CommentaryThe distributed somatotopy of tremor: A window into the motor system
Section snippets
The distributed somatotopy of tremor in the VLp
Pedrosa and colleagues investigated nine essential tremor patients and five tremor-dominant Parkinson's disease patients (Pedrosa et al., 2012). All patients were treated for disabling tremor by implantation of DBS electrodes in the VLp. This enabled peri-operative measurements of neural activity in the VLp of these patients, which the authors did at different recording depths along the electrode. By simultaneously measuring tremulous activity of two muscles (musculus extensor digitorum
Somatotopy in the healthy motor system
The presence of multiple thalamic tremor clusters reported by Pedrosa and others fits with the functional organization of the healthy motor system. That is, within the boundaries of limb-specific somatotopic areas, single muscles are represented at different locations in the motor cortex (Schieber, 2001). This representation of one muscle in different ensembles of other muscles facilitates the control of behaviorally relevant actions (Graziano, 2006). Since the motor cortex receives dense
The involvement of the cerebello-thalamo-cortical circuit in tremor
Pedrosa and colleagues measured neuro-muscular coherence in the VLp, which has strong anatomical connections to the cerebellum and primary motor cortex in the macaque (Evrard and Craig, 2008, Kultas-Ilinsky et al., 2003). The cerebello-thalamo-cortical circuit plays an important role in both essential tremor and in Parkinson's tremor. For instance, MEG and metabolic imaging (PET and fMRI) have shown increased activity in this circuit in Parkinson's disease (Helmich et al., 2011, Poston and
How does the cerebello-thalamo-cortical circuit become engaged in tremor?
Pedrosa and others showed that the cerebello-thalamo-cortical circuit becomes similarly engaged in essential tremor and in Parkinson's tremor. This is remarkable, since the pathological substrate of these two tremor disorders varies. Therefore, different mechanisms may trigger increased oscillatory activity in the cerebello-thalamo-cortical circuit.
In Parkinson's disease, the pathophysiological hallmark is dopamine depletion in the basal ganglia. Accordingly, the authors found tremor clusters
A network perspective on tremor
Traditionally, an important goal in tremor research has been to localize single oscillators driving the tremor. In the last years, experimental evidence has cast doubt on this idea, showing that many groups of neurons are only intermittently coherent with tremulous muscle activity. For example, Raethjen and colleagues have shown that cortico-muscular coherence in essential tremor was lost intermittently without observable changes in the peripheral tremor activity (Raethjen et al., 2007).
A network perspective can improve tremor therapies
Future research on tremor may focus more on network parameters, identifying the different roles of network nodes, and taking inter-regional interactions into account. A network perspective on tremor can improve existing tremor therapies. For example, a recent study in Parkinsonian primates used the known functional connectivity between pallidum and primary motor cortex to develop closed-loop DBS, where motor cortex activity is used to adaptively change stimulation parameters of pallidal DBS (
Conclusion
By reporting multiple tremor clusters in the VLp of essential tremor and Parkinson's disease patients, Pedrosa and colleagues nicely demonstrate that two different tremor pathologies share a common neural basis, both having a distributed somatotopy. This may also suggest that tremor is caused by aberrant synchronization within a pre-existing physiological network, brought about by different pathophysiological neural triggers.
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