Graduation Date

Spring 5-4-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Interdisciplinary Graduate Program in Biomedical Sciences

First Advisor

Dr. David E Warren

Abstract

Healthy and pathological aging processes can impact human memory. Current interventions for clinical memory impairment offer little opportunity for restoration of memory ability. Fortunately, a novel therapy in the form of repetitive transcranial magnetic stimulation (rTMS) has exhibited promise in this regard. In healthy adults, rTMS of the angular gyrus (AG) has been reported to improve memory. The current study sought to determine the generalizability of these findings to individuals with clinical memory impairment by administering a clinical trial replicating an rTMS protocol reported to improve hippocampal-dependent memory in healthy individuals to individuals with amnestic mild cognitive impairment (aMCI). Individuals diagnosed with aMCI (N=15) completed two five-day sessions of rTMS with a minimum two-week washout between weeks. Brain and cognitive variables were collected before the first rTMS session of each week and the day following the final session of each week. rTMS was administered as a β-frequency pulse sequence alternating 2-sec. trains of 20 Hz stimulation with 28-sec. rest for 20 min (1600 TMS pulses total) for five consecutive days. Stimulation was administered to each participant's area of left AG exhibiting peak resting-state functional connectivity (RSFC) with left hippocampus. Treatment rTMS was delivered at 100% resting motor threshold (RMT) and placebo rTMS at 10% RMT. This study followed a double-blind crossover design. The primary objective of this study was to identify any changes in hippocampal-dependent memory associated with rTMS. Secondary objectives included identifying RSFC changes of the hippocampus and AD with the DMN and any changes in the brain's functional connectome associated with rTMS. Treatment rTMS was associated with significantly improved performance on select measures of hippocampal-dependent memory, specifically verbal memory. Treatment rTMS also reduced RSFC between the hippocampus and bilateral dorsolateral prefrontal cortex. However, no change in connectomic measures was observed within this study. This study's findings suggest that rTMS can improve memory and modify hippocampal RSFC in individuals diagnosed with aMCI and may serve as a potential intervention for AD.

Comments

2024 Copyright, the authors

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