Origin Of Tremor Research Articles

Erroneous Compensation for Long-Latency Feedback Delays as Origin of Essential Tremor.

Essential tremor (ET), a movement disorder characterized by involuntary oscillations of the limbs during movement, remains to date not well understood. It has been recently suggested that the tremor originates from impaired delay compensation, affecting movement representation and online control. Here we tested this hypothesis directly with 24 ET patients (14 female; 10 male) and 28 neurologically intact (NI) human volunteers (17 female; 11 male) in an upper limb postural perturbation task. After maintaining their hand in a visual target, participants experienced perturbations of unpredictable direction and magnitude and were instructed to counter the perturbation and steer their hand back to the starting position. In comparison with NI volunteers, ET patients' early muscular responses (short and long-latency responses, 20-50 and 50-100 ms, respectively) were preserved or even slightly increased. However, they exhibited perturbation-dependent deficits when stopping and stabilizing their hand in the final target supporting the hypothesis that the tremor was generated by the feedback controller. We show in a computational model that errors in delay compensation accumulating over time produced the same small increase in initial feedback response followed by oscillations that scaled with the perturbation magnitude as observed in ET population. Our experimental results therefore validate the computational hypothesis that inaccurate delay compensation in long-latency pathways could be the origin of the tremor.

Modeling the origin of parkinsonian tremor

Even though much is known about the biophysics, anatomy and physiology of basal ganglia networks, the cellular and network basis of parkinsonian tremor remains an open question. Multiple experimental data suggest that the physiological origin of parkinsonian tremor is different from the physiological origin of other parkinsonian motor symptoms [1]. However, the exact origin of the tremor genesis in Parkinson’s disease remains unknown. A large body of experimental evidence supports the hypothesis, that the tremor arises due to pathological interaction of potentially oscillatory cells and circuits within the loop formed by basal ganglia and thalamocortical networks. We suggest a model of this circuitry, which helps to clarify this potential mechanism of tremor genesis. There seems to be consensus that tremor is centrally generated, though several different hypotheses on the central tremor generation has being suggested (reviewed in [2]). Here we consider the basal ganglia-thalamocortical loop hypothesis. There is clear evidence for involvement of the motor thalamus, the primary motor cortex, the STN and pallidum in the tremor-related activity. These structures are connected, forming a loop, and each has separate limb representations. Lesions to any of them have been shown to abolish parkinsonian tremor. Thus the possibility of such a loop being functionally significant is very plausible. Moreover, thalamic hypotheses are at odds with analysis of spike correlations within bursts of thalamic activity during parkinsonian tremor [3]. Therefore, cortico-basal gangliathalamic loop origin of parkinsonian tremor appears to be quite reasonable. We consider a conductance-based model of subthalamo-pallidal circuits (based on the models of STN and pallidal neurons, developed in [4]) embedded into a simplified representation of thalamocortical circuit to investigate the dynamics of this loop. We modulate the strength of the loop to represent the modulation of basal ganglia synapses by dopamine. A number of synaptic connections in the basal ganglia are known to be presynaptically suppressed by dopamine. Thus weaker connections in our model may correspond to healthy state or to the administration of dopaminergic medication, while stronger connections may correspond to the decreased level of dopamine in Parkinson’ sd isease. The stronger connections (“lower dopamine”) favor bursting in the tremor frequency range and this result is robust with the respect to what particular synaptic strength is changed. Similarly to this effect, when the feedback is completely removed, STN switches back to tonic or almost tonic firing. This happens for both possible locations of feedback interruption in the model – at the level of output of STN and at the level of input to pallidum and STN. However, the outcomes of these two possibilities are two different types of activity. The proposed model supports the basal ganglia – thalamocortical loop mechanism of tremor generation. Under normal conditions the behavior of this loop is not oscillatory. The dopaminergic deficit of Parkinson’s disease induces tremor-related oscillations in the loop. This suggests that thalamocortical circuits (which provide a feedback to basal ganglia) are changed in Parkinson’s disease in such a way as to promote the birth of oscillations. Surgical intervention or dopaminergic medication in parkinsonian patients can break or weaken pathological feedback so that basal ganglia circuits no longer able to produce bursting. This may be the way of how the tremor is suppressed.

Tremor.

Tremor research during the past year has focused on clinical differential diagnosis, and a new clinical classification has been developed. The origin of tremor is thought to depend on unstable central loops, and new coherence data suggest that these often involve the motor cortex. Gabapentine has been assessed for efficacy in some tremors, and deep brain stimulation of the ventrolateral thalamus has been shown to be safer and more effective for severe essential and parkinsonian tremor than thalamotomy.

Dependence of peripheral tremor on mechanical perturbations: a modeling study.

The present study scrutinizes the popular view that tremors of central origin but not those of peripheral origin are largely resistant to mechanical perturbations. We explore the effects of perturbations in a well-established model of peripheral tremor and document that (a) tremor frequency can remain unchanged when spring or weight loads are added, (b) entrainment by external drives can be limited to drives of similar frequency, and (c) resetting of tremor phase by torque pulses can remain fractional. This resistance to mechanical perturbations arises in the model because peripheral neuromuscular dynamics act as a limit-cycle oscillator which, by its very nature, will absorb moderate changes to signals and parameters. We conclude from our study that resistance to mechanical perturbations is not an exclusive property of central tremors, but rather may also be found in peripheral tremors. Other criteria are therefore needed to distinguish between different origins of tremor.