Biomedical subjects

O Hikosaka

Publications and source records attributed to O Hikosaka.

At least 19 recordsLinked to original sources

PubMed2001

Role of tonically active neurons in primate caudate in reward-oriented saccadic eye movement.

Recent studies have suggested that the basal ganglia are essential for reward-oriented behavior. A popular proposal is that the interaction between sensorimotor and reward-related signals occurs in the striatal projection neurons. However, the role of interneurons remains unclear. Using the one-direction-rewarded version of the memory-guided saccade task (1DR), we examined the activity of tonically active neurons (TANs), presumed cholinergic interneurons, in the caudate. Many TANs (73/155, 47.1%) responded, usually with a pause, to a visual cue that indicated both the saccade goal and the presence or absence of reward. For most TANs (44/73, 60.3%), the response was spatially selective (contralateral dominant), but was not modulated by the reward significance. TANs are thus distinct from caudate projection neurons, which have responses to the cue that are both spatially selective and reward contingent, and from midbrain dopamine neurons, which have cue responses that are spatially nonselective and reward contingent. TANs were nonetheless sensitive to the reward schedule: in the all-directions-rewarded version (ADR) compared with 1DR, the cue responses of TANs were smaller, less frequent, and less spatially selective. In 1DR, it would first be detected that reward is not given regularly, and this process would then promote discrimination of individual stimuli in relation to reward. We propose that TANs would contribute to the detection of the context that requires discrimination, whereas dopamine neurons would contribute to the stimulus discrimination. These features of TANs might be explained by their cytoarchitecture, namely, as large aspiny neurons.

Action Potentials↗

PubMed2001

Parallel cortico-basal ganglia mechanisms for acquisition and execution of visuomotor sequences - a computational approach.

Experimental studies have suggested that many brain areas, including the basal ganglia (BG), contribute to procedural learning. Focusing on the basal ganglia-thalamocortical (BG-TC) system, we propose a computational model to explain how different brain areas work together in procedural learning. The BG-TC system is composed of multiple separate loop circuits. According to our model, two separate BG-TC loops learn a visuomotor sequence concurrently but using different coordinates, one visual, and the other motor. The visual loop includes the dorsolateral prefrontal (DLPF) cortex and the anterior part of the BG, while the motor loop includes the supplementary motor area (SMA) and the posterior BG. The concurrent learning in these loops is based on reinforcement signals carried by dopaminergic (DA) neurons that project divergently to the anterior ("visual") and posterior ("motor") parts of the striatum. It is expected, however, that the visual loop learns a sequence faster than the motor loop due to their different coordinates. The difference in learning speed may lead to inconsistent outputs from the visual and motor loops, and this problem is solved by a mechanism called a "coordinator," which adjusts the contribution of the visual and motor loops to a final motor output. The coordinator is assumed to be in the presupplementary motor area (pre-SMA). We hypothesize that the visual and motor loops, with the help of the coordinator, achieve both the quick acquisition of novel sequences and the robust execution of well-learned sequences. A computational model based on the hypothesis is examined in a series of computer simulations, referring to the results of the 2 x 5 task experiments that have been used on both monkeys and humans. We found that the dual mechanism with the coordinator was superior to the single (visual or motor) mechanism. The model replicated the following essential features of the experimental results: (1) the time course of learning, (2) the effect of opposite hand use, (3) the effect of sequence reversal, and (4) the effects of localized brain inactivations. Our model may account for a common feature of procedural learning: A spatial sequence of discrete actions (subserved by the visual loop) is gradually replaced by a robust motor skill (subserved by the motor loop).

Basal Ganglia↗

PubMed2001

A code for behavioral inhibition on the basis of color, but not motion, in ventrolateral prefrontal cortex of macaque monkey.

