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.

Instantaneous Midbrain Control of Saccade Velocity.

The ability to interact with our environment requires the brain to transform spatially represented sensory signals into temporally encoded motor commands for appropriate control of the relevant effectors. For visually guided eye movements, or saccades, the superior colliculus (SC) is assumed to be the final stage of spatial representation, and instantaneous control of the movement is achieved through a rate code representation in the lower brain stem. We investigated whether SC activity in nonhuman primates (Macaca mulatta, 2 male and 1 female) also uses a dynamic rate code, in addition to the spatial representation. Noting that the kinematics of amplitude-matched movements exhibit trial-to-trial variability, we regressed instantaneous SC activity with instantaneous eye velocity and found a robust correlation throughout saccade duration. Peak correlation was tightly linked to time of peak velocity, the optimal efferent delay between SC activity and eye velocity was constant at ∼12 ms both at onset and during the saccade, and SC neurons with higher firing rates exhibited stronger correlations. Moreover, the strong correlative relationship and constant efferent delay observation were preserved when eye movement profiles were substantially altered by a blink-induced perturbation. These results indicate that the rate code of individual SC neurons can control instantaneous eye velocity and argue against a serial process of spatial-to-temporal transformation. They also motivated us to consider a new framework of saccade control that does not incorporate traditionally accepted elements, such as the comparator and resettable integrator, whose neural correlates have remained elusive.SIGNIFICANCE STATEMENT All movements exhibit time-varying features that are under instantaneous control of the innervating neural command. At what stage in the brain is dynamical control present? It is well known that, in the skeletomotor system, neurons in the motor cortex use dynamical control. In the oculomotor system, in contrast, instantaneous velocity control of saccadic eye movements is not thought to be enforced until the lower brainstem. Using correlations between residual signals across trials, we show that instantaneous control of saccade velocity is present earlier in the visuo-oculomotor neuraxis, at the level of superior colliculus. The results require us to consider alternate frameworks of the neural control of saccades.

Motor functions of the superior colliculus.

The mammalian superior colliculus (SC) and its nonmammalian homolog, the optic tectum, constitute a major node in processing sensory information, incorporating cognitive factors, and issuing motor commands. The resulting action-to orient toward or away from a stimulus-can be accomplished as an integrated movement across oculomotor, cephalomotor, and skeletomotor effectors. The SC also participates in preserving fixation during intersaccadic intervals. This review highlights the repertoire of movements attributed to SC function and analyzes the significance of results obtained from causality-based experiments (microstimulation and inactivation). The mechanisms potentially used to decode the population activity in the SC into an appropriate movement command are also discussed.

Disruption of Fixation Reveals Latent Sensorimotor Processes in the Superior Colliculus.

UNLABELLED: Executive control of voluntary movements is a hallmark of the mammalian brain. In the gaze-control network, this function is thought to be mediated by a critical balance between neurons responsible for generating movements and those responsible for fixating or suppressing movements, but the nature of this balance between the relevant elements-saccade-generating and fixation-related neurons-remains unclear. Specifically, it has been debated whether the two functions are necessarily coupled (i.e., push-and-pull) or independently controlled. Here we show that behavioral perturbation of ongoing fixation with the trigeminal blink reflex in monkeys (Macaca mulatta) alters the effective balance between fixation and saccade-generating neurons in the superior colliculus (SC) and can lead to premature gaze shifts reminiscent of compromised inhibitory control. The shift in balance is primarily driven by an increase in the activity of visuomovement neurons in the caudal SC, and the extent to which fixation-related neurons in the rostral SC play a role seems to be linked to the animal's propensity to make microsaccades. The perturbation also reveals a hitherto unknown feature of sensorimotor integration: the presence of a hidden visual response in canonical movement neurons. These findings offer new insights into the latent functional interactions, or lack thereof, between components of the gaze-control network, suggesting that the perturbation technique used here may prove to be a useful tool for probing the neural mechanisms of movement generation in executive function and dysfunction. SIGNIFICANCE STATEMENT: Eye movements are an integral part of how we explore the environment. Although we know a great deal about where sensorimotor transformations leading to saccadic eye movements are implemented in the brain, less is known about the functional interactions between neurons that maintain gaze fixation and neurons that program saccades. In this study, we used a novel approach to study these interactions. By transient disruption of fixation, we found that activity of saccade-generating neurons can increase independently of modulation in fixation-related neurons, which may occasionally lead to premature movements mimicking lack of impulse control. Our findings support the notion of a common pathway for sensory and movement processing and suggest that impulsive movements arise when sensory processes become "motorized."

