Suppressive control of optokinetic and vestibular nystagmus by the primate frontal eye field.

When the eyes are fixated on a spot, fixation neurons in the frontal eye field (FEF) show an increase in activity. Our previous study suggested that fixation neurons in the FEF contribute to the suppression of saccades and smooth pursuit eye movements to maintain active fixation. The present study examined the role of the FEF in the suppressive control of reflexive eye movements, optokinetic and vestibular nystagmus, in trained monkeys. Electrical stimulation in the FEF suppressed the quick and slow phases of optokinetic and vestibular nystagmus at an intensity lower than the threshold for eliciting electrically evoked saccades. Relatively weak suppression influenced the slow phase of vestibular nystagmus. During optokinetic or vestibular nystagmus, presentation of a stationary small spot to the eyes followed by fixation is known to suppress both the quick and slow phases of eye movements. We recorded the activity of fixation neurons in the FEF and found that fixation neurons usually showed a decrease in activity during optokinetic and vestibular nystagmus and an increase in activity during the suppression of nystagmus by visual fixation. The present results show that the activity of fixation neurons in the FEF is related to the suppressive control of optokinetic and vestibular nystagmus for maintaining active fixation. We discuss the role of a generalized visual fixation system that can maintain visual attention on an interesting object.NEW & NOTEWORTHY In this study, electrical stimulation in the frontal eye field (FEF) suppressed the quick and slow phases of optokinetic and vestibular nystagmus at an intensity subthreshold for eliciting saccades. Furthermore, the activity of fixation neurons in the FEF was related to the suppression of optokinetic and vestibular nystagmus by visual fixation. This suggests that a common neuronal assembly in the FEF may contribute to the suppressive control of different functional classes of eye movements.

Motor action of the frontal eye field on the eyes and neck in the monkey.

Focal stimulation in the frontal eye field (FEF) evoked eye movements that were often accompanied by neck movements. Experiments were performed with concurrent recording of both movements in trained monkeys. We recorded neck forces under a head-restrained condition with a force-measuring system. With the system, we measured forces along the x-, y-, and z-axes and torque about the z-axis. Torque about the z-axis that represented yaw rotation of the head was significantly affected by stimulation. We found that stimulation generated two types of motor actions of the eyes and neck. In the first type, contraversive neck forces were evoked by stimulation of the medial part of the FEF, where contraversive saccadic eye movements with large amplitudes were evoked. When the stimulus intensity was increased, saccades were evoked in an all-or-none manner, whereas the amplitude of neck forces increased gradually. In the second type, contraversive neck forces were evoked by stimulation of the medial and caudal part of the FEF, where ipsiversive slow eye movements were evoked. The depth profiles of amplitudes of neck forces were almost parallel to those of eye movements in individual stimulation tracks. The present results suggest that the FEF is involved in the control of motor actions of the neck as well as the eyes. The FEF area associated with contraversive saccades and contraversive neck movements may contribute to a gaze shift process, whereas that associated with ipsiversive slow eye movements and contraversive neck movements may contribute to a visual stabilization process. NEW & NOTEWORTHY Focal stimulation in the frontal eye field (FEF) evoked eye and neck movements. We recorded neck forces under a head-restrained condition with a force-measuring system. Taking advantage of this approach, we could analyze slow eye movements that were dissociated from the vestibuloocular reflex. We found ipsiversive slow eye movements in combination with contraversive neck forces, suggesting that the FEF may be a source of a corollary discharge signal for compensatory eye movements during voluntary neck movements.

Activity of fixation neurons in the monkey frontal eye field during smooth pursuit eye movements.

