High-field FMRI reveals brain activation patterns underlying saccade execution in the human superior colliculus.

BACKGROUND: The superior colliculus (SC) has been shown to play a crucial role in the initiation and coordination of eye- and head-movements. The knowledge about the function of this structure is mainly based on single-unit recordings in animals with relatively few neuroimaging studies investigating eye-movement related brain activity in humans. METHODOLOGY/PRINCIPAL FINDINGS: The present study employed high-field (7 Tesla) functional magnetic resonance imaging (fMRI) to investigate SC responses during endogenously cued saccades in humans. In response to centrally presented instructional cues, subjects either performed saccades away from (centrifugal) or towards (centripetal) the center of straight gaze or maintained fixation at the center position. Compared to central fixation, the execution of saccades elicited hemodynamic activity within a network of cortical and subcortical areas that included the SC, lateral geniculate nucleus (LGN), occipital cortex, striatum, and the pulvinar. CONCLUSIONS/SIGNIFICANCE: Activity in the SC was enhanced contralateral to the direction of the saccade (i.e., greater activity in the right as compared to left SC during leftward saccades and vice versa) during both centrifugal and centripetal saccades, thereby demonstrating that the contralateral predominance for saccade execution that has been shown to exist in animals is also present in the human SC. In addition, centrifugal saccades elicited greater activity in the SC than did centripetal saccades, while also being accompanied by an enhanced deactivation within the prefrontal default-mode network. This pattern of brain activity might reflect the reduced processing effort required to move the eyes toward as compared to away from the center of straight gaze, a position that might serve as a spatial baseline in which the retinotopic and craniotopic reference frames are aligned.

Different stimuli, different spatial codes: a visual map and an auditory rate code for oculomotor space in the primate superior colliculus.

Maps are a mainstay of visual, somatosensory, and motor coding in many species. However, auditory maps of space have not been reported in the primate brain. Instead, recent studies have suggested that sound location may be encoded via broadly responsive neurons whose firing rates vary roughly proportionately with sound azimuth. Within frontal space, maps and such rate codes involve different response patterns at the level of individual neurons. Maps consist of neurons exhibiting circumscribed receptive fields, whereas rate codes involve open-ended response patterns that peak in the periphery. This coding format discrepancy therefore poses a potential problem for brain regions responsible for representing both visual and auditory information. Here, we investigated the coding of auditory space in the primate superior colliculus(SC), a structure known to contain visual and oculomotor maps for guiding saccades. We report that, for visual stimuli, neurons showed circumscribed receptive fields consistent with a map, but for auditory stimuli, they had open-ended response patterns consistent with a rate or level-of-activity code for location. The discrepant response patterns were not segregated into different neural populations but occurred in the same neurons. We show that a read-out algorithm in which the site and level of SC activity both contribute to the computation of stimulus location is successful at evaluating the discrepant visual and auditory codes, and can account for subtle but systematic differences in the accuracy of auditory compared to visual saccades. This suggests that a given population of neurons can use different codes to support appropriate multimodal behavior.

The frontal eye field sends predictively remapped visual signals to the superior colliculus

We perceive a stable visual world even though saccades often move our retinas. One way the brain may achieve a stable visual percept is through predictive remapping of visual receptive fields: just before a saccade, the receptive field of many neurons moves from its current location ("current receptive field") to the location it is expected to occupy after the saccade ("future receptive field"). Goldberg and colleagues found such remapping in cortical areas, e.g. in the frontal eye field (FEF), as well as in the intermediate layers of the superior colliculus (SC). In the present study we investigated the source of the SC's remapped visual signals. Do some of them come from the FEF? We identified FEF neurons that project to the SC using antidromic stimulation. For neurons with a visual response, we tested whether the receptive field shifted just prior to making a saccade. Saccadic amplitudes were chosen to be as small as possible while clearly separating the current and future receptive fields; they ranged from 5-30 deg. in amplitude and were directed contraversively. The saccadic target was a small red spot. We probed visual responsiveness at the current and future receptive field locations using a white spot flashed at various times before or after the saccade. Predictive remapping was indicated by a visual response to a probe flashed in the future receptive field just before the saccade began. We found that many FEF neurons projecting to the SC exhibited predictive remapping. Moreover, the remapping was as fast and strong as any previously reported for FEF or SC. It is clear, therefore, that remapped visual signals are sent from FEF to SC, providing direct evidence that the FEF is one source of the SC's remapped visual signals. Because remapping requires information about an imminent saccade, we hypothesize that remapping in FEF depends on corollary discharge signals such as those ascending from the SC through MD thalamus (Sommer and Wurtz 2002).

