Neuromodulation in Depression: Mechanisms, Practice, and Innovation

Thesis

This thesis explores the mechanisms, clinical applications, and innovations in the use of transcranial magnetic stimulation (TMS) for treating major depressive disorder (MDD). In the first data chapter, we investigated differences in resting-state functional connec- tivity between drug-naïve and drug-experienced MDD patients. We found enhanced connectivity between the mediodorsal thalamus and the default mode network in drug- naïve patients, when compared to those who were drug-experienced. These findings align with theories around thalamocortical dysrhythmia and highlight the long-lasting impact of medication exposure on brain networks. In the second data chapter, we evaluated the real-world use of TMS for MDD treat- ment in clinical settings across clinics in the United States. We found no significant effects of resting motor thresholds, treatment timing, or patient age on clinical out- comes. However, high inter-clinic variability in data collection and measurement showed inconsistencies that appear to have an impact on TMS treatment efficacy. In the third data chapter, we piloted personalised targeting of the dorsolateral prefrontal cortex combined with monophasic intermittent theta burst stimulation (iTBS) to see whether a single stimulation session could lead to changes in cognition in patients ex- periencing low mood. We found no signal that monophasic iTBS, which is unfeasible with conventional TMS machines, leads to significant improvements in positive bias af- ter a single session compared to the standard biphasic iTBS in the small pilot sample. However, the analysis was severely limited, and further investigations are necessary. This thesis provides actionable considerations to optimise TMS for MDD, emphasising the importance of accounting for medication history, standardising clinical practices, and leveraging emerging technologies such as monophasic iTBS, networked devices and personalised targeting in future work. We hope this work will contribute to advancing TMS as an accessible and effective treatment for the growing burden of MDD.

Authors: Radyte, E

• DOI: 10.5287/ora-dmnvko5o5
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: major depressive disorder; neuromodulation; transcranial magnetic stimulation; 7T functional magnetic resonance imaging
• Subjects: Neurosciences; Psychiatry; Engineering