The macaque midbrain reticular formation sends side-specific feedback to the superior colliculus

The central mesencephalic reticular formation (cMRF) likely plays a role in gaze control, as cMRF neurons receive tectal input and provide a bilateral projection back to the superior colliculus (SC). We examined the important question of whether this feedback is excitatory or inhibitory. Biotinylated dextran amine (BDA) was injected into the cMRF of M. fascicularis monkeys to anterogradely label reticulotectal terminals and retrogradely label tectoreticular neurons. BDA labeled profiles in the ipsi- and contralateral intermediate gray layer (SGI) were examined electron microscopically. Postembedding GABA immunochemistry was used to identify putative inhibitory profiles. Nearly all (94.7%) of the ipsilateral BDA labeled terminals were GABA positive, but profiles postsynaptic to these labeled terminals were exclusively GABA negative. In addition, BDA labeled terminals were observed to contact BDA labeled dendrites, indicating the presence of a monosynaptic feedback loop connecting the cMRF and ipsilateral SC. In contrast, within the contralateral SGI, half of the BDA labeled terminals were GABA positive, while more than a third were GABA negative. All the postsynaptic profiles were GABA negative. These results indicate the cMRF provides inhibitory feedback to the ipsilateral side of the SC, but it has more complex effects on the contralateral side. The ipsilateral projection may help tune the “winner-take-all” mechanism that produces a unified saccade signal, while the contralateral projections may contribute to the coordination of activity between the two colliculi.     

Interaction of the frontal eye field and superior colliculus for saccade generation

Both the frontal eye field (FEF) in the prefrontal cortex and the superior colliculus (SC) on the roof of the midbrain participate in the generation of rapid or saccadic eye movements and both have projections to the premotor circuits of the brain stem where saccades are ultimately generated. In the present experiments, we tested the contributions of the pathway from the FEF to the premotor circuitry in the brain stem that bypasses the SC. We assayed the contribution of the FEF to saccade generation by evoking saccades with direct electrical stimulation of the FEF. To test the role of the SC in conveying information to the brain stem, we inactivated the SC, thereby removing the circuit through the SC to the brain stem, and leaving only the direct FEF-brain stem pathway. If the contributions of the direct pathway were substantial, removal of the SC should have minimal effect on the FEF stimulation, whereas if the FEF stimulation were dependent on the SC, removal of the SC should alter the effect of FEF stimulation. By acutely inactivating the SC, instead of ablating it, we were able to test the efficiency of the direct FEF-brain stem pathway before substantial compensatory mechanisms could mask the effect of removing the SC. We found two striking effects of SC inactivation. In the first, we stimulated the FEF at a site that evoked saccades with vectors that were very close to those evoked at the site of the SC inactivation, and with such optimal alignment, we found that SC inactivation eliminated the saccades evoked by FEF stimulation. The second effect was evident when the FEF evoked saccades were disparate from those evoked in the SC, and in this case we observed a shift in the direction of the evoked saccade that was consistent with the SC inactivation removing a component of a vector average. Together these observations lead to the conclusion that in the nonablated monkey the direct FEF-brain stem pathway is not functionally sufficient to generate accurate saccades in the absence of the indirect pathway that courses from the FEF through the SC to the brain stem circuitry. We suggest that the recovery of function following SC ablation that has been seen in previous studies must result not from the use of an already functioning parallel pathway but from neural plasticity within the saccadic system.     

Multielectrode evidence for spreading activity across the superior colliculus movement map

The monkey superior colliculus (SC) has maps for both visual input and movement output in the superficial and intermediate layers, respectively, and activity on these maps is generally related to visual stimuli only in one part of the visual field and/or to a restricted range of saccadic eye movements to those stimuli. For some neurons within these maps, however, activity has been reported to spread from the caudal SC to the rostral SC during the course of a saccade. This spread of activity was inferred from averages of recordings at different sites on the SC movement map during saccades of different amplitudes and even in different monkeys. In the present experiments, SC activity was recorded simultaneously in pairs of neurons to observe the spread of activity during individual saccades. Two electrodes were positioned along the rostral-caudal axis of the SC with one being more caudal than the other, and 60 neuron pairs whose movement fields were large enough to see a spread of activity were studied. During individual saccades, the relative time of discharge of the two neurons was compared using 1) the time difference between peak discharge of the two neurons, 2) the difference between the "median activation time" of the two neurons, and 3) the shift required to align the two discharge patterns using cross-correlation. All three analysis methods gave comparable results. Many pairs of neurons were activated in sequence during saccade generation, and the order of activation was most frequently caudal to rostral. Such a sequence of activation was not observed in every neuron pair, but over the sample of neuron pairs studied, the spread was statistically significant. When we compared the time of neuronal activity to the time of saccade onset, we found that the caudal neuronal activity was more likely to be before the saccade, whereas the rostral neuronal activity was more likely to be during the saccade. These results demonstrate that when individual pairs of neurons are examined during single saccades there is evidence of a caudal to rostral spread of activity within the monkey SC, and they confirm the previous inferences of a spread of activity drawn from observations on averaged neuronal activity during multiple saccades. The functional contribution of this spread of activity remains to be determined.     

