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O Hikosaka

Publications and source records attributed to O Hikosaka.

At least 55 records · Page 3Linked to original sources

Eye movements in monkeys with local dopamine depletion in the caudate nucleus. I. Deficits in spontaneous saccades.

The basal ganglia contribute to the suppression and initiation of saccadic eye movements through the inhibitory connection from the substantia nigra pars reticulata (SNr) to the superior colliculus. This mechanism consists of serial and parallel connections, which are mostly inhibitory and GABAergic. Dopamine is known to exert powerful modulatory effects on the basal ganglia function, but its nature and mechanism are still unclear, especially in relation to voluntary behavior. The purpose of this series of investigation was to study the role of dopamine in the control of saccadic eye movements. We examined, in the monkey, whether and how the deficiency of the nigrostriatal dopaminergic innervation affects saccadic eye movements. The present article is focused on spontaneous saccades that the monkey made with no incentive to obtain reward; the next paper will describe task-specific saccades. Using an osmotic minipump we infused 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) unilaterally into the head-body junction of the caudate nucleus of monkeys where presaccadic neurons were clustered. Tyrosine hydroxylase activity, visualized using an immunohistochemical method, decreased locally around the injection site with some effects extending into the ipsilateral putamen and locally in the ipsilateral substantia nigra. Changes of eye movements started to appear 3-5 d after starting the infusion. Spontaneous saccades became less frequent. The area scanned by the saccades became narrower and shifted to the hemifield ipsilateral to the infusion site. The saccade amplitudes and peak velocities decreased; durations were prolonged. These effects were more prominent for saccades directed toward the side contralateral to the infusion site. These monkeys showed no obvious skeletomotor symptoms. These results suggest that the local deprivation of the dopaminergic innervation in the caudate nucleus facilitates neuronal activity of the SNr leading to suppression of saccadic eye movements.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Eye movements in monkeys with local dopamine depletion in the caudate nucleus. II. Deficits in voluntary saccades.

Unilateral infusion of MPTP into the monkey caudate nucleus produced deficits in task-specific saccades, in addition to the deficits in spontaneous eye movements (preceding article). We trained three monkeys to perform two kinds of saccade tasks: (1) saccade task for eliciting visually guided saccades and (2) delayed saccade task for eliciting memory-guided saccades. After the MPTP infusion, dopaminergic function, estimated by tyrosine hydroxylase (TH) immunoreactivity, was shown to be decreased locally around the infusion site at the head-body junction of the caudate. We found that the deficits were prominent in the saccades directed to the side contralateral to the infusion (contralateral saccades). Memory-guided saccades were sometimes misdirected to the ipsilateral side even when the cue stimulus was presented on the contralateral side. Among the parameters of saccades, a selective change was found in the saccade latency: the latency was prolonged consistently in contralateral memory-guided saccades. The amplitude and velocity of saccades decreased in contralateral saccades, either memory guided or visually guided. The duration of saccades tended to increase in visually-guided saccades and memory-guided saccades, in both directions. Only one monkey, in which the decrease in TH activity included a large part of the putamen and the head of the caudate, showed prolongation of manual reaction time for lever release.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Effects of caudate nucleus stimulation on substantia nigra cell activity in monkey.

