Biomedical subjects

Okihide Hikosaka

Publications and source records attributed to Okihide Hikosaka.

At least 19 recordsLinked to original sources

PubMed2007

Functional differences between macaque prefrontal cortex and caudate nucleus during eye movements with and without reward.

The prefrontal cortex and the basal ganglia form mutually connected networks and are thought to play essential roles together in guiding goal-directed behaviors. Yet, these structures seem to have independent pathways to motor outputs as well, suggesting differential contributions to goal-directed behaviors. We hypothesized that the prefrontal cortex guides actions to a direction required by external demands and the basal ganglia guide actions to an internally motivated direction. To test this hypothesis, we used a task in which monkeys were required to make a memory-guided saccade to a direction indicated by a visual cue while only one direction was associated with reward. We observed a functional dissociation between the lateral prefrontal cortex (LPFC), which commonly represented the cue direction, and the caudate nucleus (CD), which commonly represented the reward-associated direction. Furthermore, cue-directed and reward-directed signals were integrated differently in the two areas; when the cue direction and the reward direction were opposite, LPFC neurons maintained tuning to the cue direction, whereas CD neurons lost the tuning. Different types of spatial tuning in the two brain areas may contribute to different types of goal-directed behavior.

Analysis of Variance↗

PubMed2006

Facilitation of saccadic eye movements by postsaccadic electrical stimulation in the primate caudate.

Sensorimotor experience followed by positive feedback leads to motor learning. Although the striatum, an input channel of the basal ganglia, has been implicated to play a key role in motor learning, little is known about how reward information modulates the neuronal processes in the striatum that causes behavioral changes. Here, we report that direct manipulation of the neuronal signal in the primate caudate yields behavioral changes comparable with those induced by natural reward. Electrical stimulation in the oculomotor region of the caudate immediately after saccades to a fixed direction led to selective facilitation of saccades in that direction. The facilitation remained even after stimulation was stopped, indicating a plastic change. These effects were observed when stimulation was applied after, not before, saccades. We propose that the caudate plays a causal role in behavioral changes by integrating selective sensorimotor and reward information in a temporally specific manner.

Animals↗

PubMed2006

Temporal development of asymmetric reward-induced bias in macaques.

Time and expected outcome are two ubiquitous factors contributing to decision-making. However, it is unclear how they interact to influence motor responses. When two differential reward outcomes are expected at the end of a waiting period, behavioral bias is consistently induced, manifested as shorter latencies for motor responses associated with the preferred reward. To examine how this bias develops in time during the waiting period, we manipulated the duration of the waiting period in an asymmetric reward saccade task in monkeys. We found that the bias increases with the duration of waiting period. Surprisingly, the bias resulted from gradual suppression of saccades to nonpreferred targets rather than from facilitation of saccades to preferred targets. These results have important implications on the neural correlates of reward-induced bias.

Animals↗

PubMed2006

Influences of rewarding and aversive outcomes on activity in macaque lateral prefrontal cortex.

Both appetitive and aversive outcomes can reinforce animal behavior. It is not clear, however, whether the opposing kinds of reinforcers are processed by specific or common neural mechanisms. To investigate this issue, we studied macaque monkeys that performed a memory-guided saccade task for three different outcomes, namely delivery of liquid reward, avoidance of air puff, and feedback sound only. Animals performed the task best in rewarded trials, intermediately in aversive trials, and worst in sound-only trials. Most task-related activity in lateral prefrontal cortex was differentially influenced by the reinforcers. Aversive avoidance had clear effects on some prefrontal neurons, although the effects of rewards were more common. We also observed neurons modulated by both positive and negative reinforcers, reflecting reinforcement or attentional processes. Our results demonstrate that information about positive and negative reinforcers is processed differentially in prefrontal cortex, which could contribute to the role of this structure in goal-directed behavior.

Analysis of Variance↗

PubMed2006

Extended LATER model can account for trial-by-trial variability of both pre- and post-processes.

