title: Impaired Motor Learning in a Disorder of the Inferior Olive: Is the Cerebellum Confused?
abstract: An attractive hypothesis about how the brain learns to keep its motor commands accurate is centered on the idea that the cerebellar cortex associates error signals carried by climbing fibers with simultaneous activity in parallel fibers. Motor learning can be impaired if the error signals are not transmitted, are incorrect, or are misinterpreted by the cerebellar cortex. Learning might also be impaired if the brain is overwhelmed with a sustained barrage of meaningless information unrelated to simultaneously appearing error signals about incorrect performance. We test this concept in subjects with syndrome of oculopalatal tremor (OPT), a rare disease with spontaneous, irregular, roughly pendular oscillations of the eyes thought to reflect an abnormal, synchronous, spontaneous discharge to the cerebellum from the degenerating neurons in the inferior olive. We examined motor learning during a short-term, saccade adaptation paradigm in patients with OPT and found a unique pattern of disturbed adaptation, quite different from the abnormal adaption when the cerebellum is involved directly. Both fast (seconds) and slow (minutes) timescales of learning were impaired. We suggest that the spontaneous, continuous, synchronous output from the inferior olive prevents the cerebellum from receiving the error signals it needs for appropriate motor learning. The important message from this study is that impaired motor adaptation and resultant dysmetria is not the exclusive feature of cerebellar disorders, but it also highlights disorders of the inferior olive and its connections to the cerebellum.
authors.affiliation: Department of Neurology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44110, USA. aasefshaikh@gmail.com.|Neurology Service, Daroff-DelOsso Ocular Motility Laboratory, Louis Stoke Cleveland VA Medical Center, Cleveland, OH, USA. aasefshaikh@gmail.com.
authors.forename: Aasef G
authors.initials: AG
authors.lastname: Shaikh
authors.affiliation: Department of Neurology, The Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Wong
authors.affiliation: Laboratory of Sensorimotor Research, National Eye Institute, NIH, DHHS, Bethesda, MD, USA.
authors.forename: Lance M
authors.initials: LM
authors.lastname: Optican
authors.affiliation: Department of Neurology, The Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Zee
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000328:Adult; D000368:Aged; D053483:Eye Movement Measurements; D005260:Female; D006801:Humans; D007858:Learning / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009207:Myoclonus / Q000503:physiopathology* / Q000523:psychology; D009483:Neuropsychological Tests; D009847:Olivary Nucleus / Q000503:physiopathology*; D012438:Saccades / Q000502:physiology*; D014202:Tremor / Q000503:physiopathology* / Q000523:psychology
keywords: Cerebellum; Dysmetria; Inferior olive; Nystagmus; Oscillations; Saccade