Visuomotor Adaptation Deficits in Patients with Essential Tremor.

Essential tremor (ET) is a progressive movement disorder whose pathophysiology is not fully understood. Current evidence supports the view that the cerebellum is critically involved in the genesis of the tremor in ET. However, it is still unknown whether cerebellar dysfunction affects not only the control of current movements but also the prediction of future movements through dynamic adaptation toward a changed environment. Here, we tested the capacity of 28 patients with ET to adapt in a visuomotor adaptation task known to depend on intact cerebellar function. We found specific impairments in that task compared to age-matched healthy controls. Adaptation to the visual perturbation was disrupted in ET patients, while de-adaptation, the phase after abrupt removal of the perturbation, developed similarly to control subjects. Baseline tremor-independent motor performance was as well similar to healthy controls, indicating that adaptation deficits in ET patients were not rooted in an inability to perform goal-directed movements. There was no association between clinical severity scores of ET and early visuomotor adaptation abilities. These results provide further evidence that the cerebellum is dysfunctional in ET.

Cross-frequency phase-amplitude coupling in repetitive movements in patients with Parkinson's disease.

Bradykinesia is a cardinal motor symptom in Parkinson's disease (PD), the pathophysiology of which is not fully understood. We analyzed the role of cross-frequency coupling of oscillatory cortical activity in motor impairment in patients with PD and healthy controls. High-density EEG signals were recorded during various motor activities and at rest. Patients performed a repetitive finger-pressing task normally, but were slower than controls during tapping. Phase-amplitude coupling (PAC) between ß (13-30 Hz) and broadband γ (50-150 Hz) was computed from individual EEG source signals in the premotor, primary motor, and primary somatosensory cortices, and the primary somatosensory complex. In all four regions, averaging the entire movement period resulted in higher PAC in patients than in controls for the resting condition and the pressing task (similar performance between groups). However, this was not the case for the tapping tasks where patients performed slower. This suggests the strength of state-related ß-γ PAC does not determine Parkinsonian bradykinesia. Examination of the dynamics of oscillatory EEG signals during motor transitions revealed a distinctive motif of PAC rise and decay around press onset. This pattern was also present at press offset and slow tapping onset, linking such idiosyncratic PAC changes to transitions between different movement states. The transition-related PAC modulation in patients was similar to controls in the pressing task but flattened during slow tapping, which related to normal and abnormal performance, respectively. These findings suggest that the dysfunctional evolution of neuronal population dynamics during movement execution is an important component of the pathophysiology of Parkinsonian bradykinesia.NEW & NOTEWORTHY Our findings using noninvasive EEG recordings provide evidence that PAC dynamics might play a role in the physiological cortical control of movement execution and may encode transitions between movement states. Results in patients with Parkinson's disease suggest that bradykinesia is related to a deficit of the dynamic regulation of PAC during movement execution rather than its absolute strength. Our findings may contribute to the development of a new concept of the pathophysiology of bradykinesia.

Spatiotemporal features of ß-γ phase-amplitude coupling in Parkinson's disease derived from scalp EEG.

