Date of Award

January 2015

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Emily Gilmore

Second Advisor

Kevin O'Connor

Subject Area(s)

Neurosciences, Medicine, Surgery

Abstract

The neural structures supporting human consciousness have importance in both neuroscience and medicine. A previously developed rodent model of temporal lobe seizures recapitulates electrophysiological and behavioral aspects of human partial seizures. It models ictal and postictal neocortical slow waves associated with behavioral impairments in level of consciousness seen in human partial seizures. The mechanism of slow wave production in epilepsy may involve suppression of the subcortical arousal systems including the brainstem and intralaminar thalamic nuclei. We hypothesized that intralaminar thalamic stimulation may lead to electrophysiological and functional rescue from postictal slow waves and behavioral arrest. We electrically stimulated the central lateral nucleus, a member of the rostral intralaminar thalamic nuclei, under anesthesia and after electrically-induced hippocampal seizures to demonstrate a proof-of-principle restoration of electrophysiological and behavioral measures of consciousness. We measured decreased cortical slow waves, increased desynchronization, and increased multiunit activity in the cortex with thalamic stimulation following seizures. Functionally, thalamic stimulation produced resumption of exploratory behaviors in the postictal state. Targeting nodes in the neural circuitry of consciousness has important medical implications. Impaired consciousness with epilepsy has dangerous consequences including decreased school/work performance, social stigmatization, impaired airway protection, and accidents (such as motor vehicle accidents, drownings, or burns). These data suggest a novel therapeutic approach for restoring consciousness after seizures. If paired with responsive neurostimulation, this may allow rapid implementation to improve level of consciousness in patients with epilepsy.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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