2016, 平成27年度 北海道大学教育総長賞（奨励賞）　　　　　　　　　　　　　　　

2013, 平成25年度 北海道大学医学研究科優秀研究賞　　　　　　　　　　　　　　　

2008, 平成20年度 文部科学大臣表彰若手科学者賞　　　　　　　　　　　　　　　

2006, 平成18年度 日本神経科学学会奨励賞　　　　　　　　　　　　　　　

2005, 平成17年度 フラテ研究奨励賞　　　　　　　　　　　　　　　

Comparison of Signals from Cerebellar Purkinje Cells and Deep Nuclei during Temporal Prediction in Primates.
Okada KI, Kameda M, Tanaka M
The Journal of neuroscience : the official journal of the Society for Neuroscience, 03 Dec. 2025
Scientific journal, The cerebellum is crucial for predictive motor control and learning, but growing evidence suggests that it also generates forward models for nonmotor functions. Previous studies have reported periodic neuronal activity in the cerebellar dentate nucleus when animals predicted the timing of regularly presented visual stimuli. Since the dentate nucleus is an output structure, this activity likely reflects computations in the cerebellar cortex. Considering that Purkinje cells (PCs), the sole output of the cerebellar cortex, are more numerous than cerebellar nuclear neurons and that nuclear neurons also receive input from mossy and climbing fibers, information integration likely occurs within the cerebellar nuclei. To explore this, we recorded PC activity in the cerebellar crus lobules of three male monkeys trained to detect the omission of periodically flashing visual stimuli and compared it with dentate nucleus data. PCs showed gradually increasing periodic simple spike activity, with amplitudes proportional to the interstimulus intervals. As a population, PC signals slightly preceded those of dentate nucleus neurons and were more temporally variable. However, the individual dentate neuron activity was 84% explained by a linear sum of signals from a small subset of PCs. These results suggest that the main components of cerebellar output signals for temporal prediction may originate from the cerebellar cortex and are integrated within the deep nuclei before being sent to other brain regions. Furthermore, changes in complex spike activity were observed in more than half of the PCs, suggesting that synaptic plasticity in the cerebellar cortex may contribute to modulating these signals.

Strategic switching in sensorimotor synchronization.
Ken-Ichi Okada, Masaki Tanaka
Journal of neurophysiology, 134, 2, 783, 785, 01 Aug. 2025, [International Magazine]
English, Scientific journal

Neural correlates of memory updating in the primate prefrontal cortex.
Ryo Sawagashira, Masaki Tanaka
Communications biology, 8, 1, 900, 900, 09 Jun. 2025, [International Magazine]
English, Scientific journal, Working memory allows temporary storage and manipulation of information during cognitive tasks. While the primate lateral prefrontal cortex (PFC) is involved in working memory, little is known about neuronal activity during memory updating. We trained macaque monkeys on an oculomotor n-back task, requiring them to remember locations of sequentially presented visual stimuli and generate a saccade to the location of the most recent or previous stimulus based on task rules. Many PFC neurons showed transient activity when a memory of a particular stimulus location was no longer needed, whereas others showed sustained activity for remembered locations. Decoding analysis successfully predicted future target selection based on the task rule from neuronal activity, indicating that these neuronal populations contain sufficient information to guide behavior. Furthermore, electrical stimulation at recording sites erased specific spatial memories, demonstrating a causal role of prefrontal neurons in maintaining and updating short-term memory.

Temporal Information Processing in the Cerebellum and Basal Ganglia.
Masaki Tanaka, Masashi Kameda, Ken-Ichi Okada
Advances in experimental medicine and biology, 1455, 95, 116, 2024, [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, Temporal information processing in the range of a few hundred milliseconds to seconds involves the cerebellum and basal ganglia. In this chapter, we present recent studies on nonhuman primates. In the studies presented in the first half of the chapter, monkeys were trained to make eye movements when a certain amount of time had elapsed since the onset of the visual cue (time production task). The animals had to report time lapses ranging from several hundred milliseconds to a few seconds based on the color of the fixation point. In this task, the saccade latency varied with the time length to be measured and showed stochastic variability from one trial to the other. Trial-to-trial variability under the same conditions correlated well with pupil diameter and the preparatory activity in the deep cerebellar nuclei and the motor thalamus. Inactivation of these brain regions delayed saccades when asked to report subsecond intervals. These results suggest that the internal state, which changes with each trial, may cause fluctuations in cerebellar neuronal activity, thereby producing variations in self-timing. When measuring different time intervals, the preparatory activity in the cerebellum always begins approximately 500 ms before movements, regardless of the length of the time interval being measured. However, the preparatory activity in the striatum persists throughout the mandatory delay period, which can be up to 2 s, with different rate of increasing activity. Furthermore, in the striatum, the visual response and low-frequency oscillatory activity immediately before time measurement were altered by the length of the intended time interval. These results indicate that the state of the network, including the striatum, changes with the intended timing, which lead to different time courses of preparatory activity. Thus, the basal ganglia appear to be responsible for measuring time in the range of several hundred milliseconds to seconds, whereas the cerebellum is responsible for regulating self-timing variability in the subsecond range. The second half of this chapter presents studies related to periodic timing. During eye movements synchronized with alternating targets at regular intervals, different neurons in the cerebellar nuclei exhibit activity related to movement timing, predicted stimulus timing, and the temporal error of synchronization. Among these, the activity associated with target appearance is particularly enhanced during synchronized movements and may represent an internal model of the temporal structure of stimulus sequence. We also considered neural mechanism underlying the perception of periodic timing in the absence of movement. During perception of rhythm, we predict the timing of the next stimulus and focus our attention on that moment. In the missing oddball paradigm, the subjects had to detect the omission of a regularly repeated stimulus. When employed in humans, the results show that the fastest temporal limit for predicting each stimulus timing is about 0.25 s (4 Hz). In monkeys performing this task, neurons in the cerebellar nuclei, striatum, and motor thalamus exhibit periodic activity, with different time courses depending on the brain region. Since electrical stimulation or inactivation of recording sites changes the reaction time to stimulus omission, these neuronal activities must be involved in periodic temporal processing. Future research is needed to elucidate the mechanism of rhythm perception, which appears to be processed by both cortico-cerebellar and cortico-basal ganglia pathways.

Sensory and motor representations of internalized rhythms in the cerebellum and basal ganglia.
Masashi Kameda, Koichiro Niikawa, Akiko Uematsu, Masaki Tanaka
Proceedings of the National Academy of Sciences of the United States of America, 120, 24, e2221641120, 13 Jun. 2023, [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Both the cerebellum and basal ganglia are involved in rhythm processing, but their specific roles remain unclear. During rhythm perception, these areas may be processing purely sensory information, or they may be involved in motor preparation, as periodic stimuli often induce synchronized movements. Previous studies have shown that neurons in the cerebellar dentate nucleus and the caudate nucleus exhibit periodic activity when the animals prepare to respond to the random omission of regularly repeated visual stimuli. To detect stimulus omission, the animals need to learn the stimulus tempo and predict the timing of the next stimulus. The present study demonstrates that neuronal activity in the cerebellum is modulated by the location of the repeated stimulus and that in the striatum (STR) by the direction of planned movement. However, in both brain regions, neuronal activity during movement and the effect of electrical stimulation immediately before stimulus omission were largely dependent on the direction of movement. These results suggest that, during rhythm processing, the cerebellum is involved in multiple stages from sensory prediction to motor control, while the STR consistently plays a role in motor preparation. Thus, internalized rhythms without movement are maintained as periodic neuronal activity, with the cerebellum and STR preferring sensory and motor representations, respectively.

Nicotine promotes the utility of short-term memory during visual search in macaque monkeys.
Ryo Sawagashira, Masaki Tanaka
Psychopharmacology, 08 Jul. 2022, [Last author, Corresponding author], [International Magazine]
English, Scientific journal, RATIONALE: The central cholinergic system is a major therapeutic target for restoring cognitive functions. Although manipulation of cholinergic signaling is known to alter working memory (WM), the underlying mechanism remains unclear. It is widely accepted that WM consists of multiple functional modules, one storing short-term memory and the other manipulating and utilizing it. A recently developed visual search task and a relevant model can be used to assess multiple components of WM during administration of acetylcholine receptor (AChR)-related substances. OBJECTIVES: The effects of systemic administration of AChR-related agents on WM and eye movements were examined during the oculomotor foraging task. METHODS: Three monkeys performing the task received an intramuscular injection of saline or the following AChR-related agents: nicotine (24 or 56 μg/kg), mecamylamine (nicotinic AChR antagonist, 1.0 mg/kg), oxotremorine (muscarinic AChR agonist, 3.0 µg/kg), and scopolamine (muscarinic AChR antagonist, 20 μg/kg). The task was to find a target among 15 identical objects by making eye movements within 6 s. The data were analyzed according to the foraging model that incorporated three parameters. RESULTS: Nicotine and mecamylamine significantly increased the utility but not the capacity of short-term memory, while muscarinic AChR-related agents did not alter any WM parameters. Further regression analyses with a mixed-effect model showed that the beneficial effect of nicotine on memory utility remained after considering eye movement variability, but the beneficial effect of mecamylamine disappeared. CONCLUSIONS: Nicotine improves visual search, mainly by increasing the utility of short-term memory, with minimal changes in oculomotor parameters.

