Differences in Olivo-Cerebellar Circuit and Cerebellar Network Connectivity in Essential Tremor: a Resting State fMRI Study.

The olivo-cerebellar circuit is thought to play a crucial role in the pathophysiology of essential tremor (ET). Whether olivo-cerebellar circuit dysfunction is also present at rest, in the absence of clinical tremor and linked voluntary movement, remains unclear. Assessing this network in detail with fMRI is challenging, considering the brainstem is close to major arteries and pulsatile cerebrospinal fluid-filled spaces obscuring signals of interest. Here, we used methods tailored to the analysis of infratentorial structures. We hypothesize that the olivo-cerebellar circuit shows altered intra-network connectivity at rest and decreased functional coupling with other parts of the motor network in ET. In 17 ET patients and 19 healthy controls, we investigated using resting state fMRI intracerebellar functional and effective connectivity on a dedicated cerebellar atlas. With independent component analysis, we investigated data-driven cerebellar motor network activations during rest. Finally, whole-brain connectivity of cerebellar motor structures was investigated using identified components. In ET, olivo-cerebellar pathways show decreased functional connectivity compared with healthy controls. Effective connectivity analysis showed an increased inhibitory influence of the dentate nucleus towards the inferior olive. Cerebellar independent component analyses showed motor resting state networks are less strongly connected to the cerebral cortex compared to controls. Our results indicate the olivo-cerebellar circuit to be affected at rest. Also, the cerebellum is "disconnected" from the rest of the motor network. Aberrant activity, generated within the olivo-cerebellar circuit could, during action, spread towards other parts of the motor circuit and potentially underlie the characteristic tremor of this patient group.

Distinct cortical activity patterns in Parkinson's disease and essential tremor during a bimanual tapping task.

BACKGROUND: Parkinson's disease (PD) and essential tremor (ET) are neurodegenerative diseases characterized by movement deficits. Especially in PD, maintaining cyclic movement can be significantly disturbed due to pathological changes in the basal ganglia and the cerebellum. Providing external cues improves timing of these movements in PD and also affects ET. The aim of this study is to determine differences in cortical activation patterns in PD and ET patients during externally and internally cued movements. METHODS: Eleven PD patients, twelve ET patients, OFF tremor suppressing medication, and nineteen age-matched healthy controls (HC) were included and asked to perform a bimanual tapping task at two predefined cue frequencies. The auditory cue, a metronome sound presented at 2 or 4 Hz, was alternately switched on and off every 30 s. Tapping at two different frequencies were used since it is expected that different brain networks are involved at different frequencies as has been shown in previous studies. Cortical activity was recorded using a 64-channel EEG cap. To establish the cortical activation pattern in each group, the task related power (TRP) was calculated for each subject. For inter-groups analysis, EEG electrodes for divided into 5 different areas. RESULTS: Inter-group analysis revealed significant differences in areas responsible for motor planning, organization and regulation and involved in initiation, maintenance, coordination and planning of complex sequences of movements. Within the area of the primary motor cortex the ET group showed a significantly lower TRP than the HC group. In the area responsible for combining somatosensory, auditory and visual information both patient groups had a higher TRP than the HC group. CONCLUSIONS: Different neurological networks are involved during cued and non-cued movements in ET, PD and HC. Distinct cortical activation patterns were revealed using task related power calculations. Different activation patterns were revealed during the 2 and 4 Hz tapping task indicating different strategies to execute movements at these rates. The results suggest that a including a cued/non-cued tapping task during clinical decision making could be a valuable tool in an objective diagnostic protocol.

A Power Spectral Density-Based Method to Detect Tremor and Tremor Intermittency in Movement Disorders.

There is no objective gold standard to detect tremors. This concerns not only the choice of the algorithm and sensors, but methods are often designed to detect tremors in one specific group of patients during the performance of a specific task. Therefore, the aim of this study is twofold. First, an objective quantitative method to detect tremor windows (TWs) in accelerometer and electromyography recordings is introduced. Second, the tremor stability index (TSI) is determined to indicate the advantage of detecting TWs prior to analysis. Ten Parkinson's disease (PD) patients, ten essential tremor (ET) patients, and ten healthy controls (HC) performed a resting, postural and movement task. Data was split into 3-s windows, and the power spectral density was calculated for each window. The relative power around the peak frequency with respect to the power in the tremor band was used to classify the windows as either tremor or non-tremor. The method yielded a specificity of 96.45%, sensitivity of 84.84%, and accuracy of 90.80% of tremor detection. During tremors, significant differences were found between groups in all three parameters. The results suggest that the introduced method could be used to determine under which conditions and to which extent undiagnosed patients exhibit tremors.