To examine the neural mechanism for behavioral inhibition, we recorded single-cell activity in macaque ventrolateral prefrontal cortex, which is known to receive visual information directly from the inferotemporal cortex. In response to a moving random pattern of colored dots, monkeys had to make a go or no-go response. In the color condition, green indicated go, whereas red indicated no-go, regardless of the motion direction; in the motion condition, upward indicated go, whereas downward indicated no-go, regardless of the color. Approximately one-half of the visual cells were go/no-go differential. A majority of these cells (64/73) showed differential activity only in the color condition; they responded nondifferentially in the motion condition, although the same set of stimuli was used. We classified these cells as "go type" (n = 41) and "no-go type" (n = 23) depending on the color for which they showed a stronger response. Interestingly, in both types of cells, the differential effects were observed only for the no-go-indicating color. Compared with the nondifferential responses in the motion condition, go-type cells in the color condition showed weaker responses to the no-go-indicating color, whereas their responses to the go-indicating color were similar; in contrast, no-go type cells showed stronger responses to the no-go-indicating color, whereas their responses to the go-indicating color were similar. Both types of cells did not show any activity change during the actual execution of the go or no-go response. These results suggest that neurons in ventrolateral prefrontal cortex contribute to stimulus-response association in complex task situations by inhibiting behavioral responses on the basis of visual information from the ventral stream.

Animals↗

PubMed2001

Responses to task-irrelevant visual features by primate prefrontal neurons.

The primate brain is equipped with prefrontal circuits for interpreting visual information, but how these circuits deal with competing stimulus-response (S-R) associations remains unknown. Here we show different types of responses to task-irrelevant visual features in three functionally dissociated groups of primate prefrontal neurons. Two Japanese macaques participated in a go/no-go task in which they had to discriminate either the color or the motion direction of a visual target to make a correct manual response. Prior to the experiment, the monkeys had been trained extensively so that they acquired fixed associations between visual features and required responses (e.g., "green = go"; "downward motion = no-go"). In this design, the monkey was confronted with a visual target from which it had to extract relevant information (e.g., color in the color-discrimination condition) while ignoring irrelevant information (e.g., motion direction in the color-discrimination condition). We recorded from 436 task-related prefrontal neurons while the monkey performed the multidimensional go/no-go task: 139 (32%) neurons showed go/no-go discrimination based on color as well as motion direction ("integration cells"); 192 neurons (44%) showed go/no-go discrimination only based on color ("color-feature cells"); and 105 neurons (24%) showed go/no-go discrimination only based on motion direction ("motion-feature cells"). Overall, however, 162 neurons (37%) were influenced by irrelevant information: 53 neurons (38%) among integration cells, 71 neurons (37%) among color-feature cells, and 38 neurons (36%) among motion-feature cells. Across all types of neurons, the response to an irrelevant feature was positively correlated with the response to the same feature when it was relevant, indicating that the influence from irrelevant information is a residual from S-R associations that are relevant in a different context. Temporal and anatomical differences among integration, color-feature and motion-feature cells suggested a sequential mode of information processing in prefrontal cortex, with integration cells situated toward the output of the decision-making process. In these cells, the response to irrelevant information appears as a congruency effect, with better go/no-go discrimination when both the relevant and irrelevant feature are associated with the same response than when they are associated with different responses. This congruency effect could be the result of the combined input from color- and motion-feature cells. Thus these data suggest that irrelevant features lead to partial activation of neurons even toward the output of the decision-making process in primate prefrontal cortex.

Animals↗

PubMed2000

What and when: parallel and convergent processing in motor control.

Successful motor behavior requires making appropriate response (response selection) at the right time (timing adjustment). Earlier psychological studies have suggested that the response selection and timing adjustment processes are performed serially in separate stages. We tested this hypothesis using functional magnetic resonance imaging. The subjects performed a choice reaction time task in four conditions: two (on-line response selection required or not) by two (on-line timing adjustment required or not). We found that the neural correlates for the two processes were indeed separate: the anterior medial premotor cortex (presupplementary motor area) was selectively active in response selection, whereas the cerebellar posterior lobe was selectively active in timing adjustment. However, the functional separation was only partial in that the lateral premotor cortex and the intraparietal sulcus were active equally for response selection and timing adjustment. The lateral premotor cortex was most active when both processes were required, suggesting that it integrates the information on response selection and the information on timing adjustment; alternatively, it might contribute to the allocation of attentional resources during dual information processing. The intraparietal sulcus was equally active when either response selection or timing adjustment was required, suggesting that it modifies, rather than integrates, these processes. Furthermore, our results suggest that these activations related to response selection and timing adjustment were distinct from sensory or motor processes.

