Project Summary/Abstract The purpose of this K01 proposal is to enable the PI to become an independent research investigator with expertise in focal neuromodulation, clinical investigations, and neuroimaging and psychophysiological biomarker research in traumatized populations and post-traumatic stress disorder (PTSD). The candidate's long-term goal is to build a NIH-funded research program to advance treatment for trauma-related disorders by understanding the neurobiological mechanisms of treatment and identifying predictive biomarkers for treatment outcome. The proposed study leverages the PI's experience with pre- and post-treatment studies in traumatized populations, PTSD biomarker research, and her strong foundation in neuroimaging and longitudinal data analyses. The training plan includes structured mentoring, hands-on training in Transcranial Magnetic Stimulation (TMS) and brain functional connectivity (FC) analyses, didactic coursework and a rigorous proposed research study in order to provide new training in 1) focal neuromodulation (TMS), 2) clinical investigations, 3) FC analyses, and additional training in 4) PTSD biomarkers, and 5) career development. With 30-50% of PTSD patients not responding to first line therapies, novel treatments are warranted; however, development is hampered by a lack of understanding of neural mechanisms underlying recovery from PTSD. TMS studies in PTSD have applied 1Hz stimulation over the rDLPFC and demonstrated a potential therapeutic effect, but the mechanism of TMS remains unclear. This K01 proposal aims to advance TMS treatment for PTSD by better understanding the mechanism of action of TMS and examining the effect of 1Hz rDLPFC stimulation on PTSD neuroimaging and psychophysiological biomarkers, particularly related to the fear neurocircuitry often implicated in PTSD and hypothesized to be improved by DLPFC stimulation. The proposed experiments leverage the infrastructure of the Grady Trauma Project (GTP), the largest civilian PTSD research study, for patient recruitment and clinical and biological assessment foundation. PTSD patients will be recruited and randomized to a TMS (N=30) or sham treatment (N=30) group. Neuroimaging and psychophysiological data will be collected in the week before and after the two-week treatment period (week 4). This K01 project will significantly contribute to the advancement of treatment for PTSD by: 1) determining if 1Hz TMS to the right DLPFC improves PTSD intermediate phenotypes; 2) suggesting novel brain modulation targets for future studies; 3) providing preliminary data for future studies examining individual differences for treatment response; and 4) advancing our understanding of neurobiology of PTSD treatment response using TMS as a probe.