Modest gaze-related discharge modulation in monkey dorsal premotor cortex during a reaching task performed with free fixation

Recent studies have shown that gaze angle modulates reach-related neural activity in many cortical areas, including the dorsal premotor cortex (PMd), when gaze direction is experimentally controlled by lengthy periods of imposed fixation. We looked for gaze-related modulation in PMd during the brief fixations that occur when a monkey is allowed to look around freely without experimentally imposed gaze control while performing a center-out delayed arm-reaching task. During the course of the instructed-delay period, we found significant effects of gaze angle in 27-51% of PMd cells. However, for 90-95% of cells, these effects accounted for <20% of the observed discharge variance. The effect of gaze was significantly weaker than the effect of reach-related variables. In particular, cell activity during the delay period was more strongly related to the intended movement expressed in arm-related coordinates than in gaze-related coordinates. Under the same experimental conditions, many cells in medial parietal cortex exhibited much stronger gaze-related modulation and expressed intended movement in gaze-related coordinates. In summary, gaze direction-related modulation of cell activity is indeed expressed in PMd during the brief fixations that occur in natural oculomotor behavior, but its overall effect on cell activity is modest.     

Correlation of primate superior colliculus and reticular formation discharge with proximal limb muscle activity

We studied the discharge of neurons from both the superior colliculus (SC) and the underlying mesencephalic reticular formation (MRF) and its relation to the simultaneously recorded activity of 11 arm muscles. The 242 neurons tested with a center-out reach task yielded 2,586 pairs of neuron/muscle cross-correlations (normalized, such that perfect correlations are +/-1.0). Of these, 43% had peaks with magnitude as large as 0.15, a value that corresponds to the 5% level of significance, and 16% were as large as 0.25. The great majority of peaks in this latter group was positive. The median lag time within this group was 52 ms, indicating that the neuronal discharge tended to precede the correlated muscle activity. We found a small but significantly higher proportion of cells with these relatively strong correlations in the MRF than in the SC. For both areas, these occurred most frequently with muscles of the shoulder girdle and became less frequent for axial as well as for increasingly distal arm musculature. The results support a role for the SC and MRF in guiding the arm during reach movements via the control of proximal limb musculature.     

Arm-movement-related neurons in the primate superior colliculus and underlying reticular formation: comparison of neuronal activity with EMGs of muscles of the shoulder, arm and trunk during reaching

 Neuronal activity was recorded from the superior colliculus (SC) and the underlying reticular formation in two monkeys during an arm reaching task. Of 744 neurons recorded, 389 (52%) clearly modulated their activity with arm movements. The temporal activity patterns of arm-movement-related neurons often had a time course similar to rectified electromyograms (EMGs) of particular muscles recorded from the shoulder, arm or trunk. These reach cells, as well as the muscles investigated, commonly exhibited mono- or biphasic (less frequently tri- or polyphasic) excitatory bursts of activity, which were related to the (pre-)movement period, the contact phase and/or the return movement. The vast majority of reach cells exhibited a consistent activity pattern from trial to trial as did most of the muscles of the shoulder, arm and trunk. Similarities between the activity patterns of the neurons and the muscles were sometimes very strong and were especially notable with the muscles of the shoulder girdle (e.g. trapezius descendens, supraspinatus, infraspinatus or the anterior and medial deltoids). This high degree of co-activation suggests a functional linkage, though not direct, between the collicular reach cells and these muscles. Neuronal activity onset was compared with that of 25 muscles of the arms, shoulders and trunk. The majority of cells (78.5%) started before movement onset with a mean lead time of 149±90 ms, and 36.5% were active even before the earliest EMG onset. The neurons exhibited the same high degree of correlation (r=0.97, Spearman rank) between activity onset and the beginning of the arm movement as did the muscles (r=0.98) involved in the task. The mean neuronal reach activity (background subtracted) ranged between 7 and 193 impulses/s (mean 40.5±24.2). The mean modulation index calculated [(reach activity −background activity)/reach activity+background activity)] was 0.75±0.23 for neurons (n=358) and 0.87±0.14 for muscles (n=25). As the monkeys fixated the reach target constantly during an arm movement, neuronal activity which was modulated in this period was not related to eye movements. The three neck muscles investigated in the reach task exhibited no reach-related activity modulation comparable to that of either the reach cells or the muscles of the shoulder, arm and trunk. However, tonic neck muscle EMG was monotonically related to horizontal eye position. The clear skeletomotor discharge characteristics of arm-movement-related SC neurons revealed in this study agree with those already known from other sensorimotor regions (for example the primary motor, the premotor and parietal cortex, the basal ganglia or the cerebellum) and are consistent with the possible role of this population of reach cells in the control of arm movements. Received: 17 June 1996 / Accepted: 24 December 1996     

Properties of reach-related neuronal activity in cortical area 7A.

