Role of Rostral Superior Colliculus in Gaze Stabilization during Visual Fixation.

Visual fixation (i.e., holding gaze on a specific visual object or location of interest) has been shown to be influenced by activity in the rostral pole of the intermediate layers of the superior colliculus (SCi)-a sensory-motor integration nucleus in the midbrain involved in visual fixation and saccadic eye movement generation. Neurons in the rostral SCi discharge tonically during visual fixation and pause during saccades to locations beyond their foveal visual-sensory or saccadic-motor response fields. Injection of muscimol to deactivate rostral SCi neurons also leads to an increase in fixation instability. However, the precise role of rostral SCi activity for controlling visual fixation has not been established and is actively debated. Here, we address whether this activity reflects signals related to task demands (i.e., maintaining visual fixation) or foveal visual stimulus properties. Two non-human primates performed an oculomotor task that required fixation of a central fixation point (FP) of varying luminance at the start of each trial. During this fixation period, we measured fixational saccades (≤ 2° of the FP, including microsaccades) and fixation-error saccades (> 2° from the FP) in combination with activity from the rostral SCi. Fixation of the lowest FP luminance increased the latency (onset time relative to initial FP foveation) for both fixational and fixation-error saccades. Fifty percent of the rostral SCi neurons exhibited activity that opposed the change in FP luminance and correlated with delayed fixational saccades and increased fixation-error saccades. Twenty-two percent of rostral SCi neurons exhibited activity that followed the change in FP luminance and correlated with earlier fixational saccades and decreased fixation-error saccades. This suggests the rostral SCi contains both sensory-driven and task-related motor signals related to foveal sensory stimuli and visual fixation. This evidence supports a role for the rostral SCi in gaze stabilization and can help inform artificial computational models of vision.

Systemic D1-R and D2-R antagonists in non-human primates differentially impact learning and memory while impairing motivation and motor performance.

Dopamine (DA) modulates cognition in part via differential activation of D1 and D2 receptors within the striatum and prefrontal cortex, yet evidence for cognitive impairments stemming from DA blockade or deficiency is inconsistent. Given the predominance of D1 over D2 receptors (R) in the prefrontal cortex of primates, D1-R blockade should more strongly influence frontal executive function (including working memory), while D2-R blockade should impair processes more strongly associated with the dorsal striatum (including cognitive flexibility, and learning). To test how systemic DA blockade disrupts cognition, we administered D1-R and D2-R like antagonists to healthy monkeys while they performed a series of cognitive tasks. Two selective DA receptor antagonist drugs (SCH-23390 hydrochloride: D1/D5-R antagonist; or Eticlopride hydrochloride: D2/D3-R antagonist) or placebo (0.9% saline) were systemically administered. Four tasks were used: (1) 'visually guided reaching', to test response time and accuracy, (2) 'reversal learning', to test association learning and attention, (3) 'self-ordered sequential search' to test spatial working memory, and (4) 'delayed match to sample' to test object working memory. Increased reach response times and decreased motivation to work for liquid reward was observed with both the D1/D5-R and D2/D3-R antagonists at the maximum dosages that still enabled task performance. The D2/D3-R antagonist impaired performance in the reversal learning task, while object and spatial working memory performance was not consistently affected in the tested tasks for either drug. These results are consistent with the theory that systemic D2/D3-R antagonists preferentially influence striatum processes (cognitive flexibility) while systemic D1/D5-R administration is less detrimental to frontal executive function.

Distinct sensory- and goal-related signals underlie the gap effect in the superior colliculus.