Adult↗

PubMed2000

Characteristics of sequential movements during early learning period in monkeys.

We previously demonstrated that the organization of a learned sequential movement, after long-term practice, is based on the entire sequence and that the information pertaining to the sequence is largely specific to the hand used for practice. However, it remained unknown whether these characteristics are present from the beginning of learning. To answer the question, we examined the performance of four monkeys for the same sequential procedure in the early stage of learning. The monkeys' task was to press five consecutive pairs of buttons (which were illuminated), in a correct order for every pair, which they had to find by trial-and-error during a block of trials. We first examined whether the memory of a sequential procedure that was learned once was specific to the hand used for practice. The second time that the monkeys attempted to learn a novel sequence, they were required to use either the same hand they used the first time or the opposite hand. The number of errors decreased to a similar degree in the same-hand condition and in the opposite-hand condition. The performance time decreased in the same-hand condition, but not in the opposite-hand condition. The results suggest that, in the early stage of learning, memory of the correct performance of a sequential procedure is not specific to the hand originally used to perform the sequence (unlike the well-learned stage, where the transfer was incomplete), whereas memory of the fast performance of a sequential procedure is relatively specific to the hand used for practice (like the well-learned stage). We then examined whether memory of a sequential procedure depends on the entire sequence, not individual stimulus sets. For the second learning block, we had the monkey learn the sequence in the same or reversed order. In the reversed order, the order within each set was identical, but the order of sets was reversed. The number of errors decreased in both the same-order and reversed-order conditions to a similar degree for two out of four monkeys; the decrease was larger in the same-order condition for the other two monkeys. For all monkeys, the performance time decreased in the same-order condition, but not in the reversed-order condition. The results suggest that the memory structure for correct performance varies among monkeys in the early stage of learning (unlike the well-learned stage, where the memory of individual sets was consistently absent). On the other hand, memory of the fast performance of a sequential procedure is relatively specific to the learned order used for practice (like the well-learned stage).

Animals↗

PubMed2000

Interference from irrelevant features on visual discrimination by macaques (Macaca fuscata): a behavioral analogue of the human Stroop effect.

To study the operation of selective attention in a conflict situation with automatic processes, we trained 4 Japanese macaques (Macaca fuscata) extensively on a manual go/no-go task. The monkey had to discriminate either the color, shape, motion direction, or location of a visual stimulus. In each trial, the behavioral meaning of the relevant feature (go or no-go) could either be congruent or incongruent with irrelevant features of the same stimulus. Reaction times were slowed, and error rates increased when irrelevant stimulus features were incongruent with the required response. The effects were obtained when the monkey attended to the color, shape, or motion direction, but not when it attended to the location of the stimulus. The effects were cumulative so that the interference from 1 incongruent feature was smaller than that from 2 incongruent features. We propose that the present paradigm provides a behavioral analogue of the human Stroop effect.

Analysis of Variance↗

PubMed2000

Role of the basal ganglia in the control of purposive saccadic eye movements.