Composition and topographic organization of signals sent from the frontal eye field to the superior colliculus

The frontal eye field (FEF) and superior colliculus (SC) contribute to saccadic eye movement generation, and much of the FEF's oculomotor influence may be mediated through the SC. The present study examined the composition and topographic organization of signals flowing from FEF to SC by recording from FEF neurons that were antidromically activated from rostral or caudal SC. The first and most general result was that, in a sample of 88 corticotectal neurons, the types of signals relayed from FEF to SC were highly diverse, reflecting the general population of signals within FEF rather than any specific subset of signals. Second, many neurons projecting from FEF to SC carried signals thought to reflect cognitive operations, namely tonic discharges during the delay period of a delayed-saccade task (delay signals), elevated discharges during the gap period of a gap task (gap increase signals), or both. Third, FEF neurons discharging during fixation were found to project to the SC, although they did not project preferentially to rostral SC, where similar fixation neurons are found. Neurons that did project preferentially to the rostral SC were those with foveal visual responses and those pausing during the gap period of the gap task. Many of the latter neurons also had foveal visual responses, presaccadic pauses in activity, and postsaccadic increases in activity. These two types of rostral-projecting neurons therefore may contribute to the activity of rostral SC fixation neurons. Fourth, conduction velocity was used as an indicator of cell size to correct for sampling bias. The outcome of this correction procedure suggested that among the most prevalent neurons in the FEF corticotectal population are those carrying putative cognitive-related signals, i.e., delay and gap increase signals, and among the least prevalent are those carrying presaccadic burst discharges but lacking peripheral visual responses. Fifth, corticotectal neurons carrying various signals were biased topographically across the FEF. Neurons with peripheral visual responses but lacking presaccadic burst discharges were biased laterally, neurons with presaccadic burst discharges but lacking peripheral visual responses were biased medially, and neurons carrying delay or gap increase signals were biased dorsally. Finally, corticotectal neurons were distributed within the FEF as a function of their visual or movement field eccentricity and projected to the SC such that eccentricity maps in both structures were closely aligned. We conclude that the FEF most likely influences the activity of SC neurons continuously from the start of fixation, through visual analysis and cognitive manipulations, until a saccade is generated and fixation begins anew. Furthermore, the projection from FEF to SC is highly topographically organized in terms of function at both its source and its termination.     

Input to the primate frontal eye field from the substantia nigra,superior colliculus,and dentate nucleus demonstrated by transneuronal transport

The purpose of these experiments was to study the subcortical input to the frontal eye field (FEF) and to determine which subcortical structures might project to the FEF via pathways that contain only a single intervening synapse. We used retrograde transneuronal transport of herpes simplex virus type 1 (HSV-1) to label second-order neurons that send information to the FEF of cebus monkeys. The saccade region of the FEF was identified physiologically using intracortical stimulation and then injected with a strain of HSV-1 known to be transported transneuronally in the retrograde direction. Retrograde transport of virus labeled neurons was observed in all the thalamic sites known to innervate the FEF. In addition, we found neurons labeled by transneuronal transport in three subcortical sites: the pars reticulata of the substantia nigra, the optic and intermediate gray layers of the superior colliculus, and a posterior portion of the dentate nucleus of the cerebellum. Each of these sites has been shown in prior studies to project to thalamic regions that innervate the FEF. Moreover, the neurons labeled through transneuronal transport were located in a subregion of each subcortical site that is known to be involved in oculomotor control. These observations demonstrate that signals from the substantia nigra, superior colliculus and dentate nucleus can have a significant influence on the output of the FEF.     