Division of labor in frontal eye field neurons during presaccadic remapping of visual receptive fields.

Our percept of visual stability across saccadic eye movements may be mediated by presaccadic remapping. Just before a saccade, neurons that remap become visually responsive at a future field (FF), which anticipates the saccade vector. Hence, the neurons use corollary discharge of saccades. Many of the neurons also decrease their response at the receptive field (RF). Presaccadic remapping occurs in several brain areas including the frontal eye field (FEF), which receives corollary discharge of saccades in its layer IV from a collicular-thalamic pathway. We studied, at two levels, the microcircuitry of remapping in the FEF. At the laminar level, we compared remapping between layers IV and V. At the cellular level, we compared remapping between different neuron types of layer IV. In the FEF in four monkeys (Macaca mulatta), we identified 27 layer IV neurons with orthodromic stimulation and 57 layer V neurons with antidromic stimulation from the superior colliculus. With the use of established criteria, we classified the layer IV neurons as putative excitatory (n = 11), putative inhibitory (n = 12), or ambiguous (n = 4). We found that just before a saccade, putative excitatory neurons increased their visual response at the RF, putative inhibitory neurons showed no change, and ambiguous neurons increased their visual response at the FF. None of the neurons showed presaccadic visual changes at both RF and FF. In contrast, neurons in layer V showed full remapping (at both the RF and FF). Our data suggest that elemental signals for remapping are distributed across neuron types in early cortical processing and combined in later stages of cortical microcircuitry.

A subcortical source of visual input to the frontal eye field

Many neurons in the frontal eye field (FEF) exhibit visual responses and are thought to play important roles in visuosaccadic behavior. The FEF, however, is far removed from striate cortex. Where do the FEF's visual signals come from? Usually they are reasonably assumed to enter the FEF through afferents from extrastriate cortex. Here we show that, surprisingly, visual signals also enter the FEF through a subcortical route: a disynaptic, ascending pathway originating in the intermediate layers of the superior colliculus (SC). We recorded from identified neurons at all three stages of this pathway (n=30-40 in each sample): FEF recipient neurons, orthodromically activated from the SC; mediodorsal thalamus (MD) relay neurons, antidromically activated from FEF and orthodromically activated from SC; and SC source neurons, antidromically activated from MD. We studied the neurons while monkeys performed delayed saccade tasks designed to temporally resolve visual responses from presaccadic discharges. We found, first, that most neurons at every stage in the pathway had visual responses, presaccadic bursts, or both. Second, we found marked similarities between the SC source neurons and MD relay neurons: in both samples, about 15% of the neurons had only a visual response, 10% had only a presaccadic burst, and 75% had both. In contrast, FEF recipient neurons tended to be more visual in nature: 50% had only a visual response, none had only a presaccadic burst, and 50% had both a visual response and a presaccadic burst. This suggests that in addition to their subcortical inputs, these FEF neurons also receive other visual inputs, e.g. from extrastriate cortex. We conclude that visual activity in the FEF results not only from cortical afferents but also from subcortical inputs. Intriguingly, this implies that some of the visual signals in FEF are pre-processed by the SC.

Influence of the thalamus on spatial visual processing in frontal cortex.

