LIFUP for Treatment of Motor Deficits in Parkinson's Disease (LIFUP)

The study will test the feasibility of using Low Intensity Focused Ultrasound Pulsation (LIFUP) to treat motor symptoms in Parkinson's Disease (PD). LIFUP is a new technique that can increase brain activity in highly specific target areas and is MRI compatible. Thus, in real-time, it is possible to directly observe how LIFUP changes the brain areas important in PD by measuring its effects on brain activity, blood flow, and brain connectivity. If successful, this research will mark the first step towards a novel, non-invasive, non-medication treatment for PD.

This trial is a proof-of-context, proof-of-mechanism study of a novel neuromodulation technology - LIFUP - to treat motor symptoms in PD. Much like Deep Brain Stimulation, LIFUP can be focused on deep brain structures with high spatial accuracy, including those implicated in PD; however, it can do so non-invasively. Other non-invasive neuromodulation tools such as Transcranial Magnetic Stimulation can only target surface brain structures and are not optimal PD treatment tools. This study will test this new technology in 30 participants with PD during simultaneous MRI (including resting-state functional MRI (fMRI), task-based fMRI, and arterial spin labeling (ASL) perfusion) in a double-blind crossover trial to determine whether LIFUP: 1) will improve motor symptoms during and after treatment; 2) can increase neural activity in the target brain region important for PD, the Putamen; and 3) enhance cortico-striatal motor circuit connectivity.

Device: Low Intensity Focused Ultrasound Device Low Intensity Focused Ultrasound Pulsation (LIFUP) of putamen (a key area for Parkinson's disease) will be performed during two sessions. The proposed experiment will involve behavioral (e.g., motor assessements) and paramedical (i.e., MRI/fMRI) measurements just before and after each of two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session). The device does not produce a sound when operating and as such, the active group is well blinded.

Sham Treatment consists of placing the device but not turning it on. The device does not produce a sound when operating and as such, the sham group is well blinded.

The participant will use their index and thumb fingers to tap rhythmically, alternating index finger and thumb. Analysis will compare the average frequency, velocity, and amplitude of taps to quantify motor performance improvements.

The participant will place and remove nine plastic pegs into a plastic pegboard. Scores are recorded as time in seconds that it takes the participant to complete the task with each hand. Analysis will compare pre- and post-treatment scores to quantify motor performance improvements.

The participant will answer 45 survey questions that characterize PD severity across four domains. Analysis will compare ratings pre- and post-treatment to assess changes in 1) mentation, behavior, and mood, 2) activity of daily living, 3) motor function, and 4) complications of therapy.

In the MRI scanner, the participant will play an experimental task designed to investigate implicit learning in PD. The paradigm will be assessed by feedback-based probabilistic classification. Analysis will compare within-subject scores between session 1 and 2 to quantify LIFUP-mediated gains in performance.

BOLD data will be collected in real-time during the ultrasound sonication, which occurs in on-off blocks. Analyses will assess the statistical relationship between BOLD signal in the brain and the time series (on vs off) of the ultrasound sonication.

Perfusion ASL fMRI data will be collected before and after sonication. Analyses will assess the statistical relationship between ASL signal throughout the brain pre- and post-sonication in a within-subject repeated measures design.

Inclusion Criteria: Diagnosis of Parkinson's disease Age 18-65 Right-handed Fluent in the English language Exclusion Criteria: Metal implants Neurological or psychiatric diagnosis other than Parkinson's Left-handed Not fluent in the English language