A novel method to estimate discharge-independent inhibition durations of spinal and brainstem circuits in humans

Abstract

Direct recordings from human motoneurons are not feasible; therefore, researchers have developed indirect methods to estimate postsynaptic potential profiles, that is, the functional inhibition or excitation, on firing motor units. Surface and intramuscular electromyography have shown that the duration of the functional inhibition varies depending on the neural circuit investigated and is influenced by stimulus intensity and muscle activity level. This study aimed to standardize the estimation of functional inhibition durations across three distinct spinal and brainstem circuits by leveraging the known dependence of inhibition duration on background motor unit discharge rate. We analyzed data from previous rat brain slice experiments in which known currents were injected into regularly discharging motoneurons. Regression of injected inhibition duration against discharge rate revealed a strong predictive relationship when extrapolated, accurately converging on the known duration. Specifically, this regression yielded the actual inhibition duration at a discharge rate of 0.98 imp/s (range: 0-5.91 imp/s). Building on these findings, we conducted three inhibition paradigms in human volunteers, targeting the masseter inhibitory reflex, the cutaneous silent period and recurrent inhibition mediated by Renshaw cells. Using extrapolated correlation plots of motor unit discharge rate versus functional inhibition duration, we derived discharge rate-independent inhibition durations. All three circuits demonstrated longer inhibition duration ranges than previously reported. This standardized approach enables more accurate estimation of inhibition duration across various circuits, independent of discharge rate. It holds promise for clinical applications in the early diagnosis and monitoring of neurological disorders affecting inhibitory circuits.NEW & NOTEWORTHY Direct recordings from human motoneurons are not feasible; therefore, synaptic inhibition must be estimated indirectly. Experiments on rat brain slices allow accurate prediction of inhibition duration, independent of motor unit discharge rate. Applying these predictions in human studies has revealed discharge rate-independent functional inhibitions across various brainstem and spinal circuits. This approach offers robust estimates of functional inhibition, with potential clinical applications for monitoring neurological disorders that affect neural circuits.