Each of our movements activates our own sensory receptors, and therefore keeping track of self-movement is a necessary part of analysing sensory input. One way in which the brain keeps track of self-movement is by monitoring an internal copy, or corollary discharge, of motor commands. This concept could explain why we perceive a stable visual world despite our frequent quick, or saccadic, eye movements: corollary discharge about each saccade would permit the visual system to ignore saccade-induced visual changes. The critical missing link has been the connection between corollary discharge and visual processing. Here we show that such a link is formed by a corollary discharge from the thalamus that targets the frontal cortex. In the thalamus, neurons in the mediodorsal nucleus relay a corollary discharge of saccades from the midbrain superior colliculus to the cortical frontal eye field. In the frontal eye field, neurons use corollary discharge to shift their visual receptive fields spatially before saccades. We tested the hypothesis that these two components-a pathway for corollary discharge and neurons with shifting receptive fields-form a circuit in which the corollary discharge drives the shift. First we showed that the known spatial and temporal properties of the corollary discharge predict the dynamic changes in spatial visual processing of cortical neurons when saccades are made. Then we moved from this correlation to causation by isolating single cortical neurons and showing that their spatial visual processing is impaired when corollary discharge from the thalamus is interrupted. Thus the visual processing of frontal neurons is spatiotemporally matched with, and functionally dependent on, corollary discharge input from the thalamus. These experiments establish the first link between corollary discharge and visual processing, delineate a brain circuit that is well suited for mediating visual stability, and provide a framework for studying corollary discharge in other sensory systems.

What the brain stem tells the frontal cortex. II. Role of the SC-MD-FEF pathway in corollary discharge.

One way we keep track of our movements is by monitoring corollary discharges or internal copies of movement commands. This study tested a hypothesis that the pathway from superior colliculus (SC) to mediodorsal thalamus (MD) to frontal eye field (FEF) carries a corollary discharge about saccades made into the contralateral visual field. We inactivated the MD relay node with muscimol in monkeys and measured corollary discharge deficits using a double-step task: two sequential saccades were made to the locations of briefly flashed targets. To make second saccades correctly, monkeys had to internally monitor their first saccades; therefore deficits in the corollary discharge representation of first saccades should disrupt second saccades. We found, first, that monkeys seemed to misjudge the amplitudes of their first saccades; this was revealed by systematic shifts in second saccade end points. Thus corollary discharge accuracy was impaired. Second, monkeys were less able to detect trial-by-trial variations in their first saccades; this was revealed by reduced compensatory changes in second saccade angles. Thus corollary discharge precision also was impaired. Both deficits occurred only when first saccades went into the contralateral visual field. Single-saccade generation was unaffected. Additional deficits occurred in reaction time and overall performance, but these were bilateral. We conclude that the SC-MD-FEF pathway conveys a corollary discharge used for coordinating sequential saccades and possibly for stabilizing vision across saccades. This pathway is the first elucidated in what may be a multilevel chain of corollary discharge circuits extending from the extraocular motoneurons up into cerebral cortex.

When strangers pass: processing of mutual and averted social gaze in the superior temporal sulcus.

Using functional magnetic resonance imaging (fMRI), we investigated brain activity evoked by mutual and averted gaze in a compelling and commonly experienced social encounter. Through virtual-reality goggles, subjects viewed a man who walked toward them and shifted his neutral gaze either toward (mutual gaze) or away (averted gaze) from them. Robust activity was evoked in the superior temporal sulcus (STS) and fusiform gyrus (FFG). For both conditions, STS activity was strongly right lateralized. Mutual gaze evoked greater activity in the STS than did averted gaze, whereas the FFG responded equivalently to mutual and averted gaze. Thus, we show that the STS is involved in processing social information conveyed by shifts in gaze within an overtly social context. This study extends understanding of the role of the STS in social cognition and social perception by demonstrating that it is highly sensitive to the context in which a human action occurs.