The superior colliculus and the steering of saccades toward a moving visual target.

Following the suggestion that a command encoding current target location feeds the oculomotor system during interceptive saccades, we tested the involvement of the deep superior colliculus (dSC). Extracellular activity of 52 saccade-related neurons was recorded in three monkeys while they generated saccades to targets that were static or moving along the preferred axis, away from (outward) or toward (inward) a fixated target with a constant speed (20°/s). Vertical and horizontal motions were tested when possible. Movement field (MF) parameters (boundaries, preferred vector, and firing rate) were estimated after spline fitting of the relation between the average firing rate during the motor burst and saccade amplitude. During radial target motions, the inner MF boundary shifted in the motion direction for some, but not all, neurons. Likewise, for some neurons, the lower boundaries were shifted upward during upward motions and the upper boundaries downward during downward motions. No consistent change was observed during horizontal motions. For some neurons, the preferred vectors were also shifted in the motion direction for outward, upward, and "toward the midline" target motions. The shifts of boundary and preferred vector were not correlated. The burst firing rate was consistently reduced during interceptive saccades. Our study demonstrates an involvement of dSC neurons in steering the interceptive saccade. When observed, the shifts of boundary in the direction of target motion correspond to commands related to past target locations. The absence of shift in the opposite direction implies that dSC activity does not issue predictive commands related to future target location.NEW & NOTEWORTHY The deep superior colliculus is involved in steering the saccade toward the current location of a moving target. During interceptive saccades, the active population consists of a continuum of cells ranging from neurons issuing commands related to past locations of the target to neurons issuing commands related to its current location. The motor burst of collicular neurons does not contain commands related to the future location of a moving target.

Context cue-dependent saccadic adaptation in rhesus macaques cannot be elicited using color.

When the head does not move, rapid movements of the eyes called saccades are used to redirect the line of sight. Saccades are defined by a series of metrical and kinematic (evolution of a movement as a function of time) relationships. For example, the amplitude of a saccade made from one visual target to another is roughly 90% of the distance between the initial fixation point (T0) and the peripheral target (T1). However, this stereotypical relationship between saccade amplitude and initial retinal error (T1-T0) may be altered, either increased or decreased, by surreptitiously displacing a visual target during an ongoing saccade. This form of motor learning (called saccadic adaptation) has been described in both humans and monkeys. Recent experiments in humans and monkeys have suggested that internal (proprioceptive) and external (target shape, color, and/or motion) cues may be used to produce context-dependent adaptation. We tested the hypothesis that an external contextual cue (target color) could be used to evoke differential gain (actual saccade/initial retinal error) states in rhesus monkeys. We did not observe differential gain states correlated with target color regardless of whether targets were displaced along the same vector as the primary saccade or perpendicular to it. Furthermore, this observation held true regardless of whether adaptation trials using various colors and intrasaccade target displacements were randomly intermixed or presented in short or long blocks of trials. These results are consistent with hypotheses that state that color cannot be used as a contextual cue and are interpreted in light of previous studies of saccadic adaptation in both humans and monkeys.

Time course of motor preparation during visual search with flexible stimulus-response association.

Whether allocation of visuospatial attention can be divorced from saccade preparation has been the subject of intense research efforts. A variant of the visual search paradigm, in which a feature singleton indicates that the correct saccade should be directed to it (prosaccade) or to the opposite distractor (antisaccade), has been influential in addressing this core topic. We performed a causal assessment of this controversy by delivering an air puff to one eye to invoke the trigeminal blink reflex as monkeys performed this visual search task. Blinks effectively remove saccadic inhibition and prematurely trigger impending saccades in reaction time tasks, thus providing a behavioral readout of the premotor plan. We found that saccades accompanied blinks during the initial allocation of attention epoch and that these movements were directed to the singleton for both prosaccade and antisaccade trials. Blinks evoked at later times were accompanied with saccades to the correct end point location: the singleton on prosaccade trials and the opposite distractor on antisaccade trials. These results provide support for concurrent encoding of visuospatial attention and saccade preparation during visual search behavior.