Deficits in tapping accuracy and variability in tremor patients.

BACKGROUND: The basal ganglia and cerebellum are brain structures involved in movement initiation, execution and termination. They are thought to be involved in the tremor generation and movement deficits in Parkinson's disease (PD) and essential tremor (ET). Especially in PD, maintaining cyclic movement, such as walking or tapping can be significantly disturbed. Providing external cues improves timing of these movements in PD but its effect on ET has not yet been studied in depth. The aim of this study is to evaluate the usefulness of a bimanual tapping task as a tool during clinical decision making. METHOD: Hand movements and tremor was recorded using accelerometers and EMG (m. extensor carpi ulnaris) from PD and ET patients and healthy controls during a bimanual tapping task as a way to distinguish PD from ET. All subjects performed the tapping task at two different frequencies, 2 Hz and 4 Hz, with and without the presence of auditory cues. RESULTS: No significant intra-group differences were found in the patient groups. Acceleration data revealed significantly less accurate tapping and more variable tapping in PD than in ET and healthy controls. ET subjects tapped less accurate and with a greater variability than healthy controls during the 4 Hz tapping task. Most interestingly the tapping accuracy improved in PD patients when kinetic tremor was recorded with EMG during the task. CONCLUSION: Providing ET and PD patients with an external cue results in different tapping performances between patient groups and healthy controls. Furthermore, the findings suggest that kinetic tremor in PD enables patients to perform the task with a greater accuracy. So far this has not been shown in other studies.

Intermittent cortical involvement in the preservation of tremor in essential tremor.

Cortical involvement in essential tremor, an involuntary action tremor supposedly of subcortical origin, is uncertain. Conflicting results of corticomuscular coherence studies in essential tremor suggest an intermittent corticomuscular coupling. On the basis of the literature, we hypothesized that corticomuscular coupling is influenced by bilateral motor synchronization and "cognitive states" such as awareness of tremor. In the present study, we investigated 1) the existence of intermittent corticomuscular coherence (CMC) in essential tremor and 2) factors that influence CMC strength. In 18 essential tremor patients and 18 healthy controls, who mimicked tremor, we simultaneously recorded 64-channel EEG and 6-channel bipolar surface EMG from right and left wrist extensors and flexors. Right-sided (mimicked) hand tremor was recorded with and without a cognitive arithmetic task and with left-sided (mimicked) hand tremor. CMC values per task were compared within and between groups. Changes in CMC strength during tasks were calculated. Our main findings are 1) significant CMC around the (mimicked) tremor frequency across all tasks in both groups; 2) significant differences in CMC between unilateral tasks, with the highest values during the cognitive task only in the essential tremor group; and 3) significant fluctuations of CMC strength over time, independent of the tremor intensity, only in the essential tremor group. Our results suggest a limited role, and certainly not a continuous steering role, of sensorimotor cortical neurons in the generation of tremor. In clinical practice, these findings might help to standardize tremor registration and the interpretation of the analysis.NEW & NOTEWORTHY The part of the motor cortex involved in essential tremor is uncertain. The current electrophysiological study is the first to assess corticomuscular coherence systematically. The study shows a dynamic nature of corticomuscular coherence and a possible influence of cognitive states. The results elucidate the involvement of the motor cortex in tremor and help interpret the varying results in the literature. In clinical practice, the findings may guide in standardizing tremor registration and its interpretation.

Stiffness Feedback for Myoelectric Forearm Prostheses Using Vibrotactile Stimulation.

The ability to distinguish object stiffness is a very important aspect in object handling, but completely lacking in current myoelectric prostheses. In human hands both tactile and proprioceptive sensory information are required for stiffness determination. Therefore, it was investigated whether it is possible to distinguish object stiffness with vibrotactile feedback of hand opening and grasping force. Three configurations consisting of an array of coin motors and a single miniature vibrotactile transducer were investigated. Ten healthy subjects and seven subjects with upper limb loss due to amputation or congenital defects performed virtual grasping tasks, in which they controlled hand opening and grasping force. They were asked to determine the stiffness of a grasped virtual object from four options. With hand opening feedback alone or in combination with grasping force feedback, correct stiffness determination was achieved in around 60% of the cases and significantly higher than the 25% achieved without feedback or grasping force feedback alone. Despite the equal performance results, the combination of hand opening and grasping force feedback was preferred by the subjects over the hand opening feedback alone. No differences between feedback configurations and between subjects with upper limb loss and healthy subjects were found.