Implications of Lateral Cerebellum in Proactive Control of Saccades

Although several lines of evidence establish the involvement of the medial and vestibular parts of the cerebellum in the adaptive control of eye movements, the role of the lateral hemisphere of the cerebellum in eye movements remains unclear. Ascending projections from the lateral cerebellum to the frontal and parietal association cortices via the thalamus are consistent with a role of these pathways in higher-order oculomotor control. In support of this, previous functional imaging studies and recent analyses in subjects with cerebellar lesions have indicated a role for the lateral cerebellum in volitional eye movements such as anti-saccades. To elucidate the underlying mechanisms, we recorded from single neurons in the dentate nucleus of the cerebellum in monkeys performing anti-saccade/pro-saccade tasks. We found that neurons in the posterior part of the dentate nucleus showed higher firing rates during the preparation of anti-saccades compared with pro-saccades. When the animals made erroneous saccades to the visual stimuli in the anti-saccade trials, the firing rate during the preparatory period decreased. Furthermore, local inactivation of the recording sites with muscimol moderately increased the proportion of error trials, while successful anti-saccades were more variable and often had shorter latency during inactivation. Thus, our results show that neuronal activity in the cerebellar dentate nucleus causally regulates anti-saccade performance. Neuronal signals from the lateral cerebellum to the frontal cortex might modulate the proactive control signals in the corticobasal ganglia circuitry that inhibit early reactive responses and possibly optimize the speed and accuracy of anti-saccades.