The removal of a fixation point (FP) prior to the appearance of a saccade target (gap effect) influences pre-motor circuits and reduces saccadic reaction time (SRT). Saccade preparation signals underlying the gap effect have been observed within the intermediate layers of the superior colliculus (SCi). Neurons in the caudal SCi, coding a target location, increase their activity during the gap, while neurons in the rostral SCi, with tonic activity related to visual fixation, decrease activity. However, the gap effect confounds two factors: (1) a goal-driven temporal warning component (upcoming saccade target appearance) and (2) a stimulus-driven sensory component (FP disappearance). These factors combine to reduce SRT and elicit pre-target responses in the SCi. To dissociate warning and sensory effects, we altered the luminance of the FP during the gap period (renamed warning period) such that it could increase, decrease, or stay the same. Faster SRTs resulted with larger decrements in FP luminance. Different categories of SCi warning period activity were evaluated: (1) always increasing or decreasing or (2) sensory-linked responses to changes in FP luminance. In the caudal SCi (at the location coding the target), all activity correlated negatively with SRT (i.e., saccade facilitation), and two categories of activity were observed (always increasing or opposing FP luminance changes). In the rostral SCi, four categories of activity were observed: activity that increased or followed the change in FP luminance correlated positively with SRT (i.e., saccade inhibition), while activity that decreased or opposed FP luminance changes correlated negatively with SRT. Such SCi activity reflected both goal-driven saccade preparation signals and FP sensory properties.

Differential effects of D1 and D2 dopamine agonists on memory, motivation, learning and response time in non-human primates.

Dopamine (DA) plays a critical role in cognition, motivation and information processing. DA action has been shown to both improve and/or impair cognition across different receptor types, species, subjects and tasks. This complex relationship has been described as an inverted U-shaped function and may be due to the differential effects of DA receptor activation in the striatum and prefrontal cortex. We have investigated the effects of selective DA agonists on cognitive performance in healthy monkeys using a touch screen running tasks from the CAmbridge Neuropsychological Test Automated Battery (CANTAB). One of two DA agonist drugs or placebo was administered prior to each daily CANTAB session: Dihydrexidine hydrochloride (selective D1 agonist, 0.4-0.9 mg/kg), or sumanirole maleate (selective D2 agonist 0.05-0.3 mg/kg). Three CANTAB tasks were tested: (a) "self-ordered sequential search task" which tested spatial working memory, (b) "reversal learning task," which tested association learning, cognitive flexibility and attention and (c) "visually guided reaching task," which tested reaction time and accuracy. At high dosages, the D2 agonist improved spatial working memory performance, while impairing reversal learning and slowing reach response latency. No consistent cognitive effects were observed with the D1 agonist across the dosages tested. A significant decrease in trial completion rate was observed at the higher dosages of both the D1 and D2 agonists which were consistent with decreased motivation. These results are consistent with task-specific effects of a D2 agonist as well as dose specific insensitivities of a D1 agonist on cognitive and motor behaviors in a healthy monkey.

Field evoked potentials in the globus pallidus of non-human primates.

Stimulation-induced field evoked potentials (fEPs) have been described in the basal ganglia output nuclei of patients with Parkinson's disease and dystonia. The aim of this study was to ascertain whether fEPs were inducible in the external (GPe) and internal (GPi) segments of the globus pallidus in normal non-human primates (NHPs). Microelectrode recording and stimulation was performed in the GPe and GPi of 2 healthy NHPs. Stimulus response curves of the fEP response to changing pulse width and amplitude examined strength-duration relationships and allowed for calculation of fEP chronaxie in the GPe and GPi. Traditional localization techniques were also used, including comparison of neuronal firing rates, optic tract activation, and internal capsule activation. Notable differences were seen in the fEPs found in GPe compared to the fEPs found in GPi. The GPe fEP had a smaller chronaxie time and larger positive deflection amplitude compared to GPi. In addition, an earlier negative deflection was identified in both nuclei and a late negative deflection was observed in the GPe in contrast to reported fEPs in patients with movement disorders. fEPs proved valuable as an ancillary method in localizing the GPe and GPi in NHPs and may be useful in the operating room during human GPi deep brain stimulation or pallidotomy procedures.

Superior colliculus neurons encode a visual saliency map during free viewing of natural dynamic video.

Models of visual attention postulate the existence of a saliency map whose function is to guide attention and gaze to the most conspicuous regions in a visual scene. Although cortical representations of saliency have been reported, there is mounting evidence for a subcortical saliency mechanism, which pre-dates the evolution of neocortex. Here, we conduct a strong test of the saliency hypothesis by comparing the output of a well-established computational saliency model with the activation of neurons in the primate superior colliculus (SC), a midbrain structure associated with attention and gaze, while monkeys watched video of natural scenes. We find that the activity of SC superficial visual-layer neurons (SCs), specifically, is well-predicted by the model. This saliency representation is unlikely to be inherited from fronto-parietal cortices, which do not project to SCs, but may be computed in SCs and relayed to other areas via tectothalamic pathways.

