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Adaptive Neurostimulation to Restore Sleep in Parkinson’s Disease: An Investigation of STN LFP Biomarkers in Sleep Dysregulation and Repair


Brief Summary:

Parkinson’s disease (PD) is a neurodegenerative disorder that leads to both motor and
non-motor symptoms. Therapies have been developed that effectively target the motor symptoms.
Non-motor symptoms are far more disabling for patients, precede the onset of motor symptoms
by a decade, are more insidious in onset, have been less apparent to clinicians, and are less
effectively treated. Sleep dysfunction is oftentimes the most burdensome of the non-motor
symptoms. There are limited options for treating sleep dysfunction in PD, and the mainstay of
therapy is the use of sedative-hypnotic drugs without addressing the underlying mechanisms.
Patients with PD who demonstrate significant motor fluctuations and dyskinesia are considered
for subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. Several studies have
reported that STN-DBS also provides benefit for sleep dysregulation. Additionally, local
field potentials recorded from STN DBS electrodes implanted for the treatment of PD, have led
to the identification of unique patterns in STN oscillatory activity that correlate with
distinct sleep cycles, offering insight into sleep dysregulation. This proposal will leverage
novel investigational DBS battery technology (RC+S Summit System; Medtronic) that allows the
exploration of sleep biomarkers and prototyping of closed-loop stimulation algorithms, to
test the hypothesis that STN contributes to the regulation and disruption of human sleep
behavior and can be manipulated for therapeutic advantage. Specifically, in PD patients
undergoing STN-DBS, the investigators will determine whether STN oscillations correlate with
sleep stage transitions, then construct and evaluate sensing and adaptive stimulation
paradigms that allow ongoing sleep-stage identification, and induce through adaptive
stimulation an increase in duration of sleep stages associated with restorative sleep.


Inclusion Criteria:

– Ability to provide informed consent for this study

– Diagnosis of Idiopathic Parkinson’s disease with motor symptoms that have been present
for a minimum of 4 years

– Motor symptoms are severe enough, despite optimized medical therapy, to warrant
surgical implantation of DBS

– UPDRS-III score off medication between 20 and 80, and an improvement in UPDRS-III
score on medications of at least 30%, or patients with tremor-dominant PD (score >/= 2
on UPDRS-III tremor sub-score)-or tremor in addition to other motor symptoms-that is
treatment-resistant and results in significant functional disability

– Appropriate trials of oral PD medications have resulted in inadequate relief of motor

– Absence of abnormalities on brain MRI suggestive of an alternate diagnosis or serving
as a contraindication to surgery

– Absence of significant cognitive deficits or significant depression (BDI-II score >
20) on formal Neuropsychological Testing

– Age 21 – 80 years

Exclusion Criteria:

– Coagulopathy, uncontrolled hypertension, history of seizures, heart disease, inability
to undergo general anesthesia

– Pregnancy

– Significant untreated depression (BDI-II score > 20)

– Personality or mood disorder symptoms that Study Personnel believe will interfere with
study requirements

– Patients requiring ongoing treatment with ECT, rTMS, or diathermy

– Pre-existing implanted stimulation system (e.g., cochlear implant, cardiac pacemaker,
defibrillator, neuro-stimulator for indication other than Parkinson’s disease) or
ferromagnetic metallic implant

– Prior intracranial surgery

– History of, or active, drug or alcohol abuse

– Meets criteria for PD with Mild Cognitive Impairment (PD-MCI), as defined by
Performance > 2 standard deviations below appropriate norms on tests from 2 or more of
the following cognitive domains: Attention, Executive Function, Language, Memory, and
Visuospatial Ability

– Patients with Restless Leg Syndrome


  • Standord University Medical Center, Stanford, California, United States, 94305
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