Date of Award

2019

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Bioengineering

First Advisor

Michael J. Kahana

Abstract

Episodic memory is essential to our daily lives, as it attaches meaning to the constant stream of sensory inputs to the brain. However, episodic memory often fails in a number of common neurocognitive disorders. Effective therapies remain elusive, owing to the complexity of brain networks and neural processes that support episodic encoding and retrieval. In particular, it is not understood how inter-regional communication within the brain supports memory function, though such communication may be critical to the highly integrative nature of episodic memory. To uncover the patterns of memory-related functional connectivity, we asked a large cohort of neurosurgical patients with indwelling electrodes to perform a verbal free-recall task, in which patients viewed lists of simple nouns and recalled them a short time later. As patients performed this task, we collected intracranial EEG (iEEG) from electrodes placed on the cortical surface and within the medial temporal lobe (MTL). First, we examined whole-brain functional networks that emerged during the encoding and retrieval phases of this task, using spectral methods to correlate frequency-specific signals between brain regions. We identified a dynamic network of regions that exhibited enhanced theta (3-8 Hz) connectivity during successful memory processing, whereas regions tended to desynchronize at high frequencies (30-100 Hz). Next, using only electrodes placed within the MTL, we asked whether functional coupling was also observed among this mesoscale subnetwork of highly specialized regions that play an outsize role in memory. Recapitulating our earlier findings, we noted broadly enhanced theta connectivity within the MTL, centering on the left entorhinal cortex during successful encoding operations. Finally, to determine whether such low-frequency functional connections reflect correlative or causal relations in the brain, we applied direct electrical stimulation via electrodes placed within the MTL. We found that low-frequency connections (5-13 Hz) predicted the emergence of theta activity at distant regions in the brain – particularly when stimulation occurred near white matter – indicating the potential causal relevance of iEEG-based functional connections. Taken together, these studies underscore the importance of low-frequency functional coupling to memory across spatial scales, and suggest this form of coupling indicates a causal relation between brain regions.

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