Visuotopic information conveyed by each eye to the opossum's superior colliculus

Summary The uniocular visual field representations on the superior colliculus (SC), as estimated from multiunit response field centres about the horizontal meridian, were compared in midpontine pretrigeminal opossums (Didelphis marsupialis aurita Wied 1826). Recordings from the rostral pole (RP) and its caudal neighbour, the direct binocular region (DBR), as defined by Rocha-Miranda et al. (1978), were distinguished by the histological control. The results showed that while the hemifield contralateral to the recording site was well represented on the DBR by both eyes, the ipsilateral hemifield was generously represented at the RP only by the contralateral eye. At the RP the ipsilateral eye usually conveyed information about the vertical meridian, bringing about an expanded representation of the central visual space. Distinct patterns of representation were also recognized on graphs which relate recording sites along the AP axis of the SC with the azimuths of response field centres. The representation of the vertical reference meridian upon this axis on an oculocentric system was estimated from the DBR data and localized in the RP, at about 500 m from the rostral end, for the ipsilateral eye (Vo') and in the DBR, at about 800 m for the other eye (Vo). Similarly, plots of the magnification factor against the AP collicular axis indicated different strategies of representation for each eye. At the segment between 500 and 800 m on this axis the magnification factors of the ipsilateral eye were usually much higher than those of the other eye. Furthermore, horizontal disparities between field centres were shown to have distinct distributions along the AP axis within the RP and DBR regions. At the latter a constant crossed disparity value (median=5.3°) was present along the AP axis while at the former greater variability and higher central disparity values were detected. An argument is developed based on this data to suggest that under our conditions the central binocular axis of the opossum are convergent with respect to the visual axis and their representation centred about the RP/DBR boundary. The different strategy of representation adopted by each eye at these two regions argue against a redundancy in the processing of visual information at the RP and the DBR on the opposite side, both of which bear a representation of the same visual space when considering only the information conveyed by the eye contralateral to the RP. The possible roles of this organization and the relevancy of these findings for studies of plastic rearrangement are discussed.Supported by Financiadora de Estudos e Projetos (FINEP/ FUJB 4.3.83.0540.00), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq — Proc. 40.0220/82; 40.0304/83) and Conselho de Ensino para Graduados da UFRJ (CEPG/ UFRJ)     

Effects of eye position upon activity of neurons in macaque superior colliculus

We examined the activity of neurons in the deep layers of the superior colliculus of awake behaving rhesus monkeys during the performance of standard oculomotor tasks as well as during self-guided eye movements made while viewing natural images. The standard tasks were used to characterize the activity of neurons based on established criteria. The natural viewing paradigm enabled the sampling of neuronal activity during saccades and fixations distributed over a wide range of eye positions. Two distinct aspects of eye-movement behavior contributed to the modulation of firing activity in these neurons. The well-established influence of saccade amplitude and direction was strongest and most prevalent surrounding the time of the start of the saccade. However, the activity of these neurons was also affected by the orbital position of the eyes, and this effect was best observed during intervals of fixation. Many neurons were sensitive to both parameters, and the directions of their saccade vector and eye position response fields tended to be aligned. The sample of neurons included visual, build-up, and burst activities, alone or in combination. All of these activity types were included in the subpopulation of neurons with significant eye-position tuning, although position tuning was more common in neurons with build-up or burst activity and less common in neurons with visual activity. The presence of both eye-position as well as saccade-vector signals in the superior colliculus is likely important for its role in the planning and guidance of combined movements of the eyes and head.     

How the frontal eye field can impose a saccade goal on superior colliculus neurons.

Saccades were electrically evoked from the frontal eye field (FEF) of two trained monkeys while saccade-cells were recorded from the intermediate layers of the superior colliculus (SC). We found that FEF microstimulation, eliciting saccades of a given vector, excited SC saccade-cells encoding the same vector and inhibited all others. Such a mechanism can prevent competing commands from arising simultaneously in different structures.     

Frontal eye field contributions to rapid corrective saccades

Visually guided movements can be inaccurate, especially if unexpected events occur while the movement is programmed. Often errors of gaze are corrected before external feedback can be processed. Evidence is presented from macaque monkey frontal eye field (FEF), a cortical area that selects visual targets, allocates attention, and programs saccadic eye movements, for a neural mechanism that can correct saccade errors before visual afferent or performance monitoring signals can register the error. Macaques performed visual search for a color singleton that unpredictably changed position in a circular array as in classic double-step experiments. Consequently, some saccades were directed in error to the original target location. These were followed frequently by unrewarded, corrective saccades to the final target location. We previously showed that visually responsive neurons represent the new target location even if gaze shifted errantly to the original target location. Now we show that the latency of corrective saccades is predicted by the timing of movement-related activity in the FEF. Preceding rapid corrective saccades, the movement-related activity of all neurons began before explicit error signals arise in the medial frontal cortex. The movement-related activity of many neurons began before visual feedback of the error was registered and that of a few neurons began before the error saccade was completed. Thus movement-related activity leading to rapid corrective saccades can be guided by an internal representation of the environment updated with a forward model of the error.     

