Frontal eye field inactivation alters the readout of superior colliculus activity for saccade generation in a task-dependent manner.

Saccades require a spatiotemporal transformation of activity between the intermediate layers of the superior colliculus (iSC) and downstream brainstem burst generator. The dynamic linear ensemble-coding model (Goossens and Van Opstal 2006) proposes that each iSC spike contributes a fixed mini-vector to saccade displacement. Although biologically-plausible, this model assumes cortical areas like the frontal eye fields (FEF) simply provide the saccadic goal to be executed by the iSC and brainstem burst generator. However, the FEF and iSC operate in unison during saccades, and a pathway from the FEF to the brainstem burst generator that bypasses the iSC exists. Here, we investigate the impact of large yet reversible inactivation of the FEF on iSC activity in the context of the model across four saccade tasks. We exploit the overlap of saccade vectors generated when the FEF is inactivated or not, comparing the number of iSC spikes for metrically-matched saccades. We found that the iSC emits fewer spikes for metrically-matched saccades during FEF inactivation. The decrease in spike count is task-dependent, with a greater decrease accompanying more cognitively-demanding saccades. Our results show that FEF integrity influences the readout of iSC activity in a task-dependent manner. We propose that the dynamic linear ensemble-coding model be modified so that FEF inactivation increases the gain of a readout parameter, effectively increasing the influence of a single iSC spike. We speculate that this modification could be instantiated by FEF and iSC pathways to the cerebellum that could modulate the excitability of the brainstem burst generator.

Impairment but not abolishment of express saccades after unilateral or bilateral inactivation of the frontal eye fields.

Express saccades are a manifestation of a visual grasp reflex triggered when visual information arrives in the intermediate layers of the superior colliculus (SCi), which in turn orchestrates the lower level brainstem saccade generator to evoke a saccade with a very short latency (~100 ms or less). A prominent theory regarding express saccades generation is that they are facilitated by preparatory signals, presumably from cortical areas, which prime the SCi before the arrival of visual information. Here, we test this theory by reversibly inactivating a key cortical input to the SCi, the frontal eye fields (FEF), while monkeys perform an oculomotor task that promotes express saccades. Across three tasks with a different combination of potential target locations and unilateral or bilateral FEF inactivation, we found a spared ability for monkeys to generate express saccades, despite decreases in express saccade frequency during FEF inactivation. This result is consistent with the FEF having a facilitatory but not critical role in express saccade generation, likely because other cortical areas compensate for the loss of preparatory input to the SCi. However, we also found decreases in the accuracy and peak velocity of express saccades generated during FEF inactivation, which argues for an influence of the FEF on the saccadic burst generator even during express saccades. Overall, our results shed further light on the role of the FEF in the shortest-latency visually-guided eye movements.NEW & NOTEWORTHY Express saccades are the shortest-latency saccade. The frontal eye fields (FEF) are thought to promote express saccades by presetting the superior colliculus. Here, by reversibly inactivating the FEF either unilaterally or bilaterally via cortical cooling, we support this by showing that the FEF plays a facilitative but not critical role in express saccade generation. We also found that FEF inactivation lowered express saccade peak velocity, emphasizing a contribution of the FEF to express saccade kinematics.

Frontal Eye Field Inactivation Reduces Saccade Preparation in the Superior Colliculus but Does Not Alter How Preparatory Activity Relates to Saccades of a Given Latency.

A neural correlate for saccadic reaction times (SRTs) in the gap saccade task is the level of low-frequency activity in the intermediate layers of the superior colliculus (iSC) just before visual target onset: greater levels of such preparatory iSC low-frequency activity precede shorter SRTs. The frontal eye fields (FEFs) are one likely source of iSC preparatory activity, since FEF preparatory activity is also inversely related to SRT. To better understand the FEF's role in saccade preparation, and the way in which such preparation relates to SRT, in two male rhesus monkeys, we compared iSC preparatory activity across unilateral reversible cryogenic inactivation of the FEF. FEF inactivation increased contralesional SRTs, and lowered ipsilesional iSC preparatory activity. FEF inactivation also reduced rostral iSC activity during the gap period. Importantly, the distributions of SRTs generated with or without FEF inactivation overlapped, enabling us to conduct a novel population-level analyses examining iSC preparatory activity just before generation of SRT-matched saccades. When matched for SRTs, we observed no change during FEF inactivation in the relationship between iSC preparatory activity and SRT-matched saccades across a range of SRTs, even for the occasional express saccade. Thus, while our results emphasize that the FEF has an overall excitatory influence on preparatory activity in the iSC, the communication between the iSC and downstream oculomotor brainstem is unaltered for SRT-matched saccades.

Frontal Eye Field Inactivation Diminishes Superior Colliculus Activity, But Delayed Saccadic Accumulation Governs Reaction Time Increases.