We recorded the activity of fixation neurons in the frontal eye field (FEF) in trained monkeys and analyzed their activity during smooth pursuit eye movements. Fixation neurons were densely located in the area of the FEF in the caudal part of the arcuate gyrus facing the inferior arcuate sulcus where focal electrical stimulation suppressed the generation of saccades and smooth pursuit in bilateral directions at an intensity lower than the threshold for eliciting electrically evoked saccades. Whereas fixation neurons discharged tonically during fixation, they showed a variety of discharge patterns during smooth pursuit, ranging from a decrease in activity to an increase in activity. Of these, more than two-thirds were found to show a reduction in activity during smooth pursuit in the ipsilateral and bilateral directions. The reduction in activity of fixation neurons began at pursuit initiation and continued during pursuit maintenance. When catch-up saccades during the initiation of pursuit were eliminated by a step-ramp target routine, the reduced activity of fixation neurons remained. The reduction in activity during pursuit was not dependent on the activity during fixation without a target. Based on these results, we discuss the role of the FEF at maintaining fixation in relation to various other brain areas. We suggest that fixation neurons in the FEF contribute to the suppression of smooth pursuit. These results suggest that FEF fixation neurons are part of a more generalized visual fixation system through which suppressive control is exerted on smooth pursuit, as well as saccades.

Neural substrate for suppression of omnipause neurons at the onset of saccades.

The saccade trigger signal was proposed by D.A. Robinson, but neural substrates for triggering saccades by inhibiting omnipause neuron (OPN) activity still remain controversial. We investigated tectal inputs to OPNs by recording intracellular potentials from OPNs and inhibitory burst neurons (IBNs) and searched for interneurons to inhibit OPNs in the brainstem of anesthetized cats. IBNs received monosynaptic excitation from the contralateral caudal superior colliculus (SC) and disynaptic inhibition via contralateral IBNs from the ipsilateral caudal SC, whereas IBNs received disynaptic inhibition from the rostral SC. The latter disynaptic inhibition was mediated by OPNs, since OPNs received monosynaptic excitation from the rostral SC and projected to IBNs. In contrast, OPNs received disynaptic inhibition from the caudal SC. This disynaptic inhibition from the caudal SC was mediated to OPNs by IBNs. These findings suggested possible roles of IBNs for triggering and maintaining saccades by actively inhibiting the tonic activity of OPNs.

Suppression of smooth pursuit eye movements induced by electrical stimulation of the monkey frontal eye field.

This study was performed to characterize the properties of the suppression of smooth pursuit eye movement induced by electrical stimulation of the frontal eye field (FEF) in trained monkeys. At the stimulation sites tested, we first determined the threshold for generating electrically evoked saccades (Esacs). We then examined the suppressive effects of stimulation on smooth pursuit at intensities that were below the threshold for eliciting Esacs. We observed that FEF stimulation induced a clear deceleration of pursuit at pursuit initiation and also during the maintenance of pursuit at subthreshold intensities. The suppression of pursuit occurred even in the absence of catch-up saccades during pursuit, indicating that suppression influenced pursuit per se. We mapped the FEF area that was associated with the suppressive effect of stimulation on pursuit. In a wide area in the FEF, suppressive effects were observed for ipsiversive, but not contraversive, pursuit. In contrast, we observed the bilateral suppression of both ipsiversive and contraversive pursuit in a localized area in the FEF. This area coincided with the area in which we have previously shown that stimulation suppressed the generation of saccades in bilateral directions and also where fixation neurons that discharged during fixation were concentrated. On the basis of these results, we compared the FEF suppression of pursuit with that of saccades with regard to several physiological properties and then discussed the role of the FEF in the suppression of both pursuit and saccades, and particularly in the maintenance of visual fixation.

Response properties of fixation neurons and their location in the frontal eye field in the monkey.

Electrical stimulation of the frontal eye field (FEF) has recently been reported to suppress the generation of saccades, which supports the idea that the FEF plays a role in maintaining attentive fixation. This study analyzed the activity of fixation neurons that discharged during fixation in the FEF in relation to visual fixation and saccades in trained monkeys. The neural activity of fixation neurons increased at the start of fixation and was maintained during fixation. When a fixation spot of light disappeared during steady fixation, different fixation neurons exhibited different categories of response, ranging from a decrease in activity to an increase in activity, indicating that there is a continuum of fixation neurons, from neurons with foveal visual-related activity to neurons with activity that is related to the motor act of fixating. Fixation neurons usually showed a decrease in their firing rate before the onset of visually guided saccades (Vsacs) and memory-guided saccades in any direction. The reduction in activity of fixation neurons nearly coincided with, or occurred slightly before, the increase in the activity of saccade-related movement neurons in the FEF in the same monkey. Although fixation neurons were scattered in the FEF, about two thirds of fixation neurons were concentrated in a localized area in the FEF at which electrical stimulation induced strong suppression of the initiation of Vsacs bilaterally. These results suggest that fixation neurons in the FEF are part of a suppression mechanism that could control the maintenance of fixation and the initiation of saccades.

