Neural signals regulating motor synchronization in the primate deep cerebellar nuclei.

Movements synchronized with external rhythms are ubiquitous in our daily lives. Despite the involvement of the cerebellum, the underlying mechanism remains unclear. In monkeys performing synchronized saccades to periodically alternating visual stimuli, we found that neuronal activity in the cerebellar dentate nucleus correlated with the timing of the next saccade and the current temporal error. One-third of the neurons were active regardless of saccade direction and showed greater activity for synchronized than for reactive saccades. During the transition from reactive to predictive saccades in each trial, the activity of these neurons coincided with target onset, representing an internal model of rhythmic structure rather than a specific motor command. The behavioural changes induced by electrical stimulation were explained by activating different groups of neurons at various strengths, suggesting that the lateral cerebellum contains multiple functional modules for the acquisition of internal rhythms, predictive motor control, and error detection during synchronized movements.

Spontaneous grouping of saccade timing in the presence of task-irrelevant objects.

Sequential movements are often grouped into several chunks, as evidenced by the modulation of the timing of each elemental movement. Even during synchronized tapping with a metronome, we sometimes feel subjective accent for every few taps. To examine whether motor segmentation emerges during synchronized movements, we trained monkeys to generate a series of predictive saccades synchronized with visual stimuli which sequentially appeared for a fixed interval (400 or 600 ms) at six circularly arranged landmark locations. We found two types of motor segmentations that featured periodic modulation of saccade timing. First, the intersaccadic interval (ISI) depended on the target location and saccade direction, indicating that particular combinations of saccades were integrated into motor chunks. Second, when a task-irrelevant rectangular contour surrounding three landmarks ("inducer") was presented, the ISI significantly modulated depending on the relative target location to the inducer. All patterns of individual differences seen in monkeys were also observed in humans. Importantly, the effects of the inducer greatly decreased or disappeared when the animals were trained to generate only reactive saccades (latency >100 ms), indicating that the motor segmentation may depend on the internal rhythms. Thus, our results demonstrate two types of motor segmentation during synchronized movements: one is related to the hierarchical organization of sequential movements and the other is related to the spontaneous grouping of rhythmic events. This experimental paradigm can be used to investigate the underlying neural mechanism of temporal grouping during rhythm production.

Roles of the Cerebellum in Motor Preparation and Prediction of Timing.

The cerebellum is thought to have a variety of functions because it developed with the evolution of the cerebrum and connects with different areas in the frontoparietal cortices. Like neurons in the cerebral cortex, those in the cerebellum also exhibit strong activity during planning in addition to the execution of movements. However, their specific roles remain elusive. In this article, we review recent findings focusing on preparatory activities found in the primate deep cerebellar nuclei during tasks requiring deliberate motor control and temporal prediction. Neurons in the cerebellum are active during anti-saccade preparation and their inactivation impairs proactive inhibitory control for saccades. Experiments using a self-timing task show that there are mechanisms for tracking elapsed time and regulating trial-by-trial variation in timing, and that the cerebellum is involved in the latter. When predicting the timing of periodic events, the cerebellum provides more accurate temporal information than the striatum. During a recently developed synchronized eye movement task, cerebellar nuclear neurons exhibited periodic preparatory activity for predictive synchronization. In all cases, the cerebellum generated preparatory activity lasting for several hundred milliseconds. These signals may regulate neuronal activity in the cerebral cortex that adjusts movement timing and predicts the timing of rhythmic events.

Spatial and temporal adaptation of predictive saccades based on motion inference.

Moving objects are often occluded behind larger, stationary objects, but we can easily predict when and where they reappear. Here, we show that the prediction of object reappearance is subject to adaptive learning. When monkeys generated predictive saccades to the location of target reappearance, systematic changes in the location or timing of target reappearance independently altered the endpoint or latency of the saccades. Furthermore, spatial adaptation of predictive saccades did not alter visually triggered reactive saccades, whereas adaptation of reactive saccades altered the metrics of predictive saccades. Our results suggest that the extrapolation of motion trajectory may be subject to spatial and temporal recalibration mechanisms located upstream from the site of reactive saccade adaptation. Repetitive exposure of visual error for saccades induces qualitatively different adaptation, which might be attributable to different regions in the cerebellum that regulate learning of trajectory prediction and saccades.

Temporal Generalization of Synchronized Saccades Beyond the Trained Range in Monkeys.

Synchronized movements with external periodic rhythms, such as dancing to a beat, are commonly observed in daily life. Although it has been well established that some vocal learning species (including parrots and humans) spontaneously develop this ability, it has only recently been shown that monkeys are also capable of predictive and tempo-flexible synchronization to periodic stimuli. In our previous study, monkeys were trained to make predictive saccades for alternately presented visual stimuli at fixed stimulus onset asynchronies (SOAs) to obtain a liquid reward. The monkeys generalized predictive synchronization to novel SOAs in the middle of trained range, suggesting a capacity for tempo-flexible synchronization. However, it is possible that when encountering a novel tempo, the monkeys might sample learned saccade sequences from those for the short and long SOAs so that the mean saccade interval matched the untrained SOA. To eliminate this possibility, in the current study we tested monkeys on novel SOAs outside the trained range. Animals were trained to generate synchronized eye movements for 600 and 900-ms SOAs for a few weeks, and then were tested for longer SOAs. The accuracy and precision of predictive saccades for one untrained SOA (1200 ms) were comparable to those for the trained conditions. On the other hand, the variance of predictive saccade latency and the proportion of reactive saccades increased significantly in the longer SOA conditions (1800 and 2400 ms), indicating that temporal prediction of periodic stimuli was difficult in this range, similar to previous results on synchronized tapping in humans. Our results suggest that monkeys might share similar synchronization mechanisms with humans, which can be subject to physiological examination in future studies.

