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Restorative Neurology and Neuroscience 29 (2011) 85–90 DOI 10.3233/RNN-2011-0582 IOS Press
Single-session tDCS-supported retraining does not improve fine motor control in musician’s dystonia Franziska Buttkusa , Volker Baura,d , Hans-Christian Jabuschb , Maria de la Cruz Gomez-Pellina , Walter Paulusc , Michael A. Nitschec and Eckart Altenm¨ullera,∗ a Institute of Music Physiology and Musicians’ Medicine, University of Music, Drama and Media, Hanover, Germany b Institute
of Musicians’ Medicine, University of Music Carl Maria von Weber, Dresden, Germany of Clinical Neurophysiology, Georg-August University, Goettingen, Germany d Psychiatric University Hospital, and Division of Neuropsychology, Institute of Psychology, University of Zurich, Zurich, Switzerland c Department
Abstract. Background: Focal dystonia in musicians (MD) is a task-specific movement disorder with a loss of voluntary motor control during instrumental playing. Defective inhibition on different levels of the central nervous system is involved in the pathophysiology. Sensorimotor retraining is a therapeutic approach to MD and aims to establish non-dystonic movements. Transcranial direct current stimulation (tDCS) modulates cortical excitability and alters motor performance. In this study, tDCS of the motor cortex was expected to assist retraining at the instrument. Methods: Nine professional pianists suffering from MD were included in a placebo-controlled double-blinded study. Retraining consisted of slow, voluntarily controlled movements on the piano and was combined with tDCS. Patients were treated with three stimulation protocols: anodal tDCS, cathodal tDCS and placebo stimulation. Results: No beneficial effects of single-session tDCS-supported sensorimotor retraining on fine motor control in pianists with MD were found in all three conditions. Conclusions: The main cause of the negative result of this study may be the short intervention time. One retraining session with a duration of 20 min seems not sufficient to improve symptoms of MD. Additionally, a single tDCS session might not be sufficient to modify sensorimotor learning of a highly skilled task in musicians with dystonia. Keywords: Focal dystonia, motor control, neuronal plasticity, transcranial direct current stimulation, retraining
Focal dystonia in musicians (MD) is a task-specific movement disorder which presents itself as a loss of motor control in extensively trained movements while ∗ Corresponding author: Prof. Dr. med. Eckart Altenm¨ uller, MD, MA, PhD, Director of the Institute of Music Physiology and Musicians’ Medicine (IMMM), University of Music, Drama and Media Hanover, Emmichplatz 1, D-30175 Hannover, Germany. Tel.: +49 0 511 3100 552; Fax: +49 0 511 3100 557; Web: www.immm. hmt-hannover.de. E-mail:
[email protected].
the musician is playing the instrument (Altenm¨uller, 2003). For those who are affected, the disorder is highly disabling and in many cases it terminates musical careers. The etiology of MD is not well understood. However, it is known that deficient inhibition at different levels of the central nervous system is involved in the pathophysiology (Hallett, 2006). Successful execution of sensorimotor programs requires a subtle balance between excitation and inhibition in neuronal circuits.