We present a new decision-making model that can account for trial-by-trial variability induced by a process ("pre-process") that occurs before an explicit sensory signal specifying a later motor response. A process after explicit sensory signals, referred to herein as the "post-process", has been investigated by a variety of so-called rise-to-threshold models including the LATER model. The LATER model formulates post-process variability but treats the pre-process as fixed within a block of an experiment. We propose an extension of the LATER model, which we call the extended LATER (ELATER) model, to account for trial-by-trial variability of both pre- and post-processes together. We present the mathematical formulation of the ELATER model and analyze its characteristics, including numerical examples and an example of saccade latency data in reward-manipulated conditions with caudate activity. The ELATER model is useful for investigating decision making by taking account of trial-by-trial variability of both pre- and post-processes.

Animals↗

PubMed2006

Comparison of reward modulation in the frontal eye field and caudate of the macaque.

The frontal eye field (FEF) influences saccade generation via direct projections to the superior colliculus and an indirect pathway through the basal ganglia. To test whether different reward information is represented in the FEF and the basal ganglia, we recorded from the FEF and the caudate nucleus in monkeys performing an asymmetrically rewarded memory-guided saccade task. A peripheral cue at one of two opposing positions was flashed briefly to indicate the saccade target. In a given block, one position was associated with big reward and the other with small reward. Big-reward position was alternated between blocks. In this task, the FEF and caudate displayed similar prevalence of neuronal activity before cue onset that was larger in blocks with specific big reward-cue position associations. They also exhibit comparable reward modulation of visual responses that were spatially selective. In contrast, visual responses that were specific to expected reward size, instead of spatial locations, were commonly observed in caudate but rarely seen in the FEF. Thus, both the FEF and basal ganglia may contribute to reward bias in saccade generation, with the FEF providing spatially relevant reward information and the basal ganglia providing additional reward-specific information.

Action Potentials↗

PubMed2006

Effects of explicit knowledge of workspace rotation in visuomotor sequence learning.

Previous experimental and theoretical studies have suggested that two separate neural networks contribute to visuomotor learning of spatial sequences, one to the accuracy of performance and the other to the speed of performance (Nakahara et al. in J Cogn Neurosci 13:626-647, 2001). This study examined the influence of explicit knowledge of stimulus configuration (workspace) in visuomotor sequence learning. Twenty-eight right-handed subjects learned the sequences of button presses by trial and error (Hikosaka et al. in J Neurophysiol 76:617-621, 1996) in the course of two sessions. In the first session, both the number of completion failures (accuracy measure) and the performance time to complete a sequence (speed measure) decreased. In the second session, the workspace was rotated without notifying the subjects. About half the subjects remained unaware of the workspace rotation, and no transfer of learning occurred (i.e., neither accuracy nor speed of performance was preserved in the second session). The remaining subjects spontaneously noticed the rotation and they were able to use this knowledge to perform the task with less completion failures in the second session. However, the knowledge of workspace rotation did not decrease the performance time in the second session. The lack of influence of explicit knowledge on the speed of performance is consistent with the two-loop model of visuomotor sequence learning (Nakahara et al. in J Cogn Neurosci 13:626-647, 2001).

Analysis of Variance↗

PubMed2006

Role of dopamine in the primate caudate nucleus in reward modulation of saccades.

Expected reward impacts behavior and neuronal activity in brain areas involved in sensorimotor processes. However, where and how reward signals affect sensorimotor signals is unclear. Here, we show evidence that reward-dependent modulation of behavior depends on normal dopamine transmission in the striatum. Monkeys performed a visually guided saccade task in which expected reward gain was different depending on the position of the target. Saccadic reaction times were reliably shorter on large-reward trials than on small-reward trials. When position-reward contingency was switched, the reaction time difference changed rapidly. Injecting dopamine D1 antagonist into the caudate significantly attenuated the reward-dependent saccadic reaction time changes. Conversely, injecting D2 antagonist into the same region enhanced the reward-dependent changes. These results suggest that reward-dependent changes in saccadic eye movements depend partly on dopaminergic modulation of neuronal activity in the caudate nucleus.