The present study provides evidence that the saccadic signals in the caudate nucleus (caudate) are transmitted to the substantia nigra pars reticulata (SNr). We inserted two microelectrodes into the caudate and SNr of monkeys trained to perform saccade tasks. After identifying the functional characteristics of a SNr neuron recorded, we stimulated the caudate (single pulse, < 100 microA) to see whether its discharge rate changed. Among 138 SNr cells tested, 60 showed responses to stimulation of the caudate: inhibition only (n = 21), inhibition-excitation (n = 17), excitation only (n = 9), and excitation-inhibition (n = 13). The latencies were 9.0-32.5 ms (mean 16.7 ms) for the initial inhibitory responses and 6.5-35.0 ms (mean 16.7 ms) for the initial excitatory responses. Pars compacta cells (n = 10) were unresponsive. The effect of caudate stimulation was selective in terms of (1) functional type of SNr cells, (2) location of SNr cells, and (3) stimulation site within the caudate. Functional type of SNr cells: saccadic, visual, expectation-related cells were more responsive than auditory, mouth/hand/arm movement-related, and reward-related cells. Many of the cells whose functional characteristics were unidentified responded to the caudate stimulation. The preferential effects were seen among the functional subtypes: cells related to memory-guided saccades, not visually guided saccades; cells with conditioned visual responses, not simple visual responses. Location of SNr cells: the stimulus effects were seen preferentially in cells in the central part of the SNr, not in the dorsal part. Stimulus site: stronger effects, whether inhibition or excitation, were obtained when the stimulation was applied to the head-body transitional zone where visuooculomotor cells were clustered. Behaviorally contingent correlation of spike activity was found between the caudate-nigral pair of cells. For example when a SNr cell with memory-contingent saccadic activity was inhibited by the caudate stimulation, a caudate cell at or close to the stimulation site may show memory-contingent saccadic activity with a similar movement field.

Animals↗

Rostrocaudal gradients in the neuronal receptive field complexity in the finger region of the alert monkey's postcentral gyrus.

In the primate postcentral gyrus, the cytoarchitectonic characteristics gradually shift from those of koniocortex to more homotypical parakoniocortex along its rostrocaudal axis. To find the physiological correlates of these changes we examined a large body of data accumulated during a series of our experiments with alert monkeys. Along the rostrocaudal axis of the postcentral gyrus, we found a gradual and continuous increase in the number of neurons with converging receptive fields and those in which receptive field positions or submodalities were not determined. Deep or skin submodality neurons were dominant in area 3a or 3b respectively. The proportion of skin submodality neurons decreased gradually from area 3b to the more caudal part of the gyrus. The proportion of deep submodality neurons was almost constant from area 3b to area 2 inclusive; they were not the majority in area 2. The data are consistent with the hierarchical scheme, i.e., within the postcentral gyrus sensory information is processed from the primary sensory receiving stage to the more associative, integrative stages.

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Focal visual attention produces illusory temporal order and motion sensation.

Spatial attention was studied using a new visual illusion of motion: a line, which was presented physically at once, was perceived to be drawn from one side when attention had been captured to that side of the line by a preceding visual cue stimulus. By comparing with a temporal order task, we showed that the line-motion illusion was produced by acceleration of visual information processing at the locus of attention. The results suggest that the facilitatory effect of attention is exerted at relatively early stages of visual information processing where visual signals are to be fed into the motion detecting mechanism.

Attention↗

Visual attention revealed by an illusion of motion.

Attention is a mechanism to select sensory information. It is a modulatory process which normally cannot be observed as overt responses. A new psychophysical method using an illusion of motion perception allowed us to visualize the field of the magnitude of attention and its dynamic changes. Based on our experiments using this method we suggest that (1) both passive (bottom-up) and active (top-down) attention exert their effects on the early stages of visual processing, (2) active attention can quickly and briefly be replaced by passive attention induced by an external event, but can be restored in about 400 ms, and (3) attention is directed to an object, not space, and follows the object as it moves.

Animals↗

Voluntary and stimulus-induced attention detected as motion sensation.

Attention may be drawn passively to a visually salient object. We may also actively direct attention to an object of interest. Do the two kinds of attention, passive and active, interact and jointly influence visual information processing at some neural level? What happens if the passive and active attentions come into conflict? These questions were addressed with the aid of a novel psychophysical technique which reveals an attentional gradient as a sensation of motion in a line which is presented instantaneously. The subjects were asked to direct attention with voluntary effort: to the side opposite to a stimulus change, to an object with a predetermined colour, and to an object moving smoothly. In every case the same motion sensation was induced in the line from the attended side to the unattended side. This voluntary attention, however, can easily and quickly be distracted by a change in the periphery, though it can be regained within a period of 200 to 500 ms. The results suggest that the line motion can be induced in voluntary (top-down) as well as stimulus-driven (bottom-up) situations, thus indicating the truly attentional nature of the effect, rather than it being some kind of retinotopic sensory artifact or response bias. The results also suggest that these two kinds of attention have facilitatory effects acting together on a relatively early stage of visual information processing.