0922-6028/11/$27.50 © 2011 – IOS Press and the authors. All rights reserved
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This balance is a crucial condition for motor programs with extreme spatiotemporal constraints that occur in the performance of music on a professional level. Pianists for example perform rapid individualized finger movements requiring selective and specific activation of muscles moving the involved fingers in the intended way and inhibiting movements of the uninvolved fingers. In musicians with MD, several studies found an abnormal vibration-induced decrease of short latency inhibition in antagonistic muscles and in neighbouring muscles when a target muscle was vibrated (Rosenkranz et al., 2000, 2005). The impairment of focused motor activation was also shown by a recent EEG-study investigating the positive shift of movement-related cortical potentials over the sensorimotor areas in a Go/NoGo paradigm in pianists with MD (Ruiz et al., 2009). Up to now, MD is difficult to treat (Frucht et al., 2001; Jabusch et al., 2005). Pedagogical retraining, i.e. supervised practice of sensorimotor exercises at the musical instrument, has been described as therapeutic approach with heterogeneous outcomes (Byl et al., 2000; Boullet, 2003; Candia et al., 2003). Retraining aims to establish new and healthy motor programs that can be voluntarily controlled by the musician. Since acquisition of new motor skills is accompanied by changes of neuronal activity and excitability, transcranial direct current stimulation (tDCS), which is known to modulate motor cortex excitability (Nitsche et al., 2000), might be a promising tool to assist motor learning processes during retraining. Anodal tDCS enhances, whereas cathodal tDCS reduces cortical excitability (Nitsche et al., 2000). Anodal tDCS of the primary motor cortex was shown to yield better results in an implicit motor learning task (Nitsche, 2003). Sensorimotor retraining in musicians with MD is based on repeated performance of exercises and includes explicit but also implicit motor learning by the musician. Cathodal tDCS has been shown to improve performances in overlearned tasks in healthy subjects, probably by an enhanced signal-to-noise ratio in neuronal signaling (Antal et al., 2004). As described earlier, sensorimotor retraining aims to establish alternative voluntary motor programs and to weaken the pathological motor impulses at the instrument. An enhanced signal-to-noise ratio applied cathodal tDCS may be able to facilitate learning processes during the sensorimotor retraining of patients with MD. In a recent study, cathodal tDCS without simultaneous motor learning did not improve fine motor
control in a group of guitarists with MD (Buttkus et al., 2010b). Another negative result was found in patients with writer’s cramp: the normal inhibitory effect of cathodal tDCS on corticospinal excitability was absent (Quartarone et al., 2005). These results indicate that cathodal tDCS alone did not elicit beneficial effects in musicians with focal dystonia. However, these studies did not investigate the effects of cathodal tDCS during the performance of a motor task (compare Antal et al., 2004). In the present study, the combination of tDCS and motor learning was tested. Based on positive effects of sensorimotor retraining in musicians with MD and on the findings of tDCS effects on motor learning, we hypothesized that retraining effects in patients with MD might be enhanced by simultaneous tDCS. We aimed to investigate whether single-session tDCS combined with sensorimotor retraining improves retraining effects in pianists with MD either by anodal or by cathodal tDCS.
1. Methods 1.1. Participants A group of nine professional pianists (all male) suffering from MD in the right hand participated in the study (mean age: 44 ± 11 years, range: 28–58 years). Task-specific dystonia was diagnosed in our out-patient clinic and presented itself in the typical manner as painless cramping of one or more fingers of the right hand while patients were playing the piano. Mean duration of MD was 9.4 ± 7.6 years (range: 9 months–26 years). None of the patients was pharmacologically treated for MD or received any medication affecting the central nervous system during the time of the study. Five pianists had received botulinum toxin in their past history of MD. One patient received a botulinum toxin injection four weeks before participating, however, the effect on weakness and motor improvement had completely faded out at the time of the experiment. In all other cases, there was at least a time interval of three months between injection and participation in the study. Other neurological disorders served as exclusion criteria. Written informed consent was obtained from all patients. The study was approved by local ethics committee and was conducted in accordance with the Declaration of Helsinki.
