb. The intraoperative electrocorticography revealed the presence of repetitive polispikes located in the left motor and pre-motor cortex.
Results: Following low-frequency Vop stimulation, we identified clear evoked potentials in ipsilateral M1, reflecting orthodromic monosynaptic neurotransmission. Interestingly, in the epileptic monkey, we observed synchronous thalamocortical connectivity enhanced during the ictal phase. The thalamic recording showed a slow potential drift accompanied by an enhancement of high frequency activity power simultaneous with the occurrence of epileptiform cortical activity. Importantly, we observed a frequency-dependent suppression of high-frequency cortical discharges with Vop stimulation. Attenuation of the epileptic M1 activity started after 50Hz stimulation, reaching an almost complete suppression at 200 Hz. These results suggest a potential neuromodulatory effect of high-frequency thalamic DBS for seizure suppression.
Conclusions: Overall, results provide evidence of the electrophysiological interaction among cortical and subcortical areas and demonstrate rolandic epileptiform activity suppression through high-frequency motor thalamus stimulation. Future studies in animal models of focal epilepsy will provide data to further validate our hypothesis.
Funding: Hamot Foundation (to Gonzalez-Martinez)
Neurophysiology