Motor "laziness" constrains fixation selection in real-world tasks.

Humans coordinate their eye, head, and body movements to gather information from a dynamic environment while maximizing reward and minimizing biomechanical and energetic costs. However, such natural behavior is not possible in traditional experiments employing head/body restraints and artificial, static stimuli. Therefore, it is unclear to what extent mechanisms of fixation selection discovered in lab studies, such as inhibition-of-return (IOR), influence everyday behavior. To address this gap, participants performed nine real-world tasks, including driving, visually searching for an item, and building a Lego set, while wearing a mobile eye tracker (169 recordings; 26.6 h). Surprisingly, in all tasks, participants most often returned to what they just viewed and saccade latencies were shorter preceding return than forward saccades, i.e., consistent with facilitation, rather than inhibition, of return. We hypothesize that conservation of eye and head motor effort ("laziness") contributes. Correspondingly, we observed center biases in fixation position and duration relative to the head's orientation. A model that generates scanpaths by randomly sampling these distributions reproduced all return phenomena we observed, including distinct 3-fixation sequences for forward versus return saccades. After controlling for orbital eccentricity, one task (building a Lego set) showed evidence for IOR. This, along with small discrepancies between model and data, indicates that the brain balances minimization of motor costs with maximization of rewards (e.g., accomplished by IOR and other mechanisms) and that the optimal balance varies according to task demands. Supporting this account, the orbital range of motion used in each task traded off lawfully with fixation duration.

A cerebro-cerebellar network for learning visuomotor associations.

Consensus is rapidly building to support a role for the cerebellum beyond motor function, but its contributions to non-motor learning remain poorly understood. Here, we provide behavioral, anatomical and computational evidence to demonstrate a causal role for the primate posterior lateral cerebellum in learning new visuomotor associations. Reversible inactivation of the posterior lateral cerebellum of male monkeys impeded the learning of new visuomotor associations, but had no effect on movement parameters, or on well-practiced performance of the same task. Using retrograde transneuronal transport of rabies virus, we identified a distinct cerebro-cerebellar network linking Purkinje cells in the posterior lateral cerebellum with a region of the prefrontal cortex that is critical in learning visuomotor associations. Together, these results demonstrate a causal role for the primate posterior lateral cerebellum in non-motor, reinforcement learning.

Neck muscle activity reflects neural patterns of sequential saccade planning in head-restrained primates.

Goal-directed behavior involves the transformation of neural movement plans into appropriate muscle activity patterns. Studies involving single saccades have shown that a rapid pathway links saccade planning in frontal eye fields (FEFs) to neck muscle activity. However, it is unknown if the rapid connection between FEF and neck muscle is also maintained during sequential saccade planning. Using neural recordings from FEF, and electromyographic (EMG) recordings from the dorsal neck muscles of head-restrained monkeys, we show that neural sequence planning signals are largely preserved in the neck EMG response. Like FEF movement neurons, we found that neck motor unit activity displayed an accumulation-to-threshold response before saccade onset. Responses of both neck motor units and FEF neurons displayed similar trends during saccade sequencing; multiple saccadic eye movements could be programmed in parallel, while processing bottlenecks, indexed by reduced accumulation rates, limited the extent of parallel programming. These results suggest that even without the need for overt head movements, neck muscle activity shows signatures of central gaze planning. We propose that multiple upcoming gaze plans are rapidly passed down from the FEF to the neck muscles to initiate recruitment for anticipated gaze movements. Similarities in neural and neck motor activity may enable synchronous yet controlled eye-head responses to sequential gaze shifts.NEW & NOTEWORTHY Gaze shifts, brought about by coordinated eye-head movements through the eye and neck muscle system, are a part of everyday behavior, yet the neuromuscular underpinnings of gaze sequences are unclear. Using a combination of behavioral analyses, neural recordings, and electromyographic recordings, we show that sequential saccade plans developing in neural oculomotor centers can be extracted from the neck muscle activity of head-restrained macaques. Neck motor units, thus provide a readout of central sequence planning signals.

Mixed Selectivity in the Cerebellar Purkinje-Cell Response during Visuomotor Association Learning.