1. In protocol 1, two macaque monkeys were trained to reach to illuminated buttons with the right arm as reach-related unit activity was monitored in area 7a of the left hemisphere. 2. Of 402 neurons recorded in area 7a, 109 changed their discharge rates during the reach task. The change could occur early or late in the trajectory, or during the return movement of the arm to the rest plate. Spatial preferences were seen in 59/109 reach-related cells, usually for the right or center buttons. 3. In protocol 2, another monkey was trained to reach with either arm to targets displayed on a touch-sensitive video monitor. Of 273 neurons sampled in area 7a (both hemispheres) during the bilateral task performance, 84 were reach-related: 33 responded similarly to reaches of either arm. Most of the rest had a contralateral arm preference. When bilateral reach-related cells had a spatial preference, that preference was the same for both arms. 4. With the use of two target sequences in either protocol, it was found that spatial preferences were observable only for primary reaches from the side of the body up to the target. Relatively few cells responded to other trajectories, and those that did usually failed to discriminate movement direction. Movement extent did not influence discharge rates. 5. Although a total of 125/270 reach cells had observable visual responses, only 4 out of 18 cells tested in both dark and light conditions showed a significant drop in reach-related activity in the dark. Thus visual input from the moving hand probably is responsible for only part of the reach activity in area 7a. 6. Reach-related activity in area 7a appears to signal specific phases of the motor performance and is often restricted to distinct spatial regions. As such, it could be used by the frontal lobe to facilitate upcoming elements of a motor sequence, including terminal corrections.     

The Mesencephalic Reticular Formation as a Conduit for Primate Collicular Gaze Control: Tectal Inputs to Neurons Targeting the Spinal Cord and Medulla

The superior colliculus (SC), which directs orienting movements of both the eyes and head, is reciprocally connected to the mesencephalic reticular formation (MRF), suggesting the latter is involved in gaze control. The MRF has been provisionally subdivided to include a rostral portion, which subserves vertical gaze, and a caudal portion, which subserves horizontal gaze. Both regions contain cells projecting downstream that may provide a conduit for tectal signals targeting the gaze control centers which direct head movements. We determined the distribution of cells targeting the cervical spinal cord and rostral medullary reticular formation (MdRF), and investigated whether these MRF neurons receive input from the SC by the use of dual tracer techniques in Macaca fascicularis monkeys. Either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin was injected into the SC. Wheat germ agglutinin conjugated horseradish peroxidase was placed into the ipsilateral cervical spinal cord or medial MdRF to retrogradely label MRF neurons. A small number of medially located cells in the rostral and caudal MRF were labeled following spinal cord injections, and greater numbers were labeled in the same region following MdRF injections. In both cases, anterogradely labeled tectoreticular terminals were observed in close association with retrogradely labeled neurons. These close associations between tectoreticular terminals and neurons with descending projections suggest the presence of a trans‐MRF pathway that provides a conduit for tectal control over head orienting movements. The medial location of these reticulospinal and reticuloreticular neurons suggests this MRF region may be specialized for head movement control. Anat Rec, 292:1162–1181, 2009. © 2009 Wiley‐Liss, Inc.     

