Activation of the Inferior Olive

Abstract

The inferior olive (IO) is a group of nuclei in the brainstem and is the sole origin of climbing fibers to the cerebellar cortex. While complete functions of the IO are unknown, it is believed to contribute to temporal processing. Functional magnetic resonance imaging (fMRI) studies have shown activation of the inferior olive by unexpected sensory stimuli. In this study, we tested the IO’s sensitivity to stimulus timing change to determine the time-change that is most efficient in activating the IO. We scanned normal human subjects while viewing sequences of visual stimuli and recognizing stimuli that deviated from isochronous stimuli by fifty to eight hundred milliseconds. The behavioral results showed that the subjects’ performance increased with timing change. The fMRI data were analyzed using event-related statistical parametric mapping of the hemodynamic responses; then we could see the activation of the inferior olive during all of the different stimulus timing changes. The 300 millisecond stimulus timing change produced the most activation of the IO, with time-changes of 200 to 600 (but not 50, 100, 700 or 800 ms) producing significant but less robust activation than 300 ms. These results were consistent with classical conditioning animal studies and indicate that reliable and robust activation of the inferior olive can be achieved in humans; they also can potentially be used to study diseases in which the IO is implicated.