Mixed Selectivity in the Cerebellar Purkinje-Cell Response during Visuomotor Association Learning.

Although the cerebellum has been traditionally considered to be exclusively involved in motor control, recent anatomic and clinical studies show that it also has a role in reward-processing. However, the way in which the movement-related and the reward-related neural activity interact at the level of the cerebellar cortex and contribute toward learning is still unclear. Here, we studied the simple spike activity of Purkinje cells in the mid-lateral cerebellum when 2 male monkeys learned to associate a right or left-hand movement with one of two visual symbolic cues. These cells had distinctly different discharge patterns between an overtrained symbol-hand association and a novel symbol-hand association, responding in association with the movement of both hands, although the kinematics of the movement did not change between the two conditions. The activity change was not related to the pattern of the visual symbols, the movement kinematics, the monkeys' reaction times, or the novelty of the visual symbols. The simple spike activity changed throughout the learning process, but the concurrent complex spikes did not instruct that change. Although these neurons also have reward-related activity, the reward-related and movement-related signals were independent. We suggest that this mixed selectivity may facilitate the flexible learning of difficult reinforcement learning problems.SIGNIFICANCE STATEMENT The cerebellum receives both motor-related and reward-related information. However, it is unclear how these two signals interact at the level of cerebellar cortex and contribute to learning nonmotor skills. Here we show that in the mid-lateral cerebellum, the reward information is encoded independently from the motor information such that during reward-based learning, only the reward information carried by the Purkinje cells inform learning while the motor information remains unchanged with learning.

Neural Correlates of Reinforcement Learning in Mid-lateral Cerebellum.

The role of the cerebellum in non-motor learning is poorly understood. Here, we investigated the activity of Purkinje cells (P-cells) in the mid-lateral cerebellum as the monkey learned to associate one arbitrary symbol with the movement of the left hand and another with the movement of the right hand. During learning, but not when the monkey had learned the association, the simple spike responses of P-cells reported the outcome of the animal's most recent decision without concomitant changes in other sensorimotor parameters such as hand movement, licking, or eye movement. At the population level, P-cells collectively maintained a memory of the most recent decision throughout the entire trial. As the monkeys learned the association, the magnitude of this reward-related error signal approached zero. Our results provide a major departure from the current understanding of cerebellar processing and have critical implications for cerebellum's role in cognitive control.

Extrafoveal preview benefit during free-viewing visual search in the monkey.

Previous studies have shown that subjects require less time to process a stimulus at the fovea after a saccade if they have viewed the same stimulus in the periphery immediately prior to the saccade. This extrafoveal preview benefit indicates that information about the visual form of an extrafoveally viewed stimulus can be transferred across a saccade. Here, we extend these findings by demonstrating and characterizing a similar extrafoveal preview benefit in monkeys during a free-viewing visual search task. We trained two monkeys to report the orientation of a target among distractors by releasing one of two bars with their hand; monkeys were free to move their eyes during the task. Both monkeys took less time to indicate the orientation of the target after foveating it, when the target lay closer to the fovea during the previous fixation. An extrafoveal preview benefit emerged even if there was more than one intervening saccade between the preview and the target fixation, indicating that information about target identity could be transferred across more than one saccade and could be obtained even if the search target was not the goal of the next saccade. An extrafoveal preview benefit was also found for distractor stimuli. These results aid future physiological investigations of the extrafoveal preview benefit.

Feature attention evokes task-specific pattern selectivity in V4 neurons.

A hallmark of visual cortical neurons is their selectivity for stimulus pattern features, such as color, orientation, or shape. In most cases this feature selectivity is hard-wired, with selectivity manifest from the beginning of the response. Here we show that when a task requires that a monkey distinguish between patterns, V4 develops a selectivity for the sought-after pattern, which it does not manifest in a task that does not require the monkey to distinguish between patterns. When a monkey looks for a target object among an array of distractors, V4 neurons become selective for the target ∼50 ms after the visual latency independent of the impending saccade direction. However, when the monkey has to only make a saccade to the spatial location of the same objects without discriminating their pattern, V4 neurons do not distinguish the search target from the distractors. This selectivity for stimulus pattern develops roughly 40 ms after the same neurons' selectivity for basic pattern features like orientation or color. We suggest that this late-developing selectivity is related to the phenomenon of feature attention and may contribute to the mechanisms by which the brain finds the target in visual search.

Activity in V4 reflects the direction, but not the latency, of saccades during visual search.

