Hans-Christian Jabusch

Etiology of musician’s dystonia: Familial or environmental?

Objective: To test the hypothesis that there is familial aggregation of dystonia and other movement disorders in relatives of patients with musician’s dystonia (MD) and to identify possible environmental triggers. Methods: The families of 28 index patients with MD (14 with a reported positive family history of focal task-specific dystonia [FTSD] and 14 with no known family history [FH−]) underwent a standardized telephone screening interview using a modified version of the Beth Israel Dystonia Screen. Videotaped neurologic examinations were performed on all participants who screened positive and consensus diagnoses established. All patients were investigated for DYT1 dystonia and suitable families were tested for linkage to DYT7. All family members were administered questionnaires covering potential triggers of FTSD. Results: A diagnosis of dystonia was established in all 28 index patients and in 19/97 examined relatives (MD: n = 8, other FTSD: n = 9, other dystonias: n = 2), 5 of whom were members of FH− families. In 27 of the 47 affected individuals, additional forms of dystonia were seen; other movement disorders were observed in 23 patients. In total, 18 families were multiplex families with two to four affected members. Autosomal dominant inheritance was compatible in at least 12 families. The GAG deletion in DYT1 was absent in all patients. Linkage to DYT7 could be excluded in 1 of the 11 informative families. With respect to potential environmental triggers, there was no significant difference between patients with MD/FTSD compared to unaffected family members. Conclusion: Our results suggest a genetic contribution to musician’s dystonia with phenotypic variability including focal task-specific dystonia. BIDS = Beth Israel Dystonia Screen; FH+ = reported positive family history of focal task-specific dystonia; FH− = no known family history of focal task-specific dystonia; FTSD = focal task-specific dystonia; MD = musician’s dystonia; WC = writer’s cramp.

Focal hand dystonia in musicians: phenomenology, etiology, and psychological trigger factors

NARRATIVE REVIEW: Musicians dystonia is a task-specific movement disorder, which manifests itself as a loss of voluntary motor control in extensively trained movements. In many cases, the disorder terminates the careers of affected musicians. Approximately 1% of all professional musicians are affected. In the past, focal dystonia (FD) was classified as a psychological disorder. Over time, the problem was classified as a neurological problem. Although the specific pathophysiology of the disorder is still unclear, it appears the etiology is multifactorial. While there may be a family history, neurophysiological, physical, and environmental factors, trauma and stress contribute to the phenotypic development of FD. This manuscript analyzes the evidence supporting the potential contribution of the emotional brain systems in the etiology of focal hand dystonia in musicians. In addition, the psychological findings from a large descriptive study comparing healthy musicians, musicians with dystonia, and musicians with chronic pain. Information about psychogenic characteristics might be used to modify intervention strategies and music instruction to reduce the incidence of musicians dystonia.

Detecting Wrong Notes in Advance: Neuronal Correlates of Error Monitoring in Pianists

Music performance is an extremely rapid process with low incidence of errors even at the fast rates of production required. This is possible only due to the fast functioning of the self-monitoring system. Surprisingly, no specific data about error monitoring have been published in the music domain. Consequently, the present study investigated the electrophysiological correlates of executive control mechanisms, in particular error detection, during piano performance. Our target was to extend the previous research efforts on understanding of the human action-monitoring system by selecting a highly skilled multimodal task. Pianists had to retrieve memorized music pieces at a fast tempo in the presence or absence of auditory feedback. Our main interest was to study the interplay between auditory and sensorimotor information in the processes triggered by an erroneous action, considering only wrong pitches as errors. We found that around 70 ms prior to errors a negative component is elicited in the event-related potentials and is generated by the anterior cingulate cortex. Interestingly, this component was independent of the auditory feedback. However, the auditory information did modulate the processing of the errors after their execution, as reflected in a larger error positivity (Pe). Our data are interpreted within the context of feedforward models and the auditory-motor coupling.