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F. Buttkus et al. / Single-session tDCS-supported retraining does not improve fine motor control in musician’s dystonia
1.2. Experimental design 1.2.1. Sensorimotor retraining Motor learning consisted of a sensorimotor retraining on the piano (20 min) based on the following principles reported previously (Boullet, 2003): 1) movements of affected body parts were limited to a tempo and force at which the dystonic movement would not occur; 2) compensatory movements (e.g. of adjacent fingers) were avoided as far as possible; 3) in one of the exercises, desired movement patterns were played by the unaffected hand and mirrored by the affected hand. During retraining, the patients received tDCS. 1.2.2. Transcranial direct current stimulation tDCS was applied in a double-blinded and placebocontrolled fashion. The stimulating electrode was placed over the left primary motor cortex (C3 according to the international 10–20 system) and the reference electrode over the right supraorbital area. In the active stimulation conditions (anodal and cathodal), tDCS was applied for 20 min with a current strength of 2 mA. In the placebo stimulation condition, current was applied with only 0.2 mA (fading out after 20 s), which caused a slight itching sensation on the patients’ head skin (Siebner et al., 2004). tDCS was induced through water-soaked sponge electrodes (surface 35 cm2 ) and delivered by a battery-driven constant-current stimulator (eldith GmbH, Germany). The method of tDCS has already been used in numerous studies and was shown to be safe (Nitsche et al., 2003). Skin irritations may occur as possible side effects. The following three treatment conditions were applied on separate days with intervals of at least one week between the conditions: 20 min retraining plus simultaneous tDCS, either anodal or cathodal tDCS or placebo stimulation. The order of stimulation conditions was balanced across subjects. 1.3. Assessment of fine motor control Motor control was assessed by musical instrument digital interface (MIDI)-based scale analysis (Jabusch et al., 2004). Patients played sequences of 10–15 C-major scales with the affected hand in a metronomepaced tempo (desired inter-onset interval 125 ms) over two octaves in both playing directions. Inter-onset intervals (characterizing the time between subsequent note onsets) were analyzed. The temporary uneven-
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ness of inter-onset intervals (IOIs) has previously been identified as a valid, reliable and precise indicator of the impairment of motor control in pianists with dystonia and was used as target parameter (Jabusch et al., 2004). For each patient, motor control was assessed before and 1 min, 30 min, 60 min, 120 min after the respective treatment session. 1.4. Statistical analysis In each performance test, temporary unevenness of IOIs was analyzed by calculating the median standard deviation (SD) of IOIs of all scales (10–15 scales) for both playing directions. For further analyses, performance measures of the more severely affected playing direction were used (as identified by the higher median SD of IOIs). Wilcoxon tests were applied to analyze performance differences between time points. The alpha level was set at 0.05. Alpha adjustment for multiple testing was done according to Bonferroni-Holm. 2. Results Table 1 shows the individual data of fine motor control in each pianist. Performance results of the group of pianists for each time point are shown in Fig. 1. Results of Wilcoxon tests revealed no statistically significant effect of treatment, neither immediately (1 min) after treatment nor in the follow-up tests (30 min, 60 min and 120 min after treatment). Motor control at baseline did not differ between the stimulation conditions. Inter-treatment comparisons were conducted between active stimulation conditions and the placebo stimulation condition. No beneficial effect of anodal or cathodal tDCS was found. 3. Discussion This paper reports on single-session tDCSsupported retraining as a treatment attempt in a group of pianists with MD. We observed no beneficial effects on their fine motor control. Immediately after the retraining sessions, improvement of symptoms was seen neither in the active tDCS conditions nor in the placebo condition. Retraining failed although each pianist received detailed video-supported instructions about the principles of sensorimotor retraining prior to every retraining session. The main cause of this
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Table 1 Assessment of fine motor control in each pianist with MIDI-based scale analysis (Jabusch et al., 2004). The median standard deviation (SD) of the inter-onset intervals (IOI) is a sensitive parameter to the quality of motor control in pianists with musician’s dystonia. In a group of healthy professional pianists, the median SD of IOI was 9.5 ± 2.1 ms (Jabusch et al., 2004). The group of pianists participating in the present study are all characterized by higher SD of IOI than the healthy pianists. Symptoms of dystonia differed considerably in their severity. Directly after treatment, there even was some worsening of fine motor control in some patients which is also present in the placebo condition. This may be due to the specific pattern of focal dystonia which manifests in many cases more clearly after prolonged playing. (A) describes the measurements of fine motor control in the placebo tDCS condition, (B) of the anodal tDCS condition and (C) of the cathodal tDCS condition Pianists with MD
Median standard deviation of the inter-onset interval (IOI) in ms. High values indicate a poor motor control Before treatment
1 min a.t.
30 min a.t.
60 min a.t.
120 min a.t.