Neural signals regulating motor synchronization in the primate deep cerebellar nuclei
Ken-ichi Okada, Ryuji Takeya, Masaki Tanaka
Nature Communications, 13, 1, Springer Science and Business Media {LLC}, 06 May 2022, [Last author, Corresponding author]
English, Scientific journal, AbstractMovements synchronized with external rhythms are ubiquitous in our daily lives. Despite the involvement of the cerebellum, the underlying mechanism remains unclear. In monkeys performing synchronized saccades to periodically alternating visual stimuli, we found that neuronal activity in the cerebellar dentate nucleus correlated with the timing of the next saccade and the current temporal error. One-third of the neurons were active regardless of saccade direction and showed greater activity for synchronized than for reactive saccades. During the transition from reactive to predictive saccades in each trial, the activity of these neurons coincided with target onset, representing an internal model of rhythmic structure rather than a specific motor command. The behavioural changes induced by electrical stimulation were explained by activating different groups of neurons at various strengths, suggesting that the lateral cerebellum contains multiple functional modules for the acquisition of internal rhythms, predictive motor control, and error detection during synchronized movements.

Effects of GABAergic and Glutamatergic Inputs on Temporal Prediction Signals in the Primate Cerebellar Nucleus.
Akiko Uematsu, Masaki Tanaka
Neuroscience, 482, 161, 171, 01 Feb. 2022, [Last author, Corresponding author], [International Magazine]
English, Scientific journal, The cerebellum has been shown to be involved in temporal information processing. We recently demonstrated that neurons in the cerebellar dentate nucleus exhibited periodic activity predicting stimulus timing when monkeys attempted to detect a single omission of isochronous repetitive visual stimulus. In this study, we assessed the relative contribution of signals from Purkinje cells and mossy and climbing fibers to the periodic activity by comparing single neuronal firing before and during local infusion of GABA or glutamate receptor antagonists (gabazine or a mixture of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide hydrate (NBQX) and (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP)). Gabazine application reduced the magnitude of periodic activity and increased the baseline firing rate in most neurons. In contrast, during the blockade of glutamate receptors, both the magnitude of periodic firing modulation and the baseline activity remained unchanged in the population, while a minority of neurons significantly altered their activity. Furthermore, the amounts of changes in the baseline activity and the magnitude of periodic activity were inversely correlated in the gabazine experiments but not in the NBQX + CPP experiments. We also found that the variation of baseline activity decreased during gabazine application but sometimes increased during the blockade of glutamate receptors. These changes were not observed during prolonged recording without drug administration. These results suggest that the predictive neuronal activity in the dentate nucleus may mainly attribute to the inputs from the cerebellar cortex, while the signals from both mossy fibers and Purkinje cells may play a role in setting the level and variance of baseline activity during the task.

Ketamine-induced alteration of working memory utility during oculomotor foraging task in monkeys.
Ryo Sawagashira, Masaki Tanaka
eNeuro, 09 Mar. 2021, [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Impairments of working memory are commonly observed in a variety of neurodegenerative disorders but they are difficult to quantitatively assess in clinical cases. Recent studies in experimental animals have used low-dose ketamine (an NMDA receptor antagonist) to disrupt working memory, partly mimicking the pathophysiology of schizophrenia. Here, we developed a novel behavioral paradigm to assess multiple components of working memory and applied it to monkeys with and without ketamine administration. In an oculomotor foraging task, the animals were presented with 15 identical objects on the screen. One of the objects was associated with a liquid reward, and monkeys were trained to search for the target by generating sequential saccades under a time constraint. We assumed that the occurrence of recursive movements to the same object might reflect working memory dysfunction. We constructed a "foraging model" that incorporated 1) memory capacity, 2) memory decay and 3) utility rate; this model was able to explain more than 92% of the variations in behavioral data obtained from three monkeys. Following systemic administration of low dosages of ketamine, the memory capacity and utility rate were dramatically reduced by 15% and 57%, respectively, while memory decay remained largely unchanged. These results suggested that the behavioral deficits during the blockade of NMDA receptors were mostly due to the decreased usage of short-term memory. Our oculomotor paradigm and foraging model appear to be useful for quantifying multiple components of working memory and could be applicable to clinical cases in future studies.Significance StatementWorking memory is often difficult to quantitatively assess in clinical cases, although deficiencies in working memory have been reported in a variety of disorders. Here, we developed a novel oculomotor foraging paradigm and devised a relevant model for accurately evaluating several parameters of working memory during visual search. We applied it to monkeys with and without administration of low-dose ketamine, which has been used to produce animal models of schizophrenia. Subanesthetic doses of ketamine dramatically reduced the use of short-term memory and increased the rate of exploratory choice, whereas the changes in memory capacity and memory decay were only modest. Our behavioral paradigm and the proposed model will provide a better understanding of the pathophysiology of working memory dysfunction.

Temporal Prediction Signals for Periodic Sensory Events in the Primate Central Thalamus.
Kei Matsuyama, Masaki Tanaka
The Journal of neuroscience : the official journal of the Society for Neuroscience, 41, 9, 1917, 1927, 03 Mar. 2021, [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Prediction of periodic event timing is an important function for everyday activities, while the exact neural mechanism remains unclear. Previous studies in nonhuman primates have demonstrated that neurons in the cerebellar dentate nucleus and those in the caudate nucleus exhibit periodic firing modulation when the animals attempt to detect a single omission of isochronous repetitive audiovisual stimuli. To understand how these subcortical signals are sent and processed through the thalamocortical pathways, we examined single-neuron activities in the central thalamus of two macaque monkeys (one female and one male). We found that three types of neurons responded to each stimulus in the sequence in the absence of movements. Reactive-type neurons showed sensory adaptation and gradually waned the transient response to each stimulus. Predictive-type neurons steadily increased the magnitude of the suppressive response, similar to neurons previously reported in the cerebellum. Switch-type neurons initially showed a transient response, but after several cycles, the direction of firing modulation reversed and the activity decreased for each repetitive stimulus. The time course of Switch-type activity was well explained by the weighted sum of activities of the other types of neurons. Furthermore, for only Switch-type neurons the activity just before stimulus omission significantly correlated with behavioral latency, indicating that this type of neuron may carry a more advanced signal in the system detecting stimulus omission. These results suggest that the central thalamus may transmit integrated signals to the cerebral cortex for temporal information processing, which are necessary to accurately predict rhythmic event timing.SIGNIFICANCE STATEMENT Several cortical and subcortical regions are involved in temporal information processing, and the thalamus will play a role in functionally linking them. The present study aimed to clarify how the paralaminar part of the thalamus transmits and modifies signals for temporal prediction of rhythmic events. Three types of thalamic neurons exhibited periodic activity when monkeys attempted to detect a single omission of isochronous repetitive stimuli. The activity of one type of neuron correlated with the behavioral latency and appeared to be generated by integrating the signals carried by the other types of neurons. Our results revealed the neuronal signals in the thalamus for temporal prediction of sensory events, providing a clue to elucidate information processing in the thalamocortical pathways.

Effects of optogenetic suppression of cortical input on primate thalamic neuronal activity during goal-directed behavior.
Tomoki W Suzuki, Ken-Ichi Inoue, Masahiko Takada, Masaki Tanaka
eNeuro, 03 Mar. 2021, [Last author, Corresponding author], [International Magazine]
English, Scientific journal, The motor thalamus relays signals from subcortical structures to the motor cortical areas. Previous studies in songbirds and rodents suggest that cortical feedback inputs crucially contribute to the generation of movement-related activity in the motor thalamus. In primates, however, it remains uncertain whether the corticothalamic projections may play a role in shaping neuronal activity in the motor thalamus. Here, using an optogenetic inactivation technique with the viral vector system expressing halorhodopsin, we investigated the role of cortical input in modulating thalamic neuronal activity during goal-directed behavior. In particular, we assessed whether suppression of signals originating from the supplementary eye field at the corticothalamic terminals could change the task-related neuronal modulation in the oculomotor thalamus in monkeys performing a self-initiated saccade task. We found that many thalamic neurons exhibited changes in their firing rates depending on saccade direction or task event, indicating that optical stimulation exerted task-specific effects on neuronal activity beyond the global changes in baseline activity. These results suggest that the corticothalamic projections might be actively involved in signal processing necessary for goal-directed behavior. However, we also found that some thalamic neurons exhibited overall, non-task-specific changes in the firing rate during optical stimulation, even in control animals without vector injections. The stimulation effects in these animals started with longer latency, implying a possible thermal effect on neuronal activity. Thus, our results not only reveal the importance of direct cortical input in neuronal activity in the primate motor thalamus, but also provide useful information for future optogenetic studies.Significance statementAlthough previous studies in songbirds and rodents have shown that corticothalamic inputs are essential for generating movement-related activity in the motor thalamus, their role in primates remains largely unknown. Here, we attempted to optogenetically suppress the corticothalamic terminals during neuronal recording from theoculomotor thalamus in monkeys performing a saccade task. We found that optical stimulation resulted in task-specific changes in the firing rate, indicating that thecorticothalamic projections are engaged in neural computations for goal-directed behavior. We also observed non-task-specific changes in baseline activity that mightbe caused by local heating of surrounding tissue, which underscores the importance of control experiments in animals without opsin expression.

Spontaneous grouping of saccade timing in the presence of task-irrelevant objects.
Ryuji Takeya, Shuntaro Nakamura, Masaki Tanaka
PloS one, 16, 3, e0248530, 2021, [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Sequential movements are often grouped into several chunks, as evidenced by the modulation of the timing of each elemental movement. Even during synchronized tapping with a metronome, we sometimes feel subjective accent for every few taps. To examine whether motor segmentation emerges during synchronized movements, we trained monkeys to generate a series of predictive saccades synchronized with visual stimuli which sequentially appeared for a fixed interval (400 or 600 ms) at six circularly arranged landmark locations. We found two types of motor segmentations that featured periodic modulation of saccade timing. First, the intersaccadic interval (ISI) depended on the target location and saccade direction, indicating that particular combinations of saccades were integrated into motor chunks. Second, when a task-irrelevant rectangular contour surrounding three landmarks ("inducer") was presented, the ISI significantly modulated depending on the relative target location to the inducer. All patterns of individual differences seen in monkeys were also observed in humans. Importantly, the effects of the inducer greatly decreased or disappeared when the animals were trained to generate only reactive saccades (latency >100 ms), indicating that the motor segmentation may depend on the internal rhythms. Thus, our results demonstrate two types of motor segmentation during synchronized movements: one is related to the hierarchical organization of sequential movements and the other is related to the spontaneous grouping of rhythmic events. This experimental paradigm can be used to investigate the underlying neural mechanism of temporal grouping during rhythm production.