Parieto-frontal coding of reaching: an integrated framework

In the last few years, anatomical and physiological studies have provided new insights into the organization of the parieto-frontal network underlying visually guided arm-reaching movements in at least three domains. (1) Network architecture. It has been shown that the different classes of neurons encoding information relevant to reaching are not confined within individual cortical areas, but are common to different areas, which are generally linked by reciprocal association connections. (2) Representation of information. There is evidence suggesting that reach-related populations of neurons do not encode relevant parameters within pure sensory or motor ”reference frames”, but rather combine them within hybrid dimensions. (3) Visuomotor transformation. It has been proposed that the computation of motor commands for reaching occurs as a simultaneous recruitment of discrete populations of neurons sharing similar properties in different cortical areas, rather than as a serial process from vision to movement, engaging different areas at different times. The goal of this paper was to link experimental (neurophysiological and neuroanatomical) and computational aspects within an integrated framework to illustrate how different neuronal populations in the parieto-frontal network operate a collective and distributed computation for reaching. In this framework, all dynamic (tuning, combinatorial, computational) properties of units are determined by their location relative to three main functional axes of the network, the visual-to-somatic, position-direction, and sensory-motor axis. The visual-to-somatic axis is defined by gradients of activity symmetrical to the central sulcus and distributed over both frontal and parietal cortices. At least four sets of reach-related signals (retinal, gaze, arm position/movement direction, muscle output) are represented along this axis. This architecture defines informational domains where neurons combine different inputs. The position-direction axis is identified by the regular distribution of information over large populations of neurons processing both positional and directional signals (concerning the arm, gaze, visual stimuli, etc.) Therefore, the activity of gaze- and arm-related neurons can represent virtual three-dimensional (3D) pathways for gaze shifts or hand movement. Virtual 3D pathways are thus defined by a combination of directional and positional information. The sensory-motor axis is defined by neurons displaying different temporal relationships with the different reach-related signals, such as target presentation, preparation for intended arm movement, onset of movements, etc. These properties reflect the computation performed by local networks, which are formed by two types of processing units: matching and condition units. Matching units relate different neural representations of virtual 3D pathways for gaze or hand, and can predict motor commands and their sensory consequences. Depending on the units involved, different matching operations can be learned in the network, resulting in the acquisition of different visuo-motor transformations, such as those underlying reaching to foveated targets, reaching to extrafoveal targets, and visual tracking of hand movement trajectory. Condition units link these matching operations to reinforcement contingencies and therefore can shape the collective neural recruitment along the three axes of the network. This will result in a progressive match of retinal, gaze, arm, and muscle signals suitable for moving the hand toward the target. Received: 1 October 1998 / Accepted: 1 July 1999     

The feedback circuit connecting the central mesencephalic reticular formation and the superior colliculus in the macaque monkey: tectal connections

The connectional and physiological characteristics of the central mesencephalic reticular formation (cMRF) indicate that it participates in gaze control. The cMRF receives projections from the ipsilateral superior colliculus (SC) via collaterals of predorsal bundle axons. These collaterals target cMRF neurons, which in turn project back upon the SC. In the present study, we examined the pattern of connections made by the cMRF reticulotectal projection by injecting the bidirectional neuroanatomical tracer, biotinylated dextran amine (BDA), into the cMRF of macaque monkeys. Anterogradely labeled reticulotectal terminals were found bilaterally in the SC, with an ipsilateral predominance, and were concentrated in the intermediate gray layer (SGI). BDA also retrogradely labeled SC neurons projecting to the cMRF. These labeled tectoreticular cells were located mainly in SGI. Injection site specific differences in the SC labeling pattern were evident, suggesting the lateral cMRF is more heavily connected to the upper sublamina of SGI, whereas the medial cMRF is more heavily connected with the lower sublamina. In view of the known downstream connections of the cMRF and these SC sublaminae, this organization intimates that the cMRF may contain subdivisions specialized to modulate the eye and the head components of gaze changes. In addition, reticulotectal terminals were observed to have close associations with retrogradely labeled tectoreticular cells in the ipsilateral SC, indicating possible synaptic contacts. Thus, the cMRF’s reciprocal connections with the SC suggest this structure plays a role in defining the gaze-related bursting behavior of collicular output neurons.     

The midbrain reticular formation as an integration center for the 'near reflex' in the cat

This report describes an experimental study on the localization of converging organization of the near-reflex triad in the chloralose-anesthetized encéphale-isolé cat, in which electromyographic (EMG) recordings were used to elicit responses from the intrinsic and extrinsic eye muscles. Electrical stimulation to several subdivisional areas in the oculomotor nuclear complex evoked EMGs in both the iris sphincter and ciliary muscles. Conduction time from the caudal Edinger-Westphal nucleus to the postganglionic ciliary nerve was about 1.8 ms, whereas that to the iris sphincter muscle was about 6.5 ms. Conduction time from the anteromedian nucleus to the muscle was about 4.5 ms; however, that from the postganglionic short ciliary nerve to the muscle was about 6.7 ms. A direct pathway without synapse in the ciliary ganglion is suggested. Excitatory responses were elicited in the effectors of the near-reflex triad by electrical stimulation of the midbrain reticular formation of the dorsomedial division adjacent to the magnocellular red nucleus (MRFdmMRN). Converging movements in electro-oculography (EOG) were also observed. Conduction time from the MRF to the iris sphincter muscle was about 5.6 ms, whereas that to the postganglionic short ciliary nerve was 5.1 ms. The neural connection between the MRF and the muscle is thought to be mediated by the anteromedian subnucleus. Electrical stimulation of the posteromedial division of the Clare-Bishop (C-B) area evoked a discharge on the MRF and EMGs of all effectors of the triad. The sum of the conduction time from the C-B area to the MRF and that from the MRF to EMGs corresponds well to the latency of EMGs evoked by C-B area stimulation. We conclude that the MRFdmMRN is the supranuclear organization which converges the sensory-motor cortical activities on the precise linkage of the near-reflex triad and becomes an integration center for each nucleus in the oculomotor nuclear complex.     