Drifting population dynamics with transient resets characterize sensorimotor transformation in the monkey superior colliculus.

To produce goal-directed eye movements known as saccades, we must channel sensory input from our environment through a process known as sensorimotor transformation. The behavioral output of this phenomenon (an accurate eye movement) is straightforward, but the coordinated activity of neurons underlying its dynamics is not well understood. We searched for a neural correlate of sensorimotor transformation in the activity patterns of simultaneously recorded neurons in the superior colliculus (SC) of three male rhesus monkeys performing a visually guided, delayed saccade task. Neurons in the intermediate layers produce a burst of spikes both following the appearance of a visual (sensory) stimulus and preceding an eye movement command, but many also exhibit a sustained activity level during the intervening time ("delay period"). This sustained activity could be representative of visual processing or motor preparation, along with countless cognitive processes. Using a novel measure we call the Visuomotor Proximity Index (VMPI), we pitted visual and motor signals against each other by measuring the degree to which each session's population activity (as summarized in a low-dimensional framework) could be considered more visual-like or more motor-like. The analysis highlighted two salient features of sensorimotor transformation. One, population activity on average drifted systematically toward a motor-like representation and intermittently reverted to a visual-like representation following a microsaccade. Two, activity patterns that drift to a stronger motor-like representation by the end of the delay period may enable a more rapid initiation of a saccade, substantiating the idea that this movement initiation mechanism is conserved across motor systems.

The relative impact of microstimulation parameters on movement generation.

Microstimulation is widely used in neurophysiology to characterize brain areas with behavior and in clinical therapeutics to treat neurological disorder. Current intensity and frequency, which respectively influence activation patterns in spatial and temporal domains, are typically selected to elicit a desired response, but their effective influence on behavior has not been thoroughly examined. We delivered microstimulation to the primate superior colliculus while systematically varying each parameter to capture effects of a large range of parameter space. We found that frequency was more effective in driving output properties, whereas properties changed gradually with intensity. Interestingly, when different parameter combinations were matched for total charge, effects on behavioral properties became seemingly equivalent. This study provides a first level resource for choosing desired parameter ranges to effectively manipulate behavior. It also provides insights into interchangeability of parameters, which can assist clinical microstimulation that looks to appropriately control behavior within designated constraints, such as power consumption.

A test of spatial temporal decoding mechanisms in the superior colliculus.

Population coding is a ubiquitous principle in the nervous system for the proper control of motor behavior. A significant amount of research is dedicated to studying population activity in the superior colliculus (SC) to investigate the motor control of saccadic eye movements. Vector summation with saturation (VSS) has been proposed as a mechanism for how population activity in the SC can be decoded to generate saccades. Interestingly, the model produces different predictions when decoding two simultaneous populations at high vs. low levels of activity. We tested these predictions by generating two simultaneous populations in the SC with high or low levels of dual microstimulation. We also combined varying levels of stimulation with visually induced activity. We found that our results did not perfectly conform to the predictions of the VSS scheme and conclude that the simplest implementation of the model is incomplete. We propose that additional parameters to the model might account for the results of this investigation.

Interactions between gaze-evoked blinks and gaze shifts in monkeys.

Rapid eyelid closure, or a blink, often accompanies head-restrained and head-unrestrained gaze shifts. This study examines the interactions between such gaze-evoked blinks and gaze shifts in monkeys. Blink probability increases with gaze amplitude and at a faster rate for head-unrestrained movements. Across animals, blink likelihood is inversely correlated with the average gaze velocity of large-amplitude control movements. Gaze-evoked blinks induce robust perturbations in eye velocity. Peak and average velocities are reduced, duration is increased, but accuracy is preserved. The temporal features of the perturbation depend on factors such as the time of blink relative to gaze onset, inherent velocity kinematics of control movements, and perhaps initial eye-in-head position. Although variable across animals, the initial effect is a reduction in eye velocity, followed by a reacceleration that yields two or more peaks in its waveform. Interestingly, head velocity is not attenuated; instead, it peaks slightly later and with a larger magnitude. Gaze latency is slightly reduced on trials with gaze-evoked blinks, although the effect was more variable during head-unrestrained movements; no reduction in head latency is observed. Preliminary data also demonstrate a similar perturbation of gaze-evoked blinks during vertical saccades. The results are compared with previously reported effects of reflexive blinks (evoked by air-puff delivered to one eye or supraorbital nerve stimulation) and discussed in terms of effects of blinks on saccadic suppression, neural correlates of the altered eye velocity signals, and implications on the hypothesis that the attenuation in eye velocity is produced by a head movement command.

