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Tremor Other Hyperkinet Mov (N Y). 2019 Sep 2;9. doi: 10.7916/tohm.v0.690. eCollection 2019.

Characterizing Thalamo-Cortical Structural Connectivity in Essential Tremor with Diffusional Kurtosis Imaging Tractography.

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Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
Department of Neuroscience, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.



Neuromodulation of the cerebello-thalamo-cortical (CTC) circuit via thalamic stimulation is an effective therapy for essential tremor (ET). In order to develop non-invasive neuromodulation approaches, clinically relevant thalamo-cortical connections must be elucidated.


Twenty-eight subjects (18 ET patients and 10 controls) underwent MRI diffusional kurtosis imaging (DKI). A deterministic fiber-tracking algorithm based on DKI was used, with a seeding region placed at the ventral intermediate nucleus (Vim-located based on intraoperative physiology) to the ending regions at the supplementary motor area (SMA), pre-SMA, or primary motor cortex. One-tailed t-tests were performed to compare groups, and associations with tremor severity were determined by Pearson correlations. All p-values were adjusted for multiple comparisons using Bonferroni correction.


There was a decrease in the mean diffusivity (MD) in patients compared to controls in all three tracts: Vim-M1 (ET 0.87, control 0.96, p < 0.01), Vim-SMA (ET 0.86, control 0.96, p < 0.05), and Vim-pre-SMA (ET 0.87, control 0.95, p < 0.05). There was a significant positive correlation between Tremor Rating Scale score and MK (r = 0.471, p = 0.033) and mean FA (r = 0.438, p = 0.045) for the Vim-SMA tract, and no significant correlation for the Vim-pre-SMA or Vim-M1 tracts was found.


Patients with ET demonstrated a reinforcement of Vim-cortical connectivity, with higher Vim-SMA connectivity being associated with greater tremor severity. This finding suggests that the Vim-SMA connection is relevant to the underlying pathophysiology of ET, and inhibition of the SMA may be an effective therapeutic approach.


Essential tremor; kurtosis; structural connectivity; thalamo-cortical; thalamus; tractography

Conflict of interest statement

Funding: This study was supported by NIH Grants 1K23NS091391-01A1, R01DC014021, RF1AG057602, R01NS097775, R01AG054159, and R01AG055132. Conflict of Interest: Jens Jensen is a co-inventor on US patents 8,811,706, 9,478,026, and 9,965,962, which are related to the MRI techniques utilized in this work; the other authors do not report any conflict of interest related to the research reported in this article. Ethics Statement: This study was reviewed by the authors’ institutional ethics committee and was considered exempted from further review.

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