This human study found elevated motoneuron excitability and PIC-related amplification in people with Parkinson's disease compared with age-matched controls, and that dopaminergic medication did not fully normalize these measures.

By implicating persistent intrinsic motoneuron changes and PICs that are insensitive to dopamine replacement, the work points to non-dopaminergic targets (ion channels, alternate monoaminergic systems) and electrophysiologic biomarkers that could be exploited for therapeutic discovery.

Dopamine is a critical neuromodulator of motor function. In Parkinson's disease (PD), the degeneration of dopaminergic neurons not only disrupts motor function but may also alter motoneuron excitability, contributing to motor deficits. The aim of this study was to investigate motoneuron excitability in people with PD during ON and OFF medication states and to compare these responses with controls of similar age. Fourteen people with PD (4 females) were tested in two sessions (ON and OFF medication), and 13 controls (5 females) completed the same protocol in one session. Participants performed slow triangular elbow flexion isometric contractions to 30% of their maximum voluntary contraction (MVC). Motor unit discharge rates, recruitment threshold, discharge rate hysteresis (∆F), brace height, acceleration and attenuation slopes, ascending and descending rate modulations and self-sustained discharge duration were calculated. People with PD showed higher initial discharge rates (p < 0.05) and lower recruitment thresholds (p < 0.001) in both medication states compared to controls, with no significant differences between the OFF and ON conditions (p > 0.05). ΔF and acceleration slope were both elevated in the OFF state compared with controls (p = 0.04 and p = 0.05, respectively), with no significant medication effects on either measure (p > 0.05). Motoneuron excitability was higher in people with PD compared with controls and dopaminergic medication does not fully normalize motoneuron excitability or suppress PIC-related amplification. These finding raising the possibility that changes associated with long-term monoaminergic loss may not be fully restored by medication.