Project Grant R44MH119872

XCSITE 300: CLOUD-ENABLED CLOSED-LOOP TRANSCRANIAL CURRENT STIMULATION DEVICE FOR AT-HOME STUDIES - PROJECT SUMMARY - PULVINAR NEURO LLC, TOWNSEND THE CAUSAL ROLE OF CIRCUIT ACTIVITY DYNAMICS IN DEPRESSION REMAINS POORLY UNDERSTOOD DUE TO THE LACK OF TOOLS FOR NON-INVASIVE, TARGETED CIRCUIT MODULATION. TODAY'S NON-INVASIVE BRAIN STIMULATION APPROACHES APPLY GENERIC STIMULATION WAVEFORMS WITHOUT TARGETING INDIVIDUAL ACTIVITY SIGNATURES AND WITHOUT DYNAMICALLY ADAPTING STIMULATION TO ONGOING FLUCTUATIONS IN BRAIN ACTIVITY. TO ADDRESS THIS GAP, THE LONG-TERM GOAL OF PULVINAR NEURO IS TO DEVELOP, EVALUATE, AND COMMERCIALIZE TARGETED CLOSED-LOOP TRANSCRANIAL ALTERNATING CURRENT STIMULATION (TACS) TECHNOLOGY, WHICH MEASURES BRAIN ACTIVITY WITH EEG AND DYNAMICALLY APPLIES WEAK RHYTHMIC ELECTRIC FIELDS TO MODULATE NETWORK OSCILLATIONS. IN THE PREVIOUS PHASE 1 SBIR, PULVINAR NEURO DEVELOPED XCSITE 100PRO, A CLOSED-LOOP TACS DEVICE THAT WAS SUCCESSFULLY TESTED FOR FEASIBILITY IN HEALTHY HUMAN PARTICIPANTS, AND XCSITE 200, A CLOUD-BASED PLATFORM FOR REMOTE STIMULATION. THE OVERALL GOAL OF THIS APPLICATION IS TO DEVELOP AND EVALUATE THE XCSITE 300 PLATFORM THAT WILL INTEGRATE CLOSED-LOOP CAPABILITIES WITH CLOUD-BASED STIMULATION AND STUDY MANAGEMENT. THE RATIONALE FOR THIS PROJECT IS THAT SUCH A SOLUTION WILL DRIVE THE NEXT GENERATION OF CIRCUIT-BASED RESEARCH IN PSYCHIATRY AND THAT CLOSED-LOOP TACS HAS THE POTENTIAL TO BECOME A SAFE AND EFFECTIVE TREATMENT FOR DEPRESSION GIVEN THE INITIAL POSITIVE FINDINGS OF OPEN-LOOP TACS FOR THE TREATMENT OF DEPRESSION AND THE SUBSTANTIAL UNMET MARKET NEED. THREE SPECIFIC AIMS WILL BE PURSUED TO ACCOMPLISH THIS GOAL. (1) INTEGRATE AND BENCH TEST CLOSED-LOOP TACS TECHNOLOGY WITH CLOUD-BASED INFRASTRUCTURE, (2) TEST XCSITE 300 FOR IN-LAB USE IN A PILOT DOUBLE-BLIND SINGLE-SITE STUDY FOR THE TREATMENT OF DEPRESSION (XCSITE 300 CLINIC), AND (3) ADAPT DEVICE FORM FACTOR AND USER INTERFACE FOR AT-HOME USE (XCSITE 300 HOME) AND ESTABLISH FEASIBILITY IN A PILOT STUDY IN PEOPLE WITH DEPRESSION. AT COMPLETION OF THE PROPOSED WORK, FEASIBILITY AND PRELIMINARY EFFICACY OF CLOSED-LOOP TACS WILL BE ESTABLISHED AND CLOSED-LOOP TACS FOR USE IN A CLINIC AND FOR AT-HOME USE BY PATIENTS WILL BE READY FOR PIVOTAL STUDIES FOR THE TREATMENT OF DEPRESSION. THE WORK IN THIS APPLICATION IS INNOVATIVE GIVEN THE LACK OF AVAILABLE CLOUD-ENABLED ("SMART") CLOSED-LOOP TACS DEVICES FOR PROBING CIRCUIT DYNAMICS AND FOR EVALUATION OF CLINICAL EFFICACY IN RIGOROUS DOUBLE-BLIND TRIALS. THE PROPOSED WORK IS SIGNIFICANT SINCE CLOSED-LOOP TACS WILL ENABLE THE INVESTIGATION OF THE CAUSAL ROLE OF SPECIFIC CIRCUIT DYNAMICS IN HUMANS AND THE DEVELOPMENT OF NOVEL TREATMENTS FOR DEPRESSION WHICH ARE URGENTLY NEEDED.