Roles of the Cerebellum in Motor Preparation and Prediction of Timing.
Masaki Tanaka, Jun Kunimatsu, Tomoki W Suzuki, Masashi Kameda, Shogo Ohmae, Akiko Uematsu, Ryuji Takeya
Neuroscience, 462, 220, 234, 30 Apr. 2020, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, The cerebellum is thought to have a variety of functions because it developed with the evolution of the cerebrum and connects with different areas in the frontoparietal cortices. Like neurons in the cerebral cortex, those in the cerebellum also exhibit strong activity during planning in addition to the execution of movements. However, their specific roles remain elusive. In this article, we review recent findings focusing on preparatory activities found in the primate deep cerebellar nuclei during tasks requiring deliberate motor control and temporal prediction. Neurons in the cerebellum are active during anti-saccade preparation and their inactivation impairs proactive inhibitory control for saccades. Experiments using a self-timing task show that there are mechanisms for tracking elapsed time and regulating trial-by-trial variation in timing, and that the cerebellum is involved in the latter. When predicting the timing of periodic events, the cerebellum provides more accurate temporal information than the striatum. During a recently developed synchronized eye movement task, cerebellar nuclear neurons exhibited periodic preparatory activity for predictive synchronization. In all cases, the cerebellum generated preparatory activity lasting for several hundred milliseconds. These signals may regulate neuronal activity in the cerebral cortex that adjusts movement timing and predicts the timing of rhythmic events.

Spatial and temporal adaptation of predictive saccades based on motion inference.
Takeshi D Itoh, Ryuji Takeya, Masaki Tanaka
Scientific reports, 10, 1, 5280, 5280, 24 Mar. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Moving objects are often occluded behind larger, stationary objects, but we can easily predict when and where they reappear. Here, we show that the prediction of object reappearance is subject to adaptive learning. When monkeys generated predictive saccades to the location of target reappearance, systematic changes in the location or timing of target reappearance independently altered the endpoint or latency of the saccades. Furthermore, spatial adaptation of predictive saccades did not alter visually triggered reactive saccades, whereas adaptation of reactive saccades altered the metrics of predictive saccades. Our results suggest that the extrapolation of motion trajectory may be subject to spatial and temporal recalibration mechanisms located upstream from the site of reactive saccade adaptation. Repetitive exposure of visual error for saccades induces qualitatively different adaptation, which might be attributable to different regions in the cerebellum that regulate learning of trajectory prediction and saccades.

Consensus Paper: Experimental Neurostimulation of the Cerebellum.
Lauren N Miterko, Kenneth B Baker, Jaclyn Beckinghausen, Lynley V Bradnam, Michelle Y Cheng, Jessica Cooperrider, Mahlon R DeLong, Simona V Gornati, Mark Hallett, Detlef H Heck, Freek E Hoebeek, Abbas Z Kouzani, Sheng-Han Kuo, Elan D Louis, Andre Machado, Mario Manto, Alana B McCambridge, Michael A Nitsche, Nordeyn Oulad Ben Taib, Traian Popa, Masaki Tanaka, Dagmar Timmann, Gary K Steinberg, Eric H Wang, Thomas Wichmann, Tao Xie, Roy V Sillitoe
Cerebellum (London, England), 18, 6, 1064, 1097, Dec. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, The cerebellum is best known for its role in controlling motor behaviors. However, recent work supports the view that it also influences non-motor behaviors. The contribution of the cerebellum towards different brain functions is underscored by its involvement in a diverse and increasing number of neurological and neuropsychiatric conditions including ataxia, dystonia, essential tremor, Parkinson's disease (PD), epilepsy, stroke, multiple sclerosis, autism spectrum disorders, dyslexia, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Although there are no cures for these conditions, cerebellar stimulation is quickly gaining attention for symptomatic alleviation, as cerebellar circuitry has arisen as a promising target for invasive and non-invasive neuromodulation. This consensus paper brings together experts from the fields of neurophysiology, neurology, and neurosurgery to discuss recent efforts in using the cerebellum as a therapeutic intervention. We report on the most advanced techniques for manipulating cerebellar circuits in humans and animal models and define key hurdles and questions for moving forward.

Entrained neuronal activity to periodic visual stimuli in the primate striatum compared with the cerebellum.
Kameda M, Ohmae S, Tanaka M
eLife, 8, Sep. 2019, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Rhythmic events recruit neuronal activity in the basal ganglia and cerebellum, but their roles remain elusive. In monkeys attempting to detect a single omission of isochronous visual stimulus, we found that neurons in the caudate nucleus showed increased activity for each stimulus in sequence, while those in the cerebellar dentate nucleus showed decreased activity. Firing modulation in the majority of caudate neurons and all cerebellar neurons was proportional to the stimulus interval, but a quarter of caudate neurons displayed a clear duration tuning. Furthermore, the time course of population activity in the cerebellum well predicted stimulus timing, whereas that in the caudate reflected stochastic variation of response latency. Electrical stimulation to the respective recording sites confirmed a causal role in the detection of stimulus omission. These results suggest that striatal neurons might represent periodic response preparation while cerebellar nuclear neurons may play a role in temporal prediction of periodic events.

Neural oscillations in the primate caudate nucleus correlate with different preparatory states for temporal production.
Tomoki W Suzuki, Masaki Tanaka
Communications biology, 2, 102, 102, 2019, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, When measuring time, neuronal activity in the cortico-basal ganglia pathways has been shown to be temporally scaled according to the interval, suggesting that signal transmission within the pathways is flexibly controlled. Here we show that, in the caudate nuclei of monkeys performing a time production task with three different intervals, the magnitude of visually-evoked potentials at the beginning of an interval differed depending on the conditions. Prior to this response, the power of low frequency components (6-20 Hz) significantly changed, showing inverse correlation with the visual response gain. Although these components later exhibited time-dependent modification during self-timed period, the changes in spectral power for interval conditions qualitatively and quantitatively differed from those associated with the reward amount. These results suggest that alteration of network state in the cortico-basal ganglia pathways indexed by the low frequency oscillations may be crucial for the regulation of signal transmission and subsequent timing behavior.

Different contributions of preparatory activity in the basal ganglia and cerebellum for self-timing.
Jun Kunimatsu, Tomoki W Suzuki, Shogo Ohmae, Masaki Tanaka
eLife, 7, 02 Jul. 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, The ability to flexibly adjust movement timing is important for everyday life. Although the basal ganglia and cerebellum have been implicated in monitoring of supra- and sub-second intervals, respectively, the underlying neuronal mechanism remains unclear. Here, we show that in monkeys trained to generate a self-initiated saccade at instructed timing following a visual cue, neurons in the caudate nucleus kept track of passage of time throughout the delay period, while those in the cerebellar dentate nucleus were recruited only during the last part of the delay period. Conversely, neuronal correlates of trial-by-trial variation of self-timing emerged earlier in the cerebellum than the striatum. Local inactivation of respective recording sites confirmed the difference in their relative contributions to supra- and sub-second intervals. These results suggest that the basal ganglia may measure elapsed time relative to the intended interval, while the cerebellum might be responsible for the fine adjustment of self-timing.

Temporal Generalization of Synchronized Saccades Beyond the Trained Range in Monkeys.
Ryuji Takeya, Aniruddh D Patel, Masaki Tanaka
Frontiers in psychology, 9, 2172, 2172, 2018, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, Synchronized movements with external periodic rhythms, such as dancing to a beat, are commonly observed in daily life. Although it has been well established that some vocal learning species (including parrots and humans) spontaneously develop this ability, it has only recently been shown that monkeys are also capable of predictive and tempo-flexible synchronization to periodic stimuli. In our previous study, monkeys were trained to make predictive saccades for alternately presented visual stimuli at fixed stimulus onset asynchronies (SOAs) to obtain a liquid reward. The monkeys generalized predictive synchronization to novel SOAs in the middle of trained range, suggesting a capacity for tempo-flexible synchronization. However, it is possible that when encountering a novel tempo, the monkeys might sample learned saccade sequences from those for the short and long SOAs so that the mean saccade interval matched the untrained SOA. To eliminate this possibility, in the current study we tested monkeys on novel SOAs outside the trained range. Animals were trained to generate synchronized eye movements for 600 and 900-ms SOAs for a few weeks, and then were tested for longer SOAs. The accuracy and precision of predictive saccades for one untrained SOA (1200 ms) were comparable to those for the trained conditions. On the other hand, the variance of predictive saccade latency and the proportion of reactive saccades increased significantly in the longer SOA conditions (1800 and 2400 ms), indicating that temporal prediction of periodic stimuli was difficult in this range, similar to previous results on synchronized tapping in humans. Our results suggest that monkeys might share similar synchronization mechanisms with humans, which can be subject to physiological examination in future studies.

