Thalamomuscular coherence in essential tremor: hen or egg in the emergence of tremor?

Thalamomuscular coherence in essential tremor (ET) has consistently been detected in numerous neurophysiological studies. Thereby, spatial properties of coherence indicate a differentiated, somatotopic organization; so far, however, little attention has been paid to temporal aspects of this interdependency. Further insight into the relationship between tremor onset and the onset of coherence could pave the way to more efficient deep brain stimulation (DBS) algorithms for tremor. We studied 10 severely affected ET patients (six females, four males) during surgery for DBS-electrode implantation and simultaneously recorded local field potentials (LFPs) and surface electromyographic signals (EMGs) from the extensor and flexor muscles of the contralateral forearm during its elevation. The temporal relationship between the onset of significant wavelet cross spectrum (WCS) and tremor onset was determined. Moreover, we examined the influence of electrode location within one recording depth on this latency and the coincidence of coherence and tremor for depths with strong overall coherence ("tremor clusters") and those without. Data analysis revealed tremor onset occurring 220 ± 460 ms before the start of significant LFP-EMG coherence. Furthermore, we could detect an anterolateral gradient of WCS onset within one recording depth. Finally, the coincidence of tremor and coherence was significantly higher in tremor clusters. We conclude that tremor onset precedes the beginning of coherence. Besides, within one recording depth there is a spread of the tremor signal. This reflects the importance of somatosensory feedback for ET and questions the suitability of thalamomuscular coherence as a biomarker for "closed-loop" DBS systems to prevent tremor emergence.

Verbal fluency in essential tremor patients: the effects of deep brain stimulation.

OBJECTIVE: To assess the effects of different frequencies of thalamic Deep-Brain-Stimulation (DBS) on cognitive performance of patients suffering from Essential Tremor (ET). METHODS: In 17 ET-patients with thalamic-DBS, Tremor-Rating-Scale (TRS), standardized phonemic and semantic verbal fluency (VF), Stroop-Color-Word-Test and Digit-span-test were investigated in three randomized stimulation-settings: i) high-frequency stimulation (HFS), ii) low-frequency stimulation (LFS) and iii) OFF-stimulation (DBS-OFF). Paired-samples t-test for TRS and one-way repeated measures analysis of variance for cognitive performance were calculated. RESULTS: Tremor was reduced during HFS (MeanTRS-HFS = 12.9 ± 9.6) compared to DBS-OFF (MeanTRS-OFF = 44.4 ± 19.8, P < .001) and to LFS (MeanTRS-10 Hz = 50.0 ± 24.2; P < .001). While performance of Stroop-task and digit-span remained unaffected by stimulation-settings (P > .05), phonemic and semantic VF differed significantly between the three conditions (FPvf = 5.28, FSvf = 3.41, both P < .05). Post-hoc comparisons revealed significant differences for both phonemic and semantic VF between LFS (MeanPvf-10 Hz = 54.6 ± 9.2, MeanSvf-10 Hz = 56.4 ± 7.9) and HFS (MeanPvf-ON = 48.3 ± 11.4, MeanSvf-ON = 51.1 ± 11.0, both P < .05), while DBS-OFF (MeanPvf-OFF = 51.2 ± 9.3, MeanSvf-OFF = 53.6 ± 12.9) and HFS and DBS-OFF and LFS did not differ significantly (P > .05). CONCLUSIONS: HFS compared to LFS or DBS-OFF significantly reduced tremor but simultaneously worsened VF while working memory and cognitive inhibition remained unaffected. In contrast, LFS enhanced VF but did not ameliorate tremor. The data emphasize the relevance of thalamocortical loops for verbal fluency but also suggest that more sophisticated DBS-regimes in ET may improve both motor and cognitive performance.

Essential tremor and tremor in Parkinson's disease are associated with distinct 'tremor clusters' in the ventral thalamus.

Different tremor entities such as Essential Tremor (ET) or tremor in Parkinson's disease (PD) can be ameliorated by the implantation of electrodes in the ventral thalamus for Deep Brain Stimulation (DBS). The exact neural mechanisms underlying this treatment, as well as the specific pathophysiology of the tremor in both diseases to date remain elusive. Since tremor-related local field potentials (LFP) have been shown to cluster with a somatotopic representation in the subthalamic nucleus, we here investigated the neurophysiological correlates of tremor in the ventral thalamus in ET and PD using power and coherence analysis. Local field potentials (LFPs) at different recording depths and surface electromyographic signals (EMGs) from the extensor and flexor muscles of the contralateral forearm were recorded simultaneously in twelve ET and five PD patients. Data analysis revealed individual electrophysiological patterns of LFP-EMG coherence at single and double tremor frequency for each patient. Patterns observed varied in their spatial distribution within the Ventral lateral posterior nucleus of the thalamus (VLp), revealing a specific topography of 'tremor clusters' for PD and ET. The data strongly suggest that within VLp individual tremor-related electrophysiological signatures exist in ET and PD tremor.