Target selection for saccadic eye movements: direction-selective visual responses in the superior colliculus.

We investigated the role of the superior colliculus (SC) in saccade target selection in rhesus monkeys who were trained to perform a direction-discrimination task. In this task, the monkey discriminated between opposed directions of visual motion and indicated its judgment by making a saccadic eye movement to one of two visual targets that were spatially aligned with the two possible directions of motion in the display. Thus the neural circuits that implement target selection in this task are likely to receive directionally selective visual inputs and be closely linked to the saccadic system. We therefore studied prelude neurons in the intermediate and deep layers of the SC that can discharge up to several seconds before an impending saccade, indicating a relatively high-level role in saccade planning. We used the direction-discrimination task to identify neurons whose prelude activity "predicted" the impending perceptual report several seconds before the animal actually executed the operant eye movement; these "choice predicting" cells comprised approximately 30% of the neurons we encountered in the intermediate and deep layers of the SC. Surprisingly, about half of these prelude cells yielded direction-selective responses to our motion stimulus during a passive fixation task. In general, these neurons responded to motion stimuli in many locations around the visual field including the center of gaze where the visual discriminanda were positioned during the direction-discrimination task. Preferred directions generally pointed toward the location of the movement field of the SC neuron in accordance with the sensorimotor demands of the discrimination task. Control experiments indicate that the directional responses do not simply reflect covertly planned saccades. Our results indicate that a small population of SC prelude neurons exhibits properties appropriate for linking stimulus cues to saccade target selection in the context of a visual discrimination task.     

Morphology of vertical canal related second order vestibular neurons in the cat

Summary The morphology of vertical canal related second order vestibular neurons in the cat was studied with the intracellular horseradish peroxidase method. Neurons were identified by their monosynaptic potentials following electrical stimulation via bipolar electrodes implanted into individual semicircular canal ampullae. Anterior and posterior canal neurons projected primarily to contralateral or ipsilateral motoneuron pools (excitatory and inhibitory pathways, respectively). The axons of contralaterally projecting neurons crossed the midline at the level of the abducens nucleus and bifurcated into an ascending and a descending main branch which travelled in the medial longitudinal fasciculus (MLF). Two types of anterior canal neurons were observed, one with unilateral and one with bilateral oculomotor projection sites. For both neuron classes, the major termination sites were in the. contralateral superior rectus and inferior oblique subdivisions of the oculomotor nucleus. In neurons which terminated bilaterally, major collaterals recrossed the midline within the oculomotor nucleus to reach the ipsilateral superior rectus motoneuron pool. Other, less extensive, termination sites of both neuron classes were in the contralateral vestibular nuclear complex, the facial nucleus, the medullary and pontine reticular formation, midline areas within and neighboring the raphé nuclei, and the trochlear nucleus. The ascending main axons continued further rostrally to reach the interstitial nucleus of Cajal and areas around the fasciculus retroflexus. The descending branches proceeded further caudal in the medial vestibulo-spinal tract but were not followed to their spinal target areas. In addition to two previously described posterior canal related neuron types (Graf et al. 1983), we found neurons with bilateral oculomotor terminals and a spinal collateral. Typical for posterior canal neurons, the major termination sites were in the trochlear nucleus (superior oblique motoneurons) and in the inferior rectus subdivision of the oculomotor nucleus. Axon collaterals recrossed the midline to reach ipsilateral inferior rectus motoneurons. The axons of ipsilaterally projecting neurons ascended through the reticular formation to join the MLF caudal to the trochlear nucleus. The main target sites of anterior canal related neurons were in the trochlear nucleus and the inferior rectus subdivision of the oculomotor nucleus. Minor collaterals reached the pontine reticular formation and areas in between the fiber bundles of the ipsilateral MLF. In some cases, small collaterals crossed the midline within the oculomotor nucleus to terminate in the inferior rectus subdivision on the contralateral side. The axon proceeded further rostral to project to the interstitial nucleus of Cajal and beyond. The main termination sites of posterior canal neurons were in the superior rectus and inferior oblique subdivisions of the oculomotor nucleus. Minor collaterals were also observed to reach the midline area within the oculomotor nucleus, however, prospective contralateral termination sites could not be identified. More rostral projections were found in the interstitial nucleus of Cajal. The described axonal arborization of second order vestibular neurons reflects the organization of intrinsic coordinate systems as exemplified by the geometry of the semicircular canal and the extraocular muscle planes. These neurons are interpreted to provide a matrix for coordinate system transformation, i.e. from vestibular into oculomotor reference frames, and to play a role in gaze control and related reflexes by distributing their signals to multiple termination sites.Abbreviations DV descending vestibular nucleus - INC interstitial nucleus of Cajal - INT nucleus intercalatus - IQ inferior oblique subdivision - LV lateral vestibular nucleus - MLF medial longitudinal fasciculus - MRF medullary reticular formation - MV medial vestibular nucleus - nVII facial nerve - PH nucleus praepositus hypoglossi - PRF pontine reticular formation - RO nucleus Roller - SR superior rectus subdivision - SV superior vestibular nucleus - III oculomotor nucleus - IV trochlear nucleus - VI abducens nucleus - VII facial nucleus - XII hypoglossal nucleus Supported by NIH grants EY04613 and NS02619     