Although the cerebellum has been traditionally considered to be exclusively involved in motor control, recent anatomic and clinical studies show that it also has a role in reward-processing. However, the way in which the movement-related and the reward-related neural activity interact at the level of the cerebellar cortex and contribute toward learning is still unclear. Here, we studied the simple spike activity of Purkinje cells in the mid-lateral cerebellum when 2 male monkeys learned to associate a right or left-hand movement with one of two visual symbolic cues. These cells had distinctly different discharge patterns between an overtrained symbol-hand association and a novel symbol-hand association, responding in association with the movement of both hands, although the kinematics of the movement did not change between the two conditions. The activity change was not related to the pattern of the visual symbols, the movement kinematics, the monkeys' reaction times, or the novelty of the visual symbols. The simple spike activity changed throughout the learning process, but the concurrent complex spikes did not instruct that change. Although these neurons also have reward-related activity, the reward-related and movement-related signals were independent. We suggest that this mixed selectivity may facilitate the flexible learning of difficult reinforcement learning problems.SIGNIFICANCE STATEMENT The cerebellum receives both motor-related and reward-related information. However, it is unclear how these two signals interact at the level of cerebellar cortex and contribute to learning nonmotor skills. Here we show that in the mid-lateral cerebellum, the reward information is encoded independently from the motor information such that during reward-based learning, only the reward information carried by the Purkinje cells inform learning while the motor information remains unchanged with learning.

Mid-lateral cerebellar complex spikes encode multiple independent reward-related signals during reinforcement learning.

Although the cerebellum has been implicated in simple reward-based learning recently, the role of complex spikes (CS) and simple spikes (SS), their interaction and their relationship to complex reinforcement learning and decision making is still unclear. Here we show that in a context where a non-human primate learned to make novel visuomotor associations, classifying CS responses based on their SS properties revealed distinct cell-type specific encoding of the probability of failure after the stimulus onset and the non-human primate's decision. In a different context, CS from the same cerebellar area also responded in a cell-type and learning independent manner to the stimulus that signaled the beginning of the trial. Both types of CS signals were independent of changes in any motor kinematics and were unlikely to instruct the concurrent SS activity through an error based mechanism, suggesting the presence of context dependent, flexible, multiple independent channels of neural encoding by CS and SS. This diversity in neural information encoding in the mid-lateral cerebellum, depending on the context and learning state, is well suited to promote exploration and acquisition of wide range of cognitive behaviors that entail flexible stimulus-action-reward relationships but not necessarily motor learning.

Neural mechanisms underlying the temporal control of sequential saccade planning in the frontal eye field.

Sequences of saccadic eye movements are instrumental in navigating our visual environment. While neural activity has been shown to ramp up to a threshold before single saccades, the neural underpinnings of multiple saccades is unknown. To understand the neural control of saccade sequences, we recorded from the frontal eye field (FEF) of macaque monkeys while they performed a sequential saccade task. We show that the concurrent planning of two saccade plans brings forth processing bottlenecks, specifically by decreasing the growth rate and increasing the threshold of saccade-related ramping activity. The rate disruption affected both saccade plans, and a computational model, wherein activity related to the two saccade plans mutually and asymmetrically inhibited each other, predicted the behavioral and neural results observed experimentally. Borrowing from models in psychology, our results demonstrate a capacity-sharing mechanism of processing bottlenecks, wherein multiple saccade plans in a sequence compete for the processing capacity by the perturbation of the saccade-related ramping activity. Finally, we show that, in contrast to movement-related neurons, visual activity in FEF neurons is not affected by the presence of multiple saccade targets, indicating that, for perceptually simple tasks, inhibition within movement-related neurons mainly instantiates capacity sharing. Taken together, we show how psychology-inspired models of capacity sharing can be mapped onto neural responses to understand the control of rapid saccade sequences.

Preparatory activity links the frontal eye field response with small amplitude motor unit recruitment of neck muscles during gaze planning.

