Electrophysiology of memory consolidation and epileptogenesis in the primate mesial temporal lobe. Effects of focal seizures with impaired awareness
Epilepsy is a disorder characterized by unprovoked, recurrent seizures and affects approximately 350,000 Canadians. A third of this population have seizures that are refractory. This leaves over 100,000 people with uncontrolled seizures. Poorly managed seizures commonly cause cognitive dysfunctions, like learning and memory impairments, which can be devastating to individuals and society. Given that epilepsy arises from disturbances in electrical brain function, there is an opportunity to learn about these disturbances by studying electrophysiologic changes, which occur in a network that supports memory consolidation, during epileptogenesis. The first aim of this project was to characterize the electrophysiology of memory consolidation in healthy non-human primates (NHPs). It was hypothesized that this characterization would approximate that of other animal models such as rodents. It was also hypothesized that pharmacologic manipulations known to impair memory would predictably disrupt baseline electrophysiology. Neural signals were recorded from rhesus macaques performing associative and spatial memory tasks in a 3D virtual reality environment. Results of aim 1 demonstrated that, in addition to being associated with learning, as it is with other animal models, sharp-wave ripple (SWR) occurrence was correlated with mismatches in expectation and perception. Incorrect target choices, steering errors and surprise rewards correlated with SWRs in NHP. Subanesthetic ketamine predictably altered excitability as measured by field-evoked potentials (fEPs) and connectivity and upper thresholds for fEP elicitation were determined. The second aim was to develop a stimulation technique to induce focal seizures with impaired awareness (FIAS) in NHP. It was hypothesized that weekly kindling would cause the stable development of FIAS and that epileptogenesis would alter baseline physiology. Electrophysiology was compared to aim 1, dynamics of electrographic seizures were examined and clinical semiology was monitored. Results of aim 2 demonstrated that kindling could be used to induce FIAS which altered electrophysiology and behaviour from baseline. This work highlights unique electrophysiologic processes underpinning memory in primates. It describes a stable model of FIAS which is used to study MTL alterations due to drugs and epileptogenesis. Together these results inform research and clinical practice regarding the generation of seizures, study of memory and use of electrical brain stimulation.
URI for this recordhttp://hdl.handle.net/1974/30288
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