In addition to their well-known role in skeletal movements, the basal ganglia control saccadic eye movements (saccades) by means of their connection to the superior colliculus (SC). The SC receives convergent inputs from cerebral cortical areas and the basal ganglia. To make a saccade to an object purposefully, appropriate signals must be selected out of the cortical inputs, in which the basal ganglia play a crucial role. This is done by the sustained inhibitory input from the substantia nigra pars reticulata (SNr) to the SC. This inhibition can be removed by another inhibition from the caudate nucleus (CD) to the SNr, which results in a disinhibition of the SC. The basal ganglia have another mechanism, involving the external segment of the globus pallidus and the subthalamic nucleus, with which the SNr-SC inhibition can further be enhanced. The sensorimotor signals carried by the basal ganglia neurons are strongly modulated depending on the behavioral context, which reflects working memory, expectation, and attention. Expectation of reward is a critical determinant in that the saccade that has been rewarded is facilitated subsequently. The interaction between cortical and dopaminergic inputs to CD neurons may underlie the behavioral adaptation toward purposeful saccades.

Animals↗

PubMed2000

[Influence of vestibular input on visually guided saccades].

A common pathway in the brainstem is thought to exist for the induction of visually guided saccades and rapid phase nystagmus (Ref. Ohki et al. 1988). This common pathway is often referred to as "the saccade generator" or "the burst generator." The presence of this pathway suggests that vestibular function can be examined by applying "visual stimuli" and "vestibular stimuli" at the same time. We therefore investigated whether caloric stimulation affects the latency, amplitude and velocity of saccadic eye movements and if so, how. Nine normal volunteers participated in the experiment. Eye movements were recorded using DC electrooculography. Caloric stimulation was applied to the right ear using an air caloric stimulator (10 degrees C) during saccades. Two experiments involving visually guided saccades were performed. Task 1: The subject was asked to fixate on a central fixation point. Another spot of light then randomly appeared at one of two different locations (20 degrees to the right or left). The subject was then asked to scan towards the second light as quickly as possible. Task 2: The procedure was the same as in Task 1, except that the target appeared only briefly and then later reappeared at the same location. The saccade latency was unaffected by caloric stimulation in Task 1, while the latency of the rightward saccades increased significantly in Task 2. The saccade amplitude and velocity increased significantly in both directions in Task 1, while the amplitude and velocity of the leftward saccades increased significantly in Task 2. These results can be explained by the synergistic activation of Burster-Driving Neurons by the saccade signal and the vestibular signals. The combinations of these saccade tasks and caloric stimulation, especially Task 2, may be useful in clinically examining vestibulo-oculomotor functions.

Adult↗

PubMed1999

Neural representation of a rhythm depends on its interval ratio.

Rhythm is determined solely by the relationship between the time intervals of a series of events. Psychological studies have proposed two types of rhythm representation depending on the interval ratio of the rhythm: metrical and nonmetrical representation for rhythms formed with small integer ratios and noninteger ratios, respectively. We used functional magnetic resonance imaging to test whether there are two neural representations of rhythm depending on the interval ratio. The subjects performed a short-term memory task for a seven-tone rhythm sequence, which was formed with 1:2:4, 1:2:3, or 1:2.5:3.5 ratios. The brain activities during the memory delay period were measured and compared with those during the retention of a control tone sequence, which had constant intertone intervals. The results showed two patterns of brain activations; the left premotor and parietal areas and right cerebellar anterior lobe were active for 1:2:4 and 1:2:3 rhythms, whereas the right prefrontal, premotor, and parietal areas together with the bilateral cerebellar posterior lobe were active for 1:2.5:3.5 rhythm. Analysis on individual subjects revealed that these activation patterns depended on the ratio of the rhythms that were produced by the subjects rather than the ratio of the presented rhythms, suggesting that the observed activations reflected the internal representation of rhythm. These results suggested that there are two neural representations for rhythm depending on the interval ratio, which correspond to metrical and nonmetrical representations.

Adult↗

PubMed1999

Presupplementary motor area activation during sequence learning reflects visuo-motor association.