We constantly make eye movements to bring objects of interest onto the fovea for more detailed processing. Activity in area V4, a prestriate visual area, is enhanced at the location corresponding to the target of an eye movement. However, the precise role of activity in V4 in relation to these saccades and the modulation of other cortical areas in the oculomotor system remains unknown. V4 could be a source of visual feature information used to select the eye movement, or alternatively, it could reflect the locus of spatial attention. To test these hypotheses, we trained monkeys on a visual search task in which they were free to move their eyes. We found that activity in area V4 reflected the direction of the upcoming saccade but did not predict the latency of the saccade in contrast to activity in the lateral intraparietal area (LIP). We suggest that the signals in V4, unlike those in LIP, are not directly involved in the generation of the saccade itself but rather are more closely linked to visual perception and attention. Although V4 and LIP have different roles in spatial attention and preparing eye movements, they likely perform complimentary processes during visual search.

Neurons in the lateral intraparietal area create a priority map by the combination of disparate signals.

Primates search for objects in the visual field with eye movements. We recorded the activity of neurons in the lateral intraparietal area (LIP) in animals performing a visual search task in which they were free to move their eyes, and reported the results of the search with a hand movement. We distinguished three independent signals: (1) a visual signal describing the abrupt onset of a visual stimulus in the receptive field; (2) a saccadic signal predicting the monkey's saccadic reaction time independently of the nature of the stimulus; (3) a cognitive signal distinguishing between the search target and a distractor independently of the direction of the impending saccade. The cognitive signal became significant on average 27 ms after the saccadic signal but before the saccade was made. The three signals summed in a manner discernable at the level of the single neuron.

Neural enhancement and pre-emptive perception: the genesis of attention and the attentional maintenance of the cortical salience map.

One of the stable hypotheses in systems neuroscience is the relationship between attention and the enhancement of visual responses when an animal attends to the stimulus in its receptive field (Goldberg and Wurtz, 1972 Journal of Neurophysiology 35 560-574). This was first discovered in the superior colliculus of the monkey: neurons in the superficial layers of the superior colliculus responded more intensely to the onset of a stimulus during blocks of trials in which the monkey had to make a saccade to it than they did during blocks of trials in which the monkey had to continue fixating a central point and not respond to the stimulus. This enhancement has been found in many brain regions, including prefrontal cortex (Boch and Goldberg, 1987 Investigative Ophthalmology 28 Supplement, 124), V4 (Moran and Desimone, 1985 Science 229 782-784), and lateral intraparietal area (Colby et al, 1996 Journal of Neurophysiology 76 2841-2852; Colby and Goldberg, 1999 Annual Review of Neuroscience 22 319-349), and even V1 (Lamme et al, 2000 Vision Research 40 1507-1521). In these studies the assumption has been that the monkey attended to the stimulus because the stimulus evoked an enhanced response. In the experiments described here we show that for abruptly appearing stimuli, attention is not related to the initial response evoked by the stimulus, but by the activity present on the salience map in the parietal cortex when the stimulus appears. Attention to the stimulus may subsequently, by a top down signal, sustain the map, but stimuli can as easily be suppressed by top down features as they can be enhanced.

LIP responses to a popout stimulus are reduced if it is overtly ignored.

Bright objects capture our attention by virtue of 'popping out' from their surroundings. This correlates with strong responses in cortical areas thought to be important in attentional allocation. Previous studies have suggested that with the right mindset or training, humans can ignore popout stimuli. We studied the activity of neurons in monkey lateral intraparietal area while monkeys performed a visual search task. The monkeys were free to move their eyes, and a distractor, but never the search target, popped out. On trials in which the monkeys made a saccade directly to the search target, the popout distractor evoked a smaller response than the non-popout distractors. The intensity of the response to the popout correlated inversely with the monkeys' ability to ignore it. We suggest that this modulation corresponds to a top-down mechanism that the brain uses to adjust the parietal representation of salience.

Activity in the lateral intraparietal area predicts the goal and latency of saccades in a free-viewing visual search task.

The purpose of saccadic eye movements is to facilitate vision, by placing the fovea on interesting objects in the environment. Eye movements are not made for reward, and they are rarely restricted. Despite this, most of our knowledge about the neural genesis of eye movements comes from experiments in which specific eye movements are rewarded or restricted. Such experiments have demonstrated that activity in the lateral intraparietal (LIP) area of the monkey correlates with the monkey's planning of a memory-guided saccade or deciding where, on the basis of motion information, to make a saccade. However, other experiments have shown that neural activity in LIP can easily be dissociated from the generation of saccadic eye movements, especially when sophisticated behavioral paradigms dissociate the monkey's locus of attention from the goal of an intended saccade. In this study, we trained monkeys to report the results of a visual search task by making a nontargeting hand movement. Once the task began, the monkeys were entirely free to move their eyes, and rewards were not contingent on the monkeys making specific eye movements. We found that neural activity in LIP predicted not only the goal of the monkey's saccades but also their saccadic latencies.