2011年06月, Motor Control研究会, 優秀発表賞　　　　　　　　　　　　　　　
サル脚橋被蓋核ニューロンの周期発火とサッカード抑制応答
岡田 研一

2010年09月, 日本神経回路学会, 論文賞　　　　　　　　　　　　　　　
Different Pedunculopontine Tegmental Neurons Signal Predicted and Actual Task Rewards.
岡田 研一

Cross-species Convergence of Functional Connectivity Changes in Thalamic Pain across Human Patients and Model Macaques.
Dong Dong, Koichi Hosomi, Takeshi Shimizu, Ken-Ichi Okada, Yoshinori Kadono, Nobuhiko Mori, Yuki Hori, Noriaki Yahata, Toshiyuki Hirabayashi, Haruhiko Kishima, Youichi Saitoh
The journal of pain, 104661, 104661, 2024年08月23日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Thalamic pain can be understood as a network reorganization disorder. This study aimed to investigate functional connectivity (FC) in human patients and a macaque model of thalamic pain. In humans, functional brain activity was compared between patients with thalamic pain and healthy individuals. Furthermore, functional brain activity was compared in macaques, before and after the induction of thalamic pain in the same individuals. FCs between the amygdala of the unaffected hemisphere and the brainstem was significantly higher in patients with thalamic pain. More specifically, a significant FC higher was observed between the basolateral amygdala (BLA) and the ventral tegmental area, which also significantly predicted the value of a visual analog scale of pain intensity in individual patients. The macaque model of thalamic pain also exhibited a significant FC higher between the amygdala of the unaffected hemisphere and the brainstem, particularly between the BLA and the midbrain. Furthermore, the previously reported significant FC higher between the amygdala and the mediodorsal nucleus of the thalamus in macaques with thalamic pain was also reproduced in the human patients. Therefore, the present results suggest that the FC changes in the regions associated with emotion, memory, motivation, and reward are part of the underlying mechanisms of thalamic pain onset present in both human patients and model macaques. This cross-species convergence provides new insights into the neurological mechanisms underlying thalamic pain, paving the way for further studies and the development of therapeutic strategies. PERSPECTIVE: This article presents that the functional connectivity changes in the regions associated with emotion, motivation, and reward are part of the underlying mechanisms of thalamic pain in humans and macaques.

An easy-to-implement, non-invasive head restraint method for monkey fMRI.
Reiji Tanaka, Kei Watanabe, Takafumi Suzuki, Kae Nakamura, Masaharu Yasuda, Hiroshi Ban, Ken-Ichi Okada, Shigeru Kitazawa
NeuroImage, 120479, 120479, 2023年11月29日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Functional magnetic resonance imaging (fMRI) in behaving monkeys has a strong potential to bridge the gap between human neuroimaging and primate neurophysiology. In monkey fMRI, to restrain head movements, researchers usually surgically implant a plastic head-post on the skull. Although time-proven to be effective, this technique could create burdens for animals, including a risk of infection and discomfort. Furthermore, the presence of extraneous objects on the skull, such as bone screws and dental cement, adversely affects signals near the cortical surface. These side effects are undesirable in terms of both the practical aspect of efficient data collection and the spirit of "refinement" from the 3R's. Here, we demonstrate that a completely non-invasive fMRI scan in awake monkeys is possible by using a plastic head mask made to fit the skull of individual animals. In all of the three monkeys tested, longitudinal, quantitative assessment of head movements showed that the plastic mask has effectively suppressed head movements, and we were able to obtain reliable retinotopic BOLD signals in a standard retinotopic mapping task. The present, easy-to-make plastic mask has a strong potential to simplify fMRI experiments in awake monkeys, while giving data that is as good as or even better quality than that obtained with the conventional head-post method.

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, 2022年05月, ［査読有り］, ［筆頭著者］
研究論文（学術雑誌）, Abstract

Movements 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.

