Motor Cortex Disinhibition Correlates with Olfactory Dysfunction in Parkinson's Disease

Motor cortex disinhibition, as measured by impaired short-interval intracortical inhibition (SICI) using transcranial magnetic stimulation (TMS), is a well-established feature of Parkinson's disease (PD). However, its substantial variability among patients remains unexplained, prompting questions about its origin, clinical relevance, and connection to disease heterogeneity.

Based on biological links between olfaction and motor function, we aimed to investigate the possible relationship between motor cortex disinhibition and olfactory dysfunction in PD.

We assessed motor cortex disinhibition, as measured by SICI, and olfactory dysfunction, as measured by the Sniffin' Stick Test 12 items (SST-12), in a new cohort of early-to-mid-stage PD patients (n = 45) and age-matched and gender-matched healthy controls (n = 35).

We obtained moderate-to-extreme Bayesian evidence that patients had the expected decrease of cortical inhibition and decrease of olfactory function, with neither feature correlating with the clinical motor severity. Cortical disinhibition and olfactory dysfunction were correlated, with strong-to-extreme evidence, both considering all subjects (n = 80), only healthy controls (n = 35), only patients (n = 45), or only levodopa-naïve patients (n = 20). We tested and excluded age as a possible confounding factor. The evidence from causal inference analysis supported a mediation role of PD that aligned more with an internal pathogenic mechanism than with an external one.

These findings suggest that motor cortex disinhibition and olfactory dysfunction might be linked by a common early pathogenic process in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.