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Basal Ganglia Network Neurophysiology of Depression in Parkinson’s Disease

Award Number: R00NS137249
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/05/2025
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Basal Ganglia Network Neurophysiology of Depression in Parkinson’s Disease - Depression is a debilitating nonmotor symptom of Parkinson’s disease (PD) that affects approximately 40% of patients and contributes to worsened quality of life. Despite its prevalence and burden, depression in PD is often inadequately treated with current therapies. Growing evidence indicates depression is likely linked to PD pathophysiology involving the basal ganglia, rather than just a reaction to general illness. Deep brain stimulation (DBS) therapy, targeted to the basal ganglia in either the globus pallidus internus (GPi) or the subthalamic nucleus (STN), is effective for improving PD motor symptoms. However, the effects of DBS on depression in PD vary across patients, from meaningful improvements to detrimental worsening. This variability is partly because the basal ganglia pathophysiology of depression is unclear, and it is unknown which brain signals and networks to modulate with DBS to improve depression in PD. The objective of this proposal is to identify basal ganglia neural activity associated with depression in PD and identify brain regions and networks associated with depression improvement with DBS in PD. My central hypothesis is that PD patients with depression exhibit altered neural activity compared to patients without depression, and these alterations (1) are localized to specific brain regions and networks, and (2) are similar across the GPi and STN, pointing to a common basal ganglia network associated with depression in PD. To investigate, I will use multimodal approaches combining neural recordings in patients who underwent GPi DBS or STN DBS for PD (N=199 patients, 291 hemispheres), neuroimaging to map brain regions and networks, and computational models to evaluate the effects of DBS. In Aim 1, I will identify basal ganglia neural activity associated with depression in PD using machine learning techniques. In Aim 2, I will determine the local and network topography of basal ganglia neural activity to identify physiological brain networks showing alterations in PD patients with versus without depression. In Aim 3, I will identify “hotspots” and brain networks associated with depression improvement with DBS for PD. During the K99 phase, I will receive training in human neurophysiology and clinical research in psychiatry, facilitated by Dr. Coralie de Hemptinne (expert in human neurophysiology), Dr. Gregory Pontone (expert in neuropsychiatry in PD), and a team of interdisciplinary advisors. After securing an independent faculty position, I will transition into the R00 phase and build on my K99 research in Aim 4 to prospectively evaluate neural activity and neuroimaging- based markers of depression in PD in a novel cohort (N=20 patients) using a DBS device capable of chronic neural recordings to test whether they correlate with longitudinal depression symptoms in the patients’ naturalistic environment and evaluate the effects of DBS and dopaminergic medication. Collectively, this K99/R00 award will enable me to pursue the technical and career development training necessary to prepare me to lead an independent research lab focused on understanding the pathophysiology of neurological and psychiatric disorders and establishing neurophysiological and network-guided neuromodulation therapies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $248,333 )
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/10/2026	EXTENSION WITH OR WITHOUT FUNDS	$0
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/17/2026	EXTENSION WITH OR WITHOUT FUNDS	$248,333
														Subtotal = $248,333

Grand Total All Awards = $248,333

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Basal Ganglia Network Neurophysiology of Depression in Parkinson’s Disease

Award Number: R00NS137249

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/05/2025

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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