Repetitive transcranial magnetic stimulation restores altered functional connectivity of central poststroke pain model monkeys
Yoshinori Kadono, Keigo Koguchi, Ken-ichi Okada, Koichi Hosomi, Motoki Hiraishi, Takashi Ueguchi, Ikuhiro Kida, Adnan Shah, Guoxiang Liu, Youichi Saitoh
Scientific Reports, 11, 1, 6126, 6126, Springer Science and Business Media LLC, 2021年12月, ［査読有り］, ［責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, Central poststroke pain (CPSP) develops after a stroke around the somatosensory pathway. CPSP is hypothesized to be caused by maladaptive reorganization between various brain regions. The treatment for CPSP has not been established; however, repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex has a clinical effect. To verify the functional reorganization hypothesis for CPSP development and rTMS therapeutic mechanism, we longitudinally pursued the structural and functional changes of the brain by using two male CPSP model monkeys (Macaca fuscata) developed by unilateral hemorrhage in the ventral posterolateral nucleus of the thalamus. Application of rTMS to the ipsilesional primary motor cortex relieved the induced pain of the model monkeys. A tractography analysis revealed a decrease in the structural connectivity in the ipsilesional thalamocortical tract, and rTMS had no effect on the structural connectivity. A region of interest analysis using resting-state functional magnetic resonance imaging revealed inappropriately strengthened functional connectivity between the ipsilesional mediodorsal nucleus of the thalamus and the amygdala, which are regions associated with emotion and memory, suggesting that this may be the cause of CPSP development. Moreover, rTMS normalizes this strengthened connectivity, which may be a possible therapeutic mechanism of rTMS for CPSP.

Impaired inhibition of return during free-viewing behaviour in patients with schizophrenia.
Ken-Ichi Okada, Kenichiro Miura, Michiko Fujimoto, Kentaro Morita, Masatoshi Yoshida, Hidenaga Yamamori, Yuka Yasuda, Masao Iwase, Mikio Inagaki, Takashi Shinozaki, Ichiro Fujita, Ryota Hashimoto
Scientific reports, 11, 1, 3237, 3237, 2021年02月05日, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）, Schizophrenia affects various aspects of cognitive and behavioural functioning. Eye movement abnormalities are commonly observed in patients with schizophrenia (SZs). Here we examined whether such abnormalities reflect an anomaly in inhibition of return (IOR), the mechanism that inhibits orienting to previously fixated or attended locations. We analyzed spatiotemporal patterns of eye movement during free-viewing of visual images including natural scenes, geometrical patterns, and pseudorandom noise in SZs and healthy control participants (HCs). SZs made saccades to previously fixated locations more frequently than HCs. The time lapse from the preceding saccade was longer for return saccades than for forward saccades in both SZs and HCs, but the difference was smaller in SZs. SZs explored a smaller area than HCs. Generalized linear mixed-effect model analysis indicated that the frequent return saccades served to confine SZs' visual exploration to localized regions. The higher probability of return saccades in SZs was related to cognitive decline after disease onset but not to the dose of prescribed antipsychotics. We conclude that SZs exhibited attenuated IOR under free-viewing conditions, which led to restricted scene scanning. IOR attenuation will be a useful clue for detecting impairment in attention/orienting control and accompanying cognitive decline in schizophrenia.

Concomitant improvement in anti-saccade success rate and postural instability gait difficulty after rTMS treatment for Parkinson's disease.
Ken-Ichi Okada, Mizuki Takahira, Tomoo Mano, Taichi Uga, Kuni Konaka, Koichi Hosomi, Youichi Saitoh
Scientific reports, 11, 1, 2472, 2472, 2021年01月28日, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）, Parkinson's disease (PD) is a progressive neurological disorder characterised by motor and non-motor deficits. Repetitive transcranial magnetic stimulation (rTMS) over the bilateral primary motor cortex at a high frequency (5 Hz or higher) is reported to be a potential treatment of PD. We aimed to assess the effect of rTMS on eye movement control in patients with PD in their 'on' state. We enrolled 14 patients with PD and assessed motor symptoms (Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale; MDS-UPDRS) and eye movement performances (visually guided saccades, volitional anti-saccades, and small involuntary saccades during fixation) at baseline and after administering bilateral 10 Hz rTMS on leg region of the motor cortex. We confirmed that rTMS improved the MDS-UPDRS motor scores and found that rTMS improved the anti-saccade success rate, which requires adequate inhibition of the reflexive response. The improvement in anti-saccade success rate was correlated with that of the postural instability gait difficulty (PIGD) sub-scores of MDS-UPDRS and lower baseline Japanese version of the Montreal Cognitive Assessment scores. This result is consistent with previous findings that PIGD and inhibitory control deficits share common brain dysfunctions in PD. rTMS may alleviate dysfunctions of that circuit and have a clinical effect.

