Background Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus (TH) is an effective therapy for suppressing tremor. One of the critical challenges to optimizing VIM-DBS therapy is the lack of robust neural biomarkers that correlate well with tremor.

Objective We conducted intraoperative local field potential (LFP) recordings from DBS electrodes placed in the TH (including VIM and ventralis oralis posterior-VOP) to quantify biomarkers of tremor. We used computational modeling to understand the biophysical basis of the recorded LFP signal.

Methods We simultaneously recorded intraoperative TH LFP and tremor from the hand dorsum (34 participants) and during DBS at different frequencies (16 participants). Then, we simulated the effects of DBS and spatial distribution of tremor cells on calculated LFPs in a TH model.

Results There was a moderate correlation between tremor and LFP spectral power in the theta and alpha bands (r = 0.445 and 0.389, respectively). There was a strong correlation between tremor and peak coherence between LFP and tremor signal (r = 0.559). Postural tremor was decoded from the LFP signal with an area under curve of ∼0.7. High frequency DBS reduced spectral power in the theta and alpha bands and tremor could be decoded from the LFP spectral power in the presence of DBS (0.429 goodness of fit R2). The theta power in the simulated LFP signal varied substantially with the specific location of the bipolar contact pair of the DBS electrode used for the LFP recordings as well as the spatial distribution of tremor cells.

Conclusions Theta power alone was not sufficient for prediction of tremor control. Simulations indicated that the number and distribution of tremor cells surrounding the DBS lead may explain the lack of strong correlation between tremor and theta power.

HIGHLIGHTS

Recorded intraoperative thalamic LFP in patients with ET, PD, or multiple sclerosis.

Moderate correlation between tremor and spectral power in theta/alpha bands.

Strong correlation between tremor and LFP-Accelerometer coherence.

Tremor can be decoded from VIM-LFP with an AUC of 0.7.

Thalamic model indicated theta power dependent on tremor cell distribution.

K.T.M. receives consulting fees from Boston Scientific and research support from Boston Scientific, Medtronic and Surgical Information Sciences. W.M.G. receives research grant support, royalty payments and consulting fees from Boston Scientific Inc.

This work was supported by a grant from the US National Institutes of Health (R37 NS040894).

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