Adult↗

Visual and oculomotor functions of monkey subthalamic nucleus.

1. Single-unit recordings were obtained from the subthalamic nuclei of three monkeys trained to perform a series of visuooculomotor tasks. The monkeys were trained to fixate on a spot of light on the screen (fixation task). When the spot was turned off and a target spot came on, they were required to fixate on the target quickly by making a saccade. Visually guided saccades were elicited when the target came on without a time gap (saccade task). Memory-guided saccades were elicited by delivering a brief cue stimulus while the monkey was fixating; after a delay, the fixation spot was turned off and the monkey made a saccade to the remembered target (delayed saccade task). 2. Of 265 neurons tested, 95 showed spike activity that was related to some aspects of the visuooculomotor tasks, whereas 66 neurons responded to active or passive limb or body movements. The task-related activities were classified into the following categories: eye fixation-related, saccade-related, visual stimulus-related, target- and reward-related, and lever release-related. 3. Activity related to eye fixation (n = 22) consisted of a sustained spike discharge that occurred while the animal was fixating on a target light during the tasks. The activity increased after the animal started fixating on the target and abruptly ceased when the target went off. The activity was unrelated to eye position. It was not elicited during eye fixation outside the tasks. The activity decreased when the target spot was removed. 4. Activity related to saccades (n = 22) consisted of a phasic increase in spike frequency that was time locked with a saccade made during the tasks. The greatest increases occurred predominantly after saccade onset. This activity usually was unrelated to spontaneous saccades made outside the task. The changes in activity typically were optimal in one direction, generally toward the contralateral side. 5. Visual responses (n = 14) consisted of a phasic excitation in response to a visual probe stimulus or target. Response latencies usually were 70-120 ms. The receptive fields generally were centered in the contralateral hemifield, sometimes extending into the ipsilateral field. The receptive fields included the foveal region in seven neurons; most of these neurons responded best to parafoveal stimulation. Peripheral stimuli sometimes suppressed the activity of visually responsive neurons. 6. Activity related to target and reward (n = 29) consisted of sustained spike discharge that occurred only when the monkey could expect a reward by detecting the dimming of the light spot that he was fixating.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Basal ganglia--possible role in motor coordination and learning.

The basal ganglia, with their inhibitory efferents, control motor outputs either directly by their projections to the midbrain motor regions or indirectly through the thalamic nuclei. Neural mechanisms in the basal ganglia act selectively to remove or enhance the inhibition so that different combinations of motor signals, which may act as neural templates for motor learning, are formed.

Animals↗

[Spontaneous saccades in MPTP-induced hemi-parkinsonian monkeys].

The basal ganglia play an important role in the control of saccadic eye movements. Parkinsonian patients have deficits in saccade initiation; the deficits are more prominent in memory-guided saccade than in visually guided saccade (Hikosaka et al, 1987). These results show that deficiency of nigrostriatal dopaminergic system affects the neural mechanism of saccadic eye movements in the basal ganglia. In order to investigate this hypothesis, we studied saccadic eye movements in MPTP-induced hemiparkinsonian monkeys. We made two models of parkinsonism using two monkeys: 1) unilateral intra-carotid injection of MPTP, and 2) intracaudate injection of MPTP using osmotic minipump. We recorded saccadic eye movements using the magnetic search coil method. After experiments, monkeys were sacrificed and investigated by histological procedures. Following the intracarotid injection, we observed hypokinesia and rigidity in the arm and leg contralateral to the injection. Eye position was shifted to the ipsilateral side and the frequency of saccades towards the contralateral side was reduced. Following the intracaudate injection, we observed hypokinesia and rigidity in the contralateral arm and leg and circling behavior towards the contralateral side. In both monkeys, the saccade amplitude and peak velocity towards contralateral side were reduced. We considered three mechanisms that might account for these results. First, dopaminergic denervation due to MPTP in the caudate nucleus may suppress the activity of neurons projecting to the pars reticulata of the substantia nigra. Second, nigra cell activity may be tonically elevated through an indirect pathway via the external pallidum and the subthalamic nucleus. Third, MPTP may enhance nigra cell activity through dendro-dendritic connections from the pars compacta to the pars reticulata in the substantia nigra.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Eye movements induced by microinjection of GABA agonist in the rat substantia nigra pars reticulata.

