Abstracts

Rationale: Cognitive dysfunction is a frequent and often disabling comorbidity in patients with epilepsy. Memory, language and executive dysfunction may be impaired by antiepileptic medications, surgical treatments or as a result of the underlying pathophysiology. Additionally, epilepsy-related injuries such as head trauma are associated with worsening cognition.  The pathophysiology underlying cognitive decline in adult onset epilepsies is poorly understood, but hippocampal dysfunction is likely to play a role in many cases. Patients with diverse neurologic and psychiatric disorders show reduced hippocampal size, activation and connectivity in structural and functional neuroimaging studies. We sought to further explore the relationship between hippocampal activity and cognitive function using intracranial electroencephalography during a verbal fluency task. Methods: Patients with drug-resistant, localization-related epilepsy were implanted with mesial temporal depth electrodes for phase II monitoring. Hippocampal activity was recorded during semantic (category-motivated) and phonemic (letter-motivated) verbal fluency tasks and at rest. Electrodes were localized by coregistration of postoperative MRI and CT to MNI space and comparison against the Harvard-Oxford Brain Atlas; they were subsequently validated by visual inspection. EEG was montaged using a common average reference and epochs were collected from 1250ms prior to 750ms after onset of each utterance. Spikes and movement artifact were excluded by visual inspection. High gamma (70-110Hz) power was estimated at hippocampal electrode contacts using the Thompson multitaper method and normalized by the resting high gamma power. For one subject, high gamma estimates were limited to 85-110Hz due to significant artifact in the 70-80Hz range. Results: Seven patients were included in the study, of which 6 had early epileptic involvement of mesial temporal regions. All patients were left-hemisphere dominant (by Wada and/or fMRI) and had epilepsy onset after language development. Left temporal lobe epilepsy (TLE) patients tended to have worse performance than right TLE patients. A significant correlation was observed between maximum (across electrode contacts) task-related hippocampal high gamma activity and production rate in semantic (p < 0.01) but not phonemic (p=0.72) verbal fluency tasks (see figure). Conclusions: We demonstrate the use of task-related high gamma activity as a measurement of mesial temporal lobe activation in verbal fluency, a free-recall paradigm dependent on expressive language and long-term memory. The results suggest that the contribution of the hippocampal complex to cognitive function is task-dependent, and that high gamma activity may be used as a marker for hippocampal involvement in cognitive tasks. These observations are consistent with results previously seen using fMRI, however our results support the notion that the relationship between hippocampal activity and verbal fluency is sustained even when analysis is restricted to more precise time periods. Additionally, this study sheds further light on the mechanisms by which the hippocampus may contribute to cognitive dysfunction in epilepsy patients. Funding: This work was supported by the National Institutes of Health (NS091006 and NS099348) and by the Mirowski Family Foundation.