Animals↗

PubMed2006

Basal ganglia orient eyes to reward.

Expectation of reward motivates our behaviors and influences our decisions. Indeed, neuronal activity in many brain areas is modulated by expected reward. However, it is still unclear where and how the reward-dependent modulation of neuronal activity occurs and how the reward-modulated signal is transformed into motor outputs. Recent studies suggest an important role of the basal ganglia. Sensorimotor/cognitive activities of neurons in the basal ganglia are strongly modulated by expected reward. Through their abundant outputs to the brain stem motor areas and the thalamocortical circuits, the basal ganglia appear capable of producing body movements based on expected reward. A good behavioral measure to test this hypothesis is saccadic eye movement because its brain stem mechanism has been extensively studied. Studies from our laboratory suggest that the basal ganglia play a key role in guiding the gaze to the location where reward is available. Neurons in the caudate nucleus and the substantia nigra pars reticulata are extremely sensitive to the positional difference in expected reward, which leads to a bias in excitability between the superior colliculi such that the saccade to the to-be-rewarded position occurs more quickly. It is suggested that the reward modulation occurs in the caudate where cortical inputs carrying spatial signals and dopaminergic inputs carrying reward-related signals are integrated. These data support a specific form of reinforcement learning theories, but also suggest further refinement of the theory.

Animals↗

PubMed2005

Immediate changes in anticipatory activity of caudate neurons associated with reversal of position-reward contingency.

The primate caudate nucleus plays a crucial role in transforming cognitive/motivational information into eye movement signals. A subset of caudate projection neurons fire before a visual target's onset. This anticipatory activity is sensitive to position-reward contingencies and correlates with saccade latency, which is shorter toward a rewarded position. We recorded single-unit activity of caudate projection neurons to examine the dynamics of change in anticipatory activity immediately after switches of the position-reward contingency. Two monkeys performed a visually guided saccade task where only one position was associated with reward. The position-reward mapping remained constant within a block, but was reversed frequently between blocks without any indication to the monkey. Therefore the switch could be detected only by unexpected reward delivery or unexpected lack of reward. After the switch, both saccade latency and anticipatory activity showed reliable changes already in the second trial, whether or not the first trial was rewarded. However, anticipatory activity in the second trial was generally higher if the first trial was rewarded, and the measured saccade latencies could be better explained by the difference in anticipatory activity between the two caudate nuclei. We suggest that anticipatory activity of caudate neurons reflects the reversal set of reward-position contingency.

Action Potentials↗

PubMed2004

A possible role of midbrain dopamine neurons in short- and long-term adaptation of saccades to position-reward mapping.

Dopamine (DA) neurons respond to sensory stimuli that predict reward. To understand how DA neurons acquire such ability, we trained monkeys on a one-direction-rewarded version of memory-guided saccade task (1DR) only when we recorded from single DA neurons. In 1DR, position-reward mapping was changed across blocks of trials. In the early stage of training of 1DR, DA neurons responded to reward delivery; in the later stages, they responded predominantly to the visual cue that predicted reward or no reward (reward predictor) differentially. We found that such a shift of activity from reward to reward predictor also occurred within a block of trials after position-reward mapping was altered. A main effect of long-term training was to accelerate the within-block reward-to-predictor shift of DA neuronal responses. The within-block shift appeared first in the intermediate stage, but was slow, and DA neurons often responded to the cue that indicated reward in the preceding block. In the advanced stage, the reward-to-predictor shift occurred quickly such that the DA neurons' responses to visual cues faithfully matched the current position-reward mapping. Changes in the DA neuronal responses co-varied with the reward-predictive differentiation of saccade latency both in short-term (within-block) and long-term adaptation. DA neurons' response to the fixation point also underwent long-term changes until it occurred predominantly in the first trial within a block. This might trigger a switch between the learned sets. These results suggest that midbrain DA neurons play an essential role in adapting oculomotor behavior to frequent switches in position-reward mapping.

