The proprioceptive representation of eye position in monkey primary somatosensory cortex

The cerebral cortex must have access to an eye position signal, as humans can report passive changes in eye position in total darkness, and visual responses in many cortical areas are modulated by eye position. The source of this signal is unknown. Here we demonstrate a representation of eye position in monkey primary somatosensory cortex, in the representation of the trigeminal nerve, near cells with a tactile representation of the contralateral brow. The neurons have eye position signals that increase monotonically with increasing orbital eccentricity from near the center of gaze, with directionally selectivity tuned in a Gaussian manner. All directions of eye position are represented in a single hemisphere. The signal is proprioceptive, because it can be obliterated by anesthetizing the contralateral orbit. It is not related to foveal or peripheral visual stimulation, and it represents the position of the eye in the head and not the angle of gaze in space.     

Dynamic properties of eye position coded neurons in the alert monkey during saccades

Summary Single units in the regions of the III, IV and VI nuclei were recorded together with EOG's for horizontal and vertical eye positions in alert macaques. The sequential analysis of several dynamic parameters of the activity patterns in correlation to the saccade velocity for saccades in the on-direction leads to the results that: 1. eye position coded neurons can clearly be separated into two main classes [early peak (EP) and late peak (LP)] by means of their activity patterns during saccades in the on-direction; 2. the maximum impulse rate of EP neurons shows a better correlation with saccade velocity than the difference between maximum and initial impulse rate while the opposite is valid for LP neurons. EP neurons are likely to be motoneurons which initiate saccadic eye movements whereas LP neurons are too slow for this task because they reach their maximum impulse rate after half the saccadic time. The dynamic properties of LP neurons have several features similar to those of primary stretch receptors during ramp-like stretches. The possible influence of fusimotor activity on the oculomotor system is discussed. The fact that the relationship between dynamic index and saccade velocity shows subgroups of data supports the assumption that the state of alertness changes instantaneously in untrained monkeys.Supported in part by the National Eye Institute, U.S. Public Health Service under grant EY-00592 to Dr. G. Westheimer and by the Deutsche Forschungsgemeinschaft.     

Influence of head position on the spatial representation of acoustic targets.

Sound localization in humans relies on binaural differences (azimuth cues) and monaural spectral shape information (elevation cues) and is therefore the result of a neural computational process. Despite the fact that these acoustic cues are referenced with respect to the head, accurate eye movements can be generated to sounds in complete darkness. This ability necessitates the use of eye position information. So far, however, sound localization has been investigated mainly with a fixed head position, usually straight ahead. Yet the auditory system may rely on head motor information to maintain a stable and spatially accurate representation of acoustic targets in the presence of head movements. We therefore studied the influence of changes in eye-head position on auditory-guided orienting behavior of human subjects. In the first experiment, we used a visual-auditory double-step paradigm. Subjects made saccadic gaze shifts in total darkness toward brief broadband sounds presented before an intervening eye-head movement that was evoked by an earlier visual target. The data show that the preceding displacements of both eye and head are fully accounted for, resulting in spatially accurate responses. This suggests that auditory target information may be transformed into a spatial (or body-centered) frame of reference. To further investigate this possibility, we exploited the unique property of the auditory system that sound elevation is extracted independently from pinna-related spectral cues. In the absence of such cues, accurate elevation detection is not possible, even when head movements are made. This is shown in a second experiment where pure tones were localized at a fixed elevation that depended on the tone frequency rather than on the actual target elevation, both under head-fixed and -free conditions. To test, in a third experiment, whether the perceived elevation of tones relies on a head- or space-fixed target representation, eye movements were elicited toward pure tones while subjects kept their head in different vertical positions. It appeared that each tone was localized at a fixed, frequency-dependent elevation in space that shifted to a limited extent with changes in head elevation. Hence information about head position is used under static conditions too. Interestingly, the influence of head position also depended on the tone frequency. Thus tone-evoked ocular saccades typically showed a partial compensation for changes in static head position, whereas noise-evoked eye-head saccades fully compensated for intervening changes in eye-head position. We propose that the auditory localization system combines the acoustic input with head-position information to encode targets in a spatial (or body-centered) frame of reference. In this way, accurate orienting responses may be programmed despite intervening eye-head movements. A conceptual model, based on the tonotopic organization of the auditory system, is presented that may account for our findings.     