Abnormal phase-amplitude coupling between ß and broadband-γ activities has been identified in recordings from the cortex or scalp of patients with Parkinson's disease. While enhanced phase-amplitude coupling has been proposed as a biomarker of Parkinson's disease, the neuronal mechanisms underlying the abnormal coupling and its relationship to motor impairments in Parkinson's disease remain unclear. To address these issues, we performed an in-depth analysis of high-density EEG recordings at rest in 19 patients with Parkinson's disease and 20 age- and sex-matched healthy control subjects. EEG signals were projected onto the individual cortical surfaces using source reconstruction techniques and separated into spatiotemporal components using independent component analysis. Compared to healthy controls, phase-amplitude coupling of Parkinson's disease patients was enhanced in dorsolateral prefrontal cortex, premotor cortex, primary motor cortex and somatosensory cortex, the difference being statistically significant in the hemisphere contralateral to the clinically more affected side. ß and γ signals involved in generating abnormal phase-amplitude coupling were not strictly phase-phase coupled, ruling out that phase-amplitude coupling merely reflects the abnormal activity of a single oscillator in a recurrent network. We found important differences for couplings between the ß and γ signals from identical components as opposed to those from different components (originating from distinct spatial locations). While both couplings were abnormally enhanced in patients, only the latter were correlated with clinical motor severity as indexed by part III of the Movement Disorder Society Unified Parkinson's Disease Rating Scale. Correlations with parkinsonian motor symptoms of such inter-component couplings were found in premotor, primary motor and somatosensory cortex, but not in dorsolateral prefrontal cortex, suggesting motor domain specificity. The topography of phase-amplitude coupling demonstrated profound differences in patients compared to controls. These findings suggest, first, that enhanced phase-amplitude coupling in Parkinson's disease patients originates from the coupling between distinct neural networks in several brain regions involved in motor control. Because these regions included the somatosensory cortex, abnormal phase-amplitude coupling is not exclusively tied to the hyperdirect tract connecting cortical regions monosynaptically with the subthalamic nucleus. Second, only the coupling between ß and γ signals from different components appears to have pathophysiological significance, suggesting that therapeutic approaches breaking the abnormal lateral coupling between neuronal circuits may be more promising than targeting phase-amplitude coupling per se.

Posttraining Alpha Transcranial Alternating Current Stimulation Impairs Motor Consolidation in Elderly People.

The retention of a new sequential motor skill relies on repeated practice and subsequent consolidation in the absence of active skill practice. While the early phase of skill acquisition remains relatively unaffected in older adults, posttraining consolidation appears to be selectively impaired by advancing age. Motor learning is associated with posttraining changes of oscillatory alpha and beta neuronal activities in the motor cortex. However, whether or not these oscillatory dynamics relate to posttraining consolidation and how they relate to the age-specific impairment of motor consolidation in older adults remains elusive. Transcranial alternating current stimulation (tACS) is a noninvasive brain stimulation technique capable of modulating such neuronal oscillations. Here, we examined whether tACS targeting M1 immediately following explicit motor sequence training is capable of modulating motor skill consolidation in older adults. In two sets of double-blind, sham-controlled experiments, tACS targeting left M1 was applied at either 10 Hz (alpha-tACS) or 20 Hz (beta-tACS) immediately after termination of a motor sequence training with the right (dominant) hand. Task performance was retested after an interval of 6 hours to assess consolidation of the training-acquired skill. EEG was recorded over left M1 to be able to detect local after-effects on oscillatory activity induced by tACS. Relative to the sham intervention, consolidation was selectively disrupted by posttraining alpha-tACS of M1, while posttraining beta-tACS of M1 had no effect on delayed retest performance compared to the sham intervention. No significant postinterventional changes of oscillatory activity in M1 were detected following alpha-tACS or beta-tACS. Our findings point to a frequency-specific interaction of tACS with posttraining motor memory processing and may suggest an inhibitory role of immediate posttraining alpha oscillations in M1 with respect to motor consolidation in healthy older adults.

Motor learning is independent of effects of subthalamic deep brain stimulation on motor execution.

Motor learning is defined as an improvement in performance through practice. The ability to learn new motor skills may be particularly challenged in patients with Parkinson's disease, in whom motor execution is impaired by the disease-defining motor symptoms such as bradykinesia. Subthalamic deep brain stimulation is an effective treatment in advanced Parkinson's disease, and its beneficial effects on Parkinsonian motor symptoms and motor execution have been widely demonstrated. Much less is known about whether deep brain stimulation directly interacts with motor learning independent of modulation of motor execution. We investigated motor sequence learning in 19 patients with Parkinson's disease treated with subthalamic deep brain stimulation and 19 age-matched controls. In a cross-over design, patients performed an initial motor sequence training session with active and inactive stimulation, respectively (experiments separated by ≥14 days). Performance was retested after 5 min and after a 6 h consolidation interval with active stimulation. Healthy controls performed a similar experiment once. We further investigated neural correlates underlying stimulation-related effects on motor learning by exploring the association of normative subthalamic deep brain stimulation functional connectivity profiles with stimulation-related differences in performance gains during training. Pausing deep brain stimulation during initial training resulted in the inhibition of performance gains that could have been indicative of learning at the behavioural level. Task performance improved significantly during training with active deep brain stimulation, but did not reach the level of learning dynamics of healthy controls. Importantly, task performance after the 6 h consolidation interval was similar across patients with Parkinson's disease independent of whether the initial training session had been performed with active or inactive deep brain stimulation. This indicates that early learning and subsequent consolidation were relatively intact despite severe impairments of motor execution during training with inactive deep brain stimulation. Normative connectivity analyses revealed plausible and significant connectivity of volumes of tissue activated by deep brain stimulation with several cortical areas. However, no specific connectivity profiles were associated with stimulation-dependent differences in learning during initial training. Our results show that motor learning in Parkinson's disease is independent of modulation of motor execution by subthalamic deep brain stimulation. This indicates an important role of the subthalamic nucleus in regulating general motor execution, whereas its role in motor learning appears negligible. Because longer-term outcomes were independent of performance gains during initial training, patients with Parkinson's disease may not need to wait for an optimal motor state to practice new motor skills.