Low profile halo head fixation in non-human primates.

BACKGROUND: We present a new halo technique for head fixation of non-human primates during electrophysiological recording experiments. Our aim was to build on previous halo designs in order to create a simple low profile system that provided long-term stability. NEW METHOD: Our design incorporates sharp skull pins that are directly threaded through a low set halo frame and are seated into implanted titanium foot plates on the skull. The inwardly directed skull pins provide an easily calibrated force against the skull. RESULTS: This device allowed for head fixation within 1 week after implantation surgery. The low-profile design maximized the area of the skull available and potential implant orientations for electrophysiological experiments. It was easily maintained and was stable in 2 animals for the 6-8 months of testing. The quality of single unit neural recordings collected while using this device to head fix was indistinguishable from traditional head-post fixation. The foot plates used in this system did not result in significant MRI distortion in the location of deep brain targets (∼0.5mm) of a 3D printed phantom skull. COMPARISON WITH EXISTING METHOD(S): The low profile design of this halo design allows greater access to the majority of the frontal, parietal, and occipital skull. It has fewer parts and can hold larger animals than previous halo designs. CONCLUSIONS: Given the stability, simplicity, immediate usability, and low profile of our head fixation device, we propose that it is a practical and useful means for performing electrophysiological recording experiments on non-human primates.

Linking express saccade occurance to stimulus properties and sensorimotor integration in the superior colliculus.

Express saccades represent the fastest possible eye movements to visual targets with reaction times that approach minimum sensory-motor conduction delays. Previous work in monkeys has identified two specific neural signals in the superior colliculus (SC: a midbrain sensorimotor integration structure involved in gaze control) that are required to execute express saccades: 1) previsual activity consisting of a low-frequency increase in action potentials in sensory-motor neurons immediately before the arrival of a visual response; and 2) a transient visual-sensory response consisting of a high-frequency burst of action potentials in visually responsive neurons resulting from the appearance of a visual target stimulus. To better understand how these two neural signals interact to produce express saccades, we manipulated the arrival time and magnitude of visual responses in the SC by altering target luminance and we examined the corresponding influences on SC activity and express saccade generation. We recorded from saccade neurons with visual-, motor-, and previsual-related activity in the SC of monkeys performing the gap saccade task while target luminance was systematically varied between 0.001 and 42.5 cd/m(2) against a black background (∼0.0001 cd/m(2)). Our results demonstrated that 1) express saccade latencies were linked directly to the arrival time in the SC of visual responses produced by abruptly appearing visual stimuli; 2) express saccades were generated toward both dim and bright targets whenever sufficient previsual activity was present; and 3) target luminance altered the likelihood of producing an express saccade. When an express saccade was generated, visuomotor neurons increased their activity immediately before the arrival of the visual response in the SC and saccade initiation. Furthermore, the visual and motor responses of visuomotor neurons merged into a single burst of action potentials, while the visual response of visual-only neurons was unaffected. A linear combination model was used to test which SC signals best predicted the likelihood of producing an express saccade. In addition to visual response magnitude and previsual activity of saccade neurons, the model identified presaccadic activity (activity occurring during the 30-ms epoch immediately before saccade initiation) as a third important signal for predicting express saccades. We conclude that express saccades can be predicted by visual, previsual, and presaccadic signals recorded from visuomotor neurons in the intermediate layers of the SC.

Spatio-temporal response properties of local field potentials in the primate superior colliculus.