Types of monocular eye movements studied by intracortical microstimulation in the cat's coronal sulcus

To study the types of the monocular eye movements, intracortical microstimulations were applied to the fundus of the cat's coronal sulcus where the monocular movements of the contralateral eye were evoked. The monocular eye movements were saccadic and directed toward the nasal side converging on a horizontal line from various eye positions. The average threshold and latency were 18.0 microA (range 8-30 microA) and 19.5 ms (range 18-20 ms), respectively.     

Thalamic projections to visual and visuomotor areas (V6 and V6A) in the Rostral Bank of the parieto-occipital sulcus of the Macaque

The medial posterior parietal cortex of the primate brain includes different functional areas, which have been defined based on the functional properties, cyto- and myeloarchitectural criteria, and cortico-cortical connections. Here, we describe the thalamic projections to two of these areas (V6 and V6A), based on 14 retrograde neuronal tracer injections in 11 hemispheres of 9 Macaca fascicularis. The injections were placed either by direct visualisation or using electrophysiological guidance, and the location of injection sites was determined post mortem based on cyto- and myeloarchitectural criteria. We found that the majority of the thalamic afferents to the visual area V6 originate in subdivisions of the lateral and inferior pulvinar nuclei, with weaker inputs originating from the central densocellular, paracentral, lateral posterior, lateral geniculate, ventral anterior and mediodorsal nuclei. In contrast, injections in both the dorsal and ventral parts of the visuomotor area V6A revealed strong inputs from the lateral posterior and medial pulvinar nuclei, as well as smaller inputs from the ventrolateral complex and from the central densocellular, paracentral, and mediodorsal nuclei. These projection patterns are in line with the functional properties of injected areas: “dorsal stream” extrastriate area V6 receives information from visuotopically organised subdivisions of the thalamus; whereas visuomotor area V6A, which is involved in the sensory guidance of arm movement, receives its primary afferents from thalamic nuclei that provide high-order somatic and visual input.     

The coding of perceived eye position

In order to reveal the mechanism of eye position coding, we measured the effect of eye position on assessing the position of a light viewed in a dark environment using a sound as a reference point, before and after adapting to prolonged periods of eccentric viewing (11° right or left). During testing, eye position was varied over ±22°. For each test position, a PEST procedure was used to align the perceived position of a light (with no visual reference points) and a fixed sound source. The perceived position of the light was veridical when looking straight ahead but large and consistent errors were found with eccentric viewing indicating that only about 77% of the eye eccentricity was taken into account, an eye position gain of 0.77, consistent with previous reports. The error was altered by prolonged eccentric viewing. There were two components to this effect: a direction bias and a gain change. The direction bias was symmetric: in a change rather like that induced by prism adaptation, the perceived straight ahead moved in the direction of the previous eccentric viewing. The gain change was asymmetric: after looking to the left, the gain of eye position increased to closer to one (0.77–0.81), in other words the subjects became more accurate. After looking right, the gain of eye position decreased (0.77–0.73): subjects consequently became less accurate. We model these systematic changes in terms of an asymmetric coding system.     

Distribution of eye position information in the monkey inferior colliculus

The inferior colliculus (IC) is thought to have two main subdivisions, a central region that forms an important stop on the ascending auditory pathway and a surrounding shell region that may play a more modulatory role. In this study, we investigated whether eye position affects activity in both the central and shell regions. Accordingly, we mapped the location of eye position-sensitive neurons in six monkeys making spontaneous eye movements by sampling multiunit activity at regularly spaced intervals throughout the IC. We used a functional map based on auditory response patterns to estimate the anatomical location of recordings, in conjunction with structural MRI and histology. We found eye position-sensitive sites throughout the IC, including at 27% of sites in tonotopically organized recording penetrations (putatively the central nucleus). Recordings from surrounding tissue showed a larger proportion of sites indicating an influence of eye position (33-43%). When present, the magnitude of the change in activity due to eye position was often comparable to that seen for sound frequency. Our results indicate that the primary ascending auditory pathway is influenced by the position of the eyes. Because eye position is essential for visual-auditory integration, our findings suggest that computations underlying visual-auditory integration begin early in the ascending auditory pathway.     