In preceding studies (Hikosaka et al., 1996; Sakai et al., 1998) we have shown that the presupplementary motor area (pre-SMA), an anterior part of the medial premotor cortex, is active during visuo-motor sequence learning. However, the paradigm required the subjects first to acquire correct visuo-motor association and then to acquire correct sequence, and it was still unknown which of the two processes the pre-SMA is involved in. To further characterize the role of pre-SMA, we have conducted another series of functional magnetic resonance imaging experiments using three learning paradigms. The three were the same in that they involved a visuo-motor association component, but they differed in terms of the involvement of sequential components; one involved no sequence learning, whereas the other two involved learning of motor sequence or perceptual sequence. Comparison of the learning conditions with the any-order button press condition revealed pre-SMA activation in all three paradigms. The pre-SMA activation remained unchanged during learning of visuo-motor associations but decreased during learning of sequences, suggesting that the pre-SMA is related to visuo-motor association rather than sequence. The decrease of pre-SMA activation in the sequential paradigms may reflect the process by which individual visuo-motor associations were replaced by the formation of sequential procedural memory, which occurs outside the pre-SMA. Thus activation of the pre-SMA was related to the extent to which the task performance depended on conscious visuo-motor associations.

Adult↗

PubMed1999

Parallel neural networks for learning sequential procedures.

Recent studies have shown that multiple brain areas contribute to different stages and aspects of procedural learning. On the basis of a series of studies using a sequence-learning task with trial-and-error, we propose a hypothetical scheme in which a sequential procedure is acquired independently by two cortical systems, one using spatial coordinates and the other using motor coordinates. They are active preferentially in the early and late stages of learning, respectively. Both of the two systems are supported by loop circuits formed with the basal ganglia and the cerebellum, the former for reward-based evaluation and the latter for processing of timing. The proposed neural architecture would operate in a flexible manner to acquire and execute multiple sequential procedures.

Animals↗

PubMed1999

Effects of local inactivation of monkey medial frontal cortex in learning of sequential procedures.

To examine the role of the medial frontal cortex, supplementary motor area (SMA), and pre-SMA in the acquisition and control of sequential movements, we locally injected muscimol into 43 sites in the medial frontal cortex while monkeys (n = 2) performed a sequential button-press task. In this task, the monkey had to press two of 16 (4 x 4 matrix) buttons illuminated simultaneously in a predetermined order. A total of five pairs were presented in a fixed order for completion of a trial. To clarify the differential contribution of the medial frontal cortex for new acquisition and control of sequential movements, we used novel and learned sequences (that had been learned after extensive practice). We found that the number of errors increased for novel sequences, but not for learned sequences, after pre-SMA inactivations. A similar, but insignificant, trend was observed after SMA injections. The reaction time of button presses for both novel and learned sequences was prolonged by inactivations of both SMA and pre-SMA, with a trend for the effect to be larger for SMA inactivations. These findings suggest that the medial frontal cortex, especially pre-SMA, is related to the acquisition, rather than the storage or execution, of the correct order of button presses.

Animals↗

PubMed1998

Separate cerebellar areas for motor control.

Cerebellar activation was measured using functional magnetic resonance imaging, while seven normal subjects tapped their fingers paced by tone sequences with or without tone omission. The cerebellar anterior lobe (Larsell's H IV-V) ipsilateral to the movement was activated to a similar degree irrespective of the presence or absence of the tone omission. In contrast, the lateral part of the bilateral posterior lobe (H VIIa) was significantly highly activated for the tone sequence with random omission, compared with either that without omission or that with regular omission. The result suggests that the H IV-V is involved in motor execution, while the lateral part of H VIIa is involved in on-line motor adjustment to unpredictable sensory stimuli.

Acoustic Stimulation↗

PubMed1998

Transition of brain activation from frontal to parietal areas in visuomotor sequence learning.