Local field potentials (LFPs) are becoming increasingly popular in neurophysiological studies. However, to date, most of the knowledge about LFPs has been obtained from cortical recordings. Here, we recorded single unit activity (SUA) and LFPs simultaneously from the superior colliculus (SC) of behaving rhesus monkeys. The SC is a midbrain structure that plays a central role in the visual orienting response. Previous studies have characterised the visual and visuomotor response properties of SUA in the superficial layers of the SC and the intermediate layers of the SC, respectively. We found that the signal properties of SUA were well preserved in the LFPs recorded from the SC. The SUA and LFPs had similar spatial and temporal properties, and the response properties of LFPs differed across layers, i.e. purely visual in the superficial layers of the SC but showing significant motor responses in the intermediate layers of the SC. There were also differences between SUA and LFPs. LFPs showed a significant reversal of activity following the phasic visual response, suggesting that the neighboring neurons were suppressed. The results indicate that the LFP can be used as a reliable measure of the SC activity in lieu of SUA, and open up a new way to assess sensorimotor processing within the SC.

Distinct local circuit properties of the superficial and intermediate layers of the rodent superior colliculus.

The superior colliculus (SC) is critical in localizing salient visual stimuli and making decisions on the location of the next saccade. Lateral interactions across the spatial map of the SC are hypothesized to help mediate these processes. Here, we investigate lateral interactions within the SC by applying whole-cell recordings in horizontal slices of mouse SC, which maintained the local structure of the superficial (SCs) visual layer, which is hypothesized to participate in localizing salient stimuli, and the intermediate (SCi) layer, which is supposed to participate in saccade decision-making. When effects of either electrical or chemical (uncaging of free glutamate) stimuli were applied to multiple sites with various distances from the recorded cell, a pattern of center excitation-surround inhibition was found to be prominent in SCs. When the interactions of synaptic effects induced by simultaneous stimulation of two sites were tested, non-linear facilitatory or inhibitory interactions were observed. In contrast, in the SCi, stimulation induced mainly excitation, which masked underlying inhibition. The excitatory synaptic effects of stimulation applied at remote sites were summed in a near linear manner. The result suggested that SCs lateral interactions appear suitable for localizing salient stimuli, while the lateral interactions within SCi are more suitable for faithfully accumulating subthreshold signals for saccadic decision-making. Implementation of this laminar-specific organization makes the SC a unique structure for serially processing signals for saliency localization and saccadic decision-making.

Competitive integration of visual and goal-related signals on neuronal accumulation rate: a correlate of oculomotor capture in the superior colliculus.

The mechanisms that underlie the integration of visual and goal-related signals for the production of saccades remain poorly understood. Here, we examined how spatial proximity of competing stimuli shapes goal-directed responses in the superior colliculus (SC), a midbrain structure closely associated with the control of visual attention and eye movements. Monkeys were trained to perform an oculomotor-capture task [Theeuwes, J., Kramer, A. F., Hahn, S., Irwin, D. E., & Zelinsky, G. J. Influence of attentional capture on oculomotor control. Journal of Experimental Psychology. Human Perception and Performance, 25, 1595-1608, 1999], in which a target singleton was revealed via an isoluminant color change in all but one item. On a portion of the trials, an additional salient item abruptly appeared near or far from the target. We quantified how spatial proximity between the abrupt-onset and the target shaped the goal-directed response. We found that the appearance of an abrupt-onset near the target induced a transient decrease in goal-directed discharge of SC visuomotor neurons. Although this was indicative of spatial competition, it was immediately followed by a rebound in presaccadic activation, which facilitated the saccadic response (i.e., it induced shorter saccadic RT). A similar suppression also occurred at most nontarget locations even in the absence of the abrupt-onset. This is indicative of a mechanism that enabled monkeys to quickly discount stimuli that shared the common nontarget feature. These results reveal a pattern of excitation/inhibition across the SC visuomotor map that acted to facilitate optimal behavior-the short duration suppression minimized the probability of capture by salient distractors, whereas a subsequent boost in accumulation rate ensured a fast goal-directed response. Such nonlinear dynamics should be incorporated into future biologically plausible models of saccade behavior.

Linking visual response properties in the superior colliculus to saccade behavior.

