Non-invasive Brain Mapping of Movement Facilitation in Parkinson's Disease

Several strategies or contexts help patients with Parkinson's disease to move more quickly or normally, however the brain mechanisms underlying these phenomena are poorly understood. The proposed studies use complimentary brain mapping techniques to understand the brain mechanisms supporting improved movements elicited by external cues. The central hypothesis is that distinct networks are involved in movement improvement depending on characteristics of the facilitating stimulus. Participants will perform movement tasks during recording of brain activity with EEG and MRI. The identified biomarkers may provide targets for future neuromodulation therapies to improve symptoms that are refractory to current treatments, such as freezing of gait.

The studies proposed here test the overarching hypothesis that different types of cues (visual targets, rhythmic auditory stimuli and reward incentives) facilitate movement through distinct neuroanatomic circuits and electrophysiological mechanisms, by leveraging known variability in behavioral cueing benefits across patients. Aim 1 is to demonstrate behavioral dissociations between different forms of movement facilitation within patients and relate variability in cueing benefits to integrity of dissociable neuroanatomic circuits as measured by resting state and diffusion tensor magnetic resonance imaging (MRI). Aim 2 is to characterize the electrophysiological correlates of behavioral benefits for the different cue types using electroencephalography (EEG). Patients will perform two computer tasks involving reaching and tapping movements during video recording of movements and electrophysiological recording of brain signals. Experimental manipulations involve different computer stimuli that manipulate the presence or absence of sensory and motivational movement cues. The same experimental manipulations are delivered to all individual subjects. 60 patients with Parkinson's disease and 30 healthy controls will perform the task during recording of brain waves from the scalp (EEG) and return for a second session to record brain activity with MRI. Each of the total of 2 sessions will last about 1.5 hours. Patients may be asked to delay taking their morning Parkinson's disease medications and perform clinical rating scales and questionnaires and undergo a movement disorders neurological exam.

All participants undergo the same behavioral interventions in which upper extremity movements are made in response to different sensory stimuli.

Blood oxygen level dependent (BOLD) resting state network activity as a function of behavioral benefits from external cues

Inclusion Criteria: Diagnosis of Parkinson's disease based on presence of at least 2 cardinal features (tremor, rigidity or bradykinesia) OR healthy adult with no neurologic disease Age > 18 years old Exclusion Criteria: Dementia as indicated by score on Montreal Cognitive Assessment < 19 Active hallucinations or psychosis Contraindications to MRI (metal implant, claustrophobia)

De-identified resting state data and diffusion tractography (in raw form) will be available through the LONI Imaging and Data Archive (IDA) along with details of acquisition methods and clinical data and distributed upon approval by the PI. Electrophysiological and behavioral data obtained during task performance will be made available upon request to Dr. Cross (PI) via secured server access. Data sharing agreement will be required for all requests.