PHASE-DEPENDENT AND ANTICIPATORY CORTICAL CONTROL OF HINDLIMB LOCOMOTION

Descending cortical control of locomotion orchestrates coordination between cortical and spinal circuits during complex movements. While sensorimotor cortex activity is known to modulate locomotion, the temporal dynamics and functional significance of this control during natural, adaptive locomotion remain poorly understood. Using in vivo electrophysiological recordings combined with unbiased 3D kinematic tracking in freely moving mice and dynamic time warping to align variable strides, we characterized cortical activity during locomotor tasks of increasing complexity. We identified two distinct modes of sensorimotor cortical involvement. Beyond the expected phase-locked activity tracking locomotor rhythm, we discovered a preparatory mode characterized by transient activity that reliably precedes specific gait transition events. The temporal lead of this anticipatory activity is incompatible with direct motor command and instead reflects a predictive signal directed toward spinal locomotor circuits. Critically, these event-locked, anticipatory neurons become more prevalent during skilled locomotion tasks and include identified corticospinal projection neurons. The presence of anticipatory signals preceding individual steps reveals a previously underappreciated role for motor cortex in continuously adjusting ongoing strides and preparing subsequent step modifications during skilled locomotion.