Neural circuits for triggering saccades in the brainstem.

Here we review the functional anatomy of brainstem circuits important for triggering saccades. Whereas the rostral part of the superior colliculus (SC) is considered to be involved in visual fixation, the caudal part of the SC plays an important role in generation of saccades. We determined the neural connections from the rostral and caudal parts of the SC to inhibitory burst neurons (IBNs) and omnipause neurons (OPNs) in the nucleus raphe interpositus. To reveal the neural mechanisms of triggering saccadic eye movements, we analysed the effects of stimulation of the SC on intracellular potentials recorded from IBNs and OPNs in anaesthetized cats. Our studies show that IBNs receive monosynaptic excitation from the contralateral caudal SC, and disynaptic inhibition from the ipsilateral caudal SC, via contralateral IBNs. Further, IBNs receive disynaptic inhibition from the rostral part of the SC, on either side, via OPNs. Intracellular recording revealed that OPNs receive excitation from the rostral parts of the bilateral SCs, and disynaptic inhibition from the caudal SC mainly via IBNs. The neural connections determined in this study are consistent with the notion that the "fixation zone" is localized in the rostral SC, and suggest that IBNs, which receive monosynaptic excitation from the caudal "saccade zone," may inhibit tonic activity of OPNs and thereby trigger saccades.

Neural organization of the pathways from the superior colliculus to trochlear motoneurons.

The neural organization of the pathways from the superior colliculus (SC) to trochlear motoneurons was analyzed in anesthetized cats using intracellular recording and transneuronal labeling techniques. Stimulation of the ipsilateral or contralateral SC evoked excitation and inhibition in trochlear motoneurons with latencies of 1.1-2.3 and 1.1-3.8 ms, respectively, suggesting that the earliest components of excitation and inhibition were disynaptic. A midline section between the two SCs revealed that ipsi- and contralateral SC stimulation evoked disynaptic excitation and inhibition in trochlear motoneurons, respectively. Premotor neurons labeled transneuronally after application of wheat germ agglutinin-conjugated horseradish peroxidase into the trochlear nerve were mainly distributed ipsilaterally in the Forel's field H (FFH) and bilaterally in the interstitial nucleus of Cajal (INC). Consequently, we investigated these two likely intermediaries between the SC and trochlear nucleus electrophysiologically. Stimulation of the FFH evoked ipsilateral mono- and disynaptic excitation and contralateral disynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the ipsilateral SC facilitated FFH-evoked monosynaptic excitation. Stimulation of the INC evoked ipsilateral monosynaptic excitation and inhibition, and contralateral monosynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the contralateral SC facilitated contralateral INC-evoked monosynaptic inhibition. These results revealed a reciprocal input pattern from the SCs to vertical ocular motoneurons in the saccadic system; trochlear motoneurons received disynaptic excitation from the ipsilateral SC via ipsilateral FFH neurons and disynaptic inhibition from the contralateral SC via contralateral INC neurons. These inhibitory INC neurons were considered to be a counterpart of inhibitory burst neurons in the horizontal saccadic system.

Long descending motor tract axons and their control of neck and axial muscles.

