Targeted modulation of neural population dynamics to improve movement control

Stroke is a leading cause of motor disability in the world. While brain stimulation to enhance motor function after stroke has shown promise, large clinical trials in human stroke patients have not found consistent benefits. These trials were conducted using open-loop stimulation, where the neural responses to stimulation were not measured. It remains unclear how to precisely tailor brain stimulation to effectively modulate neural dynamics in the motor network in order to improve motor control after stroke. Our recent studies have demonstrated that the reliability of single trial population dynamics associated with low-frequency oscillatory activity are important for movement control and can serve as a target for modulation using electrical stimulation (e.g., Ramanathan et al., Nature Medicine, 2018; Lemke et al., Nature Neuroscience, 2019; Khanna et al., Cell, 2021). Specifically, epidural cortical stimulation was found to both boost low-frequency power in animals recovering from injury and increase neural co-firing; this also reliably improved movement control during recovery from stroke. Our results have also demonstrated that relatively high electrical field strengths (∼ 3 mV/mm) were effective in regulating neural spike entrainment and co-firing. More recently, we have also studied how activity associated with movement preparation changes with recovery. We find that the reliable transition from preparation to movement control appears to be governed by ‘bistable’ transition dynamics. Notably, improvements in transition dynamics were closely correlated with recovery of prehension. Moreover, epidural electrical stimulation was found to be capable of modulating both preparatory and movement related dynamics. Our work provides insight into how to design therapeutic stimulation that selectively targets population dynamics in the distributed motor network and to improve dexterity after stroke. The information gained may also help improve approaches for non-invasive brain stimulation for stroke.