Inactivation Of Superior Colliculus Research Articles

A neural mechanism for terminating decisions

The brain makes decisions by accumulating evidence until there is enough to stop and choose. Neural mechanisms of evidence accumulation are established in association cortex, but the site and mechanism of termination are unknown. Here, we show that the superior colliculus (SC) plays a causal role in terminating decisions, and we provide evidence for a mechanism by which this occurs. We recorded simultaneously from neurons in the lateral intraparietal area (LIP) and SC while monkeys made perceptual decisions. Despite similar trial-averaged activity, we found distinct single-trial dynamics in the two areas: LIP displayed drift-diffusion dynamics and SC displayed bursting dynamics. We hypothesized that the bursts manifest a threshold mechanism applied to signals represented in LIP to terminate the decision. Consistent with this hypothesis, SC inactivation produced behavioral effects diagnostic of an impaired threshold sensor and prolonged the buildup of activity in LIP. The results reveal the transformation from deliberation to commitment.

Causal role for the primate superior colliculus in the computation of evidence for perceptual decisions.

Trained monkeys performed a two-choice perceptual decision-making task in which they reported the perceived orientation of a dynamic Glass pattern, before and after unilateral, reversible, inactivation of a brainstem area involved in preparing eye movements, the superior colliculus (SC). Surprisingly, we found that unilateral SC inactivation produced significant decision biases and changes in reaction times consistent with a causal role for the primate SC in perceptual decision-making. Fitting signal detection theory and sequential sampling models to the data revealed that SC inactivation produced a decrease in the relative evidence for contralateral decisions, as if adding a constant offset to a time-varying evidence signal for the ipsilateral choice. The results provide causal evidence for an embodied cognition model of perceptual decision-making and provide compelling evidence that the SC of primates, a brainstem structure, plays a causal role in how evidence is computed for decisions, a process usually attributed to the forebrain.

A Novel Three-Choice Touchscreen Task to Examine Spatial Attention and Orienting Responses in Rodents.

Mammalian orienting behavior consists of coordinated movements of the eyes, head, pinnae, vibrissae, or body to attend to an external stimulus. The present study aimed to develop a novel operant task using a touch-screen system to measure spatial attention. In this task, rats were trained to nose-poke a light stimulus presented in one of three locations. The stimulus was presented more frequently in the center location to develop spatial attention bias toward the center stimulus. Changes in orienting responses were detected by measuring the animals’ response accuracy and latency to stimuli at the lateral locations, following reversible unilateral chemogenetic inactivation of the superior colliculus (SC). Additionally, spontaneous turning and rotation behavior was measured using an open-field test (OFT). Our results show that right SC inactivation significantly increased the whole body turn angle in the OFT, in line with previous literature that indicated an ipsiversive orientating bias and the presence of contralateral neglect following unilateral SC lesions. In the touch screen orienting task, unilateral SC inactivation significantly increased bias toward the ipsilateral side, as measured by response frequency in various experimental conditions, and a very large left-shift of a respective psychometric function. Our results demonstrate that this novel touchscreen task is able to detect changes in spatial attention and orienting responses because of e.g. experimental manipulations or injury with very high sensitivity, while taking advantage of the touch screen technology that allows for high transferability of the task between labs and for open-source data sharing through https://www.mousebytes.ca.

Midbrain activity shapes high-level visual properties in the primate temporal cortex

Recent fMRI experiments identified an attention-related region in the macaque temporal cortex, here called the floor of the superior temporal sulcus (fSTS), as the primary cortical target of superior colliculus (SC) activity. However, it remains unclear which aspects of attention are processed by fSTS neurons and how or why these might depend on SC activity. Here, we show that SC inactivation decreases attentional modulations in fSTS neurons by increasing their activity for ignored stimuli in addition to decreasing their activity for attended stimuli. Neurons in the fSTS also exhibit event-related activity during attention tasks linked to detection performance, and this link is eliminated during SC inactivation. Finally, fSTS neurons respond selectively to particular visual objects, and this selectivity is reduced markedly during SC inactivation. These diverse, high-level properties of fSTS neurons all involve visual signals that carry behavioral relevance. Their dependence on SC activity could reflect a circuit that prioritizes cortical processing of events detected subcortically.

