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.


CONCLUSIONS
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.
Laboratory for Computational Motor Control, Department of Biomedical Engineering, and.
Yousef
Y
Salimpour
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
Zoltan K
ZK
Mari
Laboratory for Computational Motor Control, Department of Biomedical Engineering, and shadmehr@jhu.edu.
Reza
R
Shadmehr
D000368:Aged; D000704:Analysis of Variance; D001703:Biophysics; D004311:Double-Blind Method; D004566:Electrodes; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D018737:Hand Strength / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008962:Models, Theoretical; D009044:Motor Cortex / Q000503:physiopathology*; D010300:Parkinson Disease / Q000473:pathology*; D011597:Psychomotor Performance / Q000502:physiology*; D011897:Random Allocation; D013057:Spectrum Analysis; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation
Parkinson's disease; motor costs; signal-dependent noise; tDCS