Priming of head premotor circuits during oculomotor preparation

Large, rapid gaze shifts necessitate intricate coordination of the eyes and head. Brief high-frequency bursts of activity within the intermediate and deeper layers of the superior colliculus (dSC) encode desired gaze shifts regardless of component movements of the eyes and head. However, it remains unclear whether low-frequency activity emitted by oculomotor neurons within the dSC and elsewhere has any role in eye-head gaze shifts. Here we test the hypothesis that such low-frequency activity contributes to eye-head coordination by selectively priming head premotor circuits. We exploited the capacity for short-duration (10 ms, 4 pulses) dSC stimulation to evoke neck muscle responses without compromising ocular stability, stimulating at various intervals of a "gap-saccade" task. Low-frequency neural activity in many oculomotor areas (including the dSC) is known to increase during the progression of the gap-saccade task. Stimulation was passed during either a fixation-interval while a central fixation point was illuminated, a 200-ms gap-interval between fixation point offset and target onset, or a movement-interval following target onset. In the two monkeys studied, the amplitude of evoked responses on multiple neck muscles tracked the known increases in low-frequency oculomotor activity during the gap-saccade task, being greater following stimulation passed at the end of the gap- versus the fixation-interval, and greater still when the location of stimulation during the movement interval coincided with the area of the dSC generating the ensuing saccade. In one of these monkeys, we obtained a more detailed timeline of how these results co-varied with low-frequency oculomotor activity by stimulating, across multiple trials, at different times within the fixation-, gap- and movement-intervals. Importantly, in both monkeys, baseline levels of neck EMG taken immediately prior to stimulation onset did not co-vary with the known pattern of low-frequency oculomotor activity up until the arrival of a transient burst associated with visual target onset. These baseline results demonstrate that any priming of the head premotor circuits occurs without affecting the output of neck muscle motoneurons, We conclude that low-frequency oculomotor activity primes head premotor circuits well in advance of gaze shift initiation, and in a manner distinct from its effects on the eye premotor circuits. Such distinctions presumably aid the temporal coordination of the eyes and head despite fundamentally different biomechanics.     

Role of the primate superior colliculus in the control of head movements

One important behavioral role for head movements is to assist in the redirection of gaze. However, primates also frequently make head movements that do not involve changes in the line of sight. Virtually nothing is known about the neural basis of these head-only movements. In the present study, single-unit extracellular activity was recorded from the superior colliculus while monkeys performed behavioral tasks that permit the temporal dissociation of gaze shifts and head movements. We sought to determine whether superior colliculus contains neurons that modulate their activity in association with head movements in the absence of gaze shifts and whether classic gaze-related burst neurons also discharge for head-only movements. For 26% of the neurons in our sample, significant changes in average firing rate could be attributed to head-only movements. Most of these increased their firing rate immediately prior to the onset of a head movement and continued to discharge at elevated frequency until the offset of the movement. Others discharged at a tonic rate when the head was stable and decreased their activity, or paused, during head movements. For many putative head cells, average firing rate was found to be predictive of head displacement. Some neurons exhibited significant changes in activity associated with gaze, eye-only, and head-only movements, although none of the gaze-related burst neurons significantly modulated its activity in association with head-only movements. These results suggest the possibility that the superior colliculus plays a role in the control of head movements independent of gaze shifts.     

