Sensory Entrained Transcranial Magnetic Brain Stimulation (seTMS) for Major Depression

About This Grant

This is a Veteran’s Administration Career Development Award 2 proposal for Jessica M. Ross, Ph.D. entitled “Sensory Entrained Transcranial Magnetic Brain Stimulation (seTMS) for Major Depression.” The goal of this project is to study phase-aligned TMS (i.e. brain wave synchronized TMS) in Veterans, to enhance personalized neuromodulation and clinical outcome for the 60-80% currently not achieving remission while not increasing cost and burden. To bring phase-aligned TMS to Veterans, the PI developed Sensory Entrained TMS (seTMS), a clinic-ready augmentation therapy. The seTMS protocol uses music to synchronize brain waves during TMS, to deliver precisely-timed TMS when the brain is maximally excitable. seTMS operates within the guidelines of currently FDA-cleared protocols, does not require EEG or phase estimation algorithms, and is affordable and accessible because it only requires headphones and plug-and-play software that is compatible with existing equipment. This work will be a thorough investigation of seTMS for effective VA clinical use. The current study aims to 1) apply pulses of seTMS to the dlPFC in Veterans and compare brain changes (target engagement in electroencephalography, EEG) to those from standard pulses of TMS; 2) apply seTMS to the dlPFC in Veterans with depression and compare target engagement to those from standard pulses of TMS; 3) treat MDD with an accelerated form of seTMS (se-aTBS) or standard a-TBS to compare symptom reduction and long-term target engagement (lasting brain changes). Symptoms will be measured using standard clinical scales, administered during the first visit (Day 0), during the last visit following TMS, and at 1-month post-treatment. These scales are the Montgomery-Åsberg Depression Rating Scale (primary) and Columbia Suicide Severity Rating Scale (secondary), and the standard scales collected routinely in the Palo Alto MIRECC Precision Neuromodulation Clinic: Patient Health Questionnaire (PHQ-9), the Brief Symptom Inventory 18 (BSI-18), PTSD Checklist for DSM-5 (PCL-5), Beck Scale for Suicidal Ideation (BSSI), Generalized Anxiety Disorder 7-item (GAD-7), and the 36-Item Short Form Survey (SF-36) Health Survey. The PHQ-9 and GAD-7 will also be given to the Veterans on each day of treatment (Days 1-4) after the last protocol of the day. Perceptual ratings of scalp feeling and pain will also be recorded to assess tolerability and feasibility in Veterans. The overarching research hypothesis is that seTMS will enhance prefrontal circuit changes in non-depressed and depressed Veterans and improve clinical outcomes when used for treating Major Depression (MDD) while being feasible for clinical use. The specific hypotheses are that 1) seTMS will enhance TMS-induced brain changes in Veterans and 2) Veterans with MDD and 3) the se-aTBS treatment protocol will lead to greater reduction of clinical symptoms than standard aTBS, and be feasible and tolerable, in Veterans with MDD. This CDA-2 award would allow Dr. Ross to gain proficiency in 1) theory and models of brain plasticity in Veteran clinical populations, 2) traditional and innovative clinical design, 3) adaptive and personalized TMS methodologies, and 4) professional development for a career at the VA. Training and research for the project will be conducted at both the VA Palo Alto Health Care System (VAPAHCS) as part of the Mental Illness Research, Education and Clinical Center (MIRECC) and Stanford University School of Medicine, in the Department of Psychiatry and Behavioral Sciences. Both sites offer excellent intellectual and physical resources to complete the proposed work. SeTMS is a novel intervention that harnesses principles of sensorimotor neuroscience and has the potential to increase the efficacy of FDA-cleared TMS protocols without increasing cost for Veterans with Depression.