Ventral premotor cortex encodes task relevant features during eye and head movements.

Visual exploration of the environment is achieved through gaze shifts or coordinated movements of the eyes and the head. The kinematics and contributions of each component can be decoupled to fit the context of the required behavior, such as redirecting the visual axis without moving the head or rotating the head without changing the line of sight. A neural controller of these effectors, therefore, must show code relating to multiple muscle groups, and it must also differentiate its code based on context. In this study we tested whether the ventral premotor cortex (PMv) in monkey exhibits a population code relating to various features of eye and head movements. We constructed three different behavioral tasks or contexts, each with four variables to explore whether PMv modulates its activity in accordance with these factors. We found that task related population code in PMv differentiates between all task related features and conclude that PMv carries information about task relevant features during eye and head movements. Furthermore, this code represents both lower-level (effector and movement direction) and higher-level (context) information.

Population temporal structure supplements the rate code during sensorimotor transformations.

Sensorimotor transformations are mediated by premotor brain networks where individual neurons represent sensory, cognitive, and movement-related information. Such multiplexing poses a conundrum-how does a decoder know precisely when to initiate a movement if its inputs are active at times when a movement is not desired (e.g., in response to sensory stimulation)? Here, we propose a novel hypothesis: movement is triggered not only by an increase in firing rate but, critically, also by a reliable temporal pattern in the population response. Laminar recordings in the macaque superior colliculus (SC), a midbrain hub of orienting control, and pseudo-population analyses in SC and cortical frontal eye fields (FEFs) corroborated this hypothesis. Specifically, using a measure that captures the fidelity of the population code-here called temporal stability-we show that the temporal structure fluctuates during the visual response but becomes increasingly stable during the movement command. Importantly, we used spatiotemporally patterned microstimulation to causally test the contribution of population temporal stability in gating movement initiation and found that stable stimulation patterns were more likely to evoke a movement. Finally, a spiking neuron model was able to discriminate between stable and unstable input patterns, providing a putative biophysical mechanism for decoding temporal structure. These findings offer new insights into the long-standing debate on motor preparation and generation by situating the movement gating signal in temporal features of activity in shared neural substrates, and they highlight the importance of short-term population history in neuronal communication and behavior.

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.

Order of operations for decoding superior colliculus activity for saccade generation.

To help understand the order of events that occurs when generating saccades, we simulated and tested two commonly stated decoding models that are believed to occur in the oculomotor system: vector averaging (VA) and center-of-mass. To generate accurate saccades, each model incorporates two required criteria: 1) a decoding mechanism that deciphers a population response of the superior colliculus (SC) and 2) an exponential transformation that converts the saccade vector into visual coordinates. The order of these two criteria is used differently within each model, yet the significance of the sequence has not been quantified. To distinguish between each decoding sequence and hence, to determine the order of events necessary to generate accurate saccades, we simulated the two models. Distinguishable predictions were obtained when two simultaneous motor commands are processed by each model. Experimental tests of the models were performed by observing the distribution of endpoints of saccades evoked by weighted, simultaneous microstimulation of two SC sites. The data were consistent with the predictions of the VA model, in which exponential transformation precedes the decoding computation.

Matching the oculomotor drive during head-restrained and head-unrestrained gaze shifts in monkey.