Causal Role of Noradrenaline in the Timing of Internally Generated Saccades in Monkeys.
Tomoki W Suzuki, Masaki Tanaka
Neuroscience, 366, 15, 22, 16 Dec. 2017, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal

Predictive and tempo-flexible synchronization to a visual metronome in monkeys.
Ryuji Takeya, Masashi Kameda, Aniruddh D Patel, Masaki Tanaka
Scientific reports, 7, 1, 6127, 6127, 21 Jul. 2017, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal

Cerebellar Roles in Self-Timing for Sub- and Supra-Second Intervals.
Shogo Ohmae, Jun Kunimatsu, Masaki Tanaka
The Journal of neuroscience : the official journal of the Society for Neuroscience, 37, 13, 3511, 3522, 29 Mar. 2017, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal

Facilitation of temporal prediction by electrical stimulation to the primate cerebellar nuclei.
Akiko Uematsu, Shogo Ohmae, Masaki Tanaka
Neuroscience, 346, 190, 196, 27 Mar. 2017, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal

Striatal dopamine modulates timing of self-initiated saccades.
Jun Kunimatsu, Masaki Tanaka
Neuroscience, 337, 131, 142, 19 Nov. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Correlation between Pupil Size and Subjective Passage of Time in Non-Human Primates.
Tomoki W Suzuki, Jun Kunimatsu, Masaki Tanaka
The Journal of neuroscience : the official journal of the Society for Neuroscience, 36, 44, 11331, 11337, 02 Nov. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Implications of Lateral Cerebellum in Proactive Control of Saccades.
Jun Kunimatsu, Tomoki W Suzuki, Masaki Tanaka
The Journal of neuroscience : the official journal of the Society for Neuroscience, 36, 26, 7066, 74, 29 Jun. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Two Types of Neurons in the Primate Globus Pallidus External Segment Play Distinct Roles in Antisaccade Generation
Atsushi Yoshida, Masaki Tanaka
CEREBRAL CORTEX, 26, 3, 1187, 1199, Mar. 2016, [Peer-reviewed]
English, Scientific journal

Two different mechanisms for the detection of stimulus omission.
Shogo Ohmae, Masaki Tanaka
Scientific reports, 6, 20615, 20615, 05 Feb. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Application of radiosurgical techniques to produce a primate model of brain lesions
Jun Kunimatsu, Naoki Miyamoto, Masayori Ishikawa, Hiroki Shirato, Masaki Tanaka
Frontiers in Systems Neuroscience, 9, 67, Frontiers Research Foundation, 24 Apr. 2015, [Peer-reviewed]
English, Scientific journal

Differential Neuronal Representation of Spatial Attention Dependent on Relative Target Locations during Multiple Object Tracking
Ayano Matsushima, Masaki Tanaka
JOURNAL OF NEUROSCIENCE, 34, 30, 9963, 9969, Jul. 2014, [Peer-reviewed]
English, Scientific journal

Manipulation of Object Choice by Electrical Microstimulation in Macaque Frontal Eye Fields
Ayano Matsushima, Masaki Tanaka
CEREBRAL CORTEX, 24, 6, 1493, 1501, Jun. 2014, [Peer-reviewed]
English, Scientific journal

Different Neuronal Computations of Spatial Working Memory for Multiple Locations within versus across Visual Hemifields
Ayano Matsushima, Masaki Tanaka
JOURNAL OF NEUROSCIENCE, 34, 16, 5621, 5626, Apr. 2014, [Peer-reviewed]
English, Scientific journal

Temporally Specific Sensory Signals for the Detection of Stimulus Omission in the Primate Deep Cerebellar Nuclei
Shogo Ohmae, Akiko Uematsu, Masaki Tanaka
JOURNAL OF NEUROSCIENCE, 33, 39, 15432, 15441, Sep. 2013, [Peer-reviewed]
English, Scientific journal

Retrospective and prospective information coding by different neurons in the prefrontal cortex
Ayano Matsushima, Masaki Tanaka
NeuroReport, 24, 2, 73, 78, 2, 23 Jan. 2013, [Peer-reviewed]
English, Scientific journal

Thalamic roles in eye movements
Masaki Tanaka, Jun Kunimatsu
The Oxford Handbook of Eye Movements, Oxford University Press, 21 Nov. 2012, [Peer-reviewed]
English, In book

Alteration of the timing of self-initiated but not reactive saccades by electrical stimulation in the supplementary eye field
Jun Kunimatsu, Masaki Tanaka
EUROPEAN JOURNAL OF NEUROSCIENCE, 36, 9, 3258, 3268, Nov. 2012, [Peer-reviewed]
English, Scientific journal

Neuronal Correlates of Multiple Top-Down Signals during Covert Tracking of Moving Objects in Macaque Prefrontal Cortex
Ayano Matsushima, Masaki Tanaka
JOURNAL OF COGNITIVE NEUROSCIENCE, 24, 10, 2043, 2056, Oct. 2012, [Peer-reviewed]
English, Scientific journal

Contribution of the central thalamus to the generation of volitional saccades
Masaki Tanaka, Jun Kunimatsu
EUROPEAN JOURNAL OF NEUROSCIENCE, 33, 11, 2046, 2057, Jun. 2011, [Peer-reviewed]
English

Physiological analysis of the cerebellum: Roles in temporal processing
Masaki Tanaka, Shogo Ohmae, Akiko Uematsu, B. Pharin
Clinical Neurology, 51, 11, 1121, 2011, [Peer-reviewed]
Japanese, International conference proceedings

Roles of the Primate Motor Thalamus in the Generation of Antisaccades
Jun Kunimatsu, Masaki Tanaka
JOURNAL OF NEUROSCIENCE, 30, 14, 5108, 5117, Apr. 2010, [Peer-reviewed]
English, Scientific journal

Enhanced Modulation of Neuronal Activity during Antisaccades in the Primate Globus Pallidus
Atsushi Yoshida, Masaki Tanaka
CEREBRAL CORTEX, 19, 1, 206, 217, Jan. 2009, [Peer-reviewed]
English, Scientific journal

Neuronal activity in the primate globus pallidus during smooth pursuit eye movements
Atsushi Yoshida, Masaki Tanaka
NEUROREPORT, 20, 2, 121, 125, Jan. 2009, [Peer-reviewed]
English, Scientific journal

Cognitive signals in the primate motor thalamus predict saccade timing
Masaki Tanaka
JOURNAL OF NEUROSCIENCE, 27, 44, 12109, 12118, Oct. 2007, [Peer-reviewed]
English, Scientific journal

Spatiotemporal properties of eye position signals in the primate centra thalamus
Masaki Tanaka
CEREBRAL CORTEX, 17, 7, 1504, 1515, Jul. 2007, [Peer-reviewed]
English, Scientific journal

Inactivation of the central thalamus delays self-timed saccades
M Tanaka
NATURE NEUROSCIENCE, 9, 1, 20, 22, Jan. 2006, [Peer-reviewed]
English, Scientific journal

Effects of eye position on estimates of eye displacement for spatial updating
M Tanaka
NEUROREPORT, 16, 12, 1261, 1265, Aug. 2005, [Peer-reviewed]
English, Scientific journal

Involvement of the central thalamus in the control of smooth pursuit eye movements
M Tanaka
JOURNAL OF NEUROSCIENCE, 25, 25, 5866, 5876, Jun. 2005, [Peer-reviewed]
English, Scientific journal

Contribution of signals downstream from adaptation to saccade programming
M Tanaka
JOURNAL OF NEUROPHYSIOLOGY, 90, 3, 2080, 2086, Sep. 2003, [Peer-reviewed]
English, Scientific journal

Role of arcuate frontal cortex of monkeys in smooth pursuit eye movements. I. Basic response properties to retinal image motion and position
M Tanaka, SG Lisberger
JOURNAL OF NEUROPHYSIOLOGY, 87, 6, 2684, 2699, Jun. 2002, [Peer-reviewed]
English, Scientific journal

Role of arcuate frontal cortex of monkeys in smooth pursuit eye movements. II. Relation to vector averaging pursuit
M Tanaka, SG Lisberger
JOURNAL OF NEUROPHYSIOLOGY, 87, 6, 2700, 2714, Jun. 2002, [Peer-reviewed]
English, Scientific journal

Enhancement of multiple components of pursuit eye movement by microstimulation in the arcuate frontal pursuit area in monkeys
M Tanaka, SG Lisberger
JOURNAL OF NEUROPHYSIOLOGY, 87, 2, 802, 818, Feb. 2002, [Peer-reviewed]
English, Scientific journal

Regulation of the gain of visually guided smooth-pursuit eye movements by frontal cortex
M Tanaka, SG Lisberger
NATURE, 409, 6817, 191, 194, Jan. 2001, [Peer-reviewed]
English, Scientific journal

Context-dependent smooth eye movements evoked by stationary visual stimuli in trained monkeys
M Tanaka, SG Lisberger
JOURNAL OF NEUROPHYSIOLOGY, 84, 4, 1748, 1762, Oct. 2000, [Peer-reviewed]
English, Scientific journal

Latency of saccades during smooth-pursuit eye movement in man - Directional asymmetries
M Tanaka, T Yoshida, K Fukushima
EXPERIMENTAL BRAIN RESEARCH, 121, 1, 92, 98, Jul. 1998, [Peer-reviewed]
English, Scientific journal

Neuronal responses related to smooth pursuit eye movements in the periarcuate cortical area of monkeys
M Tanaka, K Fukushima
JOURNAL OF NEUROPHYSIOLOGY, 80, 1, 28, 47, Jul. 1998, [Peer-reviewed]
English, Scientific journal

Slow eye movement evoked by sudden appearance of a stationary visual stimulus observed in a step-ramp smooth pursuit task in monkey
M Tanaka, K Fukushima
NEUROSCIENCE RESEARCH, 29, 1, 93, 98, Sep. 1997, [Peer-reviewed]
English, Scientific journal

Adaptive changes in human smooth pursuit eye movement
K Fukushima, M Tanaka, Y Suzuki, J Fukushima, T Yoshida
NEUROSCIENCE RESEARCH, 25, 4, 391, 398, Aug. 1996, [Peer-reviewed]
English, Scientific journal