Ocular drift reflects volitional action preparation.
Watanabe M, Okada KI, Hamasaki Y, Funamoto M, Kobayashi Y, MacAskill M, Anderson T
The European journal of neuroscience, 2019年02月, ［査読有り］, ［国際共著］
英語, 研究論文（学術雑誌）

Reward and behavioral factors contributing to the tonic activity of monkey pedunculopontine tegmental nucleus neurons during saccade tasks
Ken-Ichi Okada, Yasushi Kobayashi
Frontiers in Systems Neuroscience, 10, 94, Frontiers Research Foundation, 2016年11月11日, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, The pedunculopontine tegmental nucleus (PPTg) in the brainstem plays a role in controlling reinforcement learning and executing conditioned behavior. We previously examined the activity of PPTg neurons in monkeys during a reward-conditioned, visually guided saccade task, and reported that a population of these neurons exhibited tonic responses throughout the task period. These tonic responses might depend on prediction of the upcoming reward, successful execution of the task, or both. Here, we sought to further distinguish these factors and to investigate how each contributes to the tonic neuronal activity of the PPTg. In our normal visually guided saccade task, the monkey initially fixated on the central fixation target (FT), then made saccades to the peripheral saccade target and received a juice reward after the saccade target disappeared. Most of the tonic activity terminated shortly after the reward delivery, when the monkey broke fixation. To distinguish between reward and behavioral epochs, we then changed the task sequence for a block of trials, such that the saccade target remained visible after the reward delivery. Under these visible conditions, the monkeys tended to continue fixating on the saccade target even after the reward delivery. Therefore, the prediction of the upcoming reward and the end of an individual trial were separated in time. Regardless of the task conditions, half of the tonically active PPTg neurons terminated their activity around the time of the reward delivery, consistent with the view that PPTg neurons might send reward prediction signals until the time of reward delivery, which is essential for computing reward prediction error in reinforcement learning. On the other hand, the other half of the tonically active PPTg neurons changed their activity dependent on the task condition. In the normal condition, the tonic responses terminated around the time of the reward delivery, while in the visible condition, the activity continued until the disappearance of the saccade target (ST) after reward delivery. Thus, for these neurons, the tonic activity might be related to maintaining attention to complete fixation behavior. These results suggest that, in addition to the reward value information, some PPTg neurons might contribute to the execution of conditioned task behavior.

The Pedunculopontine Tegmental Nucleus as a Motor and Cognitive Interface between the Cerebellum and Basal Ganglia
Fumika Mori, Ken-ichi Okada, Taishin Nomura, Yasushi Kobayashi
FRONTIERS IN NEUROANATOMY, 10, 109, FRONTIERS MEDIA SA, 2016年11月, ［査読有り］
英語, 研究論文（学術雑誌）, As an important component of ascending activating systems, brainstem cholinergic neurons in the pedunculopontine tegmental nucleus (PPTg) are involved in the regulation of motor control (locomotion, posture and gaze) and cognitive processes (attention, learning and memory). The PPTg is highly interconnected with several regions of the basal ganglia, and one of its key functions is to regulate and relay activity from the basal ganglia. Together, they have been implicated in the motor control system (such as voluntary movement initiation or inhibition), and modulate aspects of executive function (such as motivation). In addition to its intimate connection with the basal ganglia, projections from the PPTg to the cerebellum have been recently reported to synaptically activate the deep cerebellar nuclei. Classically, the cerebellum and basal ganglia were regarded as forming separated anatomical loops that play a distinct functional role in motor and cognitive behavioral control. Here, we suggest that the PPTg may also act as an interface device between the basal ganglia and cerebellum. As such, part of the therapeutic effect of PPTg deep brain stimulation (DBS) to relieve gait freezing and postural instability in advanced Parkinson's disease (PD) patients might also involve modulation of the cerebellum. We review the anatomical position and role of the PPTg in the pathway of basal ganglia and cerebellum in relation to motor control, cognitive function and PD.