Here we examined the influence of the visual response in the superior colliculus (SC) (an oculomotor control structure integrating sensory, motor and cognitive signals) on the development of the motor command that drives saccadic eye movements in monkeys. We varied stimulus luminance to alter the timing and magnitude of visual responses in the SC and examined how these changes correlated with resulting saccade behavior. Increasing target luminance resulted in multiple modulations of the visual response, including increased magnitude and decreased response onset latency. These signal modulations correlated strongly with changes in saccade latency and metrics, indicating that these signal properties carry through to the neural computations that determine when, where and how fast the eyes will move. Thus, components of the earliest part of the visual response in the SC provide important building blocks for the neural basis of the sensory-motor transformation, highlighting a critical link between the properties of the visual response and saccade behavior.

Spatial interactions in the superior colliculus predict saccade behavior in a neural field model.

During natural vision, eye movements are dynamically controlled by the combinations of goal-related top-down (TD) and stimulus-related bottom-up (BU) neural signals that map onto objects or locations of interest in the visual world. In primates, both BU and TD signals converge in many areas of the brain, including the intermediate layers of the superior colliculus (SCi), a midbrain structure that contains a retinotopically coded map for saccades. How TD and BU signals combine or interact within the SCi map to influence saccades remains poorly understood and actively debated. It has been proposed that winner-take-all competition between these signals occurs dynamically within this map to determine the next location for gaze. Here, we examine how TD and BU signals interact spatially within an artificial two-dimensional dynamic winner-take-all neural field model of the SCi to influence saccadic RT (SRT). We measured point images (spatially organized population activity on the SC map) physiologically to inform the TD and BU model parameters. In this model, TD and BU signals interacted nonlinearly within the SCi map to influence SRT via changes to the (1) spatial size or extent of individual signals, (2) peak magnitude of individual signals, (3) total number of competing signals, and (4) the total spatial separation between signals in the visual field. This model reproduced previous behavioral studies of TD and BU influences on SRT and accounted for multiple inconsistencies between them. This is achieved by demonstrating how, under different experimental conditions, the spatial interactions of TD and BU signals can lead to either increases or decreases in SRT. Our results suggest that dynamic winner-take-all modeling with local excitation and distal inhibition in two dimensions accurately reflects both the physiological activity within the SCi map and the behavioral changes in SRT that result from BU and TD manipulations.

Visual adaptation and novelty responses in the superior colliculus.

The brain's ability to ignore repeating, often redundant, information while enhancing novel information processing is paramount to survival. When stimuli are repeatedly presented, the response of visually sensitive neurons decreases in magnitude, that is, neurons adapt or habituate, although the mechanism is not yet known. We monitored the activity of visual neurons in the superior colliculus (SC) of rhesus monkeys who actively fixated while repeated visual events were presented. We dissociated adaptation from habituation as mechanisms of the response decrement by using a Bayesian model of adaptation, and by employing a paradigm including rare trials that included an oddball stimulus that was either brighter or dimmer. If the mechanism is adaptation, response recovery should be seen only for the brighter stimulus; if the mechanism is habituation, response recovery ('dishabituation') should be seen for both the brighter and dimmer stimuli. We observed a reduction in the magnitude of the initial transient response and an increase in response onset latency with stimulus repetition for all visually responsive neurons in the SC. Response decrement was successfully captured by the adaptation model, which also predicted the effects of presentation rate and rare luminance changes. However, in a subset of neurons with sustained activity in response to visual stimuli, a novelty signal akin to dishabituation was observed late in the visual response profile for both brighter and dimmer stimuli, and was not captured by the model. This suggests that SC neurons integrate both rapidly discounted information about repeating stimuli and novelty information about oddball events, to support efficient selection in a cluttered dynamic world.

Color-related signals in the primate superior colliculus.

Color is important for segmenting objects from backgrounds, which can in turn facilitate visual search in complex scenes. However, brain areas involved in orienting the eyes toward colored stimuli in our environment are not believed to have access to color information. Here, we show that neurons in the intermediate layers of the monkey superior colliculus (SC), a critical structure for the production of saccadic eye movements, can respond to isoluminant color stimuli with the same magnitude as a maximum contrast luminance stimulus. In contrast, neurons from the superficial SC layers showed little color-related activity. Crucially, visual onset latencies were 30-35 ms longer for color, implying that luminance and chrominance information reach the SC through distinct pathways and that the observed color-related activity is not the result of residual luminance signals. Furthermore, these differences in visual onset latency translated directly into differences in saccadic reaction time. The results demonstrate that the saccadic system can signal the presence of chromatic stimuli only one stage from the brainstem premotor circuitry that drives the eyes.

