Embarrassed, but Not Depressed Eye Opening Lessons for Cerebellar Learning

AbstractCellular mechanisms of plasticity must be linked to circuit mechanisms of behavior to understand learning and memory. Studies of how learning occurs in cerebellar circuits for classical conditioning of eyeblinks are meeting this challenge admirably. Several recent papers have added to the richness of our understanding of cerebellar learning by correlating complex aspects of learned behaviors with hitherto underappreciated properties of the cerebellar circuit

Vector averaging for smoothpursuit eye movements initiated by two moving targets in monkeys.

The visual input for pursuit eye movements is represented in the cerebral cortex as the distributed activity of neurons that are tuned for both the direction and speed of target motion. To probe how the motor system uses this distributed code to compute a command for smooth eye movements, we have recorded the initiation of pursuit for 150 msec presentations of two spots moving at different speeds and/or in different directions. With equal probability, one of the two spots continued to move at the same speed and in the same direction and became the tracking target, whereas the other disappeared and served as a distractor. We measured eye acceleration in the interval from 110 to 206 msec after the onset of spot motion, within both the open-loop interval for pursuit and the interval during which eye motion was affected by the two spots. Our results demonstrate that weighted vector averaging is used to combine the responses to two moving spots. We found only a minute number of responses that were consistent with either vector summation or winner-take-all computations. In addition, our data show that it is difficult for the monkey to defeat vector averaging without extended training on the use of an explicit cue about which spot will become the target. We argue that our experiment reveals the computations done by the pursuit system in the absence of attentional bias and that vector averaging is normally used to read the distributed code of image motion when there is only one target

Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease

Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were measured in three FTLD subtypes, including 24 individuals with frontotemporal dementia (FTD), 19 with semantic dementia (SD) and six with progressive non-fluent aphasia (PA), as compared to 28 individuals with Alzheimer's disease, 15 with CBS, 10 with PSP and 27 control subjects. Different combinations of oculomotor abnormalities were identified in all clinical syndromes except for SD, which had oculomotor performance that was indistinguishable from age-matched controls. Only PSP patients displayed abnormalities in saccade velocity, whereas abnormalities in saccade gain were observed in PSP > CBS > Alzheimer's disease subjects. All patient groups except those with SD were impaired on the anti-saccade task, however only the FTLD subjects and not Alzheimer's disease, CBS or PSP groups, were able to spontaneously self-correct anti-saccade errors as well as controls. Receiver operating characteristic statistics demonstrated that oculomotor findings were superior to neuropsychological tests in differentiating PSP from other disorders, and comparable to neuropsychological tests in differentiating the other patient groups. These data suggest that oculomotor assessment may aid in the diagnosis of FTLD and related disorders

The Vestibulo-Ovular Reflex

Each time we turn our heads, the vestibulo-ocular reflex (VOR) generates a smooth eye movement that is equal in amplitude and opposite in direction to the head movement. As a result, the eyes remain stationary with respect to the world, and the images from the stationary surroundings remain relatively stationary on the retina. It is extremely important for visual acuity that the VOR perform accurately. We are always turning our heads, either as part of an effort to look at a target, or involuntarily as we move through the world. Indeed, there are small head oscillations at all times, even if we attempt to hold our head still. If these head turns resulted in image motion across the retina at speeds of greater than 2 to 3 deg/s, visual acuity would be reduced

Smooth Pursuit Eye Movements: Physiological Considerations

Smooth pursuit eye movements are expressed in their finest form in primates and have been studied extensively in humans and in monkeys. Several features define pursuit and distinguish it from the other kinds of eye movements. First. pursuit requires a moving visual target and cannot generally be elicited by stationary or imagined targets. For example, attempts to "move the eyes from left to right as slowly and smoothly as possible" produce a stai rcase of small saccades. Second, pursuit can be elicited by the motion of a small target across an otherwise stationary background. In the laboratory, the pursuit stimulus is commonly a small circular spot of light less than 1 deg in diameter, and the background can be dark, diffusely illuminated or highly patterned. Although the properties of the background have some subtle effects on the quality of smooth pursuit, effective tracking can be maintained in spite of the powerful optokinetic stimulus provided by a patterned background as the eyes sweep smoothly across

Role of Plasticity at Different Sites across the Time Course of Cerebellar Motor Learning

Learning comprises multiple components that probably involve cellular and synaptic plasticity at multiple sites. Different neural sites may play their largest roles at different times during behavioral learning. We have used motor learning in smooth pursuit eye movements of monkeys to determine how and when different components of learning occur in a known cerebellar circuit. The earliest learning occurs when one climbing-fiber response to a learning instruction causes simple-spike firing rate of Purkinje cells in the floccular complex of the cerebellum to be depressed transiently at the time of the instruction on the next trial. Trial-over-trial depression and the associated learning in eye movement are forgotten in <6 s, but facilitate long-term behavioral learning over a time scale of ∼5 min. During 100 repetitions of a learning instruction, simple-spike firing rate becomes progressively depressed in Purkinje cells that receive climbing-fiber inputs from the instruction. In Purkinje cells that prefer the opposite direction of pursuit and therefore do not receive climbing-fiber inputs related to the instruction, simple-spike responses undergo potentiation, but more weakly and more slowly. Analysis of the relationship between the learned changes in simple-spike firing and learning in eye velocity suggests an orderly progression of plasticity: first on Purkinje cells with complex-spike (CS) responses to the instruction, later on Purkinje cells with CS responses to the opposite direction of instruction, and last in sites outside the cerebellar cortex. Climbing-fiber inputs appear to play a fast and primary, but nonexclusive, role in pursuit learning