Multisensory representation of limb position in human premotor cortex

Using functional magnetic resonance imaging (fMRI) in humans, we identified regions of cortex involved in the encoding of limb position. Tactile stimulation of the right hand, across the body midline, activated the right parietal cortex when the eyes were closed; activation shifted to a left parietofrontal network when the eyes were open. These data reveal important similarities between human and non-human primates in the network of brain areas involved in the multisensory representation of limb position.     

Representation of eye position in primate inferior colliculus

We studied the representation of eye-position information in the primate inferior colliculus (IC). Monkeys fixated visual stimuli at one of eight or nine locations along the horizontal meridian between -24 and 24 degrees while sounds were presented from loudspeakers at locations within that same range. Approximately 40% of our sample of 153 neurons showed statistically significant sensitivity to eye position during either the presentation of an auditory stimulus or in the absence of sound (Bonferroni corrected P < 0.05). The representation for eye position was predominantly monotonic and favored contralateral eye positions. Eye-position sensitivity was more prevalent among neurons without sound-location sensitivity: about half of neurons that were insensitive to sound location were sensitive to eye position, whereas only about one-quarter of sound-location-sensitive neurons were also sensitive to eye position. Our findings suggest that sound location and eye position are encoded using independent but overlapping rate codes at the level of the IC. The use of a common format has computational advantages for integrating these two signals. The differential distribution of eye-position sensitivity and sound-location sensitivity suggests that this process has begun by the level of the IC but is not yet complete at this stage. We discuss how these signals might fit into Groh and Sparks' vector subtraction model for coordinate transformations.     

Fifth somatosensory cortex (SV) representation of the whole body surface in the medial bank of the anterior suprasylvian sulcus of the cat.

The physiological properties of neurons in the medial bank of the anterior suprasylvian sulcus (ASSS-m) of the cat's cortex were studied using unit recording techniques. Receptive fields (RFs) on the face are represented in the most rostral aspects of the ASSS-m. Of these neurons, 84% responded to light touch of the skin on the contralateral region of the face and 12% responded to mechanical stimulation of facial hair. In addition, 4% of the neurons responded to light touch to the skin or mechanical stimulation of the hair on the contralateral face and also to visual stimuli. The RFs of neurons responsive to the hindlimb and tail are located in the most caudal aspects of the ASSS-m. 22% of these neurons responded to the light touch to the skin and 78% responded to movement of hair. The RFs of neurons responsive to the trunk area in the ASSS-m are located between the facial and hindlimb regions. Of these neurons, 2% responded to light touch of the skin and 98% responded to movements of hair. Some neurons which responded to stimulation of hair or skin on the trunk included forelimb and/or hindlimb areas. In addition, some neurons had RFs on both sides of the trunk including the shoulder area. These regions were in area 5a. Various features of representation in ASSS-m distinguish this region from other somatosensory areas. We designate the ASSS-m as the fifth somatosensory cortex (SV).     

