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

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


Background: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Keywords: Essential tremor; kurtosis; structural connectivity; thalamo-cortical; thalamus; tractography.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cerebellum / diagnostic imaging*
  • Deep Brain Stimulation
  • Diffusion Tensor Imaging
  • Essential Tremor / diagnostic imaging*
  • Essential Tremor / therapy
  • Female
  • Humans
  • Male
  • Motor Cortex / diagnostic imaging*
  • Nerve Net / diagnostic imaging*
  • Ventral Thalamic Nuclei / diagnostic imaging*