PhD Defense in Neural Engineering
Candidate: Nrupen Palatapaki
Advisor: Dominique Durand
Meeting Information:
Defense Date: Monday, February 9th
Defense Time: 12:00 PM - 2:00 PM EST
Defense Location: Wickenden 105
Join Online:
Meeting ID: 920 6329 6099
Passcode: 841638
TITLE: Bilateral Control of Epilepsy Using White Matter
The current clinical framework for managing epilepsy treats white matter tracts as passive conduits for seizure spread, severely limiting their use in electrophysiological monitoring and therapeutic intervention. This research fundamentally challenges dogma, using the corpus callosum (cc), the largest white matter tract, to demonstrate its essential active properties and establish its utility as the single, comprehensive anatomical basis for a highly efficacious closed-loop neuromodulation system.
We first established the cc's utility as an ideal active-sensing site for epilepsy monitoring. Using in vitro and in vivo 4-aminopyridine (4-AP) models, we confirmed that epileptiform discharges propagate through the cc with polysynaptic delays (24.81± 4.09 ms in vitro). This propagation was leveraged in vivo to provide clear directionality and lateralization of seizure foci via cross-correlation analysis, highlighting the cc's potential to identify the seizure-onset zone. Critically, we identified a novel, predictive physiological signature. The corpus callosum evoked echo (ccEE) is dependent on a cortico-callosal feedback loop. It is significantly increased in amplitude during the pre-ictal state, achieving an Area Under the Curve (AUC) of 0.77 for seizure prediction.
The second phase defined a highly effective and mechanistically clear strategy for seizure suppression from the cc. Low-frequency stimulation (LFS) of the cc acts as a potent inhibitory strategy, suppressing cortical seizure activity by up to 76.5% at an optimal frequency of 5 Hz in the 4-AP in vitro model. The antiepileptic effect is entirely dependent on the synergistic activation of two inhibitory pathways: the GABAB receptorand the slow after-hyperpolarization (sAHP). A complete loss of efficacy upon pharmacological blockade of these mechanisms (<5% reduction) confirms that the cc serves as an effective therapeutic delivery site by engaging deep-seated, intrinsic inhibitory mechanisms.
This research provides compelling, multifunctional evidence that the corpus callosum is an excellent strategic target, not only overcoming the clinical neglect of white matter tracts but also providing all the essential features of monitoring, lateralization, prediction, and a powerful, mechanism-based inhibitory suppression required to construct a highly effective, next-generation closed-loop neuromodulation device. The findings unequivocally validate the clinical translation of cc-based sensing and therapeutic protocols as a superior, comprehensive alternative for drug-resistant epilepsy.