Attention-related modulation of caudate neurons depends on superior colliculus activity.

Recent work has implicated the primate basal ganglia in visual perception and attention, in addition to their traditional role in motor control. The basal ganglia, especially the caudate nucleus 'head' (CDh) of the striatum, receive indirect anatomical connections from the superior colliculus (SC), a midbrain structure that is known to play a crucial role in the control of visual attention. To test the possible functional relationship between these subcortical structures, we recorded CDh neuronal activity of macaque monkeys before and during unilateral SC inactivation in a spatial attention task. SC inactivation significantly altered the attention-related modulation of CDh neurons and strongly impaired the classification of task-epochs based on CDh activity. Only inactivation of SC on the same side of the brain as recorded CDh neurons, not the opposite side, had these effects. These results demonstrate a novel interaction between SC activity and attention-related visual processing in the basal ganglia.

Cortical visual processing evokes short-latency reward-predicting cue responses in primate midbrain dopamine neurons

After classical conditioning dopamine (DA) neurons exhibit short latency responses to reward-predicting visual cues. At least two possible projections could induce such DA responses; the cortical and subcortical visual pathways. Our recent study has shown that after a lesion of the striate cortex (V1), the superior colliculus (SC), a critical node of the subcortical visual pathway, can mediate short latency cue responses in the DA neurons of macaque monkeys. An obvious question then is does the cortical pathway have a similar capacity? Using the monkeys with a unilateral V1 lesion that took part in the preceding study, we recorded DA activity while they were performing the same classical conditioning task. However, in this study conditioned visual stimuli were presented to the intact visual field, and the effects of ipsilateral SC inactivation were examined. We found that after the SC was inactivated by injections of muscimol both conditioned behavioral responding and reward-predicting, short latency (~100 ms) cue-elicited DA neuronal responses were unaffected These results indicate that the intact cortical visual pathway can also mediate short latency cue elicited responses in DA neurons in the absence of a normally functioning subcortical visual system.

Comparing frontal eye field and superior colliculus contributions to covert spatial attention

The causal roles of the frontal eye fields (FEF) and superior colliculus (SC) in spatial selective attention have not been directly compared. Reversible inactivation is an established method for testing causality but comparing results between FEF and SC is complicated by differences in size and morphology of the two brain regions. Here we exploited the fact that inactivation of FEF and SC also changes the metrics of saccadic eye movements, providing an independent benchmark for the strength of the causal manipulation. Using monkeys trained to covertly perform a visual motion-change detection task, we found that inactivation of either FEF or SC could cause deficits in attention task performance. However, SC-induced attention deficits were found with saccade changes half the size needed to get FEF-induced attention deficits. Thus, performance in visual attention tasks is vulnerable to loss of signals from either structure, but suppression of SC activity has a more devastating effect.

Emergence of visually-evoked reward expectation signals in dopamine neurons via the superior colliculus in V1 lesioned monkeys.

Responses of midbrain dopamine (DA) neurons reflecting expected reward from sensory cues are critical for reward-based associative learning. However, critical pathways by which reward-related visual information is relayed to DA neurons remain unclear. To address this question, we investigated Pavlovian conditioning in macaque monkeys with unilateral primary visual cortex (V1) lesions (an animal model of 'blindsight'). Anticipatory licking responses to obtain juice drops were elicited in response to visual conditioned stimuli (CS) in the affected visual field. Subsequent pharmacological inactivation of the superior colliculus (SC) suppressed the anticipatory licking. Concurrent single unit recordings indicated that DA responses reflecting the reward expectation could be recorded in the absence of V1, and that these responses were also suppressed by SC inactivation. These results indicate that the subcortical visual circuit can relay reward-predicting visual information to DA neurons and integrity of the SC is necessary for visually-elicited classically conditioned responses after V1 lesion.