Injection of muscimol (GABA agonist) in the substantia nigra pars reticulata (SNr) of the alert rat induced a continual repetition of fast eye movements to the contralateral side, each of which was followed by a slow returning movement. The fast eye movements were similar to spontaneous saccades. Larger saccades were accompanied by contralateral neck muscle activity. We suggest that the SNr plays an important role in control of eye movements in the rat.

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Functional properties of monkey caudate neurons. I. Activities related to saccadic eye movements.

1. We recorded single cell activities in the caudate nucleus of the monkeys trained to perform a series of visuomotor tasks. In the first part of this paper, we summarize the types and locations of neurons in the monkey caudate nucleus. In the second part, we report the characteristics of neurons related to saccadic eye movements. 2. Neurons were classified into two types in terms of spontaneous discharge pattern. A majority of the neurons (2,287/2,559, 89%) had very low-frequency discharges (mostly less than 1 Hz). The rest (n = 272) showed irregular-tonic discharges (3-8 Hz) with broad spikes. 3. Of 2,559 neurons tested, 867 showed spike activity related to some aspects of the tasks; 502 neurons showed discharges in response to environmental changes outside, not in relation to, the tasks. None of the neurons responsive in or outside the tasks belonged to the irregular-tonic type. 4. The task-related activities were classified as: Saccade-related, Visual, Auditory, Cognitive, Fixation-related, and Reward-related. The activities detected outside the tasks were classified into: Visual, Auditory, Movement-related, Reward-related, and Other. Few neurons had both task-related and task-unrelated activities. 5. The locations of recorded neurons were determined using a coordinate system based on the anterior and posterior commissures. Task-related neurons were clustered longitudinally in the central part of the caudate. Neurons responsive outside the tasks were more widely distributed; specifically, auditory neurons were in the medial part, whereas movement-related neurons were in the lateral part. The irregular-tonic neurons were dispersed all over the caudate. 6. The monkey was trained to fixate on a spot of light on the screen and, when the spot moved, to follow it by making a saccade. A visually guided saccade occurred when the spot moved to another location without a time gap (saccade task). A memory-guided saccade occurred when the spot first disappeared and after a time gap reappeared at a fixed location (saccade with gap task). By delivering a cue stimulus while the monkey was fixating, a memory-guided saccade was elicited to a randomly chosen location (delayed saccade task).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Functional properties of monkey caudate neurons. II. Visual and auditory responses.

1. Visual responses of caudate neurons were studied in monkeys trained to fixate on a small spot of light. A visual stimulus (another spot of light) was presented in various contexts of behavior using different behavioral paradigms. Visual receptive fields were usually large and centered on the contralateral hemifield. Among 217 neurons with visual responses, 184 were further classified into subtypes. 2. Visual responses in 64 neurons were not modulated by changing the paradigms (unconditional visual responses). In the other neurons, visual responses were dependent on the behavioral contexts in which the stimulus was presented. Three types of behavioral modulation were found. 3. A saccade-enhanced visual response (n = 37) was the one that was enhanced if the monkey made a saccade to the stimulus on its appearance. The enhancement was spatially selective: the response was depressed if the saccade was directed away from the stimulus. 4. Memory-contingent visual responses (n = 36) were present preferentially when the monkey remembered the location of the stimulus and a few seconds later made a saccade to the remembered location. Responses were greater when the location of the stimulus was randomized between trials. 5. Expectation-contingent visual responses (n = 46) were present preferentially when the stimulus came on while the monkey was not fixating another spot, and the stimulus was related directly to a reward. Unlike the other types, its receptive field included both contralateral and ipsilateral hemifields without a particular preference. 6. A small number of neurons (n = 16) showed a visual response that easily habituated. 7. Latencies of visual responses were usually between 100 and 200 ms. The latencies of the memory-contingent, expectation-contingent, and habituated visual responses tended to be longer than the others and tended to be more variable between trials. 8. Among auditory responsive neurons only a small proportion were related to the tasks. The response was greater to a contralateral sound. It was enhanced if the monkey used the sound as the cue for the future target location. 9. The results suggest that sensory responses of caudate neurons could be used to guide a subsequent sequence of learned behaviors by confirming predicted environmental states, renewing memory, or establishing a motor set.