Gaze-centered updating of remembered visual space during active whole-body translations

Various cortical and sub-cortical brain structures update the gaze-centered coordinates of remembered stimuli to maintain an accurate representation of visual space across eyes rotations and to produce suitable motor plans. A major challenge for the computations by these structures is updating across eye translations. When the eyes translate, objects in front of and behind the eyes' fixation point shift in opposite directions on the retina due to motion parallax. It is not known if the brain uses gaze coordinates to compute parallax in the translational updating of remembered space or if it uses gaze-independent coordinates to maintain spatial constancy across translational motion. We tested this by having subjects view targets, flashed in darkness in front of or behind fixation, then translate their body sideways, and subsequently reach to the memorized target. Reach responses showed parallax-sensitive updating errors: errors increased with depth from fixation and reversed in lateral direction for targets presented at opposite depths from fixation. In a series of control experiments, we ruled out possible biasing factors such as the presence of a fixation light during the translation, the eyes accompanying the hand to the target, and the presence of visual feedback about hand position. Quantitative geometrical analysis confirmed that updating errors were better described by using gaze-centered than gaze-independent coordinates. We conclude that spatial updating for translational motion operates in gaze-centered coordinates. Neural network simulations are presented suggesting that the brain relies on ego-velocity signals and stereoscopic depth and direction information in spatial updating during self-motion.     

Contribution of head movement to gaze command coding in monkey frontal cortex and superior colliculus

Most of what we know about the neural control of gaze comes from experiments in head-fixed animals, but several "head-free" studies have suggested that fixing the head dramatically alters the apparent gaze command. We directly investigated this issue by quantitatively comparing head-fixed and head-free gaze trajectories evoked by electrically stimulating 52 sites in the superior colliculus (SC) of two monkeys and 23 sites in the supplementary eye fields (SEF) of two other monkeys. We found that head movements made a significant contribution to gaze shifts evoked from both neural structures. In the majority of the stimulated sites, average gaze amplitude was significantly larger and individual gaze trajectories were significantly less convergent in space with the head free to move. Our results are consistent with the hypothesis that head-fixed stimulation only reveals the oculomotor component of the gaze shift, not the true, planned goal of the movement. One implication of this finding is that when comparing stimulation data against popular gaze control models, freeing the head shifts the apparent coding of gaze away from a "spatial code" toward a simpler visual model in the SC and toward an eye-centered or fixed-vector model representation in the SEF.     

Projections from the superior colliculus to a region of the central mesencephalic reticular formation (cMRF) associated with horizontal saccadic eye movements

Summary Radioactive wheatgerm agglutinin (WGA) and horseradish peroxidase (HRP) were injected into portions of the mesencephalic reticular formation at sites where electrical stimulation induced either small or large contralateral horizontal saccadic eye movements. We have designated this region as the Central MRF (cMRF). It contains both cells and fiber tracts, including the efferent output of the superior colliculus (SC), destined for the dorsal tegmental decussation and the predorsal bundle. Cells labelled by WGA and HRP injections were found in the intermediate and deep layers of the superior colliculus and the adjacent central gray matter on the ipsilateral side. Injections into the dorsal cMRF, at sites where small saccades were induced, caused labelling of cells in the rostral intermediate layer of SC. Injections into the ventral cMRF, at points where large saccades were elicited, caused labelling of cells in the caudal intermediate layer of SC. The deepest layers of SC and the adjacent central gray were also labelled from the small eye movement region of dorsal cMRF. We interpret these findings to indicate that the intermediate layers of SC send axonal projections to the horizontal eye movement region of the MRF in a topographic fashion. The projection from the intermediate layer is organized so that regions in SC and cMRF related to small or to large eye movements are interconnected. The results support the hypothesis that cMRF is a topographically organized area, involved, like SC, in the control of eye movements. Since both cMRF and the superior colliculus project to areas of the pons and medulla where saccadic eye movements are produced, they could give rise to parallel pathways for the generation of contralateral saccades.Abbreviations III oculomotor nucleus - IV trochlear nucleus - ap area pretectalis - BC brachium conjunctivum - BSC brachium of the superior colliculus - cg central gray - cMRF central MRF - d deep layer of SC - DAB diaminobenzidine - EOG electro-oculography - h habenula nuclei - HRP horseradish peroxidase - iC interstitial nucleus of Cajal - ic inferior colliculus - li nucleus limitans - mg medial geniculate body - MLF medial longitudinal fasciculus - nIII oculomotor nerve - nIV trochlear nerve - on olivary nucleus - p pulvinar - PC posterior commissure - riMLF rostral interstitial nucleus of the MLF - rn red nucleus, pars magnocellularis - rnp red nucleus, pars parvocellularis - s superficial layer of SC - SC superior colliculus - sl sublentiform nucleus - sn substantia nigra - TMB tetramethyl benzidine - TR tractus retroflexus - WGA wheatgerm agglutinin Supported by NIH Research grant EY 02296, Deutsche Forschungsgemeinschaft grant SFB 200/A3 and Core Center grant EY 01867     