A hallmark of intelligent behavior is that we can separate intention from action. To understand the mechanism that gates the flow of information between motor planning and execution, we compared the activity of frontal eye field neurons with motor unit activity from neck muscles in the presence of an intervening delay period in which spatial information regarding the target was available to plan a response. Although spatially specific delay period activity was present in the activity of frontal eye field neurons, it was absent in motor unit activity. Nonetheless, motor unit activity was correlated with the time it took to initiate saccades. Interestingly, we observed a heterogeneity of responses among motor units, such that only units with smaller amplitudes showed a clear modulation during the delay period. These small amplitude motor units also had higher spontaneous activity compared with the units which showed modulation only during the movement epoch. Taken together, our results suggest the activity of smaller motor units convey temporal information and explains how the delay period primes muscle activity leading to faster reaction times.NEW & NOTEWORTHY This study shows that the temporal aspects of a motor plan in the oculomotor circuitry can be accessed by peripheral neck muscles hundreds of milliseconds before the instruction to initiate a saccadic eye movement. The coupling between central and peripheral processes during the delay time is mediated by the recruitment pattern of motor units with smaller amplitude. These findings suggest that information processed in cortical areas could be read from periphery before execution.

Neural correlates of goal-directed and non-goal-directed movements.

What are the cortical neural correlates that distinguish goal-directed and non-goal-directed movements? We investigated this question in the monkey frontal eye field (FEF), which is implicated in voluntary control of saccades. Here, we compared FEF activity associated with goal-directed (G) saccades and non-goal-directed (nG) saccades made by the monkey. Although the FEF neurons discharged before these nG saccades, there were three major differences in the neural activity: First, the variability in spike rate across trials decreased only for G saccades. Second, the local field potential beta-band power decreased during G saccades but did not change during nG saccades. Third, the time from saccade direction selection to the saccade onset was significantly longer for G saccades compared with nG saccades. Overall, our results reveal unexpected differences in neural signatures for G versus nG saccades in a brain area that has been implicated selectively in voluntary control. Taken together, these data add critical constraints to the way we think about saccade generation in the brain.

Assessing within-trial and across-trial neural variability in macaque frontal eye fields and their relation to behaviour.

The conventional approach to understanding neural responses underlying complex computations is to study across-trial averages of repeatedly performed computations from single neurons. When neurons perform complex computations, such as processing stimulus-related information or movement planning, it has been repeatedly shown, through measures such as the Fano factor (FF), that neural variability across trials decreases. However, multiple neurons contribute to a common computation on a single trial, rather than a single neuron contributing to a computation across multiple trials. Therefore, at the level of a single trial, the concept of FF loses significance. Here, using a combination of simulations and empirical data, we show that changes in the spiking regularity on single trials produce changes in FF. Further, at the behavioural level, the reaction time of the animal was faster when the neural spiking regularity both within and across trials was lower. Taken together, our results provide further constraints on how changes in spiking statistics help neurons optimally encode visual and saccade-related information across multiple timescales and its implication on behaviour.

Neural Correlates of Reinforcement Learning in Mid-lateral Cerebellum.

The role of the cerebellum in non-motor learning is poorly understood. Here, we investigated the activity of Purkinje cells (P-cells) in the mid-lateral cerebellum as the monkey learned to associate one arbitrary symbol with the movement of the left hand and another with the movement of the right hand. During learning, but not when the monkey had learned the association, the simple spike responses of P-cells reported the outcome of the animal's most recent decision without concomitant changes in other sensorimotor parameters such as hand movement, licking, or eye movement. At the population level, P-cells collectively maintained a memory of the most recent decision throughout the entire trial. As the monkeys learned the association, the magnitude of this reward-related error signal approached zero. Our results provide a major departure from the current understanding of cerebellar processing and have critical implications for cerebellum's role in cognitive control.

Simultaneous analysis of the LFP and spiking activity reveals essential components of a visuomotor transformation in the frontal eye field.

The frontal eye field (FEF) is a key brain region to study visuomotor transformations because the primary input to FEF is visual in nature, whereas its output reflects the planning of behaviorally relevant saccadic eye movements. In this study, we used a memory-guided saccade task to temporally dissociate the visual epoch from the saccadic epoch through a delay epoch, and used the local field potential (LFP) along with simultaneously recorded spike data to study the visuomotor transformation process. We showed that visual latency of the LFP preceded spiking activity in the visual epoch, whereas spiking activity preceded LFP activity in the saccade epoch. We also found a spatially tuned elevation in gamma band activity (30-70 Hz), but not in the corresponding spiking activity, only during the delay epoch, whose activity predicted saccade reaction times and the cells' saccade tuning. In contrast, beta band activity (13-30 Hz) showed a nonspatially selective suppression during the saccade epoch. Taken together, these results suggest that motor plans leading to saccades may be generated internally within the FEF from local activity represented by gamma activity.