We studied the neural correlates of visuomotor sequence learning using functional magnetic resonance imaging (fMRI). In the test condition, subjects learned, by trial and error, the correct order of pressing two buttons consecutively for 10 pairs of buttons (2 x 10 task); in the control condition, they pressed buttons in any order. Comparison between the test condition and the control condition revealed four brain areas specifically related to learning: the dorsolateral prefrontal cortex (DLPFC), the presupplementary motor area (pre-SMA), the precuneus, and the intraparietal sulcus (IPS). We found that the time course of activation during learning was different between these areas. To normalize the individual differences in the speed of learning, we classified the performance of each subject into three learning stages: early, intermediate, and advanced stages. Both the relative increase of signal intensity and the number of activated pixels within the four areas showed significant changes across the learning stages, with different time courses. The two frontal areas, DLPFC and pre-SMA, were activated in the earlier stages of learning, whereas the two parietal areas, precuneus and IPS, were activated in the later stages. Specifically, DLPFC, pre-SMA, precuneus, and IPS were most highly activated in the early stage, in both the early and intermediate stages, in the intermediate stage, and in both the intermediate and advanced stages, respectively. The results suggest that the acquisition of visuomotor sequences requires frontal activation, whereas the retrieval of visuomotor sequences requires parietal activation, which might reflect the transition from the declarative stage to the procedural stage.

Adult↗

PubMed1998

Characteristics of a long-term procedural skill in the monkey.

The purpose of this study was to characterize the nature and structure of procedural memory. We have previously studied the process of learning sequential behavioral procedures using monkeys. The monkey's task was to press five consecutive pairs of buttons (indicated by illumination) in the correct order for every pair, which he had to find by trial-and-error in a block of trials. The whole sequence was called a "hyperset"; each pair was called a "set". We first examined whether monkeys learned to perform a hyperset as a single sequence or learned the order of button-presses individually for each set. To answer this question, we generated hypersets that were the same as the hypersets that had been extensively learned except that the order of the sets was reversed. The performance of these "reversed hypersets" was much worse than the performance of the original learned hypersets and was similar to the performance of new hypersets, as regards both the number of errors and the performance time. The result suggests that monkeys learned a hyperset as a sequence. To examine whether the learned performance was specific to the hand used for practice, we had monkeys use the same hand throughout the long-term practice of each hyperset, and then tested the opposite hand. The performance using the opposite hand was worse than the performance using the trained hand, but was better than the performance for new hypersets. This indicates that the memory for the sequential procedure is only partially accessible to the hand that was not used for the practice.

Animals↗

PubMed1998

Presaccadic omnidirectional burst activity in the basal interstitial nucleus in the monkey cerebellum.

We recorded saccade-related neurons in the vicinity of the dentate nucleus of the cerebellum in two monkeys trained to perform visually guided saccades and memory-guided saccades. Among 76 saccade-related neurons, 38 showed presaccadic bursts in all directions. More than 80% of such burst neurons were located in the area ventral to, not inside, the dentate nucleus, which corresponded to the basal interstitial nucleus (BIN as previously described). We found that the activity of the BIN neurons was correlated with saccade duration but not with saccade amplitude or velocity. Thus, when tested with visually guided saccades, the burst started about 16 ms before saccade onset and ended about 33 ms before saccade offset, regardless of saccade amplitude. The characteristic timing of the BIN cell activity was maintained for different types of saccades (visually guided, memory-guided and spontaneous saccades), which had different dynamics. Although the number of spikes in a burst for each neuron was linearly correlated with saccade amplitude for a given type of saccade, the slope varied depending on the type of saccade. Peak burst frequency was uncorrelated with saccadic peak velocity. In contrast, burst duration was highly correlated with saccade duration regardless of the type of saccade. These results suggest that BIN neurons may carry information to determine the timing of saccades.

Action Potentials↗

PubMed1998

Expectation of reward modulates cognitive signals in the basal ganglia.

Action is controlled by both motivation and cognition. The basal ganglia may be the site where these kinds of information meet. Using a memory-guided saccade task with an asymmetric reward schedule, we show that visual and memory responses of caudate neurons are modulated by expectation of reward so profoundly that a neuron's preferred direction often changed with the change in the rewarded direction. The subsequent saccade to the target was earlier and faster for the rewarded direction. Our results indicate that the caudate contributes to the determination of oculomotor outputs by connecting motivational values (for example, expectation of reward) to visual information.

Animals↗