Aya Takemura

Temporal Firing Patterns of Purkinje Cells in the Cerebellar Ventral Paraflocculus During Ocular Following Responses in Monkeys I. Simple Spikes

The simple-spike firing frequency of 30 Purkinje cells (P cells) in the ventral paraflocculus (VPFL) of alert monkeys was studied in relation to vertical slow eye movements, termed ocular following response (OFR), induced by large-field visual motions of different velocities and durations. To quantitatively analyze the relationship between eye movement and firing frequency, an inverse dynamics representation of the eye movement was used for reconstructing the temporal waveform of firing. Coefficients of eye-acceleration, velocity, and position, bias, and time lag between firing and eye movement were estimated by least-square error method. In the regression analyses for each stimulus condition, 86% (146/170) of the well-modulated temporal firing patterns taken from those 30 P cells were reconstructed successfully from eye movement. The model with acceleration, velocity, and position terms, which we used, was shown as the best among several potential models by Cp statistics, consistent with t-test of significance of each term. Reliable coefficients were obtained from 75% (109/146) of the well-reconstructed firing patterns of 28 cells among 30. The estimated coefficients were larger (statistically significant) for slow stimuli than for fast stimuli, suggesting changes in sensitivities under different conditions. However, firing patterns of each cell under several different conditions were frequently well reconstructed by an inverse dynamics representation with a single set of coefficients (13 cells among 21). This indicates that the relationships between P cell firing and OFR are roughly linear in those stimulus ranges. The estimated coefficients for acceleration and velocity suggested that the VPFL P cells properly encode the dynamic components of the motor command during vertical OFR. As for the positional component, however, these P cells are correlated with eye movement in the opposite direction. In the regression analysis without positional component, remarkable differences between observed and reconstructed firing patterns were noted especially in the initial phase of the movements, indicating that the negative positional component was not negligible during OFR. Thus we conclude that, during OFR, the VPFL P cells cannot provide the necessary final motor command, and other brain regions, downstream neural structures, or other types of P cells must provide lacking position-dependent motor commands. This finding about the negative correlation with the position is in the opposite sign with previous studies obtained from the fixation and the smooth pursuit movement. From these comparisons, how the VPFL contributes to a part of the final motor command or how other brain regions complement the VPFL is suggested to be different for early and late phases of the movements.

Deficits in Short-Latency Tracking Eye Movements after Chemical Lesions in Monkey Cortical Areas MT and MST

Past work has suggested that the medial superior temporal area (MST) is involved in the initiation of three kinds of eye movements at short latency by large-field visual stimuli. These eye movements consist of (1) version elicited by linear motion (the ocular following response), (2) vergence elicited by binocular parallax (the disparity vergence response), and (3) vergence elicited by global motion toward or away from the fovea (the radial-flow vergence response). We investigated this hypothesis by recording the effects of ibotenic acid injections in the superior temporal sulcus (STS) of both hemispheres in five monkeys. After the injections, all three kinds of eye movements were significantly impaired, with the magnitude of the impairments often showing a strong correlation with the extent of the morphological damage in the three subregions of the STS: dorsal MST on the anterior bank, lateral MST and middle temporal area on the posterior bank. However, the extent of the lesions in the three subregions often covaried, rendering it difficult to assess their relative contributions to the various deficits. The effects of the lesions on other aspects of oculomotor behavior that are known to be important for the normal functioning of the three tracking mechanisms (e.g., ocular stability, fixation disparity) were judged to be generally minor and to contribute little to the impairments. We conclude that, insofar as MST sustained significant damage in all injected hemispheres, our findings are consistent with the hypothesis that MST is a primary site for initiating all three visual tracking eye movements at ultra-short latencies.

Visually Driven Eye Movements Elicited at Ultra-short Latency Are Severely Impaired by MST Lesions

Recent studies in primates have revealed three distinct oculomotor responses that can be elicited by visual stimuli at ultrashort latencies (∼60 msec in monkeys). All three types of eye movement have a machinelike quality and are thought to help reduce the visual disturbances that we experience as we move around the environment.1–4 One of these responses has been termed “ocular following” and is thought to deal with the visual stabilization problems confronting a moving observer who looks off to one side. Ocular following responses are conjugate (version) eye movements evoked by sudden drifting movements of a large-field visual stimulus.1 The other two responses, termed “disparity vergence” and “radial-flow vergence,” are thought to deal with the binocular fusion problems of the moving observer who looks in the direction of motion. These short-latency vergence eye movements are evoked by disparity and radial flow stimuli applied to large patterns.2–4 In our recent experiments on monkeys, we have examined the discharges of single neurons in the medial superior temporal (MST) area associated with ocular following, disparity vergence, and radial-flow vergence. We have found ocular-following-related neurons that discharged in response to planar large-field motion.5 Furthermore, some MST neurons responded to horizontal disparity steps6 and some to radial flow stimuli. Most of these MST neurons increased their discharges before the associated eye movements, soon enough for them to have a causal role in producing even the earliest respective ocular responses. These electrophysiological experiments suggest that, despite their ultrashort latency, all three visually elicited eye movements are mediated by MST neurons. To further understand the role of the MST in eliciting ocular following, disparity vergence, and radial-flow vergence, we have examined the effects of injecting ibotenic acid into MST bilaterally in monkeys.