Primary histiocytosis X of the parieto-occipital lobe

Immunohistochemical and ultrastructural evidence support the concept that histiocytosis X is the result of proliferation of pathological Langerhans' cells. Central nervous system involvement by histiocytosis X has been commonly described in multisystem disease and in association with lytic skull lesions. Unifocal brain involvement by histiocytosis X without concomitant osseous involvement is rare, with only 14 cases reported in the literature to date. Ten of these cases have involved the hypothalamus; the remaining four have involved the frontal lobe (two cases) and the temporal lobe (two cases). The fifth case of extrahypothalamic unifocal histiocytosis X, the first female case, and the first case with parieto-occipital lobe involvement, is reported. Pathology demonstrated infiltration of brain parenchyma by clusters of characteristic histiocytosis X cells with an admixture of morphologically related giant cells, eosinophils, and lymphocytes. Langerhans' granules were identified in the histiocytosis X cells by electron microscopy. Immunohistochemistry showed strong S-100 protein, HLA-DR, and T6 antigen positivity by the histiocytosis X cells. Therapy included complete surgical excision and postoperative radiation therapy for the incompletely excised lesion. Patients with unifocal extrahypothalamic histiocytosis X may have a better prognosis than patients with localized hypothalamic disease.     

Encoding of eye position in the goldfish horizontal oculomotor neural integrator

Monocular organization of the goldfish horizontal neural integrator was studied during spontaneous scanning saccadic and fixation behaviors. Analysis of neuronal firing rates revealed a population of ipsilateral (37%), conjugate (59%), and contralateral (4%) eye position neurons. When monocular optokinetic stimuli were employed to maximize disjunctive horizontal eye movements, the sampled population changed to 57, 39, and 4%. Monocular eye tracking could be elicited at different gain and phase with the integrator time constant independently modified for each eye by either centripetal (leak) or centrifugal (instability) drifting visual stimuli. Acute midline separation between the hindbrain oculomotor integrators did not affect either monocularity or time constant tuning, corroborating that left and right eye positions are independently encoded within each integrator. Together these findings suggest that the "ipsilateral" and "conjugate/contralateral" integrator neurons primarily target abducens motoneurons and internuclear neurons, respectively. The commissural pathway is proposed to select the conjugate/contralateral eye position neurons and act as a feedforward inhibition affecting null eye position, oculomotor range, and saccade pattern.     

Directional pursuit deficits following lesions of the foveal representation within the superior temporal sulcus of the macaque monkey

Ibotenic acid lesions of the middle temporal visual area (MT) have previously been shown to impair a monkey's ability to initiate smooth pursuit eye movements to targets moving in the extrafoveal visual field (30). This is a retinotopic deficit: pursuit is impaired in all directions within the affected portion of the contralateral visual field. In the present experiments we analyzed the effects of lesions of the foveal representation of MT on the maintenance of foveal pursuit. Injections of ibotenic acid were directed toward the representation of the fovea within MT but spread into extrafoveal regions of MT and adjacent visual areas within the superior temporal sulcus. Chemical lesions of the foveal representation produced a directional deficit in the maintenance of pursuit: the monkey failed to match eye speed to target speed when pursuing a target that moved toward the side of the brain with the lesion. This deficit was evident regardless of the part of the visual field in which target motion began, and pursuit at higher target speeds was more severely affected. The directional deficit was qualitatively similar to pursuit deficits observed in human patients following large parietal-occipital lesions. Extension of the lesions into extrafoveal regions of the contralateral visual field representation also resulted in retinotopic deficits for pursuit initiation: the monkey was unable to match the speed of its pursuit eye movement to that of a target or to adjust the amplitude of its saccade to compensate for target motion. The errors in pursuit speed and saccade amplitude for initiation of pursuit into the contralateral visual field were linearly related, which supports the hypothesis that both deficits arise from damage to the same underlying visual motion processing mechanism. The selectivity of the retinotopic deficit for motion information was also investigated by reducing retinal motion through the use of a stabilized image. After the lesion, the monkeys continued normal pursuit when a position error was present during stabilization, supporting the view that the deficit was related to loss of motion but not position information.     

