This narrative review examines the utility of gait digital biomarkers in Parkinson’s disease (PD) research and clinical trials across four contexts: disease susceptibility/risk, disease progression, response to exercise, and fall prediction. The review of the literature to date suggests that upper body characteristics of gait (e.g., arm swing, trunk motion) may indicate susceptibility/risk of PD, while pace aspects (e.g., gait speed, stride length) are informative for tracking disease progression, exercise response, and fall likelihood. Dynamic stability aspects (e.g., trunk regularity, double-support time) worsen with disease progression but can improve with exercise. Gait variability emerges as a sensitive biomarker across all 4 contexts but with low specificity. The lack of standardized gait testing protocols and the lack of a minimum set of quantified digital gait biomarkers limit data harmonization across studies. Future studies, using a commonly agreed upon protocol, could be used to demonstrate the utility of specific gait biomarkers for clinical practice.

High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) applied to motor cortex is recognized as a useful and informative method for corticomotor mapping by evoking natural-appearing movements of the limb to consistent stable end-point positions. An important feature of these movements is that stimulation of a specific site in motor cortex evokes movement to the same spatial end point regardless of the starting position of the limb. The goal of this study was to delineate effective stimulus parameters for evoking forelimb movements to stable spatial end points from HFLD-ICMS applied to primary motor cortex (M1) in awake monkeys. We investigated stimulation of M1 as combinations of frequency (30–400 Hz), amplitude (30–200 μA), and duration (0.5–2 s) while concurrently recording electromyographic (EMG) activity from 24 forelimb muscles and movement kinematics with a motion capture system. Our results suggest a range of parameters (80–140 Hz, 80–140 μA, and 1,000-ms train duration) that are effective and safe for evoking forelimb translocation with subsequent stabilization at a spatial end point. The mean time for stimulation to elicit successful movement of the forelimb to a stable spatial end point was 475.8 ± 170.9 ms. Median successful frequency and amplitude were 110 Hz and 110 μA, respectively. Attenuated parameters resulted in inconsistent, truncated, or undetectable movements, while intensified parameters yielded no change to movement end points and increased potential for large-scale physiological spread and adverse focal motor effects. Establishing cortical stimulation parameters yielding consistent forelimb movements to stable spatial end points forms the basis for a systematic and comprehensive mapping of M1 in terms of evoked movements and associated muscle synergies. Additionally, the results increase our understanding of how the central nervous system may encode movement.