Lessons learned from the syndrome of oculopalatal tremor Mohamed Elkasaby 1 & Sinem Balta Beylergil 2,3 & Palak Gupta 2,3 & Abhimanyu Mahajan 4 & Fatema F. Ghasia 3,5 & Aasef G. Shaikh 1,2,3,6,7 Received: 4 April 2020 /Revised: 4 July 2020 /Accepted: 9 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract The syndrome of oculopalatal tremor (OPT) featuring the olivo-cerebellar hypersychrony leads to disabling pendular nystagmus and palatal myoclonus. This rare disorder provides valuable information about the motor physiology and offers insights into the mechanistic underpinning of common movement disorders. This focused review summarizes the last decade of OPT research from our laboratory and addresses three critical questions: 1) How the disease of inferior olive affects the physiology of motor learning? We discovered that our brain’s ability to compensate for the impaired motor command and implement errors to correct future movements could be affected if the cerebellum is occupied in receiving and transmitting the meaningless signal. A complete failure of OPT patients to adapt to change in rapid eye movements (saccades) provided proof of this principle. 2) Whether maladaptive olivo-cerebellar circuit offers insight into the mechanistic underpinning of the common movement disorder, dystonia, characterized by abnormal twisting and turning of the body part. We discovered that the subgroup of patients who had OPT also had dystonia affecting the neck, trunk, limbs, and face. We also found that the subjects who had tremor predominant neck dystonia (without OPT) also had impaired motor learning on a long and short timescale, just like those with OPT. Altogether, our studies focused on dystonia suggested the evidence for the maladaptive olive-cerebellar system. 3) We discovered that the OPT subjects had difficulty in perceiving the direction of their linear forward motion, i.e., heading, suggesting that olivo-cerebellar hypersynchrony also affects perception. Keywords Inferior olive . Cerebellum . Motor learning . Error signal . Dystonia . Motion perception Action and perception are two discrete but interdependent phenomena that are mastered by the human brain. In simple terms, every step that we make is associated with unique perception, and the perceptual experience is then implemented to improve future action. The action- perception interaction takes place at various levels of the neuraxis. Critical processes necessary for the accurate ac- tion include encoding the matrix of ongoing movement and correcting it when essential by perceiving our motion and coordinates in the space. Our research over the last decade examined these two questions, specifically asking whether impairments in the inferior-olive cerebellar path- way affects the tasks involving action and perception and how such abnormality is manifested. We had focused on a rare syndrome of oculopalatal tremor (OPT). This unique hyperkinetic movement disorder follows a brainstem le- sion, often a stroke, causing quasi-sinusoidal, dysconjugate, coarse oscillations of the eyes and the pal- ate. The damage leads to a breach in the continuity of the triangle that was first described by two French neurolo- gists Georges Charles Guillain (1876–1961) and Pierre Mollaret (1898–1987), hence called Guillain-Mollaret tri- angle. The triangle is comprised of the fibers that Action Editor: Jonathan David Victor * Aasef G. Shaikh aasefshaikh@gmail.com 1 Neurological Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA 2 Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA 3 Daroff-Dell’ Osso Ocular Motility and Vestibular Laboratory, Cleveland, OH, USA 4 Department of Neurology, University of Cincinnati, Cincinnati, OH, USA 5 Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA 6 Department of Neurology, Case Western Reserve University, Cleveland, OH, USA 7 Department of Neurology, University Hospitals, 11100 Euclid Avenue, Cleveland, OH 44022, USA Journal of Computational Neuroscience https://doi.org/10.1007/s10827-020-00757-2