[Neural Mechanisms of Temporal Monitoring and Prediction].

When waiting for a traffic light or dancing to a musical beat, we unconsciously keep track of elapsed time and precisely predict the timing of forthcoming sensory events. Temporal monitoring and prediction are integral to our daily life, and are regulated by neuronal processes through multiple global networks involving the frontoparietal cortices, the basal ganglia and the cerebellum. These processes are also known to be influenced by a variety of internal state and neuromodulators. Here, we review recent advance of research in the field.

Predictive and tempo-flexible synchronization to a visual metronome in monkeys.

Predictive and tempo-flexible synchronization to an auditory beat is a fundamental component of human music. To date, only certain vocal learning species show this behaviour spontaneously. Prior research training macaques (vocal non-learners) to tap to an auditory or visual metronome found their movements to be largely reactive, not predictive. Does this reflect the lack of capacity for predictive synchronization in monkeys, or lack of motivation to exhibit this behaviour? To discriminate these possibilities, we trained monkeys to make synchronized eye movements to a visual metronome. We found that monkeys could generate predictive saccades synchronized to periodic visual stimuli when an immediate reward was given for every predictive movement. This behaviour generalized to novel tempi, and the monkeys could maintain the tempo internally. Furthermore, monkeys could flexibly switch from predictive to reactive saccades when a reward was given for each reactive response. In contrast, when humans were asked to make a sequence of reactive saccades to a visual metronome, they often unintentionally generated predictive movements. These results suggest that even vocal non-learners may have the capacity for predictive and tempo-flexible synchronization to a beat, but that only certain vocal learning species are intrinsically motivated to do it.

Object-based spatial attention when objects have sufficient depth cues.

Attention directed to a part of an object tends to obligatorily spread over all of the spatial regions that belong to the object, which may be critical for rapid object-recognition in cluttered visual scenes. Previous studies have generally used simple rectangles as objects and have shown that attention spreading is reflected by amplitude modulation in the posterior N1 component (150-200 ms poststimulus) of event-related potentials, while other interpretations (i.e., rectangular holes) may arise implicitly in early visual processing stages. By using modified Kanizsa-type stimuli that provided less ambiguity of depth ordering, the present study examined early event-related potential spatial-attention effects for connected and separated objects, both of which were perceived in front of (Experiment 1) and in back of (Experiment 2) the surroundings. Typical P1 (100-140 ms) and N1 (150-220 ms) attention effects of ERP in response to unilateral probes were observed in both experiments. Importantly, the P1 attention effect was decreased for connected objects compared to separated objects only in Experiment 1, and the typical object-based modulations of N1 were not observed in either experiment. These results suggest that spatial attention spreads over a figural object at earlier stages of processing than previously indicated, in three-dimensional visual scenes with multiple depth cues.

Emergence of visual objects involves multiple stages of spatial selection.

Attention may select objects or perceptual groups as fundamental units. Previous studies with event-related potentials (ERPs) have found that obligatory attention-spreading over spatial regions within stable objects is associated with intermediate feedforward visual processing, as reflected by the posterior N1 component of the ERP at a latency of 140-180 ms. The present study examined object-based spatial attention effects in response to individual objects, by recording lateralized ERP attention effects over the posterior scalp (i.e., contralateral versus ipsilateral to the attended visual fields). The stumuli were bilateral unfilled line objects with minimal figural enhancement, and their connectedness and the difficulty of the perceptual task were manipulated. The effects of spatial attention on successive ERP components (N1, P2, and N2) provided information on the timing of the different stages of processing that underlie the formation of perceptual objects.

[Role of connectedness in early object-based attentional selection].

It has been suggested that uniform connectedness is the most fundamental factor in forming units of attentional selection, while there are evidences that attention can select a perceptual group that consists of separate elements with similar features. The present study examined the effects of connectedness and a boundary-feature similarity on early spatial-selection processes using a sustained-focal-attention paradigm of event-related potentials (ERPs). Bilateral stimuli were manipulated to have an orthogonal combination of connectedness (C-, C+) and a similarity in boundary feature (S-, S+). ERPs were recorded from 15 participants who were instructed to pay attention to the left or the right visual field and to respond to a target shape that appeared infrequently in the attended field. The ERP attention effect in the N1 latency range (125-185 ms) was decreased for stimuli with connectedness and/or boundary-feature similarity, and the effects of the two grouping factors were independent of each other. The present result suggests that multiple grouping factors, including connectedness, operate in parallel in early processes of object-based attention-spreading.

Time course of spatial and feature selective attention for partly-occluded objects.

Attention selects objects/groups as the most fundamental units, and this may be achieved by an attention-spreading mechanism. Previous event-related potential (ERP) studies have found that attention-spreading is reflected by a decrease in the N1 spatial attention effect. The present study tested whether the electrophysiological attention effect is associated with the perception of object unity or amodal completion through the use of partly-occluded objects. ERPs were recorded in 14 participants who were required to pay attention to their left or right visual field and to press a button for a target shape in the attended field. Bilateral stimuli were presented rapidly, and were separated, connected, or connected behind an occluder. Behavioral performance in the connected and occluded conditions was worse than that in the separated condition, indicating that attention spread over perceptual object representations after amodal completion. Consistently, the late N1 spatial attention effect (180-220 ms post-stimulus) and the early phase (230-280 ms) of feature selection effects (target N2) at contralateral sites decreased, equally for the occluded and connected conditions, while the attention effect in the early N1 latency (140-180 ms) shifted most positively for the occluded condition. These results suggest that perceptual organization processes for object recognition transiently modulate spatial and feature selection processes in the visual cortex.