Simple-spike activity of floccular Purkinje cells responding to sinusoidal vertical rotation and optokinetic stimuli in alert cats
K Fukushima, S Chin, J Fukushima, M Tanaka
NEUROSCIENCE RESEARCH, 24, 3, 275, 289, Feb. 1996, [Peer-reviewed]
English, Scientific journal

Further evidence for the specific involvement of the flocculus in the vertical vestibulo-ocular reflex (VOR)
Fukushima, K, Chin, S, Fukushima, J, Tanaka, M, Kurkin, S, Norita, M, B, o, T, Stein, BE
Extrageniculostriate Mechanisms Underlying Visually-Guided Orientation Behavior, 112, 1996

【注意と注意障害】視覚探索における注意と記憶
澤頭 亮, 田中 真樹, BRAIN and NERVE: 神経研究の進歩, 76, 6, 0709, 0714, Jun. 2024
(株)医学書院, Japanese

【神経疾患における時間認知障害】時間知覚と予測の神経機構　　　　　　　　　　　　　　　
田中 真樹, 岡田 研一, 亀田 将史, 脳神経内科, 100, 6, 563, 571, Jun. 2024
(有)科学評論社, Japanese

【時間の神経科学-時を生み出すこころと脳の仕組み】時間の心理学と神経科学 同期運動とリズム知覚の神経機構　　　　　　　　　　　　　　　
田中 真樹, 岡田 研一, 亀田 将史, Clinical Neuroscience, 41, 8, 1044, 1047, Aug. 2023
(株)中外医学社, Japanese

BAY：自発的運動タイミングへの大脳基底核と小脳の異なる関与
田中 真樹, 北海道医学雑誌, 93, 94, 2018

増大特集 こころの時間学の未来 【鼎談】こころの時間学の未来
北澤 茂, 田中 真樹, 河村 満, BRAIN and NERVE, 69, 11, 1177, 1185, 01 Nov. 2017
株式会社医学書院

Neural mechanisms of temporal monitoring and prediction
Masaki Tanaka, Tomoki W. Suzuki, Masashi Kameda, Ryuji Takeya, Brain and Nerve, 69, 11, 1213, 1222, 01 Nov. 2017
Igaku-Shoin Ltd, Japanese

注意の神経科学 注意の脳内ネットワーク
竹谷隆司, 田中真樹, Clinical Neuroscience, 35, 8, 938‐940, 01 Aug. 2017
Japanese

Manipulation of object choice by electrical microstimulation in macaque frontal eye fields
松嶋 藻乃, 田中 真樹, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 88, 4, 143, 143, 01 Sep. 2013
Japanese

Neural Representation of Time
田中真樹, 國松淳, 大前彰吾, Brain Nerve, 65, 8, 941, 948, 01 Aug. 2013
医学書院, Japanese

脳科学辞典「空間的注意」
松嶋 藻乃, 田中 真樹, Dec. 2012, [Peer-reviewed], [Invited]
Japanese, Others

Neuronal correlates of multiple top-down signals during covert tracking of moving objects in macaque prefrontal cortex
松嶋 藻乃, 田中 真樹, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 6, 282, 282, 01 Nov. 2012
Japanese

Alteration of the timing of self-initiated but not reactive saccades by electrical stimulation in the supplementary eye field
國松 淳, 田中 真樹, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 87, 6, 283, 283, 01 Nov. 2012
Japanese

Role of the primate thalamocortical pathways in the generation of eye movements
國松淳, 田中真樹, 比較生理生化学, 29, 4, 2012

Functional analysis of the thalamocortical pathways in eye movements
Jun Kunimatsu, Masaki Tanaka, Brain and Nerve, 63, 8, 871, 877, 01 Aug. 2011
医学書院, Japanese, Book review

PROFILE
田中 真樹, 日本生理学雜誌, 73, 3, 54, 55, 01 Mar. 2011
Japanese

自発性眼球運動のタイミングを調節する運動性視床の神経活動
田中 真樹, 日本生理学雜誌, 70, 2, 01 Feb. 2008
Japanese

標準生理学
鯉淵, 典之, 伊佐, 正, 河合, 佳子, 八木田, 和弘, 横山, 詩子, 久場, 博司, 大森, 治紀, 大橋, 俊夫, 河合, 康明, 黒沢, 美枝子, 第6章「神経回路機能／総論」
医学書院, Mar. 2025, 9784260055888, xxvi, 1148p, Japanese, [Contributor]

感覚・知覚心理学ハンドブック
和気, 典二, 重野, 純, 村上, 郁也, 第4章6節「注意の神経メカニズム」、7節「注意の障害」
誠信書房, Mar. 2025, 9784414305050, xxxi, 1756p, Japanese, [Contributor]

時間の学校
原田, 知広, 田中, 真樹
ニュートンプレス, Aug. 2024, 9784315528367, 175p, Japanese

カンデル神経科学（第2版）
Kandel, Eric R., Koester, John D., Mack, Sarah, Siegelbaum, Steven, 宮下, 保司, 岡野, 栄之, 神谷, 之康, 合田, 裕紀子, 加藤, 総夫(医学), 藤田, 一郎, 伊佐, 正, 定藤, 規弘, 大隅, 典子, 井ノ口, 馨, 笠井, 清登
メディカル・サイエンス・インターナショナル, Sep. 2022, 9784815730550, xlviii, 1653p, Japanese

時間大図鑑
原田, 知広, 田中, 真樹
ニュートンプレス, Aug. 2021, 9784315524277, 207p, Japanese

ガイトン生理学 原著第13版
John E. Hall, 石川義弘, 岡村康司, 尾仲達史, 河野憲二
エルゼビア・ジャパン株式会社, 15 Mar. 2018, 4860347749, 1100

脳神経外科医が知っておくべきニューロサイエンスの知識 (脳神経外科診療プラクティス)
橋本 信夫, 三國 信啓, 深谷 親
文光堂, Oct. 2015, 483062406X, 226

Annual Review神経〈2015〉
鈴木 則宏, 荒木 信夫, 宇川 義一, 祖父江 元, 川原 信隆
中外医学社, Jan. 2015, 4498228154, 299

誠信 心理学辞典[新版]
下山 晴彦, 遠藤 利彦, 齋木 潤, 大塚 雄作, 中村 知靖
誠信書房, 03 Sep. 2014, 4414305071, 1088

カンデル神経科学
金澤一郎, 宮下保司, Eric R. Kandel, James H. Schwartz, Steven A. Siegelbaum, Thomas M.Jessell, A. J. Hudspeth
メディカルサイエンスインターナショナル, 25 Apr. 2014, 4895927717, 1696

ブレインサイエンス・レビュー2014
廣川 信隆
クバプロ, 28 Feb. 2014, 4878051361, 290

The Oxford Handbook of Eye Movements (Oxford Library of Psychology)
Simon Liversedge, Iain Gilchrist, Stefan Everling
OUP Oxford, 18 Aug. 2011, 1026

イラストレクチャー認知神経科学―心理学と脳科学が解くこころの仕組み―
村上郁也
オーム社, 24 Feb. 2010, 4274208222, 288

実験医学 (Vol.24No.15(2006増刊)) (実験医学増刊 Vol. 24-15)
狩野 方伸
羊土社, Sep. 2006, 4758102732, 232

小脳を起点とした大脳機能連関による行動戦略のアップデート機構の解明
科学研究費助成事業
01 Apr. 2024 - 31 Mar. 2029
田中 真樹
日本学術振興会, 基盤研究(S), 北海道大学, 24H00064

感覚入力の周期性が生み出す脳機能の理解とその操作
戦略的な研究開発の推進 戦略的創造研究推進事業 CREST
2023 - 2028
田中 真樹
周期的な感覚刺激は、リズム知覚を生じさせ、運動を引き込み、注意や視知覚を変化させ、脳の可塑性を誘導します。本研究では、周期的な刺激が知覚、運動、脳波を引き込む機序を解明し、これを利用したリハビリテーション治療法や日常生活における知覚や注意の操作法を開発します。また、周期的な錯視から脳波を推定する技術を開発し、スマホに実装することで脳波と関連づけたビッグデータを構築し、新たな疫学研究につなげます。
科学技術振興機構, 北海道大学, Principal investigator

Role of cerebro-cerebellar interactions in adaptive behavioral control
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
05 Apr. 2021 - 31 Mar. 2025
田中 真樹
「慎重を要する状況における行動の制御に外側小脳と前頭葉皮質の機能連関が関与する」との作業仮説を検証する。突然現れる視覚刺激と反対方向に眼球運動を行うアンチサッカード課題をサルに訓練し、その次の試行で視覚刺激に向かうプロサッカードの潜時が延長することを行動抑制の指標として一連の実験を行う。実験は、所属機関が設置する動物実験委員会の事前の審査と承認を受けて行う。


当初の予定どおり、現在までに、アンチサッカード課題を訓練した1頭のサルの小脳歯状核から記録を行うとともに、補足眼野に多点電極を刺入して局所場電位（LFP）記録を行っている。これまでに、眼球運動の方向や種類、エラー試行、あるいは反応時間によって活動を変化させる小脳核ニューロンを少数ながら記録している。また、エラーに関連した大脳LFP成分を抽出することに成功している。ただし、前試行の行動への影響は小さく、引き続きより適切な課題パラメータを探索するとともに、LFPデータのさらに詳細な解析が必要と考えている。また、これまでニューロン記録は小脳核の背側を中心に行っており、今後、大脳連合野との関連が強いより腹側も探索する。令和4年度は、新たな個体を訓練し、2頭からのデータを蓄積することを第一の目標とする。小脳歯状核の電気刺激を行い、大脳LFPの応答性を調べる。行動の成否に加え、反応時間との神経相関を詳しく調べるとともに、今年度中に多点電極による小脳核の単一ニューロン記録を試みる。また、小脳皮質に興奮性オプシンを発現させるための諸条件を共同研究者とともに調査する。インタクトな個体に種々の条件でベクター接種を行い、小脳核終末での光刺激に対する応答変化と小脳Purkinje細胞のオプシンの発現を確認することを予定している。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 21H04810