Neurons in the monkey midbrain with activity related to vergence eye movement and accommodation

We recorded from neurons dorsal and dorsolateral to the third nerve nucleus of the monkey whose discharge rates modulated when the monkey tracked targets moving in depth but not when it tracked targets moving from side to side. The neurons' activity modulated equally well whether the target moved directly toward one eye or the other. For most neurons the amplitude of modulation was similar whether the monkey tracked monocularly (blur cue alone), binocularly with accommodation open-loop (disparity cue alone), or in normal binocular viewing. By comparing the modulation in normal binocular viewing with that when the blur and disparity cues were in conflict we were able to show that 19 neurons discharged in relation to the vergence response alone and not to accommodation. Eight neurons discharged exclusively in relation to accommodation. While the monkeys tracked targets moving in depth so that target vergence varied with a sinusoidal time course (frequency 0.1 or 0.2 Hz) the discharge modulations of identified vergence cells generally showed much more phase lead than expected of motoneurons. We examined the activity of a subset of these vergence cells in response to a range of stimulus frequencies to compare the dynamics of these neurons with motoneurons. The phase leads were larger than those expected of motoneurons over the entire frequency range tested. We speculate that vergence neurons may selectively activate (directly or indirectly) motoneurons with longer time constants than the mean.     

Delay-period activity in visual, visuomovement, and movement neurons in the frontal eye field

In the present study, we examined the role of frontal eye field neurons in the maintenance of spatial information in a delayed-saccade paradigm. We found that visual, visuomovement, and movement neurons conveyed roughly equal amounts of spatial information during the delay period. Although there was significant delay-period activity in individual movement neurons, there was no significant delay-period activity in the averaged population of movement neurons. These contradictory results were reconciled by the finding that the population of movement neurons with memory activity consisted of two subclasses of neurons, the combination of which resulted in the cancellation of delay-period activity in the population of movement neurons. One subclass consisted of neurons with significantly greater delay activity in the preferred than in the null direction ("canonical"), whereas the other subclass consisted of neurons with significantly greater delay activity in the null direction than in the preferred direction ("paradoxical"). Preferred direction was defined by the saccade direction that evoked the greatest movement-related activity. Interestingly, the peak saccade-related activity of canonical neurons occurred before the onset of the saccade, whereas the peak saccade-related activity of paradoxical neurons occurred after the onset of the saccade. This suggests that the former, but not the latter, are directly involved in triggering saccades. We speculate that paradoxical neurons provide a mechanism by which spatial information can be maintained in a saccade-generating circuit without prematurely triggering a saccade.     

The effect of frontal eye field and superior colliculus lesions on saccadic latencies in the rhesus monkey

Rhesus monkeys were trained to make saccadic eye movements to visual targets using detection and discrimination paradigms in which they were required to make a saccade either to a solitary stimulus (detection) or to that same stimulus when it appeared simultaneously with several other stimuli (discrimination). The detection paradigm yielded a bimodal distribution of saccadic latencies with the faster mode peaking around 100 ms (express saccades); the introduction of a pause between the termination of the fixation spot and the onset of the target (gap) increased the frequency of express saccades. The discrimination paradigm, on the other hand, yielded only a unimodal distribution of latencies even when a gap was introduced, and there was no evidence for short-latency "express" saccades. In three monkeys either the frontal eye field or the superior colliculus was ablated unilaterally. Frontal eye field ablation had no discernible long-term effects on the distribution of saccadic latencies in either the detection or discrimination tasks. After unilateral collicular ablation, on the other hand, express saccades obtained in the detection paradigm were eliminated for eye movements contralateral to the lesion, leaving only a unimodal distribution of latencies. This deficit persisted throughout testing, which in one monkey continued for 9 mo. Express saccades were not observed again for saccades contralateral to the lesion, and the mean latency of the contralateral saccades was longer than the mean latency of the second peak for the ipsiversive saccades. The latency distribution of saccades ipsiversive to the collicular lesion was unaffected except for a few days after surgery, during which time an increase in the proportion of express saccades was evident. Saccades obtained with the discrimination paradigm yielded a small but reliable increase in saccadic latencies following collicular lesions, without altering the shape of the distribution. Unilateral muscimol injections into the superior colliculus produced results similar to those obtained immediately after collicular lesions: saccades contralateral to the injection site were strongly inhibited and showed increased saccadic latencies. This was accompanied by a decrease of ipsilateral saccadic latencies and an increase in the number of saccades falling into the express range. The results suggest that the superior colliculus is essential for the generation of short-latency (express) saccades and that the frontal eye fields do not play a significant role in shaping the distribution of saccadic latencies in the paradigms used in this study.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neuronal activity related to rule and conflict in macaque supplementary eye field