It has been tacitly assumed that a long descending motor tract axon consists of a private line connecting the cell of origin to a single muscle, as a motoneuron innervates a single muscle. However, this notion of a long descending motor tract referred to as a private line is no longer tenable, since recent studies have showed that axons of all major long descending motor tracts send their axon collaterals to multiple spinal segments, suggesting that they may exert simultaneous influences on different groups of spinal interneurons and motoneurons of multiple muscles. The long descending motor systems are divided into two groups, the medial and the lateral systems including interneurons and motoneurons. In this chapter, we focus mainly on the medial system (vestibulospinal, reticulospinal and tectospinal systems) in relation to movement control of the neck, describe the intraspinal morphologies of single long descending motor tract axons that are stained with intracellular injection of horseradish peroxidase, and provide evidence that single long motor-tract neurons are implicated in the neural implementation of functional synergies for head movements.

Vestibular cortical area in the periarcuate cortex: its afferent and efferent projections.

Vestibular input to the periarcuate cortex in the Japanese monkey was examined by analyzing laminar field potentials evoked by electrical stimulation of the vestibular nerve. Vestibular-evoked potentials consisted of early-positive and late-negative potentials and early-negative and late-positive potentials in the superficial and deep layers of the cortex, respectively. They were distributed bilaterally in the periarcuate cortex around the junction of the spur and the arcuate sulcus. This vestibular-projecting area corresponded to the periarcuate area where retrogradely-labeled corticovestibular neurons were distributed after the injection of a tracer into the vestibular nuclei. Comparison of the vestibular-projection area with the distribution of smooth pursuit-related neurons in the same monkey revealed that such neurons existed in the vestibular-projecting area of the periarcuate cortex.

Synaptic inputs and their pathways from fixation and saccade zones of the superior colliculus to inhibitory burst neurons and pause neurons.

The caudal part of the superior colliculus (SC) plays an important role in the generation of saccades, whereas the rostral part of the SC is considered to be involved in visual fixation. The present study was performed to determine neural connections from the rostral and caudal parts of the SC to inhibitory burst neurons (IBNs) and pause neurons (PNs) in the nucleus raphe interpositus in the anesthetized cat, and to reveal the functional role of the rostral SC on eye movements. The intracellular potentials from IBNs and PNs were recorded, and the effects of stimulation of the SC on these neurons were analyzed. The results show that IBNs receive monosynaptic excitation from the contralateral caudal SC, and disynaptic inhibition from the ipsilateral caudal SC via contralateral IBNs. In addition, IBNs receive disynaptic inhibition from the rostral part of the SC on either side via inhibitory interneurons other than IBNs. Intracellular recording from PNs revealed that they receive convergent excitation from the rostral parts of the bilateral superior colliculi and that the rostral SC inhibits IBNs on both sides via PNs. The neural connections determined in this study support the functional independence of the rostral SC and are consistent with the notion that the "fixation zone" is localized in the rostral SC. These results show that the fixation zone in the rostral SC may suppress the initiation of bilateral saccades via pause neurons.

Initiation and suppression of saccades by the frontal eye field in the monkey.

After a saccadic eye movement occurs to an interesting object appearing in the visual field, visual fixation holds its image on the fovea and suppresses saccades to other objects appearing in the visual field. To understand the neural mechanism of visual fixation, the effects of electrical stimulation of the frontal eye field (FEF) on the generation of electrically evoked saccades (Esacs) and the suppression of saccades in trained monkeys were investigated. When the properties of the electrically evoked suppression of visually guided (Vsacs) and memory-guided saccades (Msacs) were examined, two types of suppression were found. Stimulation of a wide area of the FEF suppressed only ipsiversive Vsacs and Msacs at stimulus intensities lower than those for eliciting Esacs, whereas stimulation of a localized area of the FEF suppressed the initiation of both Vsacs and Msacs in any direction during and approximately 50 ms after stimulation. However, neither stimulation affected the vector of these saccades. The thresholds for suppression were usually less than 50 microA. The most effective stimulation timing for the suppression of ipsiversive and contraversive Vsacs was approximately 40 to 50 ms before saccade onset. Therefore, suppression occurred in the efferent pathway for Vsacs at the premotor rather than the motoneuronal level, most likely in the superior colliculus and/or the paramedian pontine reticular formation. The results suggest that the suppression in the FEF may play a role in maintaining visual fixation by suppressing the generation of saccades.

