Dissertation
Neurophysiological investigation of transcranial magnetic stimulation’s antidepressant effects
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2024
DOI: 10.25820/etd.007588
Abstract
Treatment resistant depression (TRD) is a form of major depressive disorder (MDD) that involves non-response to at least 2 antidepressant treatment trials. Depression is associated with reduced cortical excitability and dysfunctional autonomic nervous system balance. Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex is an effective intervention for TRD. While rTMS is hypothesized to enhance the cortical excitability of the site of stimulation, current methods are confounded by the use of the motor system and complex experimental setups. Moreover, it is unclear how rTMS modulates the autonomic nervous system balance due to its effects on the prefrontal cortices.
Thus, the goal of the current work is to identify biomarkers of rTMS treatment response to add to a personalized medicine approach to interventional psychiatric treatments. This work addresses two key aspects of depression: cortical excitability and cardiovascular activity, and how these aspects change over an interventional treatment course of repetitive transcranial magnetic stimulation (rTMS) for TRD.
In Aim 1, I measured cortical excitability with visual evoked potentials. I discovered that a treatment course of rTMS potentiated visual evoked potentials, specifically the P1 and N1 components, with no association with treatment outcome. This represents increased cortical excitability following rTMS. As this task has not been used in determining the effects of rTMS on cortical excitability, this novel mechanism of measuring rTMS-induced changes in cortical excitability informs us that rTMS can increase cortical excitability at sites distal to the site of stimulation. Additionally, this work has further validated the use of the visual evoked potentials task in measuring cortical excitability.
In Aim 2, I discovered that rTMS acutely slows heart rate during stimulation, replicating prior work. However, this change in heart rate did not last through to the end of the treatment course, where I found no changes in heart rate at the last rTMS session in the course. Furthermore, I found no changes in resting heart rate variability from before to after a treatment course of rTMS. These results suggest that impaired cardiovascular functioning may be a trait marker of depression, and not subject to change after successful treatment of depressive symptoms. Moreover, the acute changes seen during rTMS stimulation did not associate with treatment outcome.
This work contributes to the literature on rTMS mechanisms of action as a treatment for depression.
Details
- Title: Subtitle
- Neurophysiological investigation of transcranial magnetic stimulation’s antidepressant effects
- Creators
- Alexandra Adele Alario
- Contributors
- Mark J Niciu (Advisor)Nicholas T Trapp (Advisor)Aaron Boes (Committee Member)Krystal Parker (Committee Member)Jan Wessel (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Neuroscience
- Date degree season
- Autumn 2024
- DOI
- 10.25820/etd.007588
- Publisher
- University of Iowa
- Number of pages
- xiii, 128 pages
- Copyright
- Copyright 2024 Alexandra Adele Alario
- Language
- English
- Date submitted
- 11/19/2024
- Description illustrations
- illustrations, tables, graphs
- Description bibliographic
- Includes bibliographical references (pages 116-128).
- Public Abstract (ETD)
- Treatment resistant depression (TRD) is a subtype of major depressive disorder that does not improve after at least 2 antidepressant treatments including medications or talk therapies. Depression is generally associated with reduced electrical activity in the brain, and dysfunctional autonomic nervous system activity. Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for individuals with TRD that have not had a beneficial response to other therapies. While we know that rTMS modulates the electrical activity of the brain with magnetic pulses, we do not know how this treats depressive symptoms, specifically via impaired electrical activity in the brain and unhealthy cardiovascular functioning. The goal of my work is to understand how rTMS treatment for depression could change the electrical activity of the brain and cardiovascular functioning. I found that rTMS increased the electrical activity of the brain at sites far from the stimulation location. I also found that rTMS has acute, but not long-lasting effects on the cardiovascular system. This work contributes to the scientific literature on how rTMS exerts its antidepressant effects.
- Academic Unit
- Interdisciplinary Graduate Program in Neuroscience
- Record Identifier
- 9984774665902771
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