Differences in Olivo-Cerebellar Circuit and Cerebellar Network Connectivity in Essential Tremor: a Resting State fMRI Study

Sarvi Sharifi*, Arthur W.G. Buijink, Frauke Luft, Elliz P. Scheijbeler, Wouter V. Potters, Guido van Wingen, Tjitske Heida, Lo J. Bour, Anne Fleur van Rootselaar

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

The olivo-cerebellar circuit is thought to play a crucial role in the pathophysiology of essential tremor (ET). Whether olivo-cerebellar circuit dysfunction is also present at rest, in the absence of clinical tremor and linked voluntary movement, remains unclear. Assessing this network in detail with fMRI is challenging, considering the brainstem is close to major arteries and pulsatile cerebrospinal fluid–filled spaces obscuring signals of interest. Here, we used methods tailored to the analysis of infratentorial structures. We hypothesize that the olivo-cerebellar circuit shows altered intra-network connectivity at rest and decreased functional coupling with other parts of the motor network in ET. In 17 ET patients and 19 healthy controls, we investigated using resting state fMRI intracerebellar functional and effective connectivity on a dedicated cerebellar atlas. With independent component analysis, we investigated data-driven cerebellar motor network activations during rest. Finally, whole-brain connectivity of cerebellar motor structures was investigated using identified components. In ET, olivo-cerebellar pathways show decreased functional connectivity compared with healthy controls. Effective connectivity analysis showed an increased inhibitory influence of the dentate nucleus towards the inferior olive. Cerebellar independent component analyses showed motor resting state networks are less strongly connected to the cerebral cortex compared to controls. Our results indicate the olivo-cerebellar circuit to be affected at rest. Also, the cerebellum is “disconnected” from the rest of the motor network. Aberrant activity, generated within the olivo-cerebellar circuit could, during action, spread towards other parts of the motor circuit and potentially underlie the characteristic tremor of this patient group.

Original languageEnglish
Number of pages14
JournalCerebellum
Early online date22 Oct 2022
DOIs
Publication statusPublished - 2022

Keywords

  • Cerebellum
  • Connectivity
  • Essential tremor
  • fMRI resting state
  • ICA

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