Neural mechanism of updating short-term memory during oculomotor n-back task in monkeys
Grants-in-Aid for Scientific Research
30 Jun. 2022 - 31 Mar. 2024
田中 真樹
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Hokkaido University, 22K19476

Mechanism and manipulation of mental time associated with perception and action
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
29 Jun. 2018 - 31 Mar. 2023
田中 真樹, 村上 郁也, 寺尾 安生, 天野 薫
本計画研究では、時間情報の脳内機構を多面的に調べている。二年目の今年度は、これまでの研究を継続しつつ、新たな実験課題に着手した。
研究代表者の田中（神経生理学）らは、サル用の大型ケージを整備して研究の効率化を図るとともに、新たに大脳皮質をターゲットとした実験を開始した。また、リズム知覚に関連した線条体・小脳核の神経活動や眼球運動を用いた時間学習について論文を発表した。
研究分担者の村上（実験心理学）らは、秒未満の時間知覚について、オンセット時刻、持続時間、明滅テンポの知覚の観点から心理物理実験を行い、これらの心理量と他の認知機能との関係を調べた。特に、高精度で知覚時刻を実測する方法を開発し、錯視を用いて注意の移動に伴う時間知覚の変容を定量化した。その結果、復帰抑制によって標的への反応が遅れる効果が、標的のオンセットの知覚の遅れによって説明できることがわかった。
寺尾（病態生理学）らは、パーキンソニズムを呈する神経疾患患者で時間生成・再生課題・二分課題を行い、秒単位の記憶を伴う課題の成績が症状の進行とともに低下することを見出した。また、健常者で時間幅を実際と違う時間長として学習する誤学習課題を行い、学習保持の時間経過を調べた。学習前に４連発パターン磁気刺激で右一次運動野、前頭前野、側頭頭頂接合部を刺激すると前頭前野の刺激時のみ誤学習保持の時間が延長することを発見した。
天野（先端脳計測）らは、時間的に近接して呈示される二つのターゲット刺激（例えば数字）を検出する課題において、二つ目のターゲットを見落としやすくなる注意の瞬きと呼ばれる現象を用いて、視知覚のリズムについて検討した。その結果、二つ目のターゲット刺激の検出成績が、ターゲット刺激間の時間差に応じて周期的に変動し、その変動周波数は課題に関係のない妨害刺激（例えば文字）の有無によって変化することを見出した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Hokkaido University, 18H05523

Dynamic regulation of cortico-striatal transmission in non-human primates
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
01 Apr. 2017 - 31 Mar. 2020
TANAKA MASAKI
The basal ganglia are essential for adjusting the size and speed of movements along with selecting actions for given situations. During preparation of self-timed eye movements, we found that the time course of neuronal activity in the striatum differed from that in the cerebellar nucleus; the former was scaled by the length of time to be measured, while the latter correlated with trial-by-trial latency variation. We also found that the low-frequency components of local field potentials and visual evoked responses recorded from the striatum dynamically changed according to the length of time to be measured. On the other hand, the striatal evoked response to electrical stimulation of the cortex was too small to investigate the effects of behavioral conditions, so future studies should consider the use of optogenetic manipulation.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 17H03539

Analysis of predictive signals for the periodic sensory inputs
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
01 Apr. 2018 - 31 Mar. 2019
田中 真樹
リズム知覚のような周期的な時間情報を処理する神経機構を調べる目的で研究を行った。一定間隔であらわれる視覚刺激の欠落を検出するようにサルを訓練し（欠落オドボール課題）、これまでの研究で小脳核と尾状核から記録してきた繰り返し刺激に対して振幅を漸増させる周期活動について、新たな行動課題を用いてその特性を調べた。これまでに、小脳は感覚刺激の方向、線条体は運動の方向によって周期活動の振幅を変化させることを見出している。これらの実験は現在も継続中であり、平成30年7月に採択された新学術領域研究「時間生成学」の中で、計画研究「知覚や講堂に伴う心的時間の脳内機構とその操作」の一部としてさらに発展させる予定である。また、時間の情報処理に関連して、単一時間長を測定する際の線条体と小脳のニューロン活動を調べ、論文として発表した。同課題中に、本新学術領域（オシロロジー領域）と関連の深い線条体の集合電位の周期活動を発見し、現在論文を投稿している。さらに、今年度は周期的に呈示される視覚刺激に同期して眼球運動をおこなわせ、その詳細な行動解析を行うとともに小脳核からの神経活動記録を行い、本領域の班会議で報告した。以上の研究成果の一部は6月と7月にそれぞれ日本生体医工学会と日本神経科学学会でも発表した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Hokkaido University, 18H04928

The science of mental time--Investigation into the past, present, and future
Grants-in-Aid for Scientific Research
28 Jun. 2013 - 31 Mar. 2018
KITAZAWA Shigeru, TANAKA Masaki, KAWAMURA Mitsuru, OTSU Yukio, IKEGAYA Yuji, NAKANO Tamami, NISHIYAMA Yuji, MURAKAMI Ikuya, HIRATA Satoshi, YOTSUMOTO Yuko
We refer to the awareness of time, over the past, present and future, as the “mental time”. The mental time is a cognitive function that has been evolved in humans in particular. In this research project, we aimed at constructing a new research area “the science of the mental time”, through active collaborations across neuroscientists, psychologists, clinical neurologists, linguists, philosophers, and comparative ethologists. The five-year collaborative project across seven programmed and 58 proposed research teams produced more than 380 research papers, and achieved three major goals. (1) We drew the map of the mental time on the medial surface of the cerebral cortex that extended over the cingulate cortex, precuneus, retrosplenial cortex, and the hippocampus. (2) We developed a method for manipulating the mental time using lab animals, and initiated clinical applications. (3) We revealed the process of evolution and development of the episodic-like memory.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Osaka University, 25119001

Neural mechanisms of temporal monitoring and prediction
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
28 Jun. 2013 - 31 Mar. 2018
Tanaka Masaki, KUNIMATU JUN, TAKEYA RYUJI, OHMAE SHOGO, YOSHIDA ATSUSHI, MATSUSHIMA AYANO, UEMATSU AKIKO, MATSUYAMA KEI, SUZUKI TOMOKI, KAMEDA MASASHI
Temporal monitoring and prediction of event timing are essential for behavioral control in daily life. In this study, we examined neuronal activity in the striatum and the cerebellar dentate nucleus in monkeys performing a variety of timing tasks. We also conducted behavioral experiments exploring the relationship between pupil diameter and subjective passage of time, neural mechanism of rhythm perception, and the capability of synchronized movements in nonhuman primates. Through these studies in the field of neuroscience, we could contribute to the advancement of The Science of Mental Time.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Hokkaido University, 25119005

Neural mechanisms of distribution of spatio-temporal attention
Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up
28 Aug. 2015 - 31 Mar. 2017
Takeya Ryuji, TANAKA Masaki
The objective of the present study is to uncover neural mechanisms of deployment of spatio-temporal attention by single cell recording from monkeys. To achieve the task, it is necessary to develop cognitive task for monkeys and identify neural mechanisms of internal time estimation. The applicant trained monkeys synchronized saccade task in which they synchronize their eye movement with isochronously and alternatively presented left or right side targets. As results, monkeys learned the task. Moreover, the applicant recorded from cerebellum where have been considered as a part of neural mechanisms of synchronized movement, and found neural activation for adjustment of movement interval for synchronized movement.
Japan Society for the Promotion of Science, Grant-in-Aid for Research Activity Start-up, Hokkaido University, 15H05985

Functional evaluation in animal models of radiosurgical brain lesions
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
01 Apr. 2014 - 31 Mar. 2017
Tanaka Masaki, KUNIMATU JUN, TAKEYA RYUJI, ISHIKAWA MASAYORI, MIYAMOTO NAOKI
Experimental technique to produce focal brain lesions may provide opportunities for future research exploring mechanisms of brain function and recovery from injury. As a candidate method, we evaluated the radiosurgical technique. We also tried to develop behavioral and electrophysiological techniques to examine subcortical brain functions, and explored new methods to generate focal brain lesions. We evaluated the oculomotor behavior in monkeys up to 8 months following irradiation to the frontal eye field. In addition, we have developed several behavioral tasks and a method to record cortical potentials through epi-dural electrodes, both of which are usable to detect subcortical dysfunction. Further, we performed a feasible study of chemogenetic application to monkeys by injecting a viral vector into the cerebellum. Through these studies, we could obtain valuable information for future studies.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 26560454

Development of behavioral paradigms to evaluate cerebellar cognitive functions
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2012 - 31 Mar. 2015
KURKIN SERGEY, TANAKA Masaki, SASAKI Hidenao, YABE Ichiro, UEMATSU Akiko, MATSUYAMA Kei, YOSHIDA Atsushi, ITOH Sayaka, MATSUSHIMA Ayano
The cerebellum is interconnected with the association areas in the frontal and parietal cortices, and therefore is thought to play roles in non-motor cognitive functions such as time perception and prediction. We devised a variety of psychophysical tests to evaluate cerebellar cognitive functions and examined the performance of patients with spinocerebellar degeneration (type 6). We found that some behavioral parameters differed significantly between patents and matched controls, and correlated with the volume of lateral cerebellum (Crus I and II). Furthermore, we trained monkeys in similar behavioral paradigms for future physiological studies.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 24500455