Rhythmic Firing of Pedunculopontine Tegmental Nucleus Neurons in Monkeys during Eye Movement Task
Ken-ichi Okada, Yasushi Kobayashi
PLOS ONE, 10, 6, e0128147, PUBLIC LIBRARY SCIENCE, 2015年06月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, The pedunculopontine tegmental nucleus (PPTN) has been thought to be involved in the control of behavioral state. Projections to the entire thalamus and reciprocal connections with the basal ganglia nuclei suggest a potential role for the PPTN in the control of various rhythmic behaviors, including waking/sleeping and locomotion. Recently, rhythmic activity in the local field potentials was recorded from the PPTN of patients with Parkinson's disease who were treated with levodopa, suggesting that rhythmic firing is a feature of the functioning PPTN and might change with the behaving conditions even within waking. However, it remains unclear whether and how single PPTN neurons exhibit rhythmic firing patterns during various behaving conditions, including executing conditioned eye movement behaviors, seeking reward, or during resting. We previously recorded from PPTN neurons in healthy monkeys during visually guided saccade tasks and reported task-related changes in firing rate, and in this paper, we reanalyzed these data and focused on their firing patterns. A population of PPTN neurons demonstrated a regular firing pattern in that the coefficient of variation of interspike intervals was lower than what would be expected of theoretical random and irregular spike trains. Furthermore, a group of PPTN neurons exhibited a clear periodic single spike firing that changed with the context of the behavioral task. Many of these neurons exhibited a periodic firing pattern during highly active conditions, either the fixation condition during the saccade task or the free-viewing condition during the intertrial interval. We speculate that these task context-related changes in rhythmic firing of PPTN neurons might regulate the monkey's attentional and vigilance state to perform the task.

Fixational saccade-related activity of pedunculopontine tegmental nucleus neurons in behaving monkeys
Ken-ichi Okada, Yasushi Kobayashi
EUROPEAN JOURNAL OF NEUROSCIENCE, 40, 4, 2641, 2651, WILEY-BLACKWELL, 2014年08月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, Fixational saccades are small, involuntary eye movements that occur during attempted visual fixation. Recent studies suggested that several cognitive processes affect the occurrence probability of fixational saccades. Thus, there might be an interaction between fixational saccade-related motor signals and cognitive signals. The pedunculopontine tegmental nucleus (PPTN) in the brainstem has anatomical connections with numerous saccade-related and limbic areas. Previously, we reported that a group of PPTN neurons showed transient phasic bursts or a pause in activity during large visually guided and spontaneous saccades, and also showed sustained tonic changes in activity with task context. We hypothesised that single PPTN neurons would relay both fixational saccade-related and task context-related signals, and might function as an interface between the motor and limbic systems. We recorded the activity of PPTN neurons in behaving monkeys during a reward-biased task, and analysed neuronal activity for small fixational saccades during visual fixation, and compared it with the activity for large visually guided targeting saccades and large spontaneous saccades during intertrial intervals. A population of PPTN neurons exhibited a fixational saccade-related phasic increase in activity, and the majority of them also showed activity modulation with large targeting saccades. In addition, a group of these neurons showed a task-related tonic increase in activity during the fixation period, and half of them relayed the saccade signal only when the neuron exhibited higher tonic activity during the task execution period. Thus, fixational saccade-related signals of PPTN neurons overlap with tonic task-related signals, and might contribute to the cognitive modulation of fixational saccades.