Neuromuscular consequences of reflexive covert orienting

Visual stimulus presentation activates the oculomotor network without requiring a gaze shift. Here, we demonstrate that primate neck muscles are recruited during such reflexive covert orienting in a manner that parallels activity recorded from the superior colliculus (SC). Our results indicate the presence of a brainstem circuit whereby reflexive covert orienting is prevented from shifting gaze, but recruits neck muscles, predicting that similarities between SC and neck muscle activity should extend to other cognitive processes that are known to influence SC activity.     

Gaze shifts evoked by stimulation of the superior colliculus in the head-free cat conform to the motor map but also depend on stimulus strength and fixation activity

In our previous paper we demonstrated that electrical microstimulation of the fixation area at the rostral pole of the cat superior colliculus (SC) elicits no gaze movement but, rather, transiently suppresses eye-head gaze saccades. In this paper, we investigated the more caudal region of the SC and its interaction with the fixation area. In the alert head-free cat, supra-threshold stimulation in the anterior portion of the SC but outside the fixation area evoked small saccadic shifts of gaze consisting mainly of an eye movement, the head's contribution being small. Stimulating more posteriorly elicited large gaze saccades consisting of an ocular saccade combined with a rapid head movement. At these latter stimulation sites, craniocentric (goal-directed) eye movements were evoked when the cat's head was restrained. The amplitude of eye-head gaze saccades elicited at a particular stimulation site increased with stimulus duration, current strength, and pulse rate, until a constant or unit value was reached. The peak velocity of gaze shifts depended on both pulse rate and current strength. The movement direction was not affected by stimulus parameters. The unit gaze vector evoked, in the head-free condition, by stimulating one collicular site was similar to that coded by efferent neurons recorded at that site, thereby indicating a retinotopically coded gaze error representation on the collicular motor map which is not revealed by stimulating the head-fixed animal. Evoked gaze saccades were found to be influenced by fixation behavior. The amplitude of evoked gaze shifts was reduced if stimulation occurred when the hungry animal fixated a food target. Electrical activation of the collicular fixation area was found to mimic well the effects of natural fixation on evoked gaze shifts. Taken together, our results support the view that the overall distribution and level of collicular activity contributes to the encoding of the metrics of gaze saccades. We suggest that the combined levels of activity at the site being stimulated and at the fixation area influence the amplitude of evoked gaze saccades through competition. When stimulation is at low intensities, fixation-related activity reduces the amplitude of evoked gaze saccades. At high activation levels, the site being stimulated dominates and the gaze vector is specified only by that site's collicular output neurons, from which arises the close correspondence between the unit-evoked gaze saccades and the neurally coded gaze vector at that site.     

Control of orienting gaze shifts by the tectoreticulospinal system in the head-free cat. II. Sustained discharges during motor preparation and fixation.

