# The effects of parkinsonism and deep brain stimulation on basal ganglia-thalamocortical circuitry during sleep-wake behavior

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $577,227

## Abstract

PROJECT SUMMARY/ABSTRACT
Over 75% of people with Parkinson's disease (PD) have significant sleep-wake disturbances that are major
contributors to decreased quality of life and can be more disabling and resistant to treatment than the motor
symptoms of PD. Currently, the mechanisms contributing to disordered sleep in people with PD are poorly
understood and there is a critical need for therapeutic inventions to improve sleep quality. This project will provide
new insight into the pathophysiology of sleep-wake disturbances in PD by characterizing the changes in sleep-
related neuronal activity and physiological interactions that occur between subcortical and cortical structures in
the basal ganglia thalamocortical (BGTC) circuit during progressively more severe parkinsonian states. We will
expand our previous work to include the pedunculopontine nucleus (PPN) given its critical role regulating sleep-
wake states and extensive connectivity to the BGTC, exploring the changes in coupling and connectivity that
occur within and across the BGTC-PPN network that underlie disordered sleep in PD secondary to dopaminergic
loss in the substantia nigra (Aim 1). It will compare how deep brain stimulation (DBS) in the STN, GPi, and GPe
modifies subcortical-cortical interactions in the BGTC-PPN circuit to influence sleep-wake behavior and elucidate
the fiber pathway activations underlying these changes (Aims 2 and 3). This study will provide data with
immediate translational value by identifying whether DBS in one target is more effective than another in
normalizing sleep-related neuronal activity and improving sleep-wake behavior. Furthermore, knowledge about
how changes in neuronal activity across the BGTC-PPN network correlates with altered sleep from normal,
parkinsonian, and parkinsonian+DBS conditions will provide the basis to develop more effective stimulation
strategies that utilize target-specific physiological biomarkers and closed-loop DBS control paradigms tailored to
individual patient's sleep disturbances. These data will also provide the basis to target specific pathways with
DBS to optimize sleep-related outcomes in PD.

## Key facts

- **NIH application ID:** 10979519
- **Project number:** 2R01NS110613-06
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** LUKE Aaron JOHNSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $577,227
- **Award type:** 2
- **Project period:** 2024-07-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979519

## Citation

> US National Institutes of Health, RePORTER application 10979519, The effects of parkinsonism and deep brain stimulation on basal ganglia-thalamocortical circuitry during sleep-wake behavior (2R01NS110613-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10979519. Licensed CC0.

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