(A) Placebo tDCS plus retraining 1 35.69 2 19.42 3 18.93 4 12.46 5 23.07 6 17.08 7 24.67 8 24.20 9 22.65
41.76 17.57 20.65 15.82 26.98 24.30 25.09 22.52 23.58
39.84 19.46 15.89 11.99 27.95 20.11 25.38 18.80 34.12
32.12 17.71 16.88 13.06 23.42 18.60 25.29 21.29 34.28
28.87 16.96 17.57 Missing data 25.28 20.27 28.99 21.64 32.74
(B) Anodal tDCS plus retraining 1 27.94 2 18.99 3 15.28 4 12.52 5 24.71 6 19.23 7 20.69 8 22.00 9 24.11
33.14 21.82 14.78 14.39 28.83 21.06 19.49 22.02 20.75
38.40 23.87 16.52 12.57 27.76 19.73 19.12 20.72 21.02
38.20 24.62 16.13 11.99 28.67 18.29 21.22 20.23 20.93
31.04 20.91 15.64 12.36 30.08 18.78 21.50 21.12 25.05
(C) Cathodal tDCS plus retraining 1 33.24 2 16.67 3 14.79 4 13.92 5 26.12 6 17.23 7 28.16 8 19.05 9 28.57
34.38 19.05 13.96 15.78 25.77 20.25 31.75 19.96 19.46
38.35 20.93 14.42 14.07 26.33 18.24 28.41 20.68 23.63
31.33 21.53 13.92 12.57 24.41 21.50 28.22 20.53 19.59
26.72 18.44 15.34 Missing data 26.77 18.95 25.05 22.63 25.91
negative result may be the short retraining time. The session duration of 20 min seems not sufficient to improve symptoms of MD. Sensorimotor retraining in MD is intended to activate neuronal pathways related to movement preparation and execution that are not associated with dystonic movement patterns. According to previous experience, musicians suffering from dystonia often participate in retraining programs over long periods before beneficial effects remain stable (Boullet, 2003). Another aim of the study was to investigate if single-session tDCS may prolong possible retraining effects. Since no retraining effects were
present immediately after the treatment sessions, no prolongation of retraining effects could take place in the active-tDCS stimulation conditions: no improvement of motor control was seen 30 min, 60 min or 120 min after the treatment sessions. Obviously, one single tDCS-supported retraining session of 20 min is not sufficient to modify sensorimotor learning of a highly skilled task in musician’s dystonia. Treatment approaches with retraining and tDCS aim to establish new movement patterns on a behavioral and on a neurophysiological level which seems to require a certain minimum of session duration and/or a min-
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Disclosures The authors report no conflicts of interest and have no financial disclosures to make. Competing interests and funding The authors report no conflicts of interest. Funding: Franziska Buttkus
Fig. 1. Results of single session tDCS-supported retraining in a group of pianists with musician’s dystonia. Bars show motor performance of the group as the median SD of IOIs for each treatment condition and time. High values indicate poor motor control and vice versa. Treatment condition is displayed as open bars for retraining combined with placebo tDCS, as light gray bars for retraining combined with anodal tDCS and as dark gray bars for retraining combined with cathodal tDCS. Whiskers depict the 25th and the 75th percentiles of data. b.t.: before treatment; a.t.: after treatment. Motor performance after treatment vs. before treatment: n.s. for all tests (p > 0.05, Wilcoxon, Bonferroni-Holm-corrected).