Dependence of short-latency ocular following and associated activity in the medial superior temporal area (MST) on ocular vergence.

Abstract Motion of a large-field pattern elicits short-latency ocular following responses (OFR) in the monkey, which are mediated at least in part by the medial superior temporal area of the cortex (MST). The magnitude of the OFR is known to be inversely related to viewing distance, and we investigated the dependence of OFR and the associated neuronal activity in the MST on a major cue to viewing distance, ocular vergence, in alert monkeys (Macaca fuscata). The vergence angle, expressed in terms of the apparent viewing distance, ranged from infinity to 16.6 cm (0–6 m−1). The magnitude of the initial OFR increased monotonically with increases in convergence at a mean (±SD) rate of 19.6±4.5%/m−1 in four monkeys (over the range 0–4 m−1). In two monkeys, we recorded the single unit activity of 160 MST neurons that responded to motion of a large-field pattern with directional selectivity. The mean latency (±SD) of the MST discharges elicited by large-field motion was 50±7.5 ms (n=115), which preceded the onset of OFR by an average of 10±9.9 ms. The discharge modulation elicited by large-field motion showed a significant dependence on vergence in 91/160 neurons (57%), 72 of which (79%) increased their firing rate with increasing convergence (“near” neurons), and the remainder increasing their firing rate with decreasing convergence (“far” neurons). However, on average, the sensivity of these MST neurons to vergence was only about 30% of that shown by the OFR. It could be that only those neurons that are very sensitive to vergence angle contribute to the OFR, but it is also possible that much of the modulation of OFR with vergence occurs downstream from the MST or in alternative pathways (yet to be discovered) that contribute to OFR.

Sensory-to-motor processing of the ocular-following response

The ocular-following response is a slow tracking eye movement that is elicited by sudden drifting movements of a large-field visual stimulus in primates. It helps to stabilize the eyes on the visual scene. Previous single unit recordings and chemical lesion studies have reported that the ocular-following response is mediated by a pathway that includes the medial superior temporal (MST) area of the cortex and the ventral paraflocculus (VPFL) of the cerebellum. Using a linear regression model, we systematically analyzed the quantitative relationships between the complex temporal patterns of neural activity at each level with sensory input and motor output signals (acceleration, velocity, and position) during ocular-following. The results revealed the following: (1) the temporal firing pattern of the MST neurons locally encodes the dynamic properties of the visual stimulus within a limited range. On the other hand, (2) the temporal firing pattern of the Purkinje cells in the cerebellum globally encodes almost the entire motor command for the ocular-following response. We conclude that the cerebellum is the major site of the sensory-to-motor transformation necessary for ocular-following, where population coding is integrated into rate coding.

The effect of disparity on the very earliest ocular following responses and the initial neuronal activity in monkey cortical area MST

Movement of the visual scene evokes tracking movement with the eyes (ocular following response, OFR) at short latency (Miles, F.A., Kawano, K., Optican, L.M., 1986. Short-latency ocular following responses of monkey. I. Dependence on temporospatial properties of visual input. J. Neurophysiol. 56, 1321-1354). We examined the effect of binocular disparity on the initial OFR. The dependence of the OFR on horizontal disparity steps was studied in three monkeys (Macaca fuscata), and the associated unit discharges in the medial superior temporal area (MST) were studied in two of these. Based on the changes in eye position over the period 50-83 ms (measured from stimulus onset), the initial OFR showed clear dependence on the disparity imposed during the preceding centering saccade. The disparity tuning curves were S-shaped with a peak at a small crossed disparity and a trough at uncrossed disparities. Based on the changes in discharge rate over the period 40-73 ms (measured from stimulus onset), almost all OFR-related MST neurons (80/83, 96.4%) showed significant dependence on the disparity step (Students t-test, P < 0.05). The early neuronal responses of the majority of units (41/75, 55%) had disparity tuning curves resembling those for the OFR, which peaked at small crossed disparities. These findings suggest that the neurons in the MST contain information on binocular disparity in their short-latency discharges, and are involved in the neural basis of the OFRs dependence on horizontal disparity.