Free viewing of dynamic stimuli by humans and monkeys.

Due to extensive homologies, monkeys provide a sophisticated animal model of human visual attention. However, for electrophysiological recording in behaving animals simplified stimuli and controlled eye position are traditionally used. To validate monkeys as a model for human attention during realistic free viewing, we contrasted human (n = 5) and monkey (n = 5) gaze behavior using 115 natural and artificial video clips. Monkeys exhibited broader ranges of saccadic endpoints and amplitudes and showed differences in fixation and intersaccadic intervals. We compared tendencies of both species to gaze toward scene elements with similar low-level visual attributes using two computational models--luminance contrast and saliency. Saliency was more predictive of both human and monkey gaze, predicting human saccades better than monkey saccades overall. Quantifying interobserver gaze consistency revealed that while humans were highly consistent, monkeys were more heterogeneous and were best predicted by the saliency model. To address these discrepancies, we further analyzed high-interest gaze targets--those locations simultaneously chosen by at least two monkeys. These were on average very similar to human gaze targets, both in terms of specific locations and saliency values. Although substantial quantitative differences were revealed, strong similarities existed between both species, especially when focusing analysis onto high-interest targets.

The effects of bottom-up target luminance and top-down spatial target predictability on saccadic reaction times.

Saccadic reaction times (SRT) are composed of the sum of multiple processes, including bottom-up sensory processing, top-down goal oriented processing, and afferent and efferent conduction delays. In order to determine the timing dependencies and potential interactions between bottom-up and top-down processes on SRTs, we trained monkeys to perform several variants of visually guided saccade tasks. Bottom-up components of SRT were manipulated by varying target luminance from near detection threshold to supra-threshold ranges (i.e., 0.001-42.5 cd/m(2)). There was a significant reduction of mean SRT with increases in target luminance up to 3.5-17.5 cd/m(2). Luminance increases above these ranges produced significant increases in SRT when the target was within 6 degrees from the fovea. Top-down components were assessed by manipulating spatial target predictability across blocks of trials using either 1, 2, 4 or 8 possible target locations. Decreasing spatial target predictability increased SRT across target luminances from 1 to 4 targets in the gap task, but then paradoxically decreased SRT again when there were 8 possible targets in both the gap and step tasks. Finally, a gap task (200 ms gap) was used to determine the dependence of target luminance on the magnitude of the gap effect. Decreasing target luminance significantly reduced the magnitude of the gap effect indicating that the gap effect is strongly influenced by bottom-up factors.

Spatial relationships of visuomotor transformations in the superior colliculus map.

The oculomotor system is well understood compared with other motor systems; however, we do not yet know the spatial details of sensory to motor transformations. This study addresses this issue by quantifying the spatial relationships between visual and motor responses in the superior colliculus (SC), a midbrain structure involved in the transformation of visual information into saccadic motor command signals. We collected extracellular single-unit recordings from 150 visual-motor (VM) and 28 motor (M) neurons in two monkeys trained to perform a nonpredictive visually guided saccade task to 110 possible target locations. Motor related discharge was greater than visual related discharge in 94% (141/150) of the VM neurons. Across the population of VM neurons, the mean locations of the peak visual and motor responses were spatially aligned. The visual response fields (RFs) were significantly smaller than and usually contained within the motor RFs. Converting RFs into the SC coordinate system significantly reduced any misalignment between peak visual and motor locations. RF size increased with increasing eccentricity in visual space but remained invariant on the SC map beyond 1 mm of the rostral pole. RF shape was significantly more symmetric in SC map coordinates compared with visual space coordinates. These results demonstrate that VM neurons specify the same location of a target stimulus in the visual field as the intended location of an upcoming saccade with minimal misalignment to downstream structures. The computational consequences of spatially transforming visual field coordinates to the SC map resulted in increased alignment and spatial symmetry during visual-sensory to saccadic-motor transformations.