Reward prediction-related increases and decreases in tonic neuronal activity of the pedunculopontine tegmental nucleus.
Okada K, Kobayashi Y
Frontiers in integrative neuroscience, 7, 36, 2013年, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）

A neural correlate of predicted and actual reward-value information in monkey pedunculopontine tegmental and dorsal raphe nucleus during saccade tasks
Ken-Ichi Okada, Kae Nakamura, Yasushi Kobayashi
Neural Plasticity, 2011, 579840, Hindawi Publishing Corporation, 2011年, ［査読有り］, ［筆頭著者］
英語, Dopamine, acetylcholine, and serotonin, the main modulators of the central nervous system, have been proposed to play important roles in the execution of movement, control of several forms of attentional behavior, and reinforcement learning. While the response pattern of midbrain dopaminergic neurons and its specific role in reinforcement learning have been revealed, the role of the other neuromodulators remains rather elusive. Here, we review our recent studies using extracellular recording from neurons in the pedunculopontine tegmental nucleus, where many cholinergic neurons exist, and the dorsal raphe nucleus, where many serotonergic neurons exist, while monkeys performed eye movement tasks to obtain different reward values. The firing patterns of these neurons are often tonic throughout the task period, while dopaminergic neurons exhibited a phasic activity pattern to the task event. The different modulation patterns, together with the activity of dopaminergic neurons, reveal dynamic information processing between these different neuromodulator systems. © 2011 Ken-ichi Okada et al.

Characterization of oculomotor and visual activities in the primate pedunculopontine tegmental nucleus during visually guided saccade tasks
Ken-Ichi Okada, Yasushi Kobayashi
EUROPEAN JOURNAL OF NEUROSCIENCE, 30, 11, 2211, 2223, WILEY-BLACKWELL PUBLISHING, INC, 2009年12月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, The pedunculopontine tegmental nucleus (PPTN) has anatomical connections with numerous visuomotor areas including the basal ganglia, thalamus, superior colliculus and frontal eye field. Although many anatomical and physiological studies suggest a role for the PPTN in the control of conditioned behavior and associative learning, the detailed characteristics of saccade- and visual-related activities of PPTN neurons remain unclear. We recorded the activity of PPTN neurons in monkeys (Macaca fuscata ) during visually guided saccade tasks, and examined the response properties of saccade- and visual-related activities such as time course, direction selectivity and contextual modulation. Saccade-related activity occurred either during saccade execution or after saccade end. The preferred directions of the neuronal activity were biased toward the contralateral and upward sides. Half of the saccade-related neurons showed activity modulation only for task saccades and not for spontaneous saccades outside the task. Visually-responsive neurons responded with short latencies. Some responded to the appearance of the visual stimulus in a directionally selective manner, and others responded to both the appearance and disappearance of the visual stimulus in a directionally non-selective manner. Many of these neurons exhibited distinct visual responses to the appearance of two different stimuli presented under different stages of the task, whereas a population of the neurons responded equally to the disappearance of the two stimuli. Thus, many PPTN neurons exhibited context-dependent activity related to the visuomotor events, consistent with a role in controlling conditioned behavior.

Different Pedunculopontine Tegmental Neurons Signal Predicted and Actual Task Rewards
Ken-ichi Okada, Keisuke Toyama, Yuka Inoue, Tadashi Isa, Yasushi Kobayashi
JOURNAL OF NEUROSCIENCE, 29, 15, 4858, 4870, SOC NEUROSCIENCE, 2009年04月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, The dopamine system has been implicated in guiding behavior based on rewards. The pedunculopontine tegmental nucleus (PPTN) of the brainstem receives afferent inputs from reward-related structures, including the cerebral cortices and the basal ganglia, and in turn provides strong excitatory projections to dopamine neurons. This anatomical evidence predicts that PPTN neurons may carry reward information. To elucidate the functional role of the PPTN in reward-seeking behavior, we recorded single PPTN neurons while monkeys performed a visually guided saccade task in which the predicted reward value was informed by the shape of the fixation target. Two distinct groups of neurons, fixation target (FT) and reward delivery (RD) neurons, carried reward information. The activity of FT neurons persisted between FT onset and reward delivery, with the level of activity associated with the magnitude of the expected reward. RD neurons discharged phasically after reward delivery, with the levels of activity associated with the actual reward. These results suggest that separate populations of PPTN neurons signal predicted and actual reward values, both of which are necessary for the computation of reward prediction error as represented by dopamine neurons.