Attention-related BOLD modulation with and without superior colliculus inactivation

Attention-related BOLD modulation with and without superior colliculus inactivation

Requirement of Prefrontal and Midbrain Regions for Rapid Executive Control of Behavior in the Rat

To study rapid sensorimotor remapping, we developed a method to train rats in a behavior in which subjects are cued, on each trial, to apply a sensorimotor association to orient either toward a visual target ("Pro") or away from it, toward its reverse ("Anti"). Multiple behavioral asymmetries suggested that Anti behavior is cognitively demanding while Pro is easier to learn and perform. This is consistent with a prominent hypothesis in the primate literature that Anti requires prefrontal cortex (PFC), whereas Pro could be mediated by midbrain superior colliculus (SC). Pharmacological inactivation of rat medial PFC supported its expected role in Anti. Remarkably, bilateral SC inactivation substantially impaired Anti while leaving Pro essentially intact. Moreover, SC inactivation eliminated the performance cost of switching from Anti to Pro tasks. Our results establish a rodent model of single-trial sensorimotor remapping and suggest a critical role for SC in the cognitively demanding Anti task.

Superior colliculus inactivation alters the relationship between covert visual attention and microsaccades

Microsaccades are tiny saccades that occur during gaze fixation. Whereas these movements have traditionally been viewed as random, it was recently discovered that microsaccade directions can be significantly biased by covertly attended visual stimuli. The detailed mechanisms mediating such a bias are neither known nor immediately obvious, especially because the amplitudes of the movements influenced by attentional cueing could be up to two orders of magnitude smaller than the eccentricity of the attended location. Here, we tested whether activity in the peripheral superior colliculus (SC) is necessary for this correlation between attentional cueing and microsaccades. We reversibly and focally inactivated SC neurons representing peripheral regions of visual space while rhesus monkeys performed a demanding covert visual attention task. The normal bias of microsaccade directions observed in each monkey before SC inactivation was eliminated when a cue was placed in the visual region affected by the inactivation; microsaccades were, instead, biased away from the affected visual space. When the cue was placed at another location unaffected by SC inactivation, the baseline cue-induced bias of microsaccade directions remained mostly intact, because the cue was in unaffected visual space, and any remaining changes were again explained by a repulsion of microsaccades away from the inactivated region. Our results indicate that peripheral SC activity is required for the link between microsaccades and the cueing of covert visual attention, and that it could do so by altering the probability of triggering microsaccades without necessarily affecting the motor generation of these movements.

Visual fixation as equilibrium: evidence from superior colliculus inactivation.

During visual fixation, the image of an object is maintained within the fovea. Previous studies have shown that such maintenance involves the deep superior colliculus (dSC). However, the mechanisms by which the dSC supports visual fixation remain controversial. According to one view, activity in the rostral dSC maintains gaze direction by preventing neurons in the caudal dSC from issuing saccade commands. An alternative hypothesis proposes that gaze direction is achieved through equilibrium of target position signals originating from the two dSCs. Here, we show in monkeys that artificially reducing activity in the rostral half of one dSC results in a biased estimate of target position during fixation, consistent with the second hypothesis, rather than an inability to maintain gaze fixation as predicted by the first hypothesis. After injection of muscimol at rostral sites in the dSC, fixation became more stable since microsaccade rate was reduced rather than increased. Moreover, the scatter of eye positions was offset relative to preinactivation baselines. The magnitude and the direction of the offsets depended on both the target size and the injected site in the collicular map. Other oculomotor parameters, such as the accuracy of saccades to peripheral targets and the amplitude and velocity of fixational saccades, were largely unaffected. These results suggest that the rostral half of the dSC supports visual fixation through a distributed representation of behaviorally relevant target position signals. The inactivation-induced fixation offset establishes the foveal visual stimulation that is required to restore the balance of activity between the two dSCs.