Stochastic accumulator models provide a comprehensive framework for how neural activity could produce behavior. Neural activity within the frontal eye fields (FEFs) and intermediate layers of the superior colliculus (iSC) support such models for saccade initiation by relating variations in saccade reaction time (SRT) to variations in such parameters as baseline, rate of accumulation of activity, and threshold. Here, by recording iSC activity during reversible cryogenic inactivation of the FEF in four male nonhuman primates, we causally tested which parameter(s) best explains concomitant increases in SRT. While FEF inactivation decreased all aspects of ipsilesional iSC activity, decreases in accumulation rate and threshold poorly predicted accompanying increases in SRT. Instead, SRT increases best correlated with delays in the onset of saccade-related accumulation. We conclude that FEF signals govern the onset of saccade-related accumulation within the iSC, and that the onset of accumulation is a relevant parameter for stochastic accumulation models of saccade initiation.SIGNIFICANCE STATEMENT The superior colliculus (SC) and frontal eye fields (FEFs) are two of the best-studied areas in the primate brain. Surprisingly, little is known about what happens in the SC when the FEF is temporarily inactivated. Here, we show that temporary FEF inactivation decreases all aspects of functionally related activity in the SC. This combination of techniques also enabled us to relate changes in SC activity to concomitant increases in saccadic reaction time (SRT). Although stochastic accumulator models relate SRT increases to reduced rates of accumulation or increases in threshold, such changes were not observed in the SC. Instead, FEF inactivation delayed the onset of saccade-related accumulation, emphasizing the importance of this parameter in biologically plausible models of saccade initiation.

A Causal Role for the Cortical Frontal Eye Fields in Microsaccade Deployment.

Microsaccades aid vision by helping to strategically sample visual scenes. Despite the importance of these small eye movements, no cortical area has ever been implicated in their generation. Here, we used unilateral and bilateral reversible inactivation of the frontal eye fields (FEF) to identify a cortical drive for microsaccades. Unexpectedly, FEF inactivation altered microsaccade metrics and kinematics. Such inactivation also impaired microsaccade deployment following peripheral cue onset, regardless of cue side or inactivation configuration. Our results demonstrate that the FEF provides critical top-down drive for microsaccade generation, particularly during the recovery of microsaccades after disruption by sensory transients. Our results constitute the first direct evidence, to our knowledge, for the contribution of any cortical area to microsaccade generation, and they provide a possible substrate for how cognitive processes can influence the strategic deployment of microsaccades.

Bilateral saccadic deficits following large and reversible inactivation of unilateral frontal eye field.

Inactivation permits direct assessment of the functional contribution of a given brain area to behavior. Previous inactivation studies of the frontal eye field (FEF) have either used large permanent ablations or reversible pharmacological techniques that only inactivate a small volume of tissue. Here we evaluated the impact of large, yet reversible, FEF inactivation on visually guided, delayed, and memory-guided saccades, using cryoloops implanted in the arcuate sulcus. While FEF inactivation produced the expected triad of contralateral saccadic deficits (increased reaction time, decreased accuracy and peak velocity) and performance errors (neglect or misdirected saccades), we also found consistent increases in reaction times of ipsiversive saccades in all three tasks. In addition, FEF inactivation did not increase the proportion of premature saccades to ipsilateral targets, as was predicted on the basis of pharmacological studies. Consistent with previous studies, greater deficits accompanied saccades toward extinguished visual cues. Our results attest to the functional contribution of the FEF to saccades in both directions. We speculate that the comparative effects of different inactivation techniques relate to the volume of inactivated tissue within the FEF. Larger inactivation volumes may reveal the functional contribution of more sparsely distributed neurons within the FEF, such as those related to ipsiversive saccades. Furthermore, while focal FEF inactivation may disinhibit the mirroring site in the other FEF, larger inactivation volumes may induce broad disinhibition in the other FEF that paradoxically prolongs oculomotor processing via increased competitive interactions.

Ultrasound-guided insertion of intramuscular electrodes into suboccipital muscles in the non-human primate.

The head-neck system is highly complex from a biomechanical and musculoskeletal perspective. Currently, the options for recording the recruitment of deep neck muscles in experimental animals are limited to chronic approaches requiring permanent implantation of electromyographic electrodes. Here, we describe a method for targeting deep muscles of the dorsal neck in non-human primates with intramuscular electrodes that are inserted acutely. Electrode insertion is guided by ultrasonography, which is necessary to ensure placement of the electrode in the target muscle. To confirm electrode placement, we delivered threshold electrical stimulation through the intramuscular electrode and visualized the muscle twitch. In one animal, we also compared recordings obtained from acutely- and chronically-implanted electrodes. This method increases the options for accessing deep neck muscles, and hence could be used in experiments for which the invasive surgery inherent to a chronic implant is not appropriate. This method could also be extended to the injection of pharmacological agents or anatomical tracers into specific neck muscles.