1. We recorded from electrophysiologically identified output neurons of the superior colliculus (SC)--tectoreticular and tectoreticulospinal neurons [together called TR(S)Ns]--in the alert cat with head either unrestrained or immobilized. A cat actively exploring its visual surrounds typically makes a series of coordinated eye-head orienting movements that rapidly shift the visual axis from one point to another. These single-step shifts in gaze position (gaze = eye-in-space = eye-in-head + head-in-space) are separated by periods in which the visual axis remains stationary with respect to surrounding space. 2. Eighty-seven percent (86/99) of the TR(S)Ns studied during periods when the visual axis was stationary presented a sustained discharge, the intensity of which depended on the magnitude and direction of the vector drawn between current gaze position and the gaze position required to fixate a target of interest (gaze position error or GPE). The maximum sustained discharge recorded from each TR(S)N corresponded to a specific GPE vector and was correlated with the cell's position on the SC's retinotopically coded motor map. 3. The 86 TR(S)Ns could be divided into two classes. "Fixation TR(S)Ns" [fTR(S)Ns, n = 12] discharged maximally when the animal attentively fixated a target of interest, (i.e. GPE = 0 degrees). These neurons were located in the rostral SC and had visual receptive fields that included a representation of the area centralis. "Orientation TR(S)Ns" [oTR(S)Ns, n = 62] had visual receptive fields that excluded the area centralis and discharged for nonzero GPEs. The oTR(S)Ns were recorded more caudally on the SC's map. 4. For a given value of GPE, an ensemble of TR(S)Ns was active. When the cat changed its gaze position relative to a fixed target of interest, the zone of sustained activity shifted to a new collicular site. Thus, to maintain the maximum sustained discharge of a TR(S)N when target position was changed relative to the fixed body, it was necessary that gaze move to a new position that reestablished the preferred GPE. 5. The areal extent of GPEs for which a TR(S)N discharged defined a gaze position error field (GPEF) that was approximately coaligned with the cell's visual receptive field. The maximum sustained discharge occurred when GPE corresponded approximately to the center of the cell's GPEF. 6. The diameter of a TR(S)N's GPEF was related to the magnitude of that cell's optimal GPE. fTR(S)Ns had the smallest GPEFs, approximately 15-20 degrees; GPEF diameter was larger for oTR(S)Ns.(ABSTRACT TRUNCATED AT 400 WORDS)     

Brain stem pursuit pathways: dissociating visual,vestibular, and proprioceptive inputs during combined eye-head gaze tracking

Eye-head (EH) neurons within the medial vestibular nuclei are thought to be the primary input to the extraocular motoneurons during smooth pursuit: they receive direct projections from the cerebellar flocculus/ventral paraflocculus, and in turn, project to the abducens motor nucleus. Here, we recorded from EH neurons during head-restrained smooth pursuit and head-unrestrained combined eye-head pursuit (gaze pursuit). During head-restrained smooth pursuit of sinusoidal and step-ramp target motion, each neuron's response was well described by a simple model that included resting discharge (bias), eye position, and velocity terms. Moreover, eye acceleration, as well as eye position, velocity, and acceleration error (error = target movement - eye movement) signals played no role in shaping neuronal discharges. During head-unrestrained gaze pursuit, EH neuron responses reflected the summation of their head-movement sensitivity during passive whole-body rotation in the dark and gaze-movement sensitivity during smooth pursuit. Indeed, EH neuron responses were well predicted by their head- and gaze-movement sensitivity during these two paradigms across conditions (e.g., combined eye-head gaze pursuit, smooth pursuit, whole-body rotation in the dark, whole-body rotation while viewing a target moving with the head (i.e., cancellation), and passive rotation of the head-on-body). Thus our results imply that vestibular inputs, but not the activation of neck proprioceptors, influence EH neuron responses during head-on-body movements. This latter proposal was confirmed by demonstrating a complete absence of modulation in the same neurons during passive rotation of the monkey's body beneath its neck. Taken together our results show that during gaze pursuit EH neurons carry vestibular- as well as gaze-related information to extraocular motoneurons. We propose that this vestibular-related modulation is offset by inputs from other premotor inputs, and that the responses of vestibuloocular reflex interneurons (i.e., position-vestibular-pause neurons) are consistent with such a proposal.     

Target selection for saccadic eye movements: prelude activity in the superior colliculus during a direction-discrimination task.

We investigated the role of the superior colliculus (SC) in saccade target selection while macaque monkeys performed a direction-discrimination task. The monkeys selected one of two possible saccade targets based on the direction of motion in a stochastic random-dot display; the difficulty of the task was varied by adjusting the strength of the motion signal in the display. One of the two saccade targets was positioned within the movement field of the SC neuron under study while the other target was positioned well outside the movement field. Approximately 30% of the neurons in the intermediate and deep layers of the SC discharged target-specific preludes of activity that "predicted" target choices well before execution of the saccadic eye movement. Across the population of neurons, the strength of the motion signal in the display influenced the intensity of this "predictive" prelude activity: SC activity signaled the impending saccade more reliably when the motion signal was strong than when it was weak. The dependence of neural activity on motion strength could not be explained by small variations in the metrics of the saccadic eye movements. Predictive activity was particularly strong in a subpopulation of neurons with directional visual responses that we have described previously. For a subset of SC neurons, therefore, prelude activity reflects the difficulty of the direction discrimination in addition to the target of the impending saccade. These results are consistent with the notion that a restricted network of SC neurons plays a role in the process of saccade target selection.