Reward Prediction Error Computation in the Pedunculopontine Tegmental Nucleus Neurons
Y. KOBAYASHI, K.-I. OKADA
Annals of the New York Academy of Sciences, 1104, 1, 310, 323, Wiley, 2007年04月13日, ［査読有り］
英語, 研究論文（学術雑誌）

時間の神経科学-時を生み出すこころと脳の仕組み C 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, 2023年

The pedunculopontine tegmental nucleus neurons encode predicted reward signal by tonic regular firing and given reward signal phasically
Yasushi Kobayashi, Ken-ichi Okada, NEUROSCIENCE RESEARCH, 71, E72, E73, 2011年
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Neuronal coding of rewarding and aversive stimuli in the primate dorsal raphe nucleus
Kazuko Hayashi, Kazuko Nakao, Ken-ichi Okada, Yasushi Kobayashi, Kae Nakamura, NEUROSCIENCE RESEARCH, 68, E404, E404, 2010年
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

The pedunculopontine tegmental nucleus neurons relay predicted and actual reward and context dependent visuomotor information
Yasushi Kobayashi, Ken-ichi Okada, NEUROSCIENCE RESEARCH, 68, E72, E72, 2010年
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Rhythmic firing of pedunculopontine tegmental nucleus neurons in behaving monkeys
Ken-ichi Okada, Yasushi Kobayashi, NEUROSCIENCE RESEARCH, 68, E104, E104, 2010年, ［査読有り］
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Reward coding by the primate dorsal raphe neurons is context dependent
Kazuko Nakao, Ryuichi Matsuzaki, Ken-ichi Okada, Yasushi Kobayashi, Kae Nakamura, NEUROSCIENCE RESEARCH, 65, S113, S114, 2009年
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Computational mechanism of reward prediction error by the Pedunculopontine tegmental nucleus neurons
Yasushi Kobayashi, Ken-ichi Okada, NEUROSCIENCE RESEARCH, 65, S48, S48, 2009年, ［査読有り］
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Relation of pedunculopontine tegmental nucleus neurons in monkeys to reward prediction and behavior
Ken-Ichi Okada, Yasushi Kobayashi, NEUROSCIENCE RESEARCH, 65, S114, S114, 2009年, ［査読有り］
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Neural correlates of task performance in the primate pedunculopontine tegmental nucleus
Ken-ichi Okada, Yasushi Kobayashi, NEUROSCIENCE RESEARCH, 61, S60, S60, 2008年
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Using eye-movements as a research tool in children with autistic spectrum disorders
Yuri Kitamura, Koshiro Maruyama, Ken-ichi Okada, Yasushi Kobayashi, Yuji Yahata, Syoji Kobashi, Ikuko Mohri, Masako Taniike, NEUROSCIENCE RESEARCH, 61, S131, S131, 2008年, ［査読有り］
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Phasic responses of the pedunculopontine tegmental nucleus in primates
Ken-Ichi Okada, Yuka Inoue, Tadashi Isa, Yasushi Kobayashi, NEUROSCIENCE RESEARCH, 58, S45, S45, 2007年, ［査読有り］
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

Different groups of pedunculopontine tegmental nucleus neurons signal the expected and actual task reward
Yasushi Kobayashi, Ken-ichi Okada, NEUROSCIENCE RESEARCH, 58, S45, S45, 2007年, ［査読有り］
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

