Durable effects of deep brain ultrasonic neuromodulation on major depression: a case report.

BACKGROUND: Severe forms of depression have been linked to hyperactivity of the subcallosal cingulate cortex. The ability to stimulate the subcallosal cingulate cortex or associated circuits noninvasively and directly would maximize the number of patients who could receive treatment. To this end, we have developed an ultrasound-based device for effective noninvasive modulation of deep brain circuits. Here we describe an application of this tool to an individual with treatment-resistant depression. CASE PRESENTATION: A 30-year-old Caucasian woman with severe treatment-resistant non-psychotic depression was recruited into a clinical study approved by the Institutional Review Board of the University of Utah. The patient had a history of electroconvulsive therapy with full remission but without sustained benefit. Magnetic resonance imaging was used to coregister the ultrasound device to the subject's brain anatomy and to evaluate neural responses to stimulation. Brief, 30-millisecond pulses of low-intensity ultrasound delivered into the subcallosal cingulate cortex target every 4 seconds caused a robust decrease in functional magnetic resonance imaging blood-oxygen-level-dependent activity within the target. Following repeated stimulation of three anterior cingulate targets, the patient's depressive symptoms resolved within 24 hours of the stimulation. The patient remained in remission for at least 44 days afterwards. CONCLUSIONS: This case illustrates the potential for ultrasonic neuromodulation to precisely engage deep neural circuits and to trigger a durable therapeutic reset of those circuits. Trial registration ClinicalTrials.gov, NCT05301036. Registered 29 March 2022, https://clinicaltrials.gov/ct2/show/NCT05301036.

The International Neuromodulation Registry: An Informatics Framework Supporting Cohort Discovery and Analysis.

BACKGROUND: Neuromodulation therapies, such as deep brain stimulation (DBS), spinal cord stimulation (SCS), responsive neurostimulation (RNS), transcranial magnetic stimulation (TMS), transcranial direct stimulation (tDCS), and vagus nerve stimulation (VNS) are used to treat neurological and psychiatric conditions for patients who have failed to benefit from other treatment approaches. Although generally effective, seemingly similar cases often have very different levels of effectiveness. While there is ongoing interest in developing predictors, it can be difficult to aggregate the necessary data from limited cohorts of patients at individual treatment centers. OBJECTIVE: In order to increase the predictive power in neuromodulation studies, we created an informatics platform called the International Neuromodulation Registry (INR). The INR platform has a data flow process that will allow researchers to pool data across multiple centers to enable population health research. METHODS: This custom informatics platform has a Neo4j graph database and includes a harmonization process that allows data from different studies to be aggregated and compared. Users of the INR can download deidentified patient imaging, patient demographic data, device settings, and medical rating scales. The INR supports complex network analysis and patient timeline visualization. RESULTS: The INR currently houses and allows visualization of deidentified imaging and clinical data from hundreds of patients with a wide range of diagnoses and neuromodulation therapies. CONCLUSION: Ultimately, we believe that widespread adoption of the INR platform will improve population health research in neuromodulation therapy.