Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model

Shirley Sharabi, Dianne Daniels, David Last, David Guez, Zion Zivli, David Castel, Yoav Levy, Alexander Volovick, Javier Grinfeld, Itay Rachmilevich, Talia Amar, Yael Mardor, Sagi Harnof

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Essential tremor (ET) is one of the most common movement disorders of adults, characterized by postural and kinetic tremor. With drug treatment only partially efficient, new treatments are being developed. Objectives: The goal of this study was to demonstrate the feasibility of non-thermal focused-ultrasound (FUS) to induce tremor-suppression in an ET rat model. Methods: Harmaline-induced tremor rats were treated with FUS along the inferior olivary (IO) system. EMG was recorded continuously during treatment in order to quantify FUS-induced tremor suppression. T2-weighted MRI was performed immediately following treatment and periodically thereafter. Results: FUS treatment at an intensity of 27.2 W/cm 2 (Isppa) induced significant reduction of tremor in 12 out of 13 ET rats. Tremor frequency was reduced from 6.2 ± 2.8 to 2 ± 1 Hz, p < 0.0003. In 6 of the 12 responding rats, tremor was completely suppressed. Response duration was 70 ± 61s, on average. FUS induced motor response, depicted as movement of the tail and/or the limbs synchronized with the FUS sonication, was also demonstrated both in ET rats and in naïve rats when treated in the medulla oblongata region. Conclusions: These results demonstrate the feasibly for obtaining significant tremor reduction or tremor suppression induced by non-thermal, non-invasive, reversible focused-ultrasound.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalBrain Stimulation
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Essential Tremor
Tremor
Harmaline
Medulla Oblongata
Sonication
Movement Disorders
Tail
Extremities

Keywords

  • ET
  • Essential tremor
  • Essential tremor
  • FUS
  • Focused ultrasound
  • Focused ultrasound
  • Harmaline
  • ION
  • Inferior olivary nuclei
  • Intensity spatial peak pulse average
  • Isppa
  • Neuromodulation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biophysics
  • Clinical Neurology

Cite this

Sharabi, S., Daniels, D., Last, D., Guez, D., Zivli, Z., Castel, D., ... Harnof, S. (2019). Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model. Brain Stimulation, 12(1), 1-8. https://doi.org/10.1016/j.brs.2018.08.014

Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model. / Sharabi, Shirley; Daniels, Dianne; Last, David; Guez, David; Zivli, Zion; Castel, David; Levy, Yoav; Volovick, Alexander; Grinfeld, Javier; Rachmilevich, Itay; Amar, Talia; Mardor, Yael; Harnof, Sagi.

In: Brain Stimulation, Vol. 12, No. 1, 01.01.2019, p. 1-8.

Research output: Contribution to journalArticle

Sharabi, S, Daniels, D, Last, D, Guez, D, Zivli, Z, Castel, D, Levy, Y, Volovick, A, Grinfeld, J, Rachmilevich, I, Amar, T, Mardor, Y & Harnof, S 2019, 'Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model', Brain Stimulation, vol. 12, no. 1, pp. 1-8. https://doi.org/10.1016/j.brs.2018.08.014
Sharabi, Shirley ; Daniels, Dianne ; Last, David ; Guez, David ; Zivli, Zion ; Castel, David ; Levy, Yoav ; Volovick, Alexander ; Grinfeld, Javier ; Rachmilevich, Itay ; Amar, Talia ; Mardor, Yael ; Harnof, Sagi. / Non-thermal focused ultrasound induced reversible reduction of essential tremor in a rat model. In: Brain Stimulation. 2019 ; Vol. 12, No. 1. pp. 1-8.
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AU - Castel, David

AU - Levy, Yoav

AU - Volovick, Alexander

AU - Grinfeld, Javier

AU - Rachmilevich, Itay

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N2 - Background: Essential tremor (ET) is one of the most common movement disorders of adults, characterized by postural and kinetic tremor. With drug treatment only partially efficient, new treatments are being developed. Objectives: The goal of this study was to demonstrate the feasibility of non-thermal focused-ultrasound (FUS) to induce tremor-suppression in an ET rat model. Methods: Harmaline-induced tremor rats were treated with FUS along the inferior olivary (IO) system. EMG was recorded continuously during treatment in order to quantify FUS-induced tremor suppression. T2-weighted MRI was performed immediately following treatment and periodically thereafter. Results: FUS treatment at an intensity of 27.2 W/cm 2 (Isppa) induced significant reduction of tremor in 12 out of 13 ET rats. Tremor frequency was reduced from 6.2 ± 2.8 to 2 ± 1 Hz, p < 0.0003. In 6 of the 12 responding rats, tremor was completely suppressed. Response duration was 70 ± 61s, on average. FUS induced motor response, depicted as movement of the tail and/or the limbs synchronized with the FUS sonication, was also demonstrated both in ET rats and in naïve rats when treated in the medulla oblongata region. Conclusions: These results demonstrate the feasibly for obtaining significant tremor reduction or tremor suppression induced by non-thermal, non-invasive, reversible focused-ultrasound.

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