Population coding in cortical area MST.

Abstract: Disparity steps applied to large patterns elicit vergence eye movements at ultrashort latencies. Disparity tuning curves, describing the dependence of the amplitude of the initial vergence responses on the amplitude of the disparity steps, resemble the derivative of a gaussian and indicate that appropriate servo‐like behavior occurs only with small disparity steps (<1 degree). Lesion data from monkeys suggest that these vergence responses are mediated, at least in part, by neurons in the medial superior temporal area of the cerebral cortex, and we here review a recent study of the associated single unit activity in that area. Few medial superior temporal neurons have disparity tuning curves whose shapes resemble the tuning curve for vergence. Yet, when the disparity tuning curves for all of the disparity‐sensitive cells recorded from a given monkey are summed together, they match the tuning curves for the vergence responses of that monkey very closely, even reproducing that animals idiosyncracies. When all of the spike trains elicited by a given disparity step are summed together to give an average discharge profile for the whole population of recorded cells, many are noisy, but others that are less so match the temporal profile of the motor response, vergence velocity, quite well. We conclude that the discharges of the disparity‐sensitive cells in the medial superior temporal area each represent only a very limited aspect of the sensory stimulus (and/or associated motor response?), but when pooled together, they provide a complete description of the vergence velocity motor response: population coding.

The role of MST neurons during ocular tracking in 3D space.

Whenever we move around in the environment, the visual system is confronted with characteristic patterns of visual motion, termed optic flow. The optic flow contains important information about self-motion and the 3D structure of the environment as discussed in other chapters in this book. O n the other hand, visual acuity is severely affected if the images of interest on the retina move at more than a few degrees per second. A major function of eye movements is to avoid such retinal motion and thereby improve vision. The observer’s movements activate the vestibular organs and are then compensated by vestibuloocular reflexes. However, the vestibuloocular reflexes are not always perfect, and the residual disturbances of gaze are compensated by the visual tracking system(s). Until recently, visual stabilization of the eyes was regarded only in terms of providing’backup to the canal-ocular vestibular reflexes, which deal solely with rotational disturbances of the observer. This is reflected in the stimulus traditionally used to study these visual mechanisms: The subject is seated inside a cylinder with vertically striped walls that are rotated around the subject at constant speed, often for periods of a minute or more. Because of the cylinder’s bulk, it is usual to first bring the cylinder up to speed in darkness and to then suddenly expose the subject to the motion of the stripes by turning on a light. The ocu-

A mathematical model that reproduces vertical ocular following responses from visual stimuli by reproducing the simple spike firing frequency of Purkinje cells in the cerebellum

A mathematical model that accurately reproduces eye movements from visual stimuli and incorporates intermediate neural signals is useful for quantitative analysis of the neural mechanisms involved in transforming visual stimuli to eye movements. Here we describe a mathematical model consisting of two systems: a non-linear system that relates retinal slip to simple spike firing frequency of Purkinje cells in the ventral paraflocculus (VPFL) and a linear system that relates VPFL simple spike firing frequency to eye movement. This model accurately reproduced the firing frequency of Purkinje cells and ocular following responses from visual stimulation paradigms used in physiological experiments.

A mathematical analysis of the characteristics of the system connecting the cerebellar ventral paraflocculus and extraoculomotor nucleus of alert monkeys during upward ocular following responses.

Movements of the visual scene evoke short-latency ocular-following-responses (OFR). Many studies suggest that a neural pathway containing the cerebellar-ventral-paraflocculus (VPFL) mediates OFR. The relationship between eye movement and simple-spike firing in the VPFL during OFR has been studied in detail using an inverse dynamics approach. The relationship between eye movement and cell firing in the extraoculomotor nucleus (MN) has already been reported. However, no studies have examined the information transformation that occurs between the VPFL and the MN during OFR. In this paper, using an inverse dynamics approach, we derive a transfer function that represents the characteristics of the structure connecting the VPFL and the MN during upward OFR. This structure appears to contain a kind of neural integrator, which constructs eye-velocity-and-position information from eye-acceleration-and-velocity information. We propose a diagram for the neural integration commonly at work during all types of upward eye movement. This is a closed-loop circuit containing a low-pass filter. The low-pass filter can construct eye-velocity-and-position information from an eye-acceleration-velocity-position command similar to the final motor command used commonly for all upward eye movements. Anatomical and electrophysiological data suggest that the vestibular nuclei-interstitial nucleus of Cajal-vestibular nuclei loop might perform such neural integration.