Elsevier

Brain Stimulation

Volume 8, Issue 2, March–April 2015, Pages 224-230
Brain Stimulation

Transcranial Magnetic Stimulation (TMS)
Original Article
TMS Enhances Retention of a Motor Skill in Parkinson's Disease

https://doi.org/10.1016/j.brs.2014.11.005Get rights and content

Highlights

  • Retention of a visuo-motor skill is impaired in PD.

  • Retention in PD improves after rTMS to the right parietal cortex.

  • rTMS to the right posterior parietal cortex does not affect kinematics.

Abstract

Background

In Parkinson's disease (PD), skill retention is poor, even when acquisition rate is generally preserved. Recent work in normal subjects suggests that 5 Hz-repetitive transcranial magnetic stimulation (5Hz-rTMS) may induce phenomena of long-term potentiation at the cortical level.

Objective/hypothesis

We thus verified whether, in PD, 5Hz-rTMS enhances retention of a visuo-motor skill that involves the activity of the right posterior parietal cortex.

Methods

A group of patients with PD was tested in two two-day sessions, separated by one week (treatment and placebo sessions). The first day of each session, they learned to adapt their movements to a step-wise 60° visual rotation. Immediately after the task, either real 5Hz-rTMS (treatment) or sham (placebo) stimulation was applied over the right posterior parietal cortex (P6). Retention of this motor skill was tested the following day.

Results

In patients with PD, adaptation achieved at the end of training was comparable in the treatment and placebo sessions and was similar to that of a group of age-matched controls. However, retention indices tested on the following day were significantly lower in the placebo compared to the treatment session in which retention indices were restored to the level of the controls. Importantly, reaction and movement time as well as other kinematic measures were the same in the treatment and placebo sessions.

Conclusion

These results suggest that rTMS applied after the acquisition of a motor skill over specific areas involved in this process might enhance skill retention in PD.

Introduction

Although acquisition of new motor skills is generally preserved in Parkinson's Disease (PD), short- and long-term skill retention is impaired in both drug-naïve and pharmacologically treated patients. This conclusion is based on the results of earlier studies from ours and other groups using an implicit learning task in which subjects adapted their movements to rotated visual displays [1], [2], [3], [4]. Adaptation in this task requires the formation of new visuo-motor relationships and, thus, the creation of new memories or ‘internal models’ [5]. In this thoroughly characterized task [6], [7], [8], [9], learning is evident as a constant decrease of directional error that occurs without subjects' awareness; retention is sleep-dependent and is reflected in after-effects, a trace of the achieved adaptation, and in faster rate of re-adaptation at successive exposures. Importantly, learning depends on the activity of right posterior parietal areas as demonstrated by imaging and electrophysiological studies [6], [10], [11], [12]. Indeed, this area, which is involved in the integration of proprioceptive, visual and vestibular inputs, plays an important role in forming and maintaining new internal models used for movement planning. In particular, the binding of multisensory information as well as the development of memories or models such as those required for moving under new visuo-motor coordinates is reflected by activity changes occurring over this area [12], [13], [14], [15]. Importantly, the degree of skill retention highly correlates with the magnitude of EEG changes during learning over the right posterior parietal area, as well as with the occurrence of slow wave activity in subsequent sleep over that same spot [10].

Adaptation to a 30° rotation occurs similarly in patients with PD and age-matched controls: at the end of training, adaptation levels are similar in both groups [1], [2], [3]. However, re-adaptation, tested either immediately after training or one-two days later, is faster than in the first exposure only in normal controls [1], [2], [3]. A possible explanation is that formation of internal models and their retention is hampered in PD because of impaired induction of long-term potentiation (LTP)-related phenomena [3]. In fact, many studies in PD have now demonstrated deficits of LTP-like phenomena in the primary motor cortex [16], [17], [18], [19], [20]. A way to enhance LTP-like phenomena in vivo is the use of 5 Hz-repetitive transcranial magnetic stimulation (5Hz-rTMS): in normal subjects, 5Hz-rTMS increases the amplitude of muscle and cortical responses and produces local increases of slow wave activity in subsequent sleep [21], [22], [23], [24]. More direct evidence of LTP induction comes from our animal study showing that 5Hz-rTMS increases expression of brain-derived neurotrophic factor, tyrosine-receptor-kinase-B and N-methyl-d-aspartate receptor that induce dendritic translation [25]. It is then plausible that, if LTP is impaired in PD, 5Hz-rTMS applied to an area involved in learning might enhance memory formation and retention in these patients. Therefore, in this study, a group of patients with PD adapted to one of two rotation types in two separate sessions. After training, 5Hz-rTMS or sham-rTMS was applied to the right posterior parietal area. While adaptation at the end of training was comparable in the two sessions, retention on the following day was abnormal after sham-TMS but not after 5Hz-rTMS.

Section snippets

Subjects

We tested 19 patients with PD (14 men, age: 60.9 ± 5.4 yrs) and 19 age-matched (10 men, age 58.9 ± 8.7 yrs) controls. As shown in Table 1, all patients had mild to moderate PD and were treated with dopaminergic drugs. None of the patients and controls had severe medical illness or had recently received chronic treatment for sleep complaints. During all the experiments, all the patients were in ON state, in their regular medication schedule. All subjects were right-handed and were naïve to the

Results

No subject experienced adverse effects of the rTMS procedure. Importantly, the amount of sleep was the same across groups and sessions: in the night before re-adaptation, patients slept an average of 6.25 ± 1.5 h in the placebo session and 6.30 ± 1.2 h in the treatment session (paired t-test: P = 0.88), not differently from controls (6.66 ± 1.0 h, unpaired t-test: P = 0.4).

In all the experimental sessions, movements were essentially straight with a bell-shaped velocity profile in both patients

Discussion

The main result of this study is that application of 5Hz-rTMS to the right posterior parietal area after adaptation to a visuo-motor rotation enhances indices of skill retention in patients with PD. Importantly, this effect was confined to the retention of new visuo-motor coordinates without affecting the kinematic characteristics.

Twenty-four hours after the initial training, skill retention measured with both after-effects and re-adaptation gains were lower in patients during the placebo

Acknowledgments

This work was supported by grants from the McDonnell Foundation to MFG, the National Parkinson Foundation to MFG & ADR, the National Institute of Health (NS-054864 to MFG). We thank ETT s.r.l (Genova, Italy) for providing the software used for the motor task. We thank Jamika Singleton-Garvin for help in patient selection.

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