High-frequency burst neurons in the pons provide the eye velocity command (equivalently, the primary oculomotor drive) to the abducens nucleus for generation of the horizontal component of both head-restrained (HR) and head-unrestrained (HU) gaze shifts. We sought to characterize how gaze and its eye-in-head component differ when an "identical" oculomotor drive is used to produce HR and HU movements. To address this objective, the activities of pontine burst neurons were recorded during horizontal HR and HU gaze shifts. The burst profile recorded on each HU trial was compared with the burst waveform of every HR trial obtained for the same neuron. The oculomotor drive was assumed to be comparable for the pair yielding the lowest root-mean-squared error. For matched pairs of HR and HU trials, the peak eye-in-head velocity was substantially smaller in the HU condition, and the reduction was usually greater than the peak head velocity of the HU trial. A time-varying attenuation index, defined as the difference in HR and HU eye velocity waveforms divided by head velocity [alpha = (H(hr) - E(hu))/H] was computed. The index was variable at the onset of the gaze shift, but it settled at values several times greater than 1. The index then decreased gradually during the movement and stabilized at 1 around the end of gaze shift. These results imply that substantial attenuation in eye velocity occurs, at least partially, downstream of the burst neurons. We speculate on the potential roles of burst-tonic neurons in the neural integrator and various cell types in the vestibular nuclei in mediating the attenuation in eye velocity in the presence of head movements.

Sensorimotor transformation elicits systematic patterns of activity along the dorsoventral extent of the superior colliculus in the macaque monkey.

The superior colliculus (SC) is an excellent substrate to study sensorimotor transformations. To date, the spatial and temporal properties of population activity along its dorsoventral axis have been inferred from single electrode studies. Here, we recorded SC population activity in non-human primates using a linear multi-contact array during delayed saccade tasks. We show that during the visual epoch, information appeared first in dorsal layers and systematically later in ventral layers. During the delay period, the laminar organization of low-spiking rate activity matched that of the visual epoch. During the pre-saccadic epoch, spiking activity emerged first in a more ventral layer, ~ 100 ms before saccade onset. This buildup of activity appeared later on nearby neurons situated both dorsally and ventrally, culminating in a synchronous burst across the dorsoventral axis, ~ 28 ms before saccade onset. Collectively, these results reveal a principled spatiotemporal organization of SC population activity underlying sensorimotor transformation for the control of gaze.

Coordination of eye and head components of movements evoked by stimulation of the paramedian pontine reticular formation.

Constant frequency microstimulation of the paramedian pontine reticular formation (PPRF) in head-restrained monkeys evokes a constant velocity eye movement. Since the PPRF receives significant projections from structures that control coordinated eye-head movements, we asked whether stimulation of the pontine reticular formation in the head-unrestrained animal generates a combined eye-head movement or only an eye movement. Microstimulation of most sites yielded a constant-velocity gaze shift executed as a coordinated eye-head movement, although eye-only movements were evoked from some sites. The eye and head contributions to the stimulation-evoked movements varied across stimulation sites and were drastically different from the lawful relationship observed for visually-guided gaze shifts. These results indicate that the microstimulation activated elements that issued movement commands to the extraocular and, for most sites, neck motoneurons. In addition, the stimulation-evoked changes in gaze were similar in the head-restrained and head-unrestrained conditions despite the assortment of eye and head contributions, suggesting that the vestibulo-ocular reflex (VOR) gain must be near unity during the coordinated eye-head movements evoked by stimulation of the PPRF. These findings contrast the attenuation of VOR gain associated with visually-guided gaze shifts and suggest that the vestibulo-ocular pathway processes volitional and PPRF stimulation-evoked gaze shifts differently.

Removal of inhibition uncovers latent movement potential during preparation.

The motor system prepares for movements well in advance of their execution. In the gaze control system, the dynamics of preparatory neural activity have been well described by stochastic accumulation-to-threshold models. However, it is unclear whether this activity has features indicative of a hidden movement command. We explicitly tested whether preparatory neural activity in premotor neurons of the primate superior colliculus has 'motor potential'. We removed downstream inhibition on the saccadic system using the trigeminal blink reflex, triggering saccades at earlier-than-normal latencies. Accumulating low-frequency activity was predictive of eye movement dynamics tens of milliseconds in advance of the actual saccade, indicating the presence of a latent movement command. We also show that reaching a fixed threshold level is not a necessary condition for movement initiation. The results bring into question extant models of saccade generation and support the possibility of a concurrent representation for movement preparation and generation.