Distinct context- and content-dependent population codes in superior colliculus during sensation and action.

Sensorimotor transformation is the process of first sensing an object in the environment and then producing a movement in response to that stimulus. For visually guided saccades, neurons in the superior colliculus (SC) emit a burst of spikes to register the appearance of stimulus, and many of the same neurons discharge another burst to initiate the eye movement. We investigated whether the neural signatures of sensation and action in SC depend on context. Spiking activity along the dorsoventral axis was recorded with a laminar probe as Rhesus monkeys generated saccades to the same stimulus location in tasks that require either executive control to delay saccade onset until permission is granted or the production of an immediate response to a target whose onset is predictable. Using dimensionality reduction and discriminability methods, we show that the subspaces occupied during the visual and motor epochs were both distinct within each task and differentiable across tasks. Single-unit analyses, in contrast, show that the movement-related activity of SC neurons was not different between tasks. These results demonstrate that statistical features in neural activity of simultaneously recorded ensembles provide more insight than single neurons. They also indicate that cognitive processes associated with task requirements are multiplexed in SC population activity during both sensation and action and that downstream structures could use this activity to extract context. Additionally, the entire manifolds associated with sensory and motor responses, respectively, may be larger than the subspaces explored within a certain set of experiments.

Rapid Input-Output Transformation between Local Field Potential and Spiking Activity during Sensation but not Action in the Superior Colliculus.

Sensorimotor transformation is the sequential process of registering a sensory signal in the environment and then responding with the relevant movement at an appropriate time. For visually guided eye movements, neural signatures in the form of spiking activity of neurons have been extensively studied along the dorsoventral axis of the superior colliculus (SC). In contrast, the local field potential (LFP), which represents the putative input to a region, remains largely unexplored in the SC. We therefore compared amplitude levels and onset times of both spike bursts and LFP modulations recorded simultaneously with a laminar probe along the dorsoventral axis of SC in 3 male monkeys performing the visually guided delayed saccade task. Both signals displayed a gradual transition from sensory activity in the superficial layers to a predominantly motor response in the deeper layers, although the transition from principally sensory to mostly motor response occurred ∼500 µm deeper for the LFP. For the sensory response, LFP modulation preceded spike burst onset by <5 ms in the superficial and intermediate layers and only when data were analyzed on a trial-by-trial basis. The motor burst in the spiking activity led LFP modulation by >25 ms in the deeper layers. The results reveal a fast and efficient input-output transformation between LFP modulation and spike burst in the visually responsive layers activity during sensation but not during action. The spiking pattern observed during the movement phase is likely dominated by intracollicular processing that is not captured in the LFP.SIGNIFICANCE STATEMENT What is the sequence of events between local field potential (LFP) modulation and spiking activity during sensorimotor transformation? A trial-by-trial analysis reveals that the LFP activity leads the spike burst in the superficial and intermediate layers of the superior colliculus during visual processing, while both trial-by-trial and the average analyses show that the spike burst leads the LFP modulation during movement generation. These results suggest an almost instantaneous LFP input, spike burst output transformation in the visually responsive layers of the superior colliculus when registering the stimulus. In contrast, substantial intracollicular processing likely results in a saccade-related spike burst that leads LFP modulation.

Decoding the Time Course of Spatial Information from Spiking and Local Field Potential Activities in the Superior Colliculus.

Place code representation is ubiquitous in circuits that encode spatial parameters. For visually guided eye movements, neurons in many brain regions emit spikes when a stimulus is presented in their receptive fields and/or when a movement is directed into their movement fields. Crucially, individual neurons respond for a broad range of directions or eccentricities away from the optimal vector, making it difficult to decode the stimulus location or the saccade vector from each cell's activity. We investigated whether it is possible to decode the spatial parameter with a population-level analysis, even when the optimal vectors are similar across neurons. Spiking activity and local field potentials (LFPs) in the superior colliculus (SC) were recorded with a laminar probe as monkeys performed a delayed saccade task to one of eight targets radially equidistant in direction. A classifier was applied offline to decode the spatial configuration as the trial progresses from sensation to action. For spiking activity, decoding performance across all eight directions was highest during the visual and motor epochs and lower but well above chance during the delay period. Classification performance followed a similar pattern for LFP activity too, except the performance during the delay period was limited mostly to the preferred direction. Increasing the number of neurons in the population consistently increased classifier performance for both modalities. Overall, this study demonstrates the power of population activity for decoding spatial information not possible from individual neurons.

Bilateral control of interceptive saccades: evidence from the ipsipulsion of vertical saccades after caudal fastigial inactivation.

