UH3NS136631

Building mood state classifiers to inform deep brain stimulation (DBS) of treatment-resistant bipolar depression.

Bipolar disorder (BD) is a recurrent neuropsychiatric disorder characterized by wide fluctuations in mood, energy, and activity.

Although the hallmark of BD is mania in BD-I (hypomania in BD-II), depressive episodes dominate the longitudinal course and account for a disproportionate degree of the morbidity and mortality.

About 25% of patients with BD meet criteria for treatment-resistant bipolar depression (TRBD).

Given the gravity of the illness and paucity of available therapies, there exists a large unmet need for more effective interventions.

We propose an early feasibility study to advance the therapy and neurobehavioral monitoring of TRBD with deep brain stimulation (DBS) targeting the ventral capsule/ventral striatum (VC/VS) using a sensing capable device.

We will leverage a smartphone-based software platform paired with the device's chronic sensing capability to record local field potentials (LFPS) time-locked with remote, high-density measures of natural behavior (e.g., from wearables).

Our goal is to detect relevant behavioral states including both depression and mania and transitions between these states, including high risk mixed features.

Real-time, remote detection of affective states via both behavioral and neural data monitoring will enable new interventional strategies to shift behavior away from pathological behavioral states towards healthier ones, contributing to the long-term stability of patients with BD.

Aim 1: Efficacy and safety of VC/VS DBS for TRBD will be examined in a 9-month open-label early feasibility study of 10 subjects with BD-I, followed by a 3-month stabilization period, and then blinded discontinuation at month 12 to confirm active vs. sham response.

Efficacy outcome will be based on rating scale measures of initial response at 9 months, absence of recurrence of depression during follow-up at 18 months, and management of emergent (hypo)mania.

Aim 2: Mania/mixed feature detection.

2A. Given the risks of inducing mania or mixed states, a clinician-facing dashboard will be created and updated every 24 hours displaying raw data for: affect/mood, energy/activity, sleep, speech, and anxiety.

Behavioral and physiological data will be derived from multimodal methods (e.g., computer vision, voice recordings, Apple Watch, Oura Ring, etc.), in/outside the clinic, to objectively assess changes in key behavioral domains.

2B. Composite measures of mood and energy/activity will be developed using machine learning (and other methods) based upon data from the trial subjects.

The clinician will be notified when a state change (e.g., emerging mania) is identified that warrants adjustment of stimulation.

Aim 3: Identify neural markers to be used as classifiers for state changes from depression into either manic or mixed states.

Development of neural classifiers for (hypo)mania builds upon research from an NIH funded study of VC/VS DBS in subjects with OCD.

The outcome of this aim, coupled with Aim 2, has implications for advancing DBS programming with the clinician-in-the-loop and possible future development of an adaptive DBS system in BD.

Meeting all milestones could also inform studies of DBS in depression with respect to neurobehavioral feedback to drive DBS programming decisions.

Baylor College Of Medicine

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.310 - Trans-NIH Research Support

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

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Houston, Texas 770303411 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 832% from $423,509 to $3,948,909.