Adaptation, Physiological↗

PubMed2004

Dopamine neurons can represent context-dependent prediction error.

Midbrain dopamine (DA) neurons are thought to encode reward prediction error. Reward prediction can be improved if any relevant context is taken into account. We found that monkey DA neurons can encode a context-dependent prediction error. In the first noncontextual task, a light stimulus was randomly followed by reward, with a fixed equal probability. The response of DA neurons was positively correlated with the number of preceding unrewarded trials and could be simulated by a conventional temporal difference (TD) model. In the second contextual task, a reward-indicating light stimulus was presented with the probability that, while fixed overall, was incremented as a function of the number of preceding unrewarded trials. The DA neuronal response then was negatively correlated with this number. This history effect corresponded to the prediction error based on the conditional probability of reward and could be simulated only by implementing the relevant context into the TD model.

Algorithms↗

PubMed2004

Emergence of rhythm during motor learning.

Complex motor skill often consists of a fixed sequence of movements. Recent studies show that a stereotyped temporal pattern or rhythm emerges as we learn to perform a motor sequence. This is because the sequence is reorganized during learning as serial chunks of movements in both a sequence-specific and subject-specific manner. On the basis of human imaging studies we propose that the formation of chunk patterns is controlled by the cerebellum, its posterior and anterior lobes contributing, respectively, to the temporal patterns before and after chunk formation. The motor rhythm can assist the motor networks in the cerebral cortex to control automatic movements within chunks and the cognitive networks to control non-automatic movements between chunks, respectively. In this way, organized motor skill can be performed automatically and flexibly.

Cerebellum↗

PubMed2003

Neural correlates of rewarded and unrewarded eye movements in the primate caudate nucleus.

The prospect of immediate reward elicits goal-oriented behavior. However, animals often have to perform actions that do not immediately lead to reward in the pursuit of a long-term goal. Here we identify neural activity in monkey caudate nucleus that specifically correlates with rewarded and unrewarded eye movements. The monkey performed a visually guided saccade task in which only one position was associated with positive reinforcement. To advance in the experimental session, however, the monkey had no choice but to complete a saccade to an unrewarded position as well as to a rewarded position. Some caudate saccadic neurons showed enhanced activity around the time of the saccade in rewarded trials (rewarded-saccade neurons). Another subset of neurons discharged selectively around the execution of the saccade in unrewarded trials (unrewarded-saccade neurons). In both rewarded and unrewarded trials, stronger activity of these neurons was associated with reduced saccade latency. These results suggest that both rewarded and unrewarded saccades are facilitated by caudate saccadic activity. The neuronal activity of unrewarded-saccade neurons might reflect the required execution of unrewarded eye movements on the way to future reward.

Action Potentials↗

PubMed2003

Reward-predicting activity of dopamine and caudate neurons--a possible mechanism of motivational control of saccadic eye movement.

Recent studies have suggested that the basal ganglia are related to motivational control of behavior. To study how motivational signals modulate motor signals in the basal ganglia, we examined activity of midbrain dopamine (DA) neurons and caudate (CD) projection neurons while monkeys were performing a one-direction-rewarded version (1DR) of memory-guided saccade task. The cue stimulus indicated the goal position for an upcoming saccade and the presence or absence of reward after the trial. Among four monkeys we studied, three were sensitive to reward such that saccade velocity was significantly higher in the rewarded trials than in the nonrewarded trials; one monkey was insensitive to reward. In the reward-sensitive monkeys, both DA and CD neurons responded differentially to reward-indicating and no-reward-indicating cues. Thus DA neurons responded with excitation to a reward-indicating cue and with inhibition to a no-reward-indicating cue. A group of CD neurons responded to the cue in their response fields (mostly contralateral) and the cue response was usually enhanced when it indicated reward. In the reward-insensitive monkey, DA neurons showed no response to the cue, while the cue responses of CD neurons were not modulated by reward. Many CD neurons in the reward-sensitive monkeys, but not the reward-insensitive monkey, showed precue activity. These results suggest that DA neurons, with their connection to CD neurons, modulate the spatially selective signals in CD neurons in the reward-predicting manner and CD neurons in turn modulate saccade parameters with their polysynaptic connections to the oculomotor brain stem.