Animals↗

Functional properties of monkey caudate neurons. III. Activities related to expectation of target and reward.

1. The present paper reports complex neural activities in the monkey caudate nucleus that precede and anticipate visual stimuli and reward in learned visuomotor paradigms. These activities were revealed typically in the delayed saccade task in which memory and anticipation were required. We classified these activities according to their relationships to the task. 2. Activity related to expectation of a cue (n = 46) preceded the presentation of a spot of light (target cue) that signified the future location of saccade target. When the target cue was delayed, the activity was prolonged accordingly. The same spot of light was preceded by no activity if it acted as a distracting stimulus. 3. The sustained activity (n = 80) was a tonic discharge starting after the target cue as if holding the spatial information. 4. The activity related to expectation of target (n = 109) preceded the appearance of the target whose location was cued previously. It started with or after a saccade to the cued target location and ended with the appearance of the target. The activity was greater when the target was expected to appear in the contralateral visual field. 5. The activity related to expectation of reward (n = 57) preceded a task-specific reward. It started with the appearance of the final target and ended with the reward. In most cases, the activity was nonselective for how the monkey obtained the reward, i.e., by visual fixation only, by a saccade, or by a hand movement. The activity was dependent partly on visual fixation. 6. A few neurons showed tonic activity selectively before lever release and are thus considered to be related to the preparation of hand movements. 7. The activity related to breaking fixation (n = 33) occurred phasically if the monkey broke fixation, aborting the trial. 8. Activity related to reward (n = 104) was a phasic discharge that occurred before or after a reward of water was delivered. The activity was not simply related to a specific movement involved in the reward-obtaining behavior (eye, hand, or mouth movement). 9. Fixation-related activity (n = 72) was tonic activity continuing as long as the monkey attentively fixated a spot of light. It was dependent on reward expectancy in most cases. 10. The present results, together with those in the preceding papers, indicate that the activities of individual caudate neurons--sensory, motor, or cognitive--are dependent on specific contexts of learned behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Eye movement is controlled by basal ganglia-induced GABAergic inhibition].

Saccadic eye movement is controlled by a midbrain structure, superior colliculus (SC). Cells in its intermediate layer show a burst of spikes before saccades to the contralateral disc. A major input to the SC comes from the substantia nigra pars reticulata (SNr). SNr cells are characterized by their high frequency tonic discharge. Many of them stop discharging before a contralateral saccade only when the saccade is made intentionally. The mirror image-like relationship between the SNr and the SC suggests that the nigro-collicular connection is inhibitory. To determine whether the nigro-collicular inhibition is necessary for normal eye movements, we injected a small amount of GABA-related substances into the SC or the SNr. Following injection of muscimol (GABA agonist) into the SC, contralateral saccades became delayed, hypometric and slower; the monkey finally became unable to make saccades. This result indicated that the SC is crucial for normal saccades and that SC cells have ample GABA receptors. Following injection of bicuculline (GABA antagonist), irrepressible saccades occurred repeatedly to the contralateral side, suggesting that SC cells are under tonic inhibition which is mediated by GABA. Similar involuntary saccades were induced by injection of muscimol into the SNr. This suggested that the SNr is the origin of the GABAergic tonic inhibition. These results suggested that the basal ganglia control the initiation of saccadic eye movement by changing the level of the nigro-collicular inhibition.

Animals↗