Temporal information processing in the basal ganglia and the cerebellum
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
01 Apr. 2011 - 31 Mar. 2015
TANAKA Masaki, KUNIMATSU Jun, OHMAE Shogo, UEMATSU Akiko, MATSUYAMA Kei
Both the basal ganglia and cerebellum play roles in time perception and temporal control of movements. We trained monkeys to report the time interval by making eye movements, and compared neuronal activity in the striatum and the cerebellar nucleus. The time course of neuronal activity in the striatum strongly depended on the time interval to be reported, while that in the cerebellum did not. Effects of local application of neuroactive agents to the recording sites were also examined. Neuronal activity related to temporal prediction was also recorded in monkeys that attempted to detect single omission of repetitive audiovisual stimuli.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23300139

タイミング予測と意思決定に関わる皮質下信号の解析
科学研究費助成事業 新学術領域研究(研究領域提案型)
01 Apr. 2012 - 31 Mar. 2014
田中 真樹
外界の出来事を予測し、適切なタイミングで意思決定を行うためには、時間の情報が不可欠である。本研究では、主にサルを用いて時間情報処理に関わる脳内機構を２種類の行動課題で調べた。
第一の研究では、一定の時間間隔で現れる視聴覚刺激の不意の欠落を検出させる（欠落オドボール課題）。これには試行ごとに異なる刺激間隔を学習し、次に現れる刺激のタイミングを予測し、欠落に対して予測誤差の信号を生成する必要がある。これまでに、小脳歯状核に刺激提示の時間間隔をコードするニューロン群を見いだしており、H25年度はこれをJ Neurosci誌に発表した。さらに本研究では運動性視床の神経活動を解析し、一定の成果をあげることができた。視床ニューロンの一部が繰り返し刺激に対する応答を興奮性から抑制性にスイッチすることを発見し、反応性から予測性の情報変換がこのレベルで行われていると考えられた。これらの成果は学会で報告するとともに、論文作成に向けて研究を継続している。
また、第二の課題では、手がかり刺激の提示後、一定の時間経過の後に自発的に眼球運動を行わせた。この課題の際に、漸増する準備活動を基底核（線条体）および小脳核（歯状核）で探索し、両部位の神経活動を比較検討した。前者は再現時間によって活動の上昇率が変化し、目標とするタイミングまでの相対的な時間経過をコードしているのに対し、後者では再現時間に関わらず、運動に一定時間先行して活動を上昇させ、運動タイミングの微調整に関与していることが示唆された。これらの研究成果も共同研究者の助教および学生が複数の学会で報告している。
申請者はこれらの成果をさらに大きく発展させるため、H25年度に新たに発足した新学術領域「こころの時間学」に計画班員として参加することとなった。重複制限のため、本公募課題はやむなく廃止することとしたが、研究は発展的に継続する。
日本学術振興会, 新学術領域研究(研究領域提案型), 北海道大学, 24120503

Development of a research technique to create animal model of brain lesions using therapeutic linear accelerator
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
01 Apr. 2012 - 31 Mar. 2014
TANAKA Masaki, ISHIKAWA Masayori, KUNIMATU Jun, MIYAMOTO Naoki
We developed a research technique to create animal model of brain lesions using the therapeutic linear accelerator. A total of four irradiations (130-150 Gy) were performed on the right frontal eye field of three Japanese monkeys. During a few weeks following irradiation, brain edema was evident in MRI and the performance of oculomotor tasks was declined; however, it recovered thereafter. For one monkey that was followed up about 8 months, the behavioral deficits reappeared in the 4th month and gradually progressed. Postmortem histological examination in two animals revealed large necrosis in the white matter and surrounding hemorrhage, but the cortical gray matter retained layers. This technique can be applied to deep brain structures in the future study. We now plan to use lower doses and will follow up longer interval.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 24650206

Roles of the cortico-basal ganglia loop in rule-based behavioral choice
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2008 - 2010
TANAKA Masaki
We select from multiple actions depending on a given situation. Analysis of the underlying neural mechanisms may shed light on the understanding of the pathophysiology in a variety of neurological and psychiatric disorders which accompany behavioral deficits. We examined neuronal activity in the basal ganglia and the thalamus in monkeys performing eye movement tasks, and found that neuronal activity was enhanced as the animals were required to suppress impulsive behavior. Inactivation of the recording sites resulted in the increment of impulsive behavior, suggesting that the basal ganglia?thalamocortical pathways may play a causal role in the organization of purposeful behavior.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 20300136

空間的注意のトップダウン制御
科学研究費助成事業 特定領域研究
2008 - 2009
田中 真樹
空間的注意のトップダウン制御の神経機構を調べるため、注意の移動が必要となる行動課題(Covert tracking課題)をサルに訓練し、前頭眼野を含む外側前頭前野からニューロン記録をおこなってきた。今年度はこれらに加え、課題中の微小電気刺激を試みた。予備的な実験では、前頭眼野の電気刺激でmovement fieldを決め、そこに提示した視覚刺激を選択する頻度が、閾値以下の電気刺激で増加するかどうかを調べたが、一貫した傾向が認められなかった。そこで、眼球運動が誘発されない刺激部位での影響を調べることにした。色の変化によるターゲットの手がかりを与えずに4つの視覚刺激を3秒間動かしてその中のひとつを任意に選ばせた。動き始めから0,500,2000ミリ秒のいずれかで前頭眼野周囲の微小電気刺激を行った。刺激は同部位に視覚応答性のニューロンが存在することを確認してから行った。動きの方向によるバイアスを除外するため、視覚刺激はいずれも固視点から遠ざかる方向に動き始めるようにした。それぞれのタイミングでターゲット位置の平均を求め、電気刺激の有無でそれらを比較したところ、電気刺激の影響は、ターゲットが動き出すのと同時に与えたときにのみ認められることが分かった。同様の実験を眼球運動が誘発される部位で行った結果、電気刺激による明らかな影響はみられなかった。これは、眼球運動そのものではなく、視覚応答を示すニューロン群によって、空間的注意が制御されていることを示唆する。
日本学術振興会, 特定領域研究, 北海道大学, 20020001

タイミングの予測に関与する脳ネットワークの検証
戦略的な研究開発の推進 戦略的創造研究推進事業 さきがけ
2006 - 2009
田中 真樹
次に起こる出来事を予測することは、生活する上でなくてはならない能力です。これに必要となる時間情報の処理機構には、大脳皮質-基底核ループによるものと小脳が関与するものの二つがあると考えられています。本研究では、主に小脳が関与すると期待される、数百ミリ秒間隔の「リズム」の生成に関係した神経機構を調べます。神経活動や行動データをもとに、脳が採用しているタイミングの予測アルゴリズムを理解することを目指します。
科学技術振興機構, 北海道大学, Principal investigator

眼球運動関連領野による空間的注意の制御機構
科学研究費助成事業 特定領域研究
2006 - 2007
田中 真樹
われわれは視野内の複数の場所にむかって次々に、あるいは移動する物体に伴って連続的に、随意的に注意をむけることができる。こうした空間的注意のトップダウン制御には、前頭および頭頂葉の眼球運動関連領野が密接に関与すると考えられている。本研究では独自に考案した注意の移動を要する行動課題(Covert tracking課題)をサルに訓練し、その神経機構を単一ニューロンのレベルで調べた。この課題では視野内を動き回る複数の視覚刺激のうち1つを選択し、眼を動かさないでそれを内的に追跡する必要がある。前頭眼野およびその数ミリメートル前方の外側前頭前野領域からデータを収集し、解析をおこなった。
前頭眼野ニューロンの多くは、受容野内にtargetが入ったときにdistractorが入ったときと比べて視覚応答が増強した。ところがさらに前方の前頭前野からはこれらとは異なった興味深い神経活動が記録された。一部のニューロンでは受容野内にdistractorが提示されたときに活動が上昇し、また、別のニューロンではtargetが受容野内にあるだけではなく、同時にdistractorが受容野外め特定の場所にあると発火し、"conditional modulation"の様相を示した。これらのニューロンが混在していることから、こうした神経活動を統一的に説明できる神経機構が存在することが示唆された。
今後は、本研究で見出された神経活動の定量的な解析と、電気刺激実験などを組み合わせることで研究の大きな進展が見込まれる。また、大脳皮質の情報処理には視床を介した皮質下からの情報が必須であることから、視床や大脳基底核などの神経活動との関連も視野にいれて研究を進める必要がある。
日本学術振興会, 特定領域研究, 北海道大学, 18020001

運動性視床による運動のタイミングの調節機構
科学研究費助成事業 若手研究(B)
2005 - 2006
田中 真樹
眼球運動系において基底核と小脳はいずれもフィードフォワード経路を構成し、大脳から脳幹に至る運動信号を修飾・調節していると考えられている。しかし一方、基底核と小脳(とくに外側部)は視床を介して大脳皮質に信号を送っており、体性運動系ではこの上行性経路が運動の企画や意思決定に関与していることが症例研究や機能画像研究によって示されている。中でも運動のタイミングの調節にこれらの上行性の信号が重要であることがよく知られており、皮質下病変における自発運動の開始異常の神経基盤として注目されている。本研究では眼球運動をモデルとして、運動の計画段階における皮質下信号の役割をサルを用いて調べた。
これまでの研究で、運動性視床の不活化により、反対側にむかう記憶誘導性サッカードの潜時が延長することを見いだし、平成17年度にNature Neuroscience誌に発表した。本年度はこの実験の前後に得られた神経活動を詳細に解析した。サッカードに先行したburst activityの大きさは視覚刺激に応じて運動をおこなったときと自発的におこなったときで多くの場合違いがなく、その一方で遅延期間中にみられたbuildup activityの潜時はinternally triggered課題でのサッカードの潜時によく相関した。このことから運動性視床は運動信号そのものというよりも、自発運動のタイミングを決定するための時間情報を大脳皮質に供給していることが示唆される。また、運動性視床から記録された眼球位置信号、smooth pursuit信号について定量的な解析を行った。これらの研究成果は平成18年度に開催された国内外のシンポジウム・研究会で発表し、またその一部は専門誌上にて発表した。平成17年度から2年間にわたる本研究課題で得られた成果は、今後新たな研究課題の中でさらに発展させることができると期待される。
日本学術振興会, 若手研究(B), 北海道大学, 17700363