Animals↗

PubMed2003

Reward-dependent gain and bias of visual responses in primate superior colliculus.

Eye movements are often influenced by expectation of reward. Using a memory-guided saccade task with an asymmetric reward schedule, we show that visual responses of monkey SC neurons increase when the visual stimulus indicates an upcoming reward. The increase occurred in two distinct manners: (1) reactively, as an increase in the gain of the visual response when the stimulus indicated an upcoming reward; (2) proactively, as an increase in anticipatory activity when reward was expected in the neuron's response field. These effects were observed mostly in saccade-related SC neurons in the deeper layer which would receive inputs from the cortical eye fields and the basal ganglia. These results, together with recent findings, suggest that the gain modulation may be determined by the inputs from both the cortical eye fields and the basal ganglia, whereas the anticipatory bias may be derived mainly from the basal ganglia.

Animals↗

PubMed2003

Effects of motivational conflicts on visually elicited saccades in monkeys.

The prospect of reward evoked by external stimuli is a central element of goal-oriented behavior. To elucidate behavioral effects of reward expectation on saccade latency, we employed a visually guided saccade task with asymmetrical reward schedule. The monkey had to make an immediate saccade to a peripheral visual target in every trial, but was rewarded for a correct saccade to only one of four possible target positions. Reward availability was predictable on the basis of the spatial position of the target throughout a daily session. Compared with the condition where all positions were rewarded with a smaller amount, the mean saccade latency in the asymmetrical reward schedule was significantly shorter when the saccade was made toward the position associated with reward than when it was directed to no-reward positions. Furthermore, a divergence-point analysis on cumulative latency distributions showed that the expectation of reward facilitated saccades at all latency ranges. In contrast, the expected lack of reward delayed the initiation of saccades with latencies longer than about 200 ms, irrespective of whether the saccade was made to a position orthogonal or opposite to the reward position. For saccades with latencies of more than approximately 240 ms, an additional delay was observed when the saccade was made to a position opposite, as compared to orthogonal, to the reward position. These results suggest that the facilitation by predictive reward is mediated by a preparatory process that is location-specific, whereas the inhibition by the absence of reward takes about 200 ms after the target onset to become effective and is initially location nonspecific but turns location-specific over time.

Animals↗

PubMed2003

Chunking during human visuomotor sequence learning.

Motor sequence learning is a process whereby a series of elementary movements is re-coded into an efficient representation for the entire sequence. Here we show that human subjects learn a visuomotor sequence by spontaneously chunking the elementary movements, while each chunk acts as a single memory unit. The subjects learned to press a sequence of 10 sets of two buttons through trial and error. By examining the temporal patterns with which subjects performed a visuomotor sequence, we found that the subjects performed the 10 sets as several clusters of sets, which were separated by long time gaps. While the overall performance time decreased by repeating the same sequence, the clusters became clearer and more consistent. The cluster pattern was uncorrelated with the distance of hand movements and was different across subjects who learned the same sequence. We then split a learned sequence into three segments, while preserving or destroying the clusters in the learned sequence, and shuffled the segments. The performance on the shuffled sequence was more accurate and quicker when the clusters in the original sequence were preserved than when they were destroyed. The results suggest that each cluster is processed as a single memory unit, a chunk, and is necessary for efficient sequence processing. A learned visuomotor sequence is hierarchically represented as chunks that contain several elementary movements. We also found that the temporal patterns of sequence performance transferred from the nondominant to dominant hand, but not vice versa. This may suggest a role of the dominant hemisphere in storage of learned chunks. Together with our previous unit-recording and imaging studies that used the same learning paradigm, we predict specific roles of the dominant parietal area, basal ganglia, and presupplementary motor area in the chunking.

Cluster Analysis↗