Altering Effort Costs in Parkinson's Disease with Noninvasive Cortical Stimulation.

In Parkinson's disease (PD), the human brain is capable of producing motor commands, but appears to require greater than normal subjective effort, particularly for the more-affected side. What is the nature of this subjective effort and can it be altered? We used an isometric task in which patients produced a goal force by engaging both arms, but were free to assign any fraction of that force to each arm. The patients preferred their less-affected arm, but only in some directions. This preference was correlated with lateralization of signal-dependent noise: the direction of force for which the brain was less willing to assign effort to an arm was generally the direction for which that arm exhibited greater noise. Therefore, the direction-dependent noise in each arm acted as an implicit cost that discouraged use of that arm. To check for a causal relationship between noise and motor cost, we used bilateral transcranial direct current stimulation of the motor cortex, placing the cathode on the more-affected side and the anode on the less-affected side. This stimulation not only reduced the noise on the more-affected arm, it also increased the willingness of the patients to assign force to that arm. In a 3 d double-blind study and in a 10 d repeated stimulation study, bilateral stimulation of the two motor cortices with cathode on the more-affected side reduced noise and increased the willingness of the patients to exert effort. This stimulation also improved the clinical motor symptoms of the disease. SIGNIFICANCE STATEMENT: In Parkinson's disease, patients are less willing to assign force to their affected arm. Here, we find that this pattern is direction dependent: directions for which the arm is noisier coincide with directions for which the brain is less willing to assign force. We hypothesized that if we could reduce the noise on the affected arm, then we may increase the willingness for the brain to assign force to that arm. We found a way to do this via noninvasive cortical stimulation. In addition to reducing effort costs associated with the affected arm, the cortical stimulation also improved clinical motor symptoms of the disease.

Continuous Assessment of Levodopa Response in Parkinson's Disease Using Wearable Motion Sensors.

OBJECTIVE: Fluctuations in response to levodopa in Parkinson's disease (PD) are difficult to treat as tools to monitor temporal patterns of symptoms are hampered by several challenges. The objective was to use wearable sensors to quantify the dose response of tremor, bradykinesia, and dyskinesia in individuals with PD. METHODS: Thirteen individuals with PD and fluctuating motor benefit were instrumented with wrist and ankle motion sensors and recorded by video. Kinematic data were recorded as subjects completed a series of activities in a simulated home environment through transition from off to on medication. Subjects were evaluated using the unified Parkinson disease rating scale motor exam (UPDRS-III) at the start and end of data collection. Algorithms were applied to the kinematic data to score tremor, bradykinesia, and dyskinesia. A blinded clinician rated severity observed on video. Accuracy of algorithms was evaluated by comparing scores with clinician ratings using a receiver operating characteristic (ROC) analysis. RESULTS: Algorithm scores for tremor, bradykinesia, and dyskinesia agreed with clinician ratings of video recordings (ROC area > 0.8). Summary metrics extracted from time intervals before and after taking medication provided quantitative measures of therapeutic response (p < 0.01). Radar charts provided intuitive visualization, with graphical features correlated with UPDRS-III scores (R = 0.81). CONCLUSION: A system with wrist and ankle motion sensors can provide accurate measures of tremor, bradykinesia, and dyskinesia as patients complete routine activities. SIGNIFICANCE: This technology could provide insight on motor fluctuations in the context of daily life to guide clinical management and aid in development of new therapies.