Spatial object representation and its use in planning eye movements

The eye movements we make to look at objects require that the spatial information contained in the objects image on the retina be used to generate a motor command. This process is known as sensorimotor transformation and has been generally addressed using simple point targets. Here, we investigate the sensorimotor transformation involved in planning double saccade sequences directed at one or two objects. Using both visually guided saccades toward stationary objects and objects subjected to intrasaccadic displacements, and memory-guided saccades, we found that the coordinate transformations required to program the second saccade were different for saccades aimed at a new target object and saccades that scanned the same object. While saccades aimed at a new object were updated on the basis of the actual eye position, those that scanned the same object were performed with a fixed amplitude, irrespective of the actual eye position. Our findings demonstrate that different abstract representations of space are used in sensory-to-motor transformations, depending on what action is planned on the objects.     

Influence of eye and head position on the vestibulo-ocular reflex

Summary For the vestibulo-ocular reflex (VOR) to function properly, namely to ensure a stable retinal image under all circumstances, it should be able to take into account varying eye positions in the orbit and varying orientations of the head with respect to the axis about which it is rotating. We tested this capability by quantifying the gain and the time constant of the horizontal component of the VOR during rotation about an earth vertical axis when the line of sight (optical axis) was moved out of the plane of head rotation — either by rotating the eyes up or down in the orbit or by pitching the head up or down with respect to earth-horizontal. In either case the gain of the horizontal component of the VOR was attenuated precisely by the cosine of the angle made between the optical axis and the plane of head rotation. Furthermore, if the head was pitched up or down but the eye rotated oppositely in the orbit so as to keep the line of sight in the plane of head rotation the gain of the horizontal component of the VOR was the same value as with the head and eyes both straight ahead. In contrast, the time constant of the VOR varied only as a function of the orientation of the head and not as a function of eye position in the orbit. During rotation about an earth vertical axis, the time constant was longest (about 18 s) when the head was pitched forward to place the lateral canals near earth-horizontal and shortest (about 11 s) when the head was pitched backward to place the vertical canals near earth-horizontal. Finally, since during rotation in yaw the pattern of stimulation of the lateral and vertical semicircular canals varies with different head orientations one can use measurements of the horizontal component of the VOR, under varying degrees of pitch of the head, to calculate the relative ability of the lateral and vertical semicircular canals to transduce head velocity.Dr. Fetter is a visiting scientist from the Neurologische Universitätsklinik, Eberhard-Karls-Universität, Liebermeisterstr. 18-20, D-7400 Tübingen, Federal Republic of Germany     

Motor cortical representation of position and velocity during reaching

This study examines motor cortical representation of hand position and its relationship to the representation of hand velocity during reaching movements. In all, 978 motor cortical neurons were recorded from the proximal arm area of rostral motor cortex. The results demonstrate that position and velocity are simultaneously encoded by single motor cortical neurons in an additive fashion and that the relative weights of the position and velocity signals change dynamically during reaching. The two variables--hand position and hand velocity--are highly correlated in the standard center-out reaching task. A new reaching task (standard reaching) is introduced to minimize these correlations. Likewise, a new decoding method (indirect OLE) was developed to analyze the data by simultaneously decoding both three-dimensional (3D) hand position and 3D hand velocity from correlated neural activity. This method shows that, on average, the reconstructed velocity led the actual hand velocity by 122 ms, whereas the reconstructed position signal led the actual hand position by 81 ms.     

Vergence-mediated changes in the axis of eye rotation during the human vestibulo-ocular reflex can occur independent of eye position

