P50NS123109

Circuit-Based Deep Brain Stimulation for Parkinson's Disease - The overall goal of the University of Minnesota (UMN) Udall Center is to develop novel, circuit-based deep brain stimulation (DBS) therapies for Parkinson's disease (PD) based on an understanding of the changes in pathophysiological activity patterns that occur in basal ganglia thalamocortical-brainstem (BGTC-B) pathways.

Project 1 (Human) will characterize the role of oscillatory activity, coupling, and connectivity across the broader BGTC network, including the subthalamic nucleus (STN), globus pallidus internus (GPI), sensory, motor, premotor, and dorsolateral prefrontal cortices. These recordings will be performed at rest and during cognitive-motor tasks, with and without therapeutic interventions (DBS, L-DOPA, DBS+L-DOPA). It will also clarify the relative effect of stimulation in different functional subregions of the STN and GPI on motor and cognitive function.

Project 2 (Human) will explore the mechanisms and effects of pallidal DBS on levodopa-resistant motor signs using MRI-derived computational models and fMRI to examine the pathways mediating these changes. It will use new sensing technology (PERCEPT) to identify and correlate the physiological changes in the GP to worsening of, or improvement in, gait dysfunction.

Project 3 (Non-Human Primate) will examine the electrophysiological changes in pallidopeduncular, pallidointralaminar, and pallidohabenular activity that are related to cognitive-motor symptoms, providing further network-level insights into cognitive motor gait impairments, task-shifting difficulties, and loss of motivation. These insights will complement the results from the human studies in Projects 1 and 2.

All center components have synergistic interactions with the Catalyst Project, which will support research efforts of a promising early-stage investigator who will use a novel closed-loop DBS approach to probe circuit dynamics in PD patients and their relationship to PD motor signs.

The Imaging Core will acquire state-of-the-art, high-field structural MRI as well as rest and task-based fMRI for PD patients in Projects 1 and 2 (using a 7T scanner) and structural MRI for the NHPS in Project 3 (using the first of its kind 10.5T scanner).

The Clinical Core will obtain clinical and quantitative motor and neuropsychological assessments that will be correlated to physiological data obtained acutely in the operating room, subacutely in patients with externalized DBS leads and electrocorticography arrays, and chronically through postoperative recordings using PERCEPT.

The Biostatistics Core will provide overall data management, quality control, statistical and machine learning analysis, and data entry into the NINDS Data Management Resource.

The Administrative Core will orchestrate all aspects of the UMN Udall Center, implement and support patient education and public outreach efforts, and develop and monitor individualized career enhancement plans for the next generation of PD researchers.

Together, these approaches will provide critical data towards the development and translation of novel patient-specific DBS therapies.

Regents Of The University Of Minnesota

(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.

93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders

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

Minneapolis, Minnesota 554550356 United States

Single Zip Code

NINDS Morris K. Udall Centers of Excellence for Parkinson's Disease Research (P50 Clinical Trial Optional) (RFA-NS-21-001)

Amendment Since initial award the total obligations have increased 497% from $1,889,088 to $11,268,567.