The caudal fastigial nuclei (cFN) are the output nuclei by which the medio-posterior cerebellum influences the production of saccades toward a visual target. On the basis of the organization of their efferences to the premotor burst neurons and the bilateral control of saccades, the hypothesis was proposed that the same unbalanced activity accounts for the dysmetria of all saccades during cFN unilateral inactivation, regardless of whether the saccade is horizontal, oblique, or vertical. We further tested this hypothesis by studying, in two head-restrained macaques, the effects of unilaterally inactivating the caudal fastigial nucleus on saccades toward a target moving vertically with a constant, increasing or decreasing speed. After local muscimol injection, vertical saccades were deviated horizontally toward the injected side with a magnitude that increased with saccade size. The ipsipulsion indeed depended on the tested target speed but not its instantaneous value because it did not increase (decrease) when the target accelerated (decelerated). By subtracting the effect on contralesional horizontal saccades from the effect on ipsilesional ones, we found that the net bilateral effect on horizontal saccades was strongly correlated with the effect on vertical saccades. We explain how this correlation corroborates the bilateral hypothesis and provide arguments against the suggestion that the instantaneous saccade velocity would somehow be "encoded" by the discharge of Purkinje cells in the oculomotor vermis.NEW & NOTEWORTHY Besides causing dysmetric horizontal saccades, unilateral inactivation of caudal fastigial nucleus causes an ipsipulsion of vertical saccades. This study is the first to quantitatively describe this ipsipulsion during saccades toward a moving target. By subtracting the effects on contralesional (hypometric) and ipsilesional (hypermetric) horizontal saccades, we find that this net bilateral effect is strongly correlated with the ipsipulsion of vertical saccades, corroborating the suggestion that a common disorder affects all saccades.

Neurophysiology of visually guided eye movements: critical review and alternative viewpoint.

In this article, we perform a critical examination of assumptions that led to the assimilation of measurements of the movement of a rigid body in the physical world to parameters encoded within brain activity. In many neurophysiological studies of goal-directed eye movements, equivalence has indeed been made between the kinematics of the eyes or of a targeted object and the associated neuronal processes. Such a way of proceeding brings up the reduction encountered in projective geometry when a multidimensional object is being projected onto a one-dimensional segment. The measurement of a movement indeed consists of generation of a series of numerical values from which magnitudes such as amplitude, duration, and their ratio (speed) are calculated. By contrast, movement generation consists of activation of multiple parallel channels in the brain. Yet, for many years, kinematic parameters were supposed to be encoded in brain activity, even though the neuronal image of most physical events is distributed both spatially and temporally. After explaining why the "neuronalization" of such parameters is questionable for elucidating the neural processes underlying the execution of saccadic and pursuit eye movements, we propose an alternative to the framework that has dominated the last five decades. A viewpoint is presented in which these processes follow principles that are defined by intrinsic properties of the brain (population coding, multiplicity of transmission delays, synchrony of firing, connectivity). We propose reconsideration of the time course of saccadic and pursuit eye movements as the restoration of equilibria between neural populations that exert opposing motor tendencies.

Pursuit disorder and saccade dysmetria after caudal fastigial inactivation in the monkey.

The caudal fastigial nuclei (cFN) are the output nuclei by which the medio-posterior cerebellum influences the production of saccadic and pursuit eye movements. We investigated the consequences of unilateral inactivation on the pursuit eye movement made immediately after an interceptive saccade toward a centrifugal target. We describe here the effects when the target moved along the horizontal meridian with a 10 or 20°/s speed. After muscimol injection, the monkeys were unable to track the present location of the moving target. During contralesional tracking, the velocity of postsaccadic pursuit was reduced. This slowing was associated with a hypometria of interceptive saccades such that gaze direction always lagged behind the moving target. No correlation was found between the sizes of saccade undershoot and the decreases in pursuit speed. During ipsilesional tracking, the effects on postsaccadic pursuit were variable across the injection sessions, whereas the interceptive saccades were consistently hypermetric. Here also, the ipsilesional pursuit disorder was not correlated with the saccade hypermetria either. The lack of correlation between the sizes of saccade dysmetria and changes of postsaccadic pursuit speed suggests that cFN activity exerts independent influences on the neural processes generating the saccadic and slow eye movements. It also suggests that the cFN is one locus where the synergy between the two motor categories develops in the context of tracking a moving visual target. We explain how the different fastigial output channels can account for these oculomotor tracking disorders. NEW & NOTEWORTHY Inactivation of the caudal fastigial nucleus impairs the ability to track a moving target. The accuracy of interceptive saccades and the velocity of postsaccadic pursuit movements are both altered, but these changes are not correlated. This absence of correlation is not compatible with an impaired common command feeding the circuits producing saccadic and pursuit eye movements. However, it suggests an involvement of caudal fastigial nuclei in their synergy to accurately track a moving target.