Neuronal activity in macaque supplementary eye field (SEF) is enhanced during performance of the antisaccade task. This could be related to the selection of targets by a difficult rule (move to a location diametrically opposite the cue) or to conflict between the automatic tendency to look at the cue and the voluntary intention to look away. To distinguish between rule- and conflict-based mechanisms of enhancement, we monitored neuronal activity in the SEF during performance of a delayed response task in which monkeys selected saccade targets in response to peripheral visual cues. In spatial trials, the monkey had to select as target the location marked by the cue. In color trials, the monkey had to select as target the location associated with the color of the cue. 'Color-congruent' trials resembled spatial trials in that saccades were directed to the location occupied by the cue. Nevertheless, many SEF neurons were sensitive to the rule being used, with the majority firing more strongly under the color-rule condition. 'Color-incongruent' trials resembled 'color-congruent' trials in that a color rule guided target selection. Nevertheless, many SEF neurons were sensitive to the spatial relation between cue and saccade, with the majority firing more strongly on trials in which they were incongruent. We conclude that neuronal activity in the SEF is enhanced in connection both with the use of a more difficult rule and with conflict.     

Saccadic eye movements following injection of lidocaine into the superior colliculus

Summary Ablation of the superior colliculus (SC) has generally produced limited deficits in the initiation of saccadic eye movements, usually an increase in the latency of saccades. However, recent studies using muscimol, a GABA agonist, to block afferents to the SC showed deficits in not only latency but in amplitude and velocity of saccades as well. These greater deficits might be dependent upon the testing of saccades shortly after the damage of SC before any compensation for the deficits could develop. The present experiments tested this hypothesis by injecting a local anesthetic into SC. The anesthetic inactivated the cells entirely rather than just deafferenting them, but still allowed testing immediately after the injection. Clear deficits were observed following injection of lidocaine into the SC. The amplitudes of saccades to visual targets were shortened, and the peak velocities of the saccades were reduced even if the reduced amplitude of the saccades was taken into account. Latency of saccades usually increased. The deficits were limited to the area of the visual field that overlapped the movement fields of the cells near the injection site. If the movement fields were in the periphery, saccades to the periphery were shortened following the injection of lidocaine. If the movement fields were near the center of gaze, saccades into the area were shortened, but the monkey was able to make saccades over the visual field related to the affected area to more peripheral targets. These experiments support the view that the SC normally conveys information on the amplitude and velocity of saccadic eye movements, but that gradual compensation can be made over time by other pathways when damage to the structure occurs.     

Frontal eye field lesions impair predictive and visually-guided pursuit eye movements

Summary The study initially explored the frontal eye field's (FEF) control of predictive eye movements, i.e., eye movements driven by previous rather than current sensory signals. Five monkeys were trained to pursue horizontal target motion, including sinusoidal targets and random-walk targets which sometimes deviated from a sine motion. Some subjects also tracked other target trajectories and optokinetic motion. FEF ablations or cold lesions impaired predictive pursuit, but also degraded visually guided foveal pursuit of all targets. Unilateral lesions impaired pursuit of targets moving in both horizontal orbital fields and in both directions of movement. Saccadic estimates of target motion were generally accurate. The slow-phase velocity of optokinetic pursuit (collected after 54 s of OKN) also appeared normal. Pursuit recovered over 1–3 weeks after surgery but the deficits were then reinstated by removal of FEF in the other hemisphere. Thereafter, a slight deficit persisted for up to 10 weeks of observation in two subjects. The pattern of symptoms suggests that FEF lies subsequent to parietal area MST and prior to the pontine nuclei in controlling pursuit eye movements.     

Hemodynamic response to emotional memory recall with eye movement

Previous studies on rapid eye movement sleep have demonstrated the effect of eye movement on emotional memory. However, the brain mechanism involved in the influence of the eye movement on the emotional recall remains unclear. We investigated the prefrontal response during an emotional memory recall with and without eye movement. Ten healthy volunteers were recruited. The changes in concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex were examined using near-infrared spectroscopy (NIRS) during a task that involved emotional recall with and without eye movement. Six participants demonstrated a significant increase in [oxy-Hb] during emotional recall, and the level of increase was reduced through repeated emotional recall with eye movement. The results suggest that eye movement is associated with a reduction in the hemodynamic response to emotional memory recall.