EEG oscillatory patterns are associated with error prediction during music performance and are altered in musician's dystonia

Skilled performance requires the ability to monitor ongoing behavior, detect errors in advance and modify the performance accordingly. The acquisition of fast predictive mechanisms might be possible due to the extensive training characterizing expertise performance. Recent EEG studies on piano performance reported a negative event-related potential (ERP) triggered in the ACC 70 ms before performance errors (pitch errors due to incorrect keypress). This ERP component, termed pre-error related negativity (pre-ERN), was assumed to reflect processes of error detection in advance. However, some questions remained to be addressed: (i) Does the electrophysiological marker prior to errors reflect an error signal itself or is it related instead to the implementation of control mechanisms? (ii) Does the posterior frontomedial cortex (pFMC, including ACC) interact with other brain regions to implement control adjustments following motor prediction of an upcoming error? (iii) Can we gain insight into the electrophysiological correlates of error prediction and control by assessing the local neuronal synchronization and phase interaction among neuronal populations? (iv) Finally, are error detection and control mechanisms defective in pianists with musicians dystonia (MD), a focal task-specific dystonia resulting from dysfunction of the basal ganglia-thalamic-frontal circuits? Consequently, we investigated the EEG oscillatory and phase synchronization correlates of error detection and control during piano performances in healthy pianists and in a group of pianists with MD. In healthy pianists, the main outcomes were increased pre-error theta and beta band oscillations over the pFMC and 13-15 Hz phase synchronization, between the pFMC and the right lateral prefrontal cortex, which predicted corrective mechanisms. In MD patients, the pattern of phase synchronization appeared in a different frequency band (6-8 Hz) and correlated with the severity of the disorder. The present findings shed new light on the neural mechanisms, which might implement motor prediction by means of forward control processes, as they function in healthy pianists and in their altered form in patients with MD.

The influence of practice on the development of motor skills in pianists: A longitudinal study in a selected motor task

A longitudinal study was conducted to investigate the influence of practice on the long-term development of expert pianists motor skills in a relevant musical context. Temporal evenness in standardized scale playing was assessed twice in 19 pianists within an average time interval of 27 months. Questionnaires were used for retrospective assessment of practice quantity and several qualitative parameters related to practicing of scales. The development of temporal evenness in scale playing over the follow-up period correlated with the practice time accumulated during that period and with the average daily practice time. Expert pianists with an average daily practice time of 3.75h or more showed an improvement of performance in this selected motor skill. No significant association was observed between motor skill development during the follow-up period and the content of practice. Stepwise linear regression revealed a model predicting 43% of the variance of motor skill development, with practice time accumulated during the follow-up period as the only predictor. It was concluded that, in expert pianists, maintenance of motor skills in the selected motor task was strongly influenced by practice quantity.

Musician's dystonia in pianists: Long-term evaluation of retraining and other therapies

OBJECTIVEnMusicians dystonia is characterized by loss of voluntary motor control in extensively trained movements on an instrument. The condition is difficult to treat. This retrospective study reports on the interventions received by a homogeneous cohort of pianists with musicians dystonia and the subjective and objective changes reported in task performance.nnnMETHODSnThis is a retrospective descriptive study. Fifty four pianists with musicians dystonia who had received care in a Movement Disorders Clinic completed a self report questionnaire regarding type and effectiveness of treatment received over the last 4 years. Pianists fine motor control was assessed objectively by measuring the temporal regularity of their scale playing.nnnRESULTSnNearly all patients (98.0%) reported deficits in motor tasks other than musical playing. Half of the patients were taking medications (Botulinum toxin (53%), Trihexyphenidyl (51%)). Subjects reported participating in multiple therapies: retraining (87%), hand therapy (42%), relaxation techniques (38%), physiotherapy (30%), psychotherapy (23%), acupuncture (21%) and body techniques (21%). Self-reported improvements in motor performance were reported by 81.5% of the subjects with 5.6% reporting a complete recovery. Objective gains in task-specific motor performance were documented in 42.9% of the subjects (with deterioration in 4.8%). Retraining therapy, relaxation techniques and change in teacher explained 52% of the variance in subjective outcomes.nnnCONCLUSIONSnMusicians dystonia not only interferes with musical performance but other fine motor tasks. Objectively, approximately 50% of patients improved task performance following participation in a variety of intervention strategies, but subjectively, 80% of subjects reported improvement.

Defective Inhibition and Inter-Regional Phase Synchronization in Pianists With Musician's Dystonia: An EEG Study