F. Buttkus, MSc, receives a scholarship “GeorgChristoph-Lichtenberg” of lower Saxony, Germany, as a PhD student. She won the “Ernst-August-SchraderPreis” at the University of Music and Drama, Hanover, Germany, in the category “Science”. Funding: Volker Baur V. Baur, MSc, receives grants from the Swiss National Science Foundation as a PhD student. Funding: Hans-Christian Jabusch
imum of session numbers. Deep brain stimulation, as an example for an established treatment option for generalized dystonia, also requires time to elicit beneficial effects: as was recently shown, plasticity changes similar to short-latency intracortical inhibition and long-term potentiation improved over months after implantation in patients with generalized dystonia (Ruge et al., 2009). Taken together, findings suggest that transcranial stimulation methods have to be applied regularly over a longer period in order to achieve beneficial effects. Safety studies in animals and humans have demonstrated that the currently used tDCS protocols are safe and can be repeated daily for 5 or 10 days (Nitsche et al., 2003). In summary, we conclude that one single session of tDCS-supported retraining did not improve fine motor control in MD in the present study. Future studies with modified treatment protocols including longer retraining periods and repeated tDCS sessions are required to clarify the potential effects of a tDCS-supported retraining on fine motor control in musicians with dystonia. A subsequently performed single-case study with repeated treatment sessions is reported elsewhere (Buttkus/Baur et al., 2010a), however, studies with larger numbers of patients will be required.
Dr. Jabusch is chair and full professor paid by the University of Music, Carl Maria von Weber, Dresden, Germany. He is co-investigator of a research project funded by the Dystonia Medical Research Foundation, USA. He contributed to a CME course funded by Merz Pharma GmbH, Germany. Funding: Maria de la Cruz Gomez-Pellin Maria de la Cruz Gomez-Pellin, cand.med., receives a grant of the Deutscher Akademischer Austauschdienst (DAAD). Funding: Walter Paulus Dr. Paulus is director of the department of Clinical Neurophysiology paid by the University Medicine of G¨ottingen, Germany. He has received support for projects involving transcranial magnetic and direct current stimulation from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG), the German Federal Ministry of Education and Research (Bundesministerium f¨ur Bildung und Forschung, BMBF), the European Union, the Volkswagen Foundation, the Rose Foundation, and that he has served
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as an advisor for several companies working on the development of stimulating apparatus of these types. Funding: Michael A. Nitsche Dr. Nitsche has received support for projects involving transcranial magnetic and direct current stimulation from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and the German Federal Ministry of Education and Research (Bundesministerium f¨ur Bildung und Forschung, BMBF). Funding: Eckart Altenm¨uller Dr. Altenm¨uller is chair and full professor paid by the University of Music and Drama, Hannover, Germany. He serves in the Editorial board of following Journals: Journal of Interdisciplinary Music Studies, Medical Problems of Performing Artists, Musicae Scientiae, Music and Medicine. He receives grants from the German Research Foundation (Al 269/5-3, Al 269/7-3) and the Dystonia Medical Research Foundation, USA. He receives royalties from the publication in the book “Music, Brain and Motor Control” which appeared at Oxford University Press, 2006.
Candia, V., Wienbruch, C., Elbert, T., Rockstroh, B. & Ray, W. (2003). Effective behavioral treatment of focal hand dystonia in musicians alters somatosensory cortical organization. Proc Natl Acad Sci USA, 100, 7942-7946. Frucht, S.J., Fahn, S. & Greene, P.E. (2001). The natural history of embouchure dystonia. Mov Disord, 16, 899-906. Hallett, M. (2006). Pathophysiology of dystonia. J Neural Transm Suppl, 70, 485-488. Jabusch, H.C., Vauth, H. & Altenm¨uller, E. (2004). Quantification of focal dystonia in pianists using scale analysis. Mov Disord, 19, 171-180. Jabusch, H.C., Zschucke, D., Schmidt, A., Schuele, S. & Altenm¨uller, E. (2005). Focal dystonia in muscians: treatment strategies and long-term outcome in 144 patients. Mov Disord, 20, 1623-1626. Nitsche, M.A. & Paulus, W. (2000). Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol, 527, 633-639. Nitsche, M.A., Liebetanz, D., Lang, N., Antal, A., Tergau, F. & Paulus, W. (2003a). Safety criteria for transcranial direct current stimulation (tDCS) in humans. Clin Neurophysiol, 114, 22202222. Nitsche, M.A., Schauenburg, A., Lang, N., Liebetanz, D., Exner, C., Paulus, W. & Tergau, F. (2003b). Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. J Cogn Neurosci, 15, 619-626.
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