The caudal fastigial nucleus and the steering of saccades toward a moving visual target.

The caudal fastigial nuclei (cFN) are the output nuclei by which the medio-posterior cerebellum influences the production of visual saccades. We investigated in two head-restrained monkeys their contribution to the generation of interceptive saccades toward a target moving centrifugally by analyzing the consequences of a unilateral inactivation (10 injection sessions). We describe here the effects on saccades made toward a centrifugal target that moved along the horizontal meridian with a constant (10, 20, or 40°/s), increasing (from 0 to 40°/s over 600 ms), or decreasing (from 40 to 0°/s over 600 ms) speed. After muscimol injection, the monkeys were unable to foveate the current location of the moving target. The horizontal amplitude of interceptive saccades was reduced during contralesional target motions and hypermetric during ipsilesional ones. For both contralesional and ipsilesional saccades, the magnitude of dysmetria increased with target speed. However, the use of accelerating and decelerating targets revealed that the dependence of dysmetria upon target velocity was not due to the current velocity but to the required amplitude of saccade. We discuss these results in the framework of two hypotheses, the so-called "dual drive" and "bilateral" hypotheses. NEW & NOTEWORTHY Unilateral inactivation of the caudal fastigial nucleus impairs the accuracy of saccades toward a moving target. Like saccades toward a static target, interceptive saccades are hypometric when directed toward the contralesional side and hypermetric when they are ipsilesional. The dysmetria depends on target velocity, but the use of accelerating or decelerating targets reveals that velocity is not the crucial parameter. We extend the bilateral fastigial control of saccades and fixation to the production of interceptive saccades.

Synchronizing the tracking eye movements with the motion of a visual target: Basic neural processes.

In primates, the appearance of an object moving in the peripheral visual field elicits an interceptive saccade that brings the target image onto the foveae. This foveation is then maintained more or less efficiently by slow pursuit eye movements and subsequent catch-up saccades. Sometimes, the tracking is such that the gaze direction looks spatiotemporally locked onto the moving object. Such a spatial synchronism is quite spectacular when one considers that the target-related signals are transmitted to the motor neurons through multiple parallel channels connecting separate neural populations with different conduction speeds and delays. Because of the delays between the changes of retinal activity and the changes of extraocular muscle tension, the maintenance of the target image onto the fovea cannot be driven by the current retinal signals as they correspond to past positions of the target. Yet, the spatiotemporal coincidence observed during pursuit suggests that the oculomotor system is driven by a command estimating continuously the current location of the target, i.e., where it is here and now. This inference is also supported by experimental perturbation studies: when the trajectory of an interceptive saccade is experimentally perturbed, a correction saccade is produced in flight or after a short delay, and brings the gaze next to the location where unperturbed saccades would have landed at about the same time, in the absence of visual feedback. In this chapter, we explain how such correction can be supported by previous visual signals without assuming "predictive" signals encoding future target locations. We also describe the basic neural processes which gradually yield the synchronization of eye movements with the target motion. When the process fails, the gaze is driven by signals related to past locations of the target, not by estimates to its upcoming locations, and a catch-up is made to reinitiate the synchronization.

Learning the trajectory of a moving visual target and evolution of its tracking in the monkey.

An object moving in the visual field triggers a saccade that brings its image onto the fovea. It is followed by a combination of slow eye movements and catch-up saccades that try to keep the target image on the fovea as long as possible. The accuracy of this ability to track the "here-and-now" location of a visual target contrasts with the spatiotemporally distributed nature of its encoding in the brain. We show in six experimentally naive monkeys how this performance is acquired and gradually evolves during successive daily sessions. During the early exposure, the tracking is mostly saltatory, made of relatively large saccades separated by low eye velocity episodes, demonstrating that accurate (here and now) pursuit is not spontaneous and that gaze direction lags behind its location most of the time. Over the sessions, while the pursuit velocity is enhanced, the gaze is more frequently directed toward the current target location as a consequence of a 25% reduction in the number of catch-up saccades and a 37% reduction in size (for the first saccade). This smoothing is observed at several scales: during the course of single trials, across the set of trials within a session, and over successive sessions. We explain the neurophysiological processes responsible for this combined evolution of saccades and pursuit in the absence of stringent training constraints. More generally, our study shows that the oculomotor system can be used to discover the neural mechanisms underlying the ability to synchronize a motor effector with a dynamic external event.