Evaluating a Novel Method to Determine the rTMS Dose Needed for Treating Depression After Spinal Cord Injury

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Depression is a leading cause of disability worldwide and is one of the most prevalent neuropsychiatric disorders following spinal cord injury (SCI). The burden of depression post-SCI is significant, as it is associated with higher cost, lower quality of life, and shorter survival time. Treating depression can be complicated, but it is vital. Repetitive transcranial magnetic stimulation (rTMS), a type of non-invasive brain stimulation, is an FDA-approved treatment option for depression that is utilized throughout the Veterans Affairs (VA) health system. However, no published studies have examined the effectiveness of rTMS for depression post-SCI. The updated Clinical Practice Guidelines for Spinal Cord Medicine for the Management of Mental Health Disorders (2020) by the Paralyzed Veterans of America recommends explicitly that future research examines rTMS in the SCI population. The critical challenge of administering rTMS for depression post-SCI is dosing. Currently, the resting motor threshold, a motor response of the right abductor pollicis brevis, is used to dose rTMS. Over half of the SCI population has incomplete or complete tetraplegia, indicating some degree of upper extremity [(UE)] impairment. Thus, if using current rTMS dosing parameters, it is plausible to conclude that over half the SCI population could be excluded from receiving rTMS for depression or may receive an improper dose, impacting the intervention's safety and effectiveness. [This study specifically addresses current limitations in treating depression post- SCI using rTMS and will: (1) identify the target electric-field (e-field) for rTMS; (2) evaluate a novel method, reverse-calculation e-field modeling, to determine the rTMS dose to treat depression in individuals with SCI; (3) conduct a pilot clinical trial using reverse-calculation e-field modeling to dose rTMS for depression post-SCI; (4) provide the appropriate training environment for the applicant to develop into an independent VA researcher; and (5) generate the necessary pilot data to support a future VA Merit Award application.] E-field modeling is a computational model that accounts for the TMS coil type, circuitry and placement, individual anatomy obtained through T1 and T2- weighted magnetic resonance images, and conductivity variance between tissue types. [First, using existing trial data, e-field modeling will be used to determine the target e-field dose for treating depression with rTMS.] Next, twenty-four individuals with SCI and depression will be randomized to receive either 6-weeks of rTMS treatment dosed using reverse-calculation e- field modeling (n=18) or sham treatment (n=6). We will examine the between-group effects of treatment on depressive symptoms using the Hamilton Rating Scale for Depression. The dose identified by reverse-calculation e-field modeling will be used in combination with FDA-approved parameters: 3,000 pulses/session at 10 Hz, 5 days/week for 6 weeks. Study outcomes will include changes in depressive symptoms, quality of life [(QOL)], and participation. During the award period, the applicant will capitalize on resources available through the Ralph H. Johnson VA Medical Center and its affiliated academic institution, Medical University of South Carolina. One primary example is the National Center for Neuromodulation for Rehabilitation (NIH P2 CHD086844). By utilizing these resources and hands-on training from renowned local experts, the applicant aims to develop the requisite skills and understanding of data acquisition, analysis, and interpretation of neurobiological variables, imaging, and e-field modeling. The overall goal of this CDA-2 application is to expose the candidate to a rich local environment for SCI recovery research, providing the foundation for developing into an independent VA researcher studying the effects of and viable treatment options for depression post-SCI to improve the lives and rehabilitation outcomes of Veterans. The proposed training plan will enhance the candidate's understanding of neuromodulation, neuropsychiatric disorders, and the design and delivery of neurorehabilitation trials. The data generated will inform the development of additional interventions focused on neuromodulation to improve function and QOL for individuals following SCI and other patient populations with UE motor impairment.