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

Abstract

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.

From Inhibition to Excitation and Why: The Role of Temporal Urgency in Modulating Corticospinal Activity

“…In conditions like Parkinson’s disease (PD), which is associated with cognitive dysfunction and can affect patients early on (Dirnberger & Jahanshahi, 2013), there is some evidence supporting this idea. More relevant to our conceptual model, recent work by Wilhelm et al (2022) found that PD patients display reduced CS suppression during movement preparation in comparison to healthy control individuals. Relatedly, alcohol dependent individuals and binge drinkers, who commonly show abnormalities in prefrontal networks, show a similar impairment of CS suppression during action preparation (Grandjean & Duque, 2020; Quoilin et al, 2018).…”

Overnight Distribution of REM Sleep Features in People with Parkinson’s Disease (PD) and Non-PD Controls

“…Rapid eye movements, a phasic REM sleep activity, have been associated with the activation of the motor cortex during sleep [32]. One possible explanation for the reduced REM density in PD may be reduced cortical activation during REM sleep, which parallels the reduced cortical activation observed during wakefulness in individuals with bradykinesia [14,33,34]. The similarity between the two phenomena and the negative correlation between REM density and the bradykinesia score suggests a potential common underlying mechanism.…”

Relationship between transcranial magnetic stimulation markers of motor control and clinical recovery in obsessive compulsive disorder/Gilles de la Tourette syndrome: a proof of concept case study

“…That is, MEPs were reduced relative to resting conditions, indicating a strong suppression of corticospinal excitability in the patient, consistently reported in healthy subjects ( 47 , 72 , 79 , 86 ). As mentioned earlier, this neural suppression of motor excitability during action preparation has been related to some sort of inhibitory control allowing to avoid premature responding during action preparation ( 42 , 43 , 58 ), even if there are also alternative views though not necessarily incompatible [( 48 , 51 ) for an alternative view]. Our interpretation of rather good inhibitory control in the patient (based on the observation of normal preparatory suppression) is in line with growing evidence indicating normal inhibitory functions in GTS.…”

“…When probed before the imperative, MEPs elicited in taskrelevant and task-irrelevant muscles of both hands are strongly suppressed relative to resting conditions (42,(45)(46)(47). This drastic suppression of motor excitability is thought to help inhibit premature or inappropriate responses and, more generally, to ensure some sort of inhibitory control during action preparation [ (42,43); but see also (48)(49)(50)(51) for an alternative hypothesis]. This idea comes from the observation that motor suppression is deeper when movement preparation entails overcoming sensory conflict (52,53).…”