Gamma Synchrony Predicts Neuron–Neuron Correlations and Correlations with Motor Behavior in Extrastriate Visual Area MT

Correlated variability of neuronal responses is an important factor in estimating sensory parameters from a population response. Large correlations among neurons reduce the effective size of a neural population and increase the variation of the estimates. They also allow the activity of one neuron to be informative about impending perceptual decisions or motor actions on single trials. In extrastriate visual area MT of the rhesus macaque, for example, some but not all neurons show nonzero "choice probabilities" for perceptual decisions or non-zero "MT-pursuit" correlations between the trial-by-trial variations in neural activity and smooth pursuit eye movements. To understand the functional implications of zero versus nonzero correlations between neural responses and impending perceptions or actions, we took advantage of prior observations that specific frequencies of local field potentials reflect the correlated activity of neurons. We found that the strength of the spike-field coherence of a neuron in the gamma-band frequency range is related to the size of its MT-pursuit correlations for eye direction, as well as to the size of the neuron-neuron correlations. Spike-field coherence predicts MT-pursuit correlations better for direction than for speed, perhaps because the topographic organization of direction preference in MT is more amenable to creating meaningful local field potentials. We suggest that the relationship between spiking and local-field potentials is stronger for neurons that have larger correlations with their neighbors; larger neuron-neuron correlations create stronger MT-pursuit correlations. Neurons that lack strong correlations with their neighbors also have weaker correlations with pursuit behavior, but still could drive pursuit strongly

Role of the Lateral Intraparietal Area in Modulation of the Strength of Sensory-Motor Transmission for Visually Guided Movements

The lateral intraparietal area (LIP) has been implicated as a salience map for control of saccadic eye movements and visual attention. Here, we report evidence to link the encoding of saccades and saliency in LIP to modulation of several other sensory-motor behaviors in monkeys. In many LIP neurons, there was a significant trial-by-trial correlation between the firing rate just before a saccade and the postsaccadic or presaccadic pursuit eye velocity. Some neurons also showed trail-by-trial correlations of the firing rate of LIP neurons with the speed of "glissades" that occur at the end of saccades to stationary targets. LIP-pursuit correlations were spatially specific and were strong only when the target appeared in the receptive/movement field of the neuron under study. We suggest that LIP is a component of a salience representation that modulates the strength of visual-motor transmission for pursuit, and that may play a similar role for many movements, beyond its traditional roles in guiding saccadic eye movements and localizing attention

Saccades exert spatial control of motion processing for smooth pursuit eye movements

Saccades modulate the relationship between visual motion and smooth eye movement. Before a saccade, pursuit eye movements reflect a vector average of motion across the visual field. After a saccade, pursuit primarily reflects the motion of the target closest to the endpoint of the saccade. We tested the hypothesis that the saccade produces a spatial weighting of motion around the endpoint of the saccade. Using a moving pursuit stimulus that stepped to a new spatial location just before a targeting saccade, we controlled the distance between the endpoint of the saccade and the position of the moving target. We demonstrate that the smooth eye velocity following the targeting saccade weights the presaccadic visual motion inputs by the distance from their location in space to the endpoint of the saccade, defining the extent of a spatiotemporal filter for driving the eyes. The center of the filter is located at the endpoint of the saccade in space, not at the position of the fovea. The filter is stable in the face of a distracter target, is present for saccades to stationary and moving targets, and affects both the speed and direction of the postsaccadic eye movement. The spatial filter can explain the target-selecting gain change in postsaccadic pursuit, and has intriguing parallels to the process by which perceptual decisions about a restricted region of space are enhanced by attention. The effect of the spatial saccade plan on the pursuit response to a given retinal motion describes the dynamics of a coordinate transformation

Role of the Lateral Intraparietal Area in Modulation of the Strength of Sensory-Motor Transmission for Visually Guided Movements

The lateral intraparietal area (LIP) has been implicated as a salience map for control of saccadic eye movements and visual attention. Here, we report evidence to link the encoding of saccades and saliency in LIP to modulation of several other sensory-motor behaviors in monkeys. In many LIP neurons, there was a significant trial-by-trial correlation between the firing rate just before a saccade and the postsaccadic or presaccadic pursuit eye velocity. Some neurons also showed trail-by-trial correlations of the firing rate of LIP neurons with the speed of "glissades" that occur at the end of saccades to stationary targets. LIP-pursuit correlations were spatially specific and were strong only when the target appeared in the receptive/movement field of the neuron under study. We suggest that LIP is a component of a salience representation that modulates the strength of visual-motor transmission for pursuit, and that may play a similar role for many movements, beyond its traditional roles in guiding saccadic eye movements and localizing attention