Enhancement of motor consolidation by post-training transcranial direct current stimulation in older people.

Consolidation, by which performance increments after a training intervention are secured and sometimes generated, is reduced in elderly humans. The present study addressed the question whether transcranial direct current stimulation (tDCS) applied after motor training improves consolidation of explicit motor sequence learning in healthy older humans. In the first experiment, anodal or cathodal tDCS to the left primary motor cortex, anodal tDCS to premotor cortex, or sham tDCS was applied immediately after completion of a finger sequence learning task. Performance was retested at 8 and 22 hours after the initial training session. Whereas all groups achieved similar performance at the end of training, off-line improvements differed between groups at later retesting, depending on the type of intervention. Relative to the other 3 interventions, anodal tDCS to primary motor cortex (M1) led to performance improvements already at retesting 8 hours after initial learning and were maintained on the next day. In the second experiment, effects of the timing of post-training anodal tDCS to M1 with respect to the end of training were studied. Participants received anodal tDCS of M1 immediately or 60 or 120 minutes after training and were retested on sequence performance 8 hours post training. Only application of tDCS immediately after the end of training, but not after 1 or 2 hours, enhanced off-line consolidation. These findings suggest that anodal tDCS applied off-line immediately post training to M1 interacts specifically with early processes promoting consolidation of motor sequence learning in healthy older individuals.

The Learning Objective Catalogue for Patient Safety in Undergraduate Medical Education--A Position Statement of the Committee for Patient Safety and Error Management of the German Association for Medical Education.

BACKGROUND: Since the report "To err is human" was published by the Institute of Medicine in the year 2000, topics regarding patient safety and error management are in the focal point of interest of science and politics. Despite international attention, a structured and comprehensive medical education regarding these topics remains to be missing. GOALS: The Learning Objective Catalogue for Patient Safety described below the Committee for Patient Safety and Error Management of the German Association for Medical Education (GMA) has aimed to establish a common foundation for the structured implementation of patient safety curricula at the medical faculties in German-speaking countries. METHODS: The development the Learning Objective Catalogue resulted via the participation of 13 faculties in two committee meetings, two multi-day workshops, and additional judgments of external specialists. RESULTS: The Committee of Patient Safety and Error Management of GMA developed the present Learning Objective Catalogue for Patient Safety in Undergraduate Medical Education, structured in three chapters: Basics, Recognize Causes as Foundation for Proactive Behavior, and Approaches for Solutions. The learning objectives within the chapters are organized on three levels with a hierarchical organization of the topics. Overall, the Learning Objective Catalogue consists of 38 learning objectives. All learning objectives are referenced with the National Competency-based Catalogue of Learning Objectives for Undergraduate Medical Education. DISCUSSION: The Learning Objective Catalogue for Patient Safety in Undergraduate Medical Education is a product that was developed through collaboration of members from 13 medical faculties. In the German-speaking countries, the Learning Objective Catalogue should advance discussion regarding the topics of patient safety and error management and help develop subsequent educational structures. The Learning Objective Catalogue for Patient Safety can serve as a common ground for an intensified, constructive, subject-specific discussion about these topics at the medical faculties, and guide the implementation of hopefully multiple patient safety curricula in undergraduate medical education.