Recent neurophysiological studies have associated focal‐task specific dystonia (FTSD) with impaired inhibitory function. However, it remains unknown whether FTSD also affects the inhibition (INH) of long‐term overlearned motor programs. Consequently, we investigated in a Go/NoGo paradigm the neural correlates associated with the activation (ACT) and inhibition of long‐term overlearned motor memory traces in pianists with musicians dystonia (MD), a form of FTSD, during a relevant motor task under constraint timing conditions with multichannel EEG. In NoGo trials, the movement related cortical potentials showed a positive shift after the NoGo signal related to inhibition and was significantly smaller over sensorimotor areas in musicians with MD. Further, we observed an increase at 850–900 ms in the power of beta oscillations which was significantly weaker for the patient group. The role of the inter‐electrode phase coupling in the sensorimotor integration of inhibitory processes turned out to be the most relevant physiological marker: the global phase synchronization during INH exhibited an increase between 230 and 330 ms and 7–8 Hz, increase which was significantly smaller for pianists with MD. This effect was due to a weaker phase synchronization between the supplementary motor cortex and left premotor and sensorimotor electrodes in patients. Thus, our findings support the hypothesis of a deficient phase coupling between the neuronal assemblies required to inhibit motor memory traces in patients with MD. EMG recorded from the right flexor pollicis longus muscle confirmed that patients with MD had a disrupted INH in NoGo trials. Hum Brain Mapp 2009.

Challenges of Making Music: What Causes Musician’s Dystonia?

Challenges of Making Music: What Causes Musician’s Dystonia? Musician’s dystonia, a task-specific movement disorder, affects 1% to 2% of professional musicians and is thought to be environmentally acquired, related to years of practice.1,2 Indeed, professional musicians will have spent more than 10 000 hours on the instrument by the age of 20 years.3 Recently, a clustering of different types of dystonia was reported in the families of patients with musician’s dystonia, suggesting also a genetic contribution to the disease.4 However, the underlying molecular genetic factors are currently unknown. We here investigated in a case-control design whether intensive practice or other environmental factors are associated with musician’s dystonia in combination with genetic susceptibility.

Genome-wide association study in musician's dystonia: A risk variant at the arylsulfatase G locus?

Musicians dystonia (MD) affects 1% to 2% of professional musicians and frequently terminates performance careers. It is characterized by loss of voluntary motor control when playing the instrument. Little is known about genetic risk factors, although MD or writers dystonia (WD) occurs in relatives of 20% of MD patients. We conducted a 2‐stage genome‐wide association study in whites. Genotypes at 557,620 single‐nucleotide polymorphisms (SNPs) passed stringent quality control for 127 patients and 984 controls. Ten SNPs revealed Pu2009<u200910−5 and entered the replication phase including 116 MD patients and 125 healthy musicians. A genome‐wide significant SNP (Pu2009<u20095 × 10−8) was also genotyped in 208 German or Dutch WD patients, 1,969 Caucasian, Spanish, and Japanese patients with other forms of focal or segmental dystonia as well as in 2,233 ethnically matched controls. Genome‐wide significance with MD was observed for an intronic variant in the arylsulfatase G (ARSG) gene (rs11655081; Pu2009=u20093.95 × 10−9; odds ratio [OR], 4.33; 95% confidence interval [CI], 2.66‐7.05). rs11655081 was also associated with WD (Pu2009=u20092.78 × 10−2) but not with any other focal or segmental dystonia. The allele frequency of rs11655081 varies substantially between different populations. The population stratification in our sample was modest (λu2009=u20091.07), but the effect size may be overestimated. Using a small but homogenous patient sample, we provide data for a possible association of ARSG with MD. The variant may also contribute to the risk of WD, a form of dystonia that is often found in relatives of MD patients.

THE D216H VARIANT IN THE DYT1 GENE: A SUSCEPTIBILITY FACTOR FOR DYSTONIA IN FAMILIAL CASES?

Primary focal dystonia is a clinically and genetically heterogeneous disorder. In contrast, early-onset generalized torsion dystonia is often caused by a heterozygous deletion of three nucleotides (GAG) in the DYT1 gene leading to the loss of a glutamic acid residue (deltaE) of the gene product TorsinA.1 Interestingly, the only nonsynonymous coding sequence variation in DYT1 , rs1801968 (D216H), was demonstrated to reduce penetrance of the GAG deletion when present in trans to this mutation.2 While one study suggested a protective effect of H216 in a small number of tested Indian patients with primary dystonia, other reports failed to show any association.3–5 The aim of the present study was to evaluate the role of D216H in German patients with familial primary dystonia and, in case of association, to establish the frequency of this variant in patients with dystonia regardless of their family history.nn### Subjects.nnStudy subjects were recruited from four movement disorders centers in Northern Germany. After obtaining informed consent and approval of the study by the local ethical standards committee, all participants underwent a standardized neurologic examination by a movement disorders specialist, and blood samples were drawn. We included 111 unrelated familial cases with primary focal or segmental dystonia, along with 241 unrelated control subjects. Family history was regarded as positive when at least one …