Corticospinal Suppression Underlying Intact Movement Preparation Fades in Parkinson's Disease.

BACKGROUND: In Parkinson's disease (PD), neurophysiological abnormalities within the primary motor cortex (M1) have been shown to contribute to bradykinesia, but exact modalities are still uncertain. We propose that such motor slowness could involve alterations in mechanisms underlying movement preparation, especially the suppression of corticospinal excitability-called "preparatory suppression"-which is considered to propel movement execution by increasing motor neural gain in healthy individuals. METHODS: On two consecutive days, 29 PD patients (on and off medication) and 29 matched healthy controls (HCs) underwent transcranial magnetic stimulation over M1, eliciting motor-evoked potentials (MEPs) in targeted hand muscles, while they were either at rest or preparing a left- or right-hand response in an instructed-delay choice reaction time task. Preparatory suppression was assessed by expressing MEP amplitudes during movement preparation relative to rest. RESULTS: Contrary to HCs, PD patients showed a lack of preparatory suppression when the side of the responding hand was analyzed, especially when the latter was the most affected one. This deficit, which did not depend on dopamine medication, increased with disease duration and also tended to correlate with motor impairment, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III (both total and bradykinesia scores). CONCLUSIONS: Our novel findings indicate that preparatory suppression fades in PD, in parallel with worsening motor symptoms, including bradykinesia. Such results suggest that an alteration in this marker of intact movement preparation could indeed cause motor slowness and support its use in future studies on the relation between M1 alterations and motor impairment in PD. © 2022 International Parkinson and Movement Disorder Society.

Subthalamic DBS does not restore deficits in corticospinal suppression during movement preparation in Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) patients exhibit changes in mechanisms underlying movement preparation, particularly the suppression of corticospinal excitability - termed "preparatory suppression" - which is thought to facilitate movement execution in healthy individuals. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) being an attractive treatment for advanced PD, we aimed to study the potential contribution of this nucleus to PD-related changes in such corticospinal dynamics. METHODS: On two consecutive days, we applied single-pulse transcranial magnetic stimulation to the primary motor cortex of 20 advanced PD patients treated with bilateral STN-DBS (ON vs. OFF), as well as 20 healthy control subjects. Motor-evoked potentials (MEPs) were elicited at rest or during movement preparation in an instructed-delay choice reaction time task including left- or right-hand responses. Preparatory suppression was assessed by expressing MEPs during movement preparation relative to rest. RESULTS: PD patients exhibited a deficit in preparatory suppression when it was probed on the responding hand side, particularly when this corresponded to their most-affected hand, regardless of their STN-DBS status. CONCLUSIONS: Advanced PD patients displayed a reduction in preparatory suppression which was not restored by STN-DBS. SIGNIFICANCE: The current findings confirm that PD patients lack preparatory suppression, as previously reported. Yet, the fact that this deficit was not responsive to STN-DBS calls for future studies on the neural source of this regulatory mechanism during movement preparation.