Suppression of visually and memory-guided saccades induced by electrical stimulation of the monkey frontal eye field. I. Suppression of ipsilateral saccades.

When a saccade occurs to an interesting object, visual fixation holds its image on the fovea and suppresses saccades to other objects. Electrical stimulation of the frontal eye field (FEF) has been reported to elicit saccades, and recently also to suppress saccades. This study was performed to characterize properties of the suppression of visually guided (Vsacs) and memory-guided saccades (Msacs) induced by electrical stimulation of the FEF in trained monkeys. For any given stimulation site, we determined the threshold for electrically evoked saccades (Esacs) at < or =50 microA and then examined suppressive effects of stimulation at the same site on Vsacs and Msacs. FEF stimulation suppressed the initiation of both Vsacs and Msacs during and about 50 ms after stimulation at stimulus intensities lower than those for eliciting Esacs, but did not affect the vector of these saccades. Suppression occurred for ipsiversive but not contraversive saccades, and more strongly for saccades with larger amplitudes and those with initial eye positions shifted more in the saccadic direction. The most effective stimulation timing for suppression was about 50 ms before saccade onset, which suggests that suppression occurred in the efferent pathway for generating Vsacs at the premotor rather than the motoneuronal level, most probably in the superior colliculus and/or the paramedian pontine reticular formation. Suppression sites of ipsilateral saccades were distributed over the classical FEF where saccade-related movement neurons were observed. The results suggest that the FEF may play roles in not only generating contraversive saccades but also maintaining visual fixation by suppressing ipsiversive saccades.

Suppression of visually and memory-guided saccades induced by electrical stimulation of the monkey frontal eye field. II. Suppression of bilateral saccades.

To understand the neural mechanism of fixation, we investigated effects of electrical stimulation of the frontal eye field (FEF) and its vicinity on visually guided (Vsacs) and memory-guided saccades (Msacs) in trained monkeys and found that there were two types of suppression induced by the electrical stimulation: suppression of ipsilateral saccades and suppression of bilateral saccades. In this report, we characterized the properties of the suppression of bilateral Vsacs and Msacs. Stimulation of the bilateral suppression sites suppressed the initiation of both Vsacs and Msacs in all directions during and approximately 50 ms after stimulation but did not affect the vector of these saccades. The suppression was stronger for ipsiversive larger saccades and contraversive smaller saccades, and saccades with initial eye positions shifted more in the saccadic direction. The most effective stimulation timing for the suppression of ipsilateral and contralateral Vsacs was approximately 40-50 ms before saccade onset, indicating that the suppression occurred most likely in the superior colliculus and/or the paramedian pontine reticular formation. Suppression sites of bilateral saccades were located in the prearcuate gyrus facing the inferior arcuate sulcus where stimulation induced suppression at < or =40 microA but usually did not evoke any saccades at 80 microA and were different from those of ipsilateral saccades where stimulation evoked saccades at < or =50 microA. The bilateral suppression sites contained fixation neurons. The results suggest that fixation neurons in the bilateral suppression area of the FEF may play roles in maintaining fixation by suppressing saccades in all directions.

Functional synergies among neck muscles revealed by branching patterns of single long descending motor-tract axons.

In this chapter, we describe our recent work on the divergent properties of single, long descending motor-tract neurons in the spinal cord, using the method of intra-axonal staining with horseradish peroxidase, and serial-section, three-dimensional reconstruction of their axonal trajectories. This work provides evidence that single motor-tract neurons are implicated in the neural implementation of functional synergies for head movements. Our results further show that single medial vestibulospinal tract (MVST) neurons innervate a functional set of multiple neck muscles, and thereby implement a canal-dependent, head-movement synergy. Additionally, both single MVST and reticulospinal axons may have similar innervation patterns for neck muscles, and thereby control the same functional sets of neck muscles. In order to stabilize redundant control systems in which many muscles generate force across several joints, the CNS routinely uses a combination of a control hierarchy and sensory feedback. In addition, in the head-movement system, the elaboration of functional synergies among neck muscles is another strategy, because it helps to decrease the degrees of freedom in this particularly complicated control system.