Stephen G. Lisberger

The Cerebellum: A Neuronal Learning Machine?

Comparison of two seemingly quite different behaviors yields a surprisingly consistent picture of the role of the cerebellum in motor learning. Behavioral and physiological data about classical conditioning of the eyelid response and motor learning in the vestibulo-ocular reflex suggest that (i) plasticity is distributed between the cerebellar cortex and the deep cerebellar nuclei; (ii) the cerebellar cortex plays a special role in learning the timing of movement; and (iii) the cerebellar cortex guides learning in the deep nuclei, which may allow learning to be transferred from the cortex to the deep nuclei. Because many of the similarities in the data from the two systems typify general features of cerebellar organization, the cerebellar mechanisms of learning in these two systems may represent principles that apply to many motor systems.

Stimulus onset quenches neural variability: a widespread cortical phenomenon

Neural responses are typically characterized by computing the mean firing rate, but response variability can exist across trials. Many studies have examined the effect of a stimulus on the mean response, but few have examined the effect on response variability. We measured neural variability in 13 extracellularly recorded datasets and one intracellularly recorded dataset from seven areas spanning the four cortical lobes in monkeys and cats. In every case, stimulus onset caused a decline in neural variability. This occurred even when the stimulus produced little change in mean firing rate. The variability decline was observed in membrane potential recordings, in the spiking of individual neurons and in correlated spiking variability measured with implanted 96-electrode arrays. The variability decline was observed for all stimuli tested, regardless of whether the animal was awake, behaving or anaesthetized. This widespread variability decline suggests a rather general property of cortex, that its state is stabilized by an input.

Tuning for Spatiotemporal Frequency and Speed in Directionally Selective Neurons of Macaque Striate Cortex

We recorded the responses of direction-selective simple and complex cells in the primary visual cortex (V1) of anesthetized, paralyzed macaque monkeys. When studied with sine-wave gratings, almost all simple cells in V1 had responses that were separable for spatial and temporal frequency: the preferred temporal frequency did not change and preferred speed decreased as a function of the spatial frequency of the grating. As in previous recordings from the middle temporal visual area (MT), approximately one-quarter of V1 complex cells had separable responses to spatial and temporal frequency, and one-quarter were “speed tuned” in the sense that preferred speed did not change as a function of spatial frequency. Half fell between these two extremes. Reducing the contrast of the gratings caused the population of V1 complex cells to become more separable in their tuning for spatial and temporal frequency. Contrast dependence is explained by the contrast gain of the neurons, which was relatively higher for gratings that were either both of high or both of low temporal and spatial frequency. For stimuli that comprised two spatially superimposed sine-wave gratings, the preferred speeds and tuning bandwidths of V1 neurons could be predicted from the sum of the responses to the component gratings presented alone, unlike neurons in MT that showed nonlinear interactions. We conclude that spatiotemporal modulation of contrast gain creates speed tuning from separable inputs in V1 complex cells. Speed tuning in MT could be primarily inherited from V1, but processing that occurs after V1 and possibly within MT computes selective combinations of speed-tuned signals of special relevance for downstream perceptual and motor mechanisms.

A sensory source for motor variation.

Suppose that the variability in our movements is caused not by noise in the motor system itself, nor by fluctuations in our intentions or plans, but rather by errors in our sensory estimates of the external parameters that define the appropriate action. For tasks in which precision is at a premium, performance would be optimal if no noise were added in movement planning and execution: motor output would be as accurate as possible given the quality of sensory inputs. Here we use visually guided smooth-pursuit eye movements in primates as a testing ground for this notion of optimality. In response to repeated presentations of identical target motions, nearly 92% of the variance in eye trajectory can be accounted for as a consequence of errors in sensory estimates of the speed, direction and timing of target motion, plus a small background noise that is observed both during eye movements and during fixations. The magnitudes of the inferred sensory errors agree with the observed thresholds for sensory discrimination by perceptual systems, suggesting that the very different neural processes of perception and action are limited by the same sources of noise.

Maldevelopment of visual motion processing in humans who had strabismus with onset in infancy

Binocular experience in infancy is necessary for the normal development of the visual cortex. However, it is not known whether binocular experience also affects the processing of specific kinds of visual information such as motion. We now report deficits in visual motion processing in 7 adult humans who lacked binocularity in infancy because of strabismus. As probes for assessing visual motion processing, we used the initiation of smooth pursuit eye movements and the judgment of target velocity independent of eye movement. Monocular viewing was essential to reveal the deficits. For horizontal pursuit, strabismic subjects showed nasal-temporal asymmetries, such that nasally directed target motion evoked more vigorous pursuit. For vertical pursuit, strabismics showed up-down asymmetries, such that upward target motion evoked more vigorous pursuit. In addition, strabismics had abnormalities in the relative effectiveness of different parts of the visual field for initiating both horizontal and vertical pursuit. Psychophysical judgements of horizontal target velocity revealed deficits analogous motion was perceived as faster than temporally directed motion, even when the 2 directions of motion were actually presented at the same speed. The magnitude of the motion processing deficits in each subject was correlated with the severity of the clinical signs of the strabismus. Our results suggest 2 possible interpretations. Maldevelopments of visual motion processing may cause strabismus in infancy, or alternatively, strabismus in the critical period for visual development may cause a maldevelopment of visual motion processing.

