Modulation of corticomotor excitability after maximal or sustainable-rate repetitive finger movement is impaired in Parkinson’s disease and is reversed by levodopa

https://doi.org/10.1016/j.clinph.2013.09.004Get rights and content

Highlights

  • The normal reduction in corticomotor excitability that occurs after performing non-fatiguing finger movement tasks is absent in PD patients when off medication.

  • Dopamine deficiency is associated with impaired modulation of corticomotor excitability after repetitive finger movements.

  • Administration of levodopa improves movement kinematics and restores normal post-exercise modulation of corticomotor excitability.

Abstract

Objectives

In healthy subjects, fatiguing exercises induce a period of post-exercise corticomotor depression (PECD) that is absent in Parkinson’s disease (PD). Our objective is to determine the time-course of corticomotor excitability changes following a 10-s repetitive index finger flexion–extension task performed at maximal voluntary rate (MVR) and a slower sustainable rate (MSR) in PD patients OFF and ON levodopa.

Methods

In 11 PD patients and 10 healthy age-matched controls, motor evoked potentials (MEPs) were recorded from the extensor indicis proprius (EIP) and first dorsal interosseous (FDI) muscles of the dominant arm immediately after the two tasks and at 2-min intervals for 10 min.

Results

In the OFF condition the PECD was absent in the two test muscles after both the MVR and MSR tasks. In the ON condition finger movement kinematics improved and a period of PECD comparable to that in controls was present after both tasks.

Conclusion

The absence of PECD in PD subjects off medication indicates a persisting increase in corticomotor excitability after non-fatiguing repetitive finger movement that is reversed by levodopa.

Significance

Dopamine depletion is associated with impaired modulation of corticomotor excitability after non-fatiguing repetitive finger movement.

Introduction

We have shown previously that in control subjects there is a rapid breakdown in the kinematics of a repetitive finger flexion–extension task performed at a maximal voluntary rate (MVR), which is likely to be due to a breakdown in central motor control rather than to peripheral fatigue (Rodrigues et al., 2009, Teo et al., 2012b). Further, with transcranial magnetic stimulation (TMS) we have shown that the MVR task is followed by a transient period of increased corticomotor excitability, and then a longer-lasting (up to 8–10 min) period of post-exercise corticomotor depression (PECD), as measured by a reduction in the amplitude of the motor evoked potential (MEP). In contrast, when the same task was performed at a moderate sustainable rate (MSR), there was no post-exercise increase in excitability, and the period of PECD was more pronounced (Teo et al., 2012a, Teo et al., 2012b). These findings suggested that while both the MVR and MSR tasks were associated with PECD, the corticomotor excitability after the MVR task remained at a higher relative level than after the less demanding MSR task. PECD is also known to be present after exhaustive muscle fatiguing exercise protocols (Samii et al., 1996, Sacco et al., 2000) and may therefore represent a more general phenomenon related to both fatiguing and non-fatiguing exercise.

Parkinson’s disease (PD) is a neurodegenerative disorder in which there is progressive depletion of dopamine within the basal ganglia circuitry. In PD, neuromodulation of the sensorimotor cortex has been shown to be suppressed (Morgante et al., 2006, Ueki et al., 2006, Suppa et al., 2010), and there is a state of hyper-excitability (Valls-Sole et al., 1994, Tremblay and Tremblay, 2002) and reduced inhibition of the motor cortex (Ridding et al., 1995, Bares et al., 2003, MacKinnon et al., 2005). It has been shown that PECD is reduced in PD following fatiguing exercises such as maximal voluntary contractions or repetitive submaximal contractions, and that this can be normalized following administration of levodopa (LD) (Lou et al., 2003, Khedr et al., 2007). However, the PECD has not been investigated after non-fatiguing finger movements with different levels of motor demand.

The current study has investigated the degree and time course of PECD, as well as the changes in movement kinematics, with an MVR and MSR finger flexion–extension task performed before and after LD administration in a group of PD patients, and in healthy age-matched controls. It was hypothesized that because of the abnormalities in cortical excitatory and inhibitory network responses resulting from dopamine deficiency, there would be a levodopa-related modulation of PECD after the motor tasks in PD.

Section snippets

Participants

Eleven right-handed LD-responsive PD patients (58–64 years of age; disease duration 5–9 years; Hoehn and Yahr scores 1–3; Table 1) were recruited through the Movement Disorders Clinics at the Australian Neuro-Muscular Research Institute, Western Australia. Ten healthy aged-matched participants served as a control group (CTRL) (54–66 years of age). Prior to the commencement of the experiment, all subjects filled out a medical questionnaire and provided their informed consent. The study was approved

Experimental procedure

The MVR and MSR tasks were performed in a pseudo-randomized order in a within-session design, separated by 15 min. The PD patients were asked to delay taking their morning LD dose prior to a morning test session (“OFF”). By delaying the morning dose, all patients were at least 12 h “OFF” medication. Baseline FDI and EIP MEP amplitude were determined from 2 sets of 12 single-pulsed TMS delivered at 5-s intervals (total duration of 1 min). After each task, MEP amplitude was tracked for 10 min, with

Data and statistical analyses

Kinematic measurements were analyzed with a custom-designed LabView program. Mean movement rate (Hz, RATE) and amplitude (degrees, AMP) were calculated for the first 2 s (START) and last 2 s (END) of each task. MEP amplitude (mean of the 12 MEPs in each post-task run) was expressed as a percentage (MEP%) of the mean of the 2 baseline runs prior to each task.

As experiments were carried out in a control group, and in a PD group under two conditions (ON and OFF medication), to simplify statistical

Kinematic measures

Table 2 provides the START and END rates for each of the tasks (MVR and MSR) performed by the control group (CTRL), and the PD group (OFF and ON medication). In both groups rate declined from START to END for the MVR task, but not for the MSR task.

The MANOVA revealed a significant effect for CATEGORY (F(2,63) = 27.34, p < 0.001), TIME (F(1,63) = 12.42, p < 0.001), and TASK (F(1,63) = 54.73, p < 0.001). Rate declined by 5.3% for CTRL (5.84 ± 0.07 Hz vs. 5.53 ± 0.07 Hz; START vs. END). There was a significantly

Discussion

The major finding of this study was that the PECD, which is present ∼6 min after both the MVR and MSR tasks in normal subjects, was absent in PD patients off medication but was restored to normal levels after administration of LD and improvement in movement kinematics. The findings suggest that dopamine depletion is associated with impaired modulation of corticomotor excitability after non-fatiguing repetitive finger movement which is reversed following administration of LD.

The decline in

Acknowledgements

We thank all of the participants in the study and Jonathan Green for designing and developing the data acquisition program in Labview. Wei-Peng Teo was supported by a Scholarship for International Research Fees, University of Western Australia Postgraduate Award and the Enid and Arthur Home Memorial Scholarship. The authors also acknowledge support from the Neuromuscular Foundation and Muscular Dystrophy Association of Western Australia.

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