Post-traumatic stress disorder (PTSD) is a highly debilitating mental illness that is incited by various types of trauma and causes core symptoms of re-experiencing, hyperarousal, avoidance of trauma-related stimuli, and negative cognition and mood. It is accompanied by functional, social, and occupational impairment, as well as higher risks of medical comorbidities and mortality. Estimates indicate that PTSD affects 3.9% of the global population, and 7-9% of the US population, with only 50% of those with persistent PTSD treatment-seeking. The gold standard of PTSD treatment is prolonged exposure therapy and cognitive processing theory, with the addition of antidepressants; however, dropout rates are high likely due to the adverse effects of worsening re-experiencing of trauma and exacerbating behaviors of avoidance. As a result, alternative therapies such as transcranial magnetic stimulation (TMS) represent more tolerable treatment options. Historically, literature on TMS is promising for its low risk of side effects and efficacy, but there is no general consensus on treatment-specific targets, frequency of treatment delivery, or long-term efficacy. This proposed study will evaluate the use of neuroimaging guided intermittent theta burst stimulation, a form of TMS, for core PTSD symptom reduction and its efficacy up to one year in duration to potentially reduce the morbidity and mortality sequelae of PTSD.

Introduction: Memory is a complex cognitive process formerly linked to mechanisms of brain plasticity that can be estimated in the left dorsolateral prefrontal cortex (DLPFC) using transcranial magnetic stimulation and electroencephalography (TMS-EEG). Also, cortical thickness in the DLPFC may be a potential proxy measure of brain plasticity as previous literature reports a link between better memory and thicker cortex. However, the link between brain plasticity and memory performance as well as DLPFC thickness remains to be clarified. Methods: Intermittent theta burst stimulation (iTBS) probed plasticity-like mechanisms in the left DLPFC in 17 cognitively healthy participants. TMS-EEG recordings were performed before and after sham and active iTBS to quantify plasticity via transcranial magnetic stimulation-evoked potentials (TEPs). Composite memory scores for each domain (verbal episodic, visual episodic and working memory) were obtained using the Cambridge Neuropsychological Test Automated Battery. Anatomical T1 images were acquired by magnetic resonance imaging and processed by open-source software (CIVET) and the Automated Anatomical Labeling atlas to extract cortical thickness of the DLPFC. All statistical analyses (linear mixed model, Tukey's post hoc test and Pearson's correlations) were completed in R Studio. Results: iTBS resulted in increased TEP amplitude P30 (F= 5.239, p = 0.029), as shown by a significant interaction between condition (iTBS, sham) and time (pre- and post-condition). Specifically, Tukey's post hoc test revealed that the P30 increase was near trending significant post-iTBS compared to pre-iTBS for the active condition (p = 0.166) but not for the sham condition (p = 0.294). A trending significant relationship was observed between the magnitude of P30 change post-iTBS and thicker left DLPFC (r = 0.488; p = 0.108). Lastly, no significant relationships between P30 change and memory performance were observed. Conclusion: These preliminary findings suggest there could be a relationship between increased capacity for brain plasticity and a thicker left DLPFC. To further investigate these relationships, we plan to recruit additional cognitively healthy participants. Our preliminary findings support the foundation for future clinical studies in which DLPFC thickness could be explored as a predictive factor for response to plasticity-targeting iTBS treatment.