Motivational modulation of bradykinesia in Parkinson's disease off and on dopaminergic medication.

Motivational influence on bradykinesia in Parkinson's disease may be observed in situations of emotional and physical stress, a phenomenon known as paradoxical kinesis. However, little is known about motivational modulation of movement speed beyond these extreme circumstances. In particular, it is not known if motivational factors affect movement speed by improving movement preparation/initiation or execution (or both) and how this effect relates to the patients' medication state. In the present study, we tested if provision of motivational incentive through monetary reward would speed-up movement initiation and/or execution in Parkinson's disease patients and if this effect depended on dopaminergic medication. We studied the effect of monetary incentive on simple reaction time in 11 Parkinson's disease patients both "off" and "on" dopaminergic medication and in 11 healthy participants. The simple reaction time task was performed across unrewarded and rewarded blocks. The initiation time and movement time were quantified separately. Anticipation errors and long responses were also recorded. The prospect of reward improved initiation times in Parkinson's disease patients both "off" and "on" dopaminergic medication, to a similar extent as in healthy participants. However, for "off" medication, this improvement was associated with increased frequency of anticipation errors, which were eliminated by dopamine replacement. Dopamine replacement had an additional, albeit small effect, on reward-related improvement of movement execution. Motivational strategies are helpful in overcoming bradykinesia in Parkinson's disease. Motivational factors may have a greater effect on bradykinesia when patients are "on" medication, as dopamine appears to be required for overcoming speed-accuracy trade-off and for improvement of movement execution. Thus, medication status should be an important consideration in movement rehabilitation programmes for patients with Parkinson's disease

Enhanced Motivational Modulation of Motor Behaviour with Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease

[Background] Motivational improvement of movement speed in Parkinson’s disease (PD) is observed in life-threatening situations and has been empirically demonstrated in experimental studies using reaction time paradigms.[Objectives] To address two clinically relevant questions: first, if in PD, motivational modulation through provision of monetary incentive on a sorting task that approximates performance on everyday life tasks affects movement speed. Second, how this effect is compared between PD patients treated with medication or subthalamic deep brain stimulation.[Methods] We used the Card Arranging Reward Responsivity Objective Test that shares component processes with everyday life tasks to compare reward responsivity of movement speed in 10 PD patients with STN-DBS, 10 nonoperated medicated PD patients, both OFF and ON their usual medications/stimulation, and 11 age-matched healthy controls.[Results] Despite longer disease duration and more severe motor symptoms, STN-DBS PD patients with the stimulator turned ON showed greater improvement of movement speed with the prospect of monetary incentive compared to both medicated PD patients and healthy participants.[Discussion] The effect of monetary incentive on movement speed in PD patients is more pronounced with STN-DBS than dopaminergic medications, suggesting that motivational modulation of movement speed may be enhanced as a direct consequence of STN stimulation.Peer reviewe

Botulinum toxin injections reduce associative plasticity in patients with primary dystonia

Botulinum toxin injections ameliorate dystonic symptoms by blocking the neuromuscular junction and weakening dystonic contractions. We asked if botulinum toxin injections in dystonia patients might also affect the integrity of sensorimotor cortical plasticity, one of the key pathophysiological features of dystonia. We applied a paired associative stimulation protocol, known to induce long-term potentiation–like changes in the primary motor cortex hand area to 12 patients with cervical dystonia before and 1 and 3 months after botulinum toxin injections to the neck muscles. Primary motor cortex excitability was probed by measuring transcranial magnetic stimulation-evoked motor evoked potentials before and after paired associative stimulation. We also measured the input–output curve, short-interval intracortical inhibition, intracortical facilitation, short afferent inhibition, and long afferent inhibition in hand muscles and the clinical severity of dystonia. Before botulinum toxin injections, paired associative stimulation significantly facilitated motor evoked potentials in hand muscles. One month after injections, this effect was abolished, with partial recovery after 3 months. There were significant positive correlations between the facilitation produced by paired associative stimulation and (1) the time elapsed since botulinum toxin injections and (2) the clinical dystonia score. One effect of botulinum toxin injection treatment is to modulate afferent input from the neck. We propose that subsequent reorganization of the motor cortex representation of hand muscles may explain the effect of botulinum toxin on motor cortical plasticity

Reversal of practice-related effects on corticospinal excitability has no immediate effect on behavioral outcome

Background: Motor training usually increases the excitability of corticospinal outputs to the trained muscles. However, it is uncertain to what extent the change in excitability is a critical component of behavioral learning or whether it is a non-specific side effect. Objective/Hypothesis: We used a depotentiation protocol to abolish the training-induced increase of corticospinal excitability and tested whether this had any immediate effect on the improved motor performance. Methods: We used an index finger abduction task in which behavioral improvement is known to be associated with M1 excitability changes as monitored by the amplitude of motor-evoked potentials produced by single-pulse transcranial magnetic stimulation (TMS). These effects could be reversed by a depotentiation protocol using a short form of continuous theta-burst stimulation (cTBS150). Participants underwent three experimental interventions: 'motor training', 'motor training plus cTBS150' and 'cTBS150'. M1 excitability and TMS-evoked finger movements were assessed before the experimental interventions and 5 min, 15 min, and 30 min thereafter. Motor retention was tested 45 min after the experimental interventions. Results: During training, acceleration of the practiced movement improved. At the end of training, M1 excitability and the acceleration of TMS-evoked index finger movements in the direction of training had increased and the enhanced performance was retained when tested 45 min later. The depotentiation protocol, delivered immediately after the end of training, reversed the excitability changes in M1 but did not affect the acceleration of the TMS-evoked finger movement nor the retention of performance. The depotentiation protocol alone did not modify M1 excitability. Conclusions: The present study indicates that in the short term, increases in corticospinal excitability are not related to immediate changes in behavioral motor outcome