The aim of this study was to determine whether vergence-mediated changes in the axis of eye rotation in the human vestibulo-ocular reflex (VOR) would obey Listing's Law (normally associated with saccadic eye movements) independent of the initial eye position. We devised a paradigm for disassociating the saccadic velocity axis from eye position by presenting near and far targets that were centered with respect to one eye. We measured binocular 3-dimensional eye movements using search coils in ten normal subjects and 3-dimensional linear head acceleration using Optotrak in seven normal subjects. The stimuli consisted of passive, unpredictable, pitch head rotations with peak acceleration of ~2,000°/s² and amplitude of ~20°. During the pitch head rotation, each subject fixated straight ahead with one eye, whereas the other eye was adducted 4° during far viewing (94 cm) and 25° during near viewing (15 cm). Our data showed expected compensatory pitch rotations in both eyes, and a vergence-mediated horizontal rotation only in the adducting eye. In addition, during near viewing we observed torsional eye rotations not only in the adducting eye but also in the eye looking straight ahead. In the straight-ahead eye, the change in torsional eye velocity between near and far viewing, which began ~40 ms after the start of head rotation, was 10±6°/s (mean ± SD). This change in torsional eye velocity resulted in a 2.4±1.5° axis tilt toward Listing's plane in that eye. In the adducting eye, the change in torsional eye velocity between near and far viewing was 16±6°/s (mean ± SD) and resulted in a 4.1±1.4° axis tilt. The torsional eye velocities were conjugate and both eyes partially obeyed Listing's Law. The axis of eye rotation tilted in the direction of the line of sight by approximately one-third of the angle between the line of sight and a line orthogonal to Listing's plane. This tilt was higher than predicted by the one-quarter rule. The translational acceleration component of the pitch head rotation measured 0.5 g and may have contributed to the increased torsional component observed during near viewing. Our data show that vergence-mediated eye movements obey a VOR/Listing's Law compromise strategy independent of the initial eye position.     

Effect of passive eye position changes on retinogeniculate transmission in the cat

1. Extracellular recordings were made from single neurons in layer A of the left dorsal lateral geniculate nucleus (LGNd) of anesthetized and paralyzed adult cats. Responses to retinotopically identical visual stimuli (presented through the right eye) were recorded at several positions of the left eye in its orbit. Visual stimuli consisted of drifting sinusoidal gratings of optimal temporal and spatial frequencies at twice threshold contrast. Visual stimulation of the left eye was blocked by a variety of methods, including intravitreal injection of tetrodotoxin (TTX). The change in position of the left eye was achieved by passive movements in a randomized and interleaved fashion. Of 237 neurons studied, responses were obtained from 143 neurons on 20-100 trials of identical visual stimulation at each of six eye positions. Neurons were classified as X- or Y- on the basis of a standard battery of physiological tests (primarily linearity of spatial summation and response latency to electrical stimulation of the optic chiasm). 2. The effect of eye position on the visual response of the 143 neurons was analyzed with respect to the number of action potentials elicited and the peak firing rate. Fifty-seven (40%) neurons had a significant effect [by one-factor repeated-measure analysis of variance (ANOVA), P less than 0.05] of eye position on the visual response by either criterion (number of action potentials or peak firing rate). Of these 57 neurons, 47 had a significant effect (P less than 0.05) with respect to the number of action potentials and 23 had a significant effect (P less than 0.05) by both criteria. Thus the permissive measure by either criterion and the conservative measure by both criteria resulted in 40% and 16%, respectively, of all neurons' visual responses being significantly affected by eye position. 3. For the 47 neurons with a significant effect of eye position (number of action potentials criterion), a trend analysis of eye position versus visual response showed a linear trend (P less than 0.05) for 9 neurons, a quadratic trend (P less than 0.05) for 32 neurons, and no significant trend for the 6 remaining neurons. The trends were approximated with linear and nonlinear gain fields (range of eye position change over which the visual response was modulated). The gain fields of individual neurons were compared by measuring the normalized gain (change in neuronal response per degree change of eye position). The mean normalized gain for the 47 neurons was 4.3. 4. The nonlinear gain fields were generally symmetric with respect to nasal versus temporal changes in eye position.(ABSTRACT TRUNCATED AT 400 WORDS)     

Supplementary eye field: influence of eye position on neural signals of fixation

Summary Single units were recorded in the supplementary eye field of monkeys performing visual-oculomotor tasks. Two patterns of unit activity were observed while the animals fixated photic stimuli. One consisted of a step in tonic firing frequency (either an increase or a decrease, depending on the cell), lasting as long as fixation. The occurrence of this pattern did not require the continuous presence of a stimulus but the animal had to be provided with an incentive to fixate a given location. The other pattern was a monotonically varying firing rate dependent on the eye orientation along a particular axis, indicative of eye eccentricity in orbit.