UH3NS141080

Multimodal biometrics to optimize and scale decision support for depression.

DBS - Deep Brain Stimulation (DBS) of the subcallosal cingulate (SCC) white matter is an evolving treatment strategy for treatment resistant depression (TRD) with published studies demonstrating sustained long-term antidepressant effects in 40-60% of implanted patients.

Converging evidence from positron emission tomography (PET), electroencephalography (EEG) and diffusion tractography (DTI) strongly suggests that DBS mediates its clinical benefits by direct modulation of the SCC -- a key hub in an aberrant neural circuit.

Despite encouraging sustained long-term effects in this notoriously difficult to treat patient population, randomized controls trials of SCC DBS and other DBS targets for TRD are now on hold as initial results failed to meet predefined clinical endpoints.

In our recently completed first UH3, we were successful in developing a generalizable LFP brain-based biomarker in a non-commercial prototype research device that defines a depression specific clinical depression state (sick vs. well) in all patients.

This biomarker can further guide needed dose adjustments in individual patients during ongoing DBS treatment.

In this project, we propose to develop a control policy that integrates this novel biomarker with additional measures to fully capture ongoing clinical decisions during long term DBS treatment, allowing for implementation and scaling of the use of biomarkers in SCC DBS into the next generation commercial clinical DBS sensing devices.

We will leverage previously acquired UH3 data (LFP, EEG, imaging and video diary) from 3 consecutive experimental trials of SCC DBS involving 3 independent TRD cohorts similarly recruited, implanted and treated with chronic high frequency stimulation and studied using 3 models of the Medtronic DBS Stim/Sense DBS system (PC+S, RC+S, Percept) during long-term clinical monitoring and ongoing data collection, to design control policies that minimize subjective decision-making during the adjustment of stimulation settings and adjunctive therapy decisions.

We will then test utility of the control policy over the course of 52 weeks of SCC DBS in a new cohort of 10 patients who will be implanted with the Medtronic Percept RC system to anticipate and/or improve on DBS and adjunctive treatment adjustment decisions.

These methods will be assessed relative to previous cohorts receiving SCC DBS treatment-as-usual in which all clinical decision making was made based on the intuition of the treating psychiatrist.

The primary outcome measure will be to determine if comparable efficacy can be achieved while minimizing subjective decision-making.

If successful, the data-driven model and control strategy will enable objective, rational clinical programming of DBS stimulation for depression and provide a new model and approach for stimulation initiation and long-term monitoring and management of patients receiving this treatment.

Icahn School Of Medicine At Mount Sinai

NOT APPLICABLE

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

New York, New York 100296504 United States

Single Zip Code

BRAIN Initiative: Clinical Studies to Advance Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UH3 Clinical Trial Optional) (RFA-NS-21-024)

Amendment Since initial award the total obligations have increased 89% from $2,113,446 to $3,996,207.