Validation of next-generation TMS system optimizing for widely scalable, personalized treatment of depression

SUMMARY Depression affects approximately 280 million people worldwide. Despite widespread access to antidepressant medications and psychotherapy, the prevalence of depression and, in turn, suicidality is increasing. In 2008, the US Food and Drug Administration (FDA) approved transcranial magnetic stimulation (TMS), an effective non-pharmaceutical treatment that alleviates depression, even in cases otherwise deemed treatment-resistant. More recently, the FDA approved Stanford Neuromodulation Therapy (SNT), an advanced TMS protocol that fine-tunes the stimulation target using functional magnetic resonance imaging (fMRI). This protocol boosts TMS efficacy (~80% symptom remission) and speed (5 treatment days). However, SNT-type therapy requires large, expensive, difficult-to-operate equipment and highly specialized personnel, which severely limits its scalability, accessibility, and overall capability to yield meaningful reductions in the nationwide prevalence of depression and suicidality. Ampa Health has an overarching goal to democratize access to state-of-the-art depression treatment by developing a next-generation TMS system that eliminates the need for large equipment and highly skilled technicians, thereby making treatment dramatically less expensive and more scalable. The technology we are developing will make it possible for patients to receive highly effective SNT-type therapy in almost any setting. Our NextGenTM TMS system comprises three key innovations: (1) Precision TMS targeting based on neurocardiac response signals to replace fMRI-derived targeting; (2) neuronavigation using a camera + scalp cap system instead of cumbersome, hard-to-master, fMRI-based frameless stereotaxy; and (3) optimizing the stimulation pulse waveform to minimize power requirements, in turn minimizing the size and weight of the overall TMS device. Having demonstrated proof-of-concept across all three system elements in Phase 1-equivalent work, we propose Phase 2 work to optimize and validate the NextGen TMS system for commercialization. Specifically, we will: Validate our neurocardiac response markers against gold-standard fMRI target localization (Aim 1); validate the precision of our FoveaTM Coil + navigation cap system for coil placement against gold-standard frameless stereotaxy (Aim 2); and identify the optimal pulse width for maximum power efficiency (Aim 3). As evidence of the therapeutic potential for TMS to alleviate severe, treatment-resistant depression continues to accumulate, the clinical necessity of these advancements is difficult to overstate. Our portable, cost-efficient, easy-to-operate system promises to maximize access to highly effective depression treatment, including the potential for at-home TMS in the future.