Characterizing the memory deficits from asynchronous distributed hippocampal stimulation Open Access
Ghetiya, Mihir (Spring 2019)
Abstract
Epilepsy is a group of debilitating neurological disorders characterized by chronic, spontaneous seizures. Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. It is characterized by complex partial seizures that arise from the limbic structures of the brain, such as the hippocampus and the adjacent temporal lobe structures. Current treatments for TLE include anti-epileptic drugs (AED) and surgery. However, seizures are controllable with medication in only 70% of patients and surgery is not possible if the epileptic focus is in an eloquent area of brain, such motor, sensory, or memory regions. Neuromodulation through deep brain stimulation (DBS) offers an alternative therapy to suppress seizures in patients with refractory TLE. Various clinical studies have shown the effect of vagus nerve stimulation, anterior nucleus of thalamus stimulation, and direct hippocampal stimulation in suppressing seizures. However, these DBS approaches are limited by low efficacy and significant inter-subject variability in seizure reduction outcome. Recent work suggests that asynchronous distributed multielectrode stimulation (ADMES) delivered at theta frequencies to the hippocampus has the potential for providing a superior therapy for patients with TLE. Preliminary work suggests that 2V and 4V ADMES causes memory impairments in normal rats. However, it is possible that the rats can tolerate certain voltages before showing memory impairments. A simple grid search is straightforward to analyze, but it requires many experiments and does not explain the effect on memory as a continuous function of increasing voltage of stimulation. We utilize a black-box Bayesian optimization (BaO) algorithm to efficiently and quickly explore the voltage parameter space. We performed spatial object recognition memory task to assess spatial memory in rats as they received ADMES stimulation. We obtained subject specific model of memory performance with increasing voltages and observed considerable inter-subject variability in response to increasing voltages. We also did a preliminary grid search looking at the effect of ADMES frequency on memory in normal rats using novel object recognition task. Our BaO approach shows promise for further multi-objective function optimization for fine-tuning stimulation parameters to reduce seizure frequency while preserving memory performance.
Table of Contents
Chapter 1: Background and Introduction……………………………………………….............................................................…….....1
Chapter 2: Bayesian optimization to search for voltage parameters to maximize and minimize memory task performance ……...9
Chapter 3: Exploring voltage and frequency domain of ADMES and its effect on memory……...................................................22
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Characterizing the memory deficits from asynchronous distributed hippocampal stimulation () | 2019-04-16 13:11:15 -0400 |
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