Function-based Accelerated Stimulation Therapy (FAST-therapy) for Freezing of Gait (FOG) After Parkinson's Disease (PD)

* The proposed research will characterize how inter-individual brain and behavior differences (i.e., gait function behavior and fMRI functional connectivity) at baseline relate to the treatment response. * This knowledge will provide important information about how interventions can be personalized and optimized. * The work may increase understanding of the underlying neurobiological mechanisms of neuromodulation for rehabilitation in patients with gait disturbances due to PD. * Impact: Results will provide insights into the effects of the neuromodulatory treatment on gait and motor dysfunction and could dramatically improve quality of life for patients with PD. The results also will (1) provide a mechanistic foundation for studies of therapeutic iTBS for PD patients, (2) evaluate novel stimulation targets, and (3) markedly condense the duration of treatment into a more manageable timeframe for patients. Our overall objectives in the current study are to: 1. To establish safety, feasibility, and tolerability of a high-dose, resting-state functional connectivity-guided iTBS 2. To elucidate the neural mechanism by which such a highly efficient and personalized stimulation approach leads to improvements in freezing of gait in PD. 3. To promote rehabilitation neuroscience research that expands current neuromodulatory methods 4. To increase understanding of the neurobiological mechanisms underlying such neuromodulatory treatment The specific aims / hypotheses in the current study are: \- Aim 1: Demonstrate the safety, feasibility and tolerability of high-dose, accelerated, network targeted rTMS in the basal ganglia-cerebellar-motor network. Working hypothesis: The approach will be safe, feasible and well tolerated by the patients. \- Aim 2: Demonstrate preliminary efficacy of high-dose, accelerated, network-targeted rTMS on freezing of gait. Working hypothesis: The approach facilitates recovery in motor network dysconnectivity, and thereby will improve FOG after treatment compared to pre-treatment. \- Aim 3: Demonstrate modulation of functional connectivity aftereffects of high-dose, accelerated, network-targeted rTMS. Working hypothesis: Functional connectivity as assessed with fMRI will change after the high-dose, accelerated, functionally-guided stimulation treatment compared to pre-treatment.