Send to

Choose Destination
Tremor Other Hyperkinet Mov (N Y). 2017 Jul 13;7:473. doi: 10.7916/D8FF40RX. eCollection 2017.

The Olivary Hypothesis of Essential Tremor: Time to Lay this Model to Rest?

Louis ED1,2,3, Lenka A4,5.

Author information

Division of Movement Disorders, Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT, USA.
Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA.
Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, CT, USA.
Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences, Bangalore, India.
Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India.



Although essential tremor (ET) is the most common tremor disorder, its pathogenesis is not fully understood. The traditional model of ET, proposed in the early 1970s, posited that the inferior olivary nucleus (ION) was the prime generator of tremor in ET and that ET is a disorder of electrophysiological derangement, much like epilepsy. This article comprehensively reviews the origin and basis of this model, its merits and problems, and discusses whether it is time to lay this model to rest.


A PubMed search was performed in March 2017 to identify articles for this review.


The olivary model gains support from the recognition of neurons with pacemaker property in the ION and the harmaline-induced tremor models (as the ION is the prime target of harmaline). However, the olivary model is problematic, as neurons with pacemaker property are not specific to the ION and the harmaline model does not completely represent the human disease ET. In addition, a large number of neuroimaging studies in ET have not detected structural or functional changes in the ION; rather, abnormalities have been reported in structures related to the cerebello-thalamo-cortical network. Moreover, a post-mortem study of microscopic changes in the ION did not detect any differences between ET cases and controls.


The olivary model largely remains a physiological construct. Numerous observations have cast considerable doubt as to the validity of this model in ET. Given the limitations of the model, we conclude that it is time now to lay this model to rest.


Essential tremor; cerebellum; harmaline; inferior olive; pathogenesis

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Funding: Dr. Louis has received research support from the National Institutes of Health: NINDS #R01 NS094607 (principal investigator), NINDS #R01 NS39422 (principal investigator), NINDS #R01 NS046436 (principal investigator), NINDS #R01 NS073872 (principal investigator), NINDS #R01 NS085136 (principal investigator) and NINDS #R01 NS088257 (principal investigator). He has also received support from the Claire O’Neil Essential Tremor Research Fund (Yale University). Dr. Lenka is sponsored by the Indian Council of Medical Research (ICMR, New Delhi) for his MD-PhD (Clinical Neurosciences) fellowship at the National Institute of Mental Health and Neurosciences, Bangalore, India. Conflicts of interest: The authors report no conflict of interest. Ethics Statement: Not applicable for this category of article.

Supplemental Content

Full text links

Icon for Center for Digital Research and Scholarship, Columbia University Icon for PubMed Central
Loading ...
Support Center