Effects of cerebellar disease on sequences of rapid eye movements

Abstract

Summary Studying saccades can illuminate the more complex decision-making processes required for everyday movements. The double-step task, in which a target jumps to two successive locations before the subject has time to react, has proven a powerful research tool to investigate the brain’s ability to program sequential responses. We asked how patients with a range of cerebellar disorders responded to the double-step task, specifically, whether the initial saccadic response made to a target is affected by the appearance of a second target jump. We also sought to determine whether cerebellar patients were able to make corrective saccades towards the remembered second target location, if it were turned off soon after presentation. We tested saccades to randomly interleaved single- and double-step target jumps to eight locations on a circle. Patient’s initial responses to double-step stimuli showed 50% more error than saccades to single target jumps, and often, they failed to make a saccade to the first target jump. The presence of a second target jump had similar, but smaller effects in control subjects (error increased by 18%). During memory-guided double-step trials, both patients and controls made corrective saccades in darkness to the remembered location of the second jump. We conclude that in cerebellar patients, the second target jump interferes with programming of the saccade to the first target jump of a double-step stimulus; this defect highlights patients’ impaired ability to respond appropriately to sudden, conflicting changes in their environment. Conversely, since cerebellar patients can make corrective memory-guided saccades in darkness, they retain the ability to remember spatial locations, possibly due to non-retinal neural signals (corollary discharge) from cerebral hemispheric areas concerned with spatial localization.

Implications of Lateral Cerebellum in Proactive Control of Saccades

“…Inactivation did not alter saccade velocity, acceleration, and duration, or the coefficient of variation of latencies in any condition, except for contraversive anti-saccade deceleration (paired t test, p ϭ 0.04; Table 1). These results suggest that inactivation of the dentate nucleus in our experiments did not alter neuronal activity in the oculomotor-related regions in the interposed and the fastigial nuclei that directly control saccade dynamics (Robinson and Fuchs, 2001;Iwamoto and Kaku, 2010).…”

“…Cerebellar Crus I and II constitute a large portion of the primate cerebellar hemispheres, and send outputs to the ventral part of the dentate nucleus, which in turn transmits signals to the frontal and parietal cortices via the thalamus (for review, see Ramnani, 2006;Strick et al, 2009;Prevosto et al, 2010;Lu et al, 2012). This portion of the cerebellum appears to be involved in higher-order cognitive functions, such as executive function and motor planning, rather than the on-line adjustment of movement parameters (Leiner et al, 1986;Ito, 2002;Bellebaum et al, 2012;Stoodley et al, 2012). In this study, we found many saccade-related neurons in the ventral posterior portion of the dentate nucleus that might transmit signals from the lateral cerebellum to the medial and lateral prefrontal cortex.…”

“…In contrast to reactive control that is triggered externally, proactive control relies on internal decision in anticipation of future events that require a variety of processes such as response selection, motor preparation, and the maintenance of the behavioral goal (Braver, 2012). One such strategy is to globally suppress any reactive response to reduce inappropriate impulsive choice ( and that global and specific inhibition might be regulated by different basal ganglia pathways (for review, see Aron, 2011;Jahanshahi et al, 2015;Yoshida and Tanaka, 2016). Because response inhibition also requires an intact cerebellum (Brunamonti et al, 2014), the increased error rate and reduced anti-saccade latency during inactivation of the dentate nucleus might result from the impairment of proactive control.…”

“…In particular, many previous studies show that the floccular complex and the vermal lobules (V-VII and IX-X) of the cerebellar cortex regulate signals in the brainstem, playing an essential role in the adaptive control of eye movements (for review, see Nagao, 2004;Shadmehr and Krakauer, 2008;Lisberger, 2009;Iwamoto and Kaku, 2010;Kheradmand and Zee, 2011). However, how the lateral hemisphere of the cerebellar cortex is involved in eye movements remains largely unknown.…”

Critical role of cerebellar fastigial nucleus in programming sequences of saccades

“…In a prior study, 1 we showed that in response to the rapid presentation of a sequence of two visual stimuli (double‐step paradigm), cerebellar patients showed greater inaccuracy of their first saccade compared with saccades made to single target jumps. Moreover, cerebellar patients often failed to make a saccade to the first target jump.…”