運動のタイミングを制御する皮質下信号の探索
科学研究費助成事業 特定領域研究
2005 - 2005
田中 真樹
眼球運動系において基底核と小脳はいずれもフィードフォワード経路を構成し、大脳から脳幹に至る運動信号を修飾・調節していると考えられている。しかし一方、基底核と小脳外側部は視床を介して大脳皮質に信号を送っており、体性運動系ではこの上行経路が運動の企画や意思決定に関与していることが症例研究や機能画像研究によって示されている。中でも運動のタイミングの調節にこれらの経路が重要であることがよく知られており、皮質下病変における自発運動の開始異常の神経基盤として注目されている。本研究では眼球運動の計画段階における皮質下信号の役割をサルを用いて調べた。
これまでの研究で、運動性視床の不活化により、反対側にむかう記憶誘導性サッカードの潜時が延長することを見いだした。とくに、固視点を消すことによって運動を開始させる従来の課題よりも、手がかり刺激が提示された後、一定時間の後に自発的に記憶誘導性サッカードをおこなわせるinternally triggered課題で障害効果が大きかった。このことは視床を経由する信号が自発性眼球運動の発現、特にその時間的調節に関与する可能性を示唆する。本年度はこの現象の再現性を確認した上で専門誌に発表し、さらには不活化実験の前後に得られた神経活動を詳細に解析した。サッカードに先行したburst activityの大きさは視覚刺激に応じて運動をおこなったときと自発的におこなったときで多くの場合違いがなく、その一方で遅延期間中にみられたbuildup activityの潜時はinternally triggered課題でのサッカードの潜時によく相関した。このことから運動性視床は運動信号そのものというよりも、自発運動のタイミングを決定するための時間情報を大脳皮質に供給していることが示唆される。
日本学術振興会, 特定領域研究, 北海道大学, 17022003

背側視床における眼球運動信号の役割
科学研究費助成事業 特定領域研究
2004 - 2004
田中 真樹
運動性視床は皮質下の運動情報を大脳皮質につたえる上行性経路として重要であり、その信号は自身の行動をモニターすることに利用され、また、体性運動系においては随意運動の発現にも関与することが知られている。これまで、眼球運動系の研究では大脳皮質から直接、あるいは大脳基底核を経由して間接的に脳幹・小脳にいたる下行性の経路がよく調べられてきた。しかし、解剖学的には運動性視床の多くのニューロンが眼球運動関連領野に投射することが知られており、また、髄板内核群周辺からは眼球運動に関連したニューロンが記録される。本課題ではこれらの神経活動を解析するとともに、記録部位に微量のムシモールを注入し、眼球運動系における上行性信号の役割を調べた。
2種類の眼球運動について検討した。(1)滑動性眼球運動の最中に活動を変化させるニューロンの約8割には方向選択性があり、多くは同側に至適方向をもっていた。運動性視床を不活化すると滑動性眼球運動のゲインがわずかながら低下し、その効果は同側にむかう運動で大きかった。多くの場合、障害は運動の開始後数十ミリ秒であらわれ、このことは運動性視床が同眼球運動系の内在性の正の帰還経路の一部であることを示唆する。(2)視床の障害によって反対側にむかう記憶誘導性サッカードの潜時が延長した。とくに、固視点を消すことによって運動を開始させる従来のexternally triggered課題よりも、手がかり刺激が提示された後、一定時間の後に自発的に記憶誘導性サッカードをおこなわせるinternally triggered課題で障害効果が大きかった。このことは上行性信号が自発性眼球運動の発現、特にその時間的調節に関与する可能性を示唆する。この障害効果を裏付ける神経活動として、遅延期間中にみられたbuildup activityが有力であると考えられる。
日本学術振興会, 特定領域研究, 北海道大学, 16015204

眼球運動系における上行性経路の役割の解明
科学研究費助成事業 特定領域研究
2003 - 2003
田中 真樹
運動系の各段階における情報処理の結果は帰還性経路を経てより上位の中枢につたえられ、運動計画の更新や感覚入力の解釈に利用される。視床-大脳経路は脳幹、小脳、大脳基底核などの皮質下運動中枢から発した信号を上行性につたえ、その特性を知ることは運動の制御機構を理解する上で重要である。本課題では行動中のサルの運動性視床から単一ニューロン活動を記録した。髄板内核群の周辺領域からサッカードあるいは眼球位置に関連した細胞を多数記録した。いずれも約半数が眼球運動にわずかに先行して活動を変化させた。サッカードに先行してバーストするものの多くは方向選択性をもち、その至適方向は視野のあらゆる方向に分布していた。これに対し、眼球位置に対応するものは水平あるいは垂直方向に至適方向をもち、あきらかなmovement fieldをもたなかった。また、サッカードに関連したものの中には視覚誘導性サッカード課題よりも記憶誘導性課題で活動が増強するものが見いだされた。これらの結果から視床におけるサッカード信号と眼球位置信号はそれぞれ眼球運動系の異なった段階から供給されていることが示唆された。具体的にはサッカード信号は基底核あるいは上丘からもたらされ、眼球位置信号は基本的には脳幹にある神経積分器からの信号をうけていると考えられる。しかし、眼球位置に関連したものの多くはヒステリシスをもっており、忠実に眼球位置をコードしているわけではなく、視床内あるいは視床に至るまでに何らかの修飾をうけていると予想される。さらに、これら記憶誘導性サッカード、遅延期間、あるいは眼球位置に関連した細胞の一部は滑動性眼球運動の最中にも活動を変化させた。これらのことから大脳皮質は、視床を介した経路により、皮質下運動中枢の複数の段階における情報処理の結果をモニターしていることが明らかになった。
日本学術振興会, 特定領域研究, 北海道大学, 15016005

眼球運動の調節における運動性視床の役割
科学研究費助成事業 若手研究(B)
2002 - 2003
田中 真樹
運動系の各段階における情報処理の結果は帰還性経路を経てより上位の中枢につたえられ、運動計画の更新や感覚入力の解釈に利用される。視床-大脳経路は脳幹、小脳、大脳基底核などの皮質下運動中枢から発した信号を上行性につたえ、その特性を知ることは運動の制御機構を理解する上で重要である。本課題では行動中のサルの運動性視床から単一ニューロン活動を記録した。髄板内核群の周辺領域からサッカードあるいは眼球位置に関連した細胞を多数記録した。いずれも約半数が眼球運動にわずかに先行して活動を変化させた。サッカードに先行してバーストするものの多くは方向選択性をもち、その至適方向は視野のあらゆる方向に分布していた。これに対し、眼球位置に対応するものは水平あるいは垂直方向に至適方向をもち、あきらかなmovement fieldをもたなかった。また、サッカードに関連したものの中には視覚誘導性サッカード課題よりも記憶誘導性課題で活動が増強するものが見いだされた。これらの結果から視床におけるサッカード信号と眼球位置信号はそれぞれ眼球運動系の異なった段階から供給されていることが示唆された。具体的にはサッカード信号は基底核あるいは上丘からもたらされ、眼球位置信号は基本的には脳幹にある神経積分器からの信号をうけていると考えられる。しかし、眼球位置に関連したものの多くはヒステリシスをもっており、忠実に眼球位置をコードしているわけではなく、視床内あるいは視床に至るまでに何らかの修飾をうけていると予想される。さらに、これら記憶誘導性サッカード、遅延期間、あるいは眼球位置に関連した細胞の一部は滑動性眼球運動の最中にも活動を変化させた。これらのことから大脳皮質は、視床を介した経路により、皮質下運動中枢の複数の段階における情報処理の結果をモニターしていることが明らかになった。
日本学術振興会, 若手研究(B), 北海道大学, 14780616

随意性眼球運動の制御における内側および腹側視床の役割の解明
科学研究費助成事業 特定領域研究
2002 - 2002
田中 真樹
交付を受けた研究助成金により、サルの慢性実験用のシステムを構築して2頭のサルを訓練し、行動解析および運動性視床からの単一神経細胞外記録をおこなった。訓練と並行して行った行動実験では、行動のモニターに運動系のどのレベルの信号が用いられるのか、眼球運動系における小脳学習課題によって調べた。この実験ではふたつの視標を短時間提示し、サルはこれらが消えた後にそれぞれの位置向かって順にサッカードをするように要求された。このとき、ひとつ目のサッカードのベクトルは視標の網膜座標に一致するが、ふたつ目のサッカードは視標の網膜位置から直前の眼球運動を引き算して計算される。ひとつ目のサッカードを学習課題によって変化させたところ、ふたつ目のサッカードの振幅が変化した。この結果から、小脳より下流から発し、運動性視床を介して大脳皮質に至る上行性の経路が随意性眼球運動の制御に重要であることが示された。この成果は現在投稿中てある。また、これらのサルの運動性視床から眼球運動に関連した神経活動を記録し、サッカード、眼球位置、遅延期間などに特異的に応答するニューロン群を見いだした。サッカードに関連するものの多くは運動に遅れて活動を変化させ、眼球位置に関連するものはその方向選択性が水平または垂直方向にほぼ限られていた。このことは視床が運動の発現よりもその評価に関係している可能性を示唆し、その信号は脳幹からの上行性の投射によってもたらされていると考えられる。また、遅延期間に応答するニューロンの一部は滑動性眼球運動の際にも活動を変化させた。今後はこれらの神経活動の定量的な解析をおこない、その信号が運動の制御にどのように用いられるのかを調べていく必要がある。
日本学術振興会, 特定領域研究, 北海道大学, 14017004