Links from complex spikes to local plasticity and motor learning in the cerebellum of awake-behaving monkeys

The hypothesis of cerebellar learning proposes that complex spikes in Purkinje cells engage mechanisms of plasticity in the cerebellar cortex; in turn, changes in the cerebellum depress the simple-spike response of Purkinje cells to a given stimulus and cause the adaptive modification of a motor behavior. Many elements of this hypothesis have been supported by prior experiments, and correlations have been found between complex spikes, simple-spike plasticity and behavior during the learning process. We carried out a trial-by-trial analysis of Purkinje cell responses in awake-behaving monkeys and found evidence for a causal role for complex spikes in the induction of cerebellar plasticity during a simple motor learning task. We found that the presence of a complex spike on one learning trial was linked to a substantial depression of simple-spike responses on the subsequent trial, at a time when behavioral learning was expressed.The hypothesis of cerebellar learning proposes that complex spikes in Purkinje cells engage mechanisms of plasticity in the cerebellar cortex; in turn, changes in the cerebellum depress the simple-spike response of Purkinje cells to a given stimulus and cause the adaptive modification of a motor behavior. Many elements of this hypothesis have been supported by prior experiments, and correlations have been found [corrected] between complex spikes, simple-spike plasticity and behavior [corrected] during the learning process. We carried out a trial-by-trial analysis of Purkinje cell responses in awake-behaving monkeys and found evidence for a causal role for complex spikes in the induction of cerebellar plasticity during a simple motor learning task. We found that the presence of a complex spike on one learning trial was linked to a substantial depression of simple-spike responses on the subsequent trial, at a time when behavioral learning was expressed.

Visual guidance of smooth pursuit eye movements: sensation, action, and what happens in between

Smooth-pursuit eye movements transform 100 ms of visual motion into a rapid initiation of smooth eye movement followed by sustained accurate tracking. Both the mean and variation of the visually driven pursuit response can be accounted for by the combination of the mean tuning curves and the correlated noise within the sensory representation of visual motion in extrastriate visual area MT. Sensory-motor and motor circuits have both housekeeping and modulatory functions, implemented in the cerebellum and the smooth eye movement region of the frontal eye fields. The representation of pursuit is quite different in these two regions of the brain, but both regions seem to control pursuit directly with little or no noise added downstream. Finally, pursuit exhibits a number of voluntary characteristics that happen on short timescales. These features make pursuit an excellent exemplar for understanding the general properties of sensory-motor processing in the brain.

Time course of information about motion direction in visual area MT of macaque monkeys.

We used the responses of neurons in extrastriate visual area MT to determine how well neural noise can be reduced by averaging the responses of neurons across time. For individual MT neurons, we calculated the time course of Shannon information about motion direction from sustained motion at constant velocities. Stimuli were random dot patterns moving at the preferred speed of the cell for 256 msec, in a direction chosen randomly with 15° increments. Information about motion direction calculated from cumulative spike count rose rapidly from the onset of the neural response and then saturated, reaching 80% of maximum information in the first 100 msec. Most of the early saturation of information could be attributed to correlated fluctuations in the spike counts of individual neurons on time scales in excess of 100 msec. Thus, temporal correlations limit the benefits of averaging across time, much as correlations among the responses of different neurons limit the benefits of averaging across large populations. Although information about direction was available quickly from MT neurons, the direction discrimination by individual MT neurons was poor, with mean thresholds above 30° in most neurons. We conclude that almost all available directional information could be extracted from the first few spikes of the response of the neuron, on a time scale comparable with the initiation of smooth pursuit eye movements. However, neural responses still must be pooled across the population in MT to account for the direction discrimination of the pursuit behavior.

Initial tracking conditions modulate the gain of visuo-motor transmission for smooth pursuit eye movements in monkeys

Smooth pursuit eye movements allow primates to keep gaze pointed at small objects moving across stationary surroundings. In monkeys trained to track a small moving target, we have injected brief perturbations of target motion under different initial conditions as probes to read out the state of the visuo-motor pathways that guide pursuit. A large eye movement response was evoked if the perturbation was applied to a moving target the monkey was tracking. A small response was evoked if the same perturbation was applied to a stationary target the monkey was fixating. The gain of the response to the perturbation increased as a function of the initial speed of target motion and as a function of the interval from the onset of target motion to the time of the perturbation. The response to the perturbation also was direction selective. Gain was largest if the perturbation was along the axis of ongoing target motion and smallest if the perturbation was orthogonal to the axis of target motion. We suggest that two parallel sets of visual motion pathways through the extrastriate visual cortex may mediate, respectively, the visuo-motor processing for pursuit and the modulation of the gain of transmission through those pathways.

A model of visually-guided smooth pursuit eye movements based on behavioral observations

We report a model that reproduces many of the behavioral properties of smooth pursuit eye movements. The model is a negative-feedback system that uses three parallel visual motion pathways to drive pursuit. The three visual pathways process image motion, defined as target motion with respect to the moving eye, and provide signals related to image velocity, image acceleration, and a transient that occurs at the onset of target motion. The three visual motion signals are summed and integrated to produce the eye velocity output of the model. The model reproduces the average eye velocity evoked by steps of target velocity in monkeys and humans and accounts for the variation among individual responses and subjects. When its motor pathways are expanded to include positive feedback of eye velocity and a “switch”, the model reproduces the exponential decay in eye velocity observed when a moving target stops. Manipulation of this expanded model can mimic the effects of stimulation and lesions in the arcuate pursuit area, the middle temporal visual area (MT), and the medial superior temporal visual area (MST).