Project Grant R61MH134943

NONINVASIVE MODULATION OF DEEP BRAIN CIRCUITS FOR TREATMENT-RESISTANT DEPRESSION - CURRENT INTERVENTIONS FOR DEPRESSION LACK THE CAPABILITY TO DIRECTLY, PRECISELY, AND NONINVASIVELY ENGAGE THE DEEP BRAIN CIRCUITS AT THE CORE OF THE ILLNESS. WE HAVE DEVELOPED A NON-SIGNIFICANT-RISK, MRI-COMPATIBLE, INDIVIDUALLY-TARGETED, ULTRASONIC NEUROMODULATION DEVICE THAT CAN STIMULATE DEEP CIRCUITS IN HUMANS NONINVASIVELY WITH A PRECISION PREVIOUSLY ACHIEVABLE ONLY WITH SURGICALLY IMPLANTED ELECTRODES. THIS R61/R33 PROJECT WILL EVALUATE THE POTENTIAL FOR THIS NOVEL DEVICE TO ENGAGE DEEP BRAIN TARGETS AND MODULATE MOOD SYMPTOMS IN INDIVIDUALS WITH TREATMENT-RESISTANT DEPRESSION. THE R61 PHASE WILL DEMONSTRATE TARGET ENGAGEMENT BY DELIVERING LOW-INTENSITY ULTRASOUND TO THE SUBCALLOSAL CINGULATE DURING FUNCTIONAL MAGNETIC RESONANCE IMAGING. THIS PHASE AIMS TO EVALUATE THE INTENSITY DEPENDENCE, TARGET SPECIFICITY, AND TOLERABILITY OF THIS NEUROMODULATION INTERVENTION. IF PREDEFINED GO/NO-GO CRITERIA ARE MET, THE R33 PHASE WILL THEN EVALUATE THE SHORT-TERM EFFECTS OF SUBCALLOSAL CINGULATE NEUROMODULATION USING A RANDOMIZED SHAM-CONTROLLED STUDY DESIGN. THE AIMS OF THIS PHASE ARE TO EXAMINE THE ASSOCIATIONS BETWEEN TARGET ENGAGEMENT, SHORT-TERM MOOD CHANGES, AND IMMEDIATE CHANGES IN BRAIN FUNCTIONAL CONNECTIVITY. THE R33 ALSO AIMS TO EVALUATE TOLERABILITY AND FEASIBILITY OF A SUBSEQUENT EFFICACY TRIAL. THIS PROJECT WILL ADDRESS AN UNMET NEED BY PROVIDING NEW, NONINVASIVE, CIRCUIT-DIRECTED TREATMENT OPTIONS FOR PATIENTS WITH TREATMENT-RESISTANT DEPRESSION. BECAUSE THIS ULTRASONIC NEUROMODULATION DEVICE OFFERS ACCESS TO DEEP BRAIN STRUCTURES WITH A UNIQUE COMBINATION OF FLEXIBILITY, PRECISION, AND NONINVASIVENESS, THE PROPOSED WORK IS EXPECTED TO HAVE BROADER POSITIVE IMPACTS FOR UNDERSTANDING AND TREATING OTHER DISORDERS OF DEEP BRAIN CIRCUITS.