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats.

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses.

Superior colliculus inactivation alters the influence of covert attention shifts on microsaccades

Superior colliculus inactivation alters the influence of covert attention shifts on microsaccades

Superior colliculus inactivation impairs covert selective attention to motion but does not alter gain modulation of motion signals in areas MT and MST

Superior colliculus inactivation impairs covert selective attention to motion but does not alter gain modulation of motion signals in areas MT and MST

Contribution of the retino‐tectal pathway to visually guided saccades after lesion of the primary visual cortex in monkeys

Previous reports on 'blindsight' have shown that some patients with lesions of the primary visual cortex (V1) could localize visual targets in their scotoma with hand and/or eye movements without visual awareness. A role of the retino-tectal pathway on residual vision has been proposed but the direct evidence for this still remains sparse. To examine this possibility, we inactivated the superior colliculus (SC) of unilateral V1-lesioned monkeys using microinjections of muscimol, and analysed the effects on visually guided saccades. Following muscimol injections into the contralesional SC, the monkeys performed the visually guided saccade task with relatively minor deficits. The effects of ipsilesional SC inactivation were more severe. After injections, the monkeys failed to localize the target within the visual field represented at the injection site on the SC map. The effects of ipsilesional SC inactivation may result from sensory deficits, motor deficits or a combination of both. To examine these possibilities, we tested the effects of SC inactivation on the motor system by investigating spontaneous saccades. After inactivation of the ipsilesional SC, spontaneous saccades toward the injection site were not abolished, suggesting that impairment of visually guided saccades following inactivation of the ipsilesional SC could not be explained solely by a motor deficit and was primarily due to a visual deficit, presumably by interfering with processing in the superficial layer. We conclude that the retino-tectal pathway plays an essential role in residual vision after V1 lesion. The results suggest that this pathway may be involved in mediating unconscious vision in blindsight patients.

Superior Colliculus Inactivation Alters the Weighted Integration of Visual Stimuli

The primate superior colliculus (SC) is important for the winner-take-all selection of targets for orienting movements. Such selection takes time, however, and the earliest motor responses typically are guided by a weighted vector average of the visual stimuli, before the winner-take-all selection of a single target. We tested whether SC activity plays a role in this initial stage of orienting by inactivating the SC in two macaques (Macaca mulatta) with local muscimol injections. After SC inactivation, initial orienting responses still followed a vector average, but the contribution of the visual stimulus inside the affected field was decreased, and the contribution of the stimulus outside the affected field was increased. These results demonstrate that the SC plays an important role in the weighted integration of visual signals for orienting, in addition to its role in the winner-take-all selection of the target.

Inactivation of Primate Superior Colliculus Biases Target Choice for Smooth Pursuit, Saccades, and Button Press Responses

In addition to its well-known role in the control of saccades, the primate superior colliculus (SC) has been implicated in the processes of target choice for overt orienting movements and for covert spatial attention. We focally inactivated the SC, by muscimol injection, while monkeys selected the target of a smooth pursuit, saccade, or button press response from two competing stimuli. The choice stimuli were placed so that one appeared within and the other appeared outside the affected visual field. SC inactivation biased the subject to choose stimuli out of the affected visual field for all three types of responses, although the effects on target choice were significantly smaller for button presses. Inactivation caused no changes in the selection of single stimuli within or out of the affected visual field, indicating the choice bias was not caused by deficits in response execution. The inactivation-induced bias for smooth pursuit and button press responses indicates SC activity is important for selecting the target, independent of any role in saccade preparation.

Superior colliculus inactivation biases target selection for smooth pursuit, saccades, and manual responses

Superior colliculus inactivation biases target selection for smooth pursuit, saccades, and manual responses

Deficits in saccade target selection after temporary inactivation of superior colliculus

Deficits in saccade target selection after temporary inactivation of superior colliculus