Modulation of Spinal Circuits Following Phase-Dependent Electrical Stimulation of Afferent Pathways

Objective. Peripheral electrical stimulation (PES) of afferent pathways is a tool commonly used to induce neural adaptations in some neural disorders such as pathological tremor or stroke. However, the neuromodulatory effects of stimulation interventions synchronized with physiological activity (closed-loop strategies) have been scarcely researched in the upper-limb. Here, the short-term spinal effects of a 20-minute stimulation protocol where afferent pathways were stimulated with a closed-loop strategy named selective and adaptive timely stimulation (SATS) were explored in 11 healthy subjects. Approach. SATS was applied to the radial nerve in-phase (INP) or out-of-phase (OOP) with respect to the muscle activity of the extensor carpi radialis (ECR). The neural adaptations at the spinal cord level were assessed for the flexor carpi radialis (FCR) by measuring disynaptic Group I inhibition, Ia presynaptic inhibition, Ib facilitation from the H-reflex and estimation of the neural drive before, immediately after, and 30 minutes after the intervention. Main results. SATS strategy delivered electrical stimulation synchronized with the real-time muscle activity measured, with an average delay of 17 +/- 8 ms. SATS-INP induced increased disynaptic Group I inhibition (77 +/- 23% of baseline conditioned FCR H-reflex), while SATS-OOP elicited the opposite effect (125 +/- 46% of baseline conditioned FCR H-reflex). Some of the subjects maintained the changes after 30 minutes. No other significant changes were found for the rest of measurements. Significance. These results suggest that the short-term modulatory effects of phase-dependent PES occur at specific targeted spinal pathways for the wrist muscles in healthy individuals. Importantly, timely recruitment of afferent pathways synchronized with specific muscle activity is a fundamental principle that shall be considered when tailoring PES protocols to modulate specific neural circuits. (NCT number 04501133).