Myoclonic disorders: a practical approach for diagnosis and treatment

Myoclonus is a sudden, brief, involuntary muscle jerk. It is caused by abrupt muscle contraction, in the case of positive myoclonus, or by sudden cessation of ongoing muscular activity, in the case of negative myoclonus (NM). Myoclonus may be classified in a number of ways, although classification based on the underlying physiology is the most useful from the therapeutic viewpoint. Given the large number of possible causes of myoclonus, it is essential to take a good history, to clinically characterize myoclonus and to look for additional findings on examination in order to limit the list of possible investigations. With regards to the history, the age of onset, the character of myoclonus, precipitating or alleviating factors, family history and associated symptoms and signs are important. On examination, it is important to see whether the myoclonus appears at rest, on keeping posture or during action, to note the distribution of jerks and to look for the stimulus sensitivity. Electrophysiological tests are very helpful in determining whether myoclonus is cortical, subcortical or spinal. A single pharmacological agent rarely control myoclonus and therefore polytherapy with a combination of drugs, often in large dosages, is usually needed. Generally, antiepileptic drugs such as valproate, levetiracetam and piracetam are effective in cortical myoclonus, but less effective in other forms of myoclonus. Clonazepam may be helpful with all types of myoclonus. Focal and segmental myoclonus, irrespective of its origin, may be treated with botulinum toxin injections, with variable success

Sex differences in Parkinson's disease: A transcranial magnetic stimulation study

Background Demographic and clinical studies imply that female sex may be protective for PD, but pathophysiological evidence to support these observations is missing. In early PD, functional changes may be detected in primary motor cortex using transcranial magnetic stimulation. Objective We hypothesised that if pathophysiology differs between sexes in PD, this will be reflected in differences of motor cortex measurements. Methods Forty‐one newly diagnosed PD patients (22 males, 19 females) were clinically assessed using MDS‐UPDRS part III, and various measures of cortical excitability and sensorimotor cortex plasticity were measured over both hemispheres, corresponding to the less and more affected side, using transcranial magnetic stimulation. Twenty‐three healthy (10 men, 13 women) participants were studied for comparison. Results Among patients, no significant differences between sexes were found in age, age of diagnosis, symptom duration, and total or lateralized motor score. However, male patients had disturbed interhemispheric balance of motor thresholds, caused by decreased resting and active motor thresholds in the more affected hemisphere. Short interval intracortical inhibition was more effective in female compared to male patients in both hemispheres. Female patients had a preserved physiological focal response to sensorimotor plasticity protocol, whereas male patients showed an abnormal spread of the protocol effect. Conclusion The study provides one of the first neurophysiological evidences of sex differences in early PD. Female patients have a more favorable profile of transcranial magnetic stimulation measures, possibly reflecting a more successful cortical compensation or delayed maladaptive changes in the sensorimotor cortex. © 2019 International Parkinson and Movement Disorder Societ

The syndrome of deafness-dystonia: Clinical and genetic heterogeneity

The syndrome of deafness-dystonia is rare and refers to the association of hearing impairment and dystonia when these are dominant features of a disease. Known genetic causes include Mohr-Tranebjaerg syndrome, Woodhouse-Sakati syndrome, and mitochondrial disorders, but the cause frequently remains unidentified. The aim of the current study was to better characterize etiological and clinical aspects of deafness-dystonia syndrome. We evaluated 20 patients with deafness-dystonia syndrome who were seen during the period between 1994 and 2011. The cause was identified in only 7 patients and included methylmalonic aciduria, meningoencephalitis, perinatal hypoxic-ischemic injury, large genomic deletion on chromosome 7q21, translocase of inner mitochondrial membrane 8 homolog A (TIMM8A) mutation (Mohr-Tranebjaerg syndrome), and chromosome 2 open reading frame 37 (C2orf37) mutation (Woodhouse-Sakati syndrome). The age of onset and clinical characteristics in these patients varied, depending on the etiology. In 13 patients, the cause remained unexplained despite extensive work-up. In the group of patients who had unknown etiology, a family history for deafness and/or dystonia was present the majority of patients, suggesting a strong genetic component. Sensory-neural deafness always preceded dystonia. Two clinical patterns of deafness-dystonia syndrome were observed: patients who had an onset in childhood had generalized dystonia (10 of 13 patients) with frequent bulbar involvement, whereas patients who had a dystonia onset in adulthood had segmental dystonia (3 of 13 patients) with the invariable presence of laryngeal dystonia. Deafness-dystonia syndrome is etiologically and clinically heterogeneous, and most patients have an unknown cause. The different age at onset and variable family history suggest a heterogeneous genetic background, possibly including currently unidentified genetic conditions. (c) 2013 Movement Disorder Societ