サル脚橋被蓋核ニューロンの視覚運動関連活動に報酬や課題状況が及ぼす影響の解析
岡田 研一, 井上 由香, 伊佐 正, 小林 康, 日本生理学会大会発表要旨集, 2007, 0, 161, 161, 2007年
The cholinergic pedunculopontine tegmental nucleus (PPTN) in the brainstem is thought to associated with reward-related behaviors by integrating polymodal signals related to the motivational state of animal, sensory information, motor control and reward. Here, we examined the effect of behavioral and reward context on neuronal activity of the pedunculopontine tegmental nucleus (PPTN) in primates during visually guided saccade tasks. About half of movement-related activities occurred for only the saccades to the saccade target in the task, but they did not occur for the saccades outside the task. On the other hand, for the other half of neurons, movement-related activities occurred for every saccade regardless of the task condition. For visual responses, some neurons responded either the initial fixation point or saccade target, and others responded equally to both stimuli. We further analyzed mutual relationship among modulation timing, preferred direction, effect of reward expectation and this context dependency of the activities, and discussed the visuo-motor processing of PPTN. [J Physiol Sci. 2007;57 Suppl:S161], 日本生理学会

脚橋被蓋核における報酬予測誤差生成機構
小林 康, 岡田 研一, 日本生理学会大会発表要旨集, 2007, 0, 56, 56, 2007年
We address the neuronal activity in pathways of brainstem-midbrain circuit that provides advantages over previous reinforcement learning theory. Several lines of evidence lead the reward based learning theory that midbrain dopamine (DA) neurons send a teaching signal (the reward prediction error signal) to control synaptic plasticity of the projection area. However, the underling mechanism of where and how to compute reward prediction error signal still remains unclear. Since the pedunculopontine tegmental nucleus (PPTN) in the brainstem is one of the strongest excitatory input sources to DA neurons, we hypothesized that the PPTN may play an important role in activating DA neurons and reinforcement learning by relaying necessary signals for reward prediction error computation on DA neurons. To investigate the involvement of the PPTN neurons in computation of reward prediction error, we used visually guided saccade task during recording of neuronal activity in monkeys. Here, we predict that PPTN neurons may relay excitatory component of tonic reward prediction and phasic primary reward signals, allowing new computational theory of reward prediction error in DA neurons. [J Physiol Sci. 2007;57 Suppl:S56], 日本生理学会

Context dependent property of visuomotor activities of pedunculopontine tegmental nucleus in primates
Ken-ichi Okada, Yuka Inoue, Tadashi Isa, Yasushi Kobayashi, NEUROSCIENCE RESEARCH, 55, S59, S59, 2006年
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

【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
(有)科学評論社, 2024年06月, 日本語

Temporal Information Processing in the Cerebellum and Basal Ganglia.
Masaki Tanaka, Masashi Kameda, Ken-Ichi Okada
2024年, 英語, 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.

【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
(株)中外医学社, 2023年08月, 日本語

Decision Making―意思決定・行動選択の神経科学 意思決定・行動選択の神経科学 ドパミンと報酬の予測誤差
小林康, 岡田研一
2014年01月01日, 日本語

中脳における報酬予測誤差計算機構 (特集 予測と意思決定の神経科学)
小林 康, 岡田 研一
金原一郎記念医学医療振興財団 ; 1949-, 2013年07月, 日本語

Advances in Reinforcement Learning　　　　　　　　　　　　　　　
小林康, 岡田研一, Reward prediction error computation in the pedunculopontine tegmental nucleus neurons
INTECH, 2011年01月, ［分担執筆］

大脳基底核の報酬機能--脚橋被蓋核の修飾機能 (特集 大脳基底核--分子基盤から臨床まで)
小林 康, 岡田 研一
医学書院, 2009年04月, 日本語

[Reward processing of the basal ganglia--reward function of pedunculopontine tegmental nucleus].　　　　　　　　　　　　　　　
Kobayashi- Y, Okada K
4, 2009年04月, ［査読有り］

視床痛における機能結合変化：異種間神経画像研究　　　　　　　　　　　　　　　
董 冬, 細見 晃一, 清水 豪士, 岡田 研一, 角野 喜則, 森 信彦, 堀 祐樹, 八幡 憲明, 平林 敏行, 貴島 晴彦, 齋藤 洋一
第53回日本臨床神経生理学会学術大会, 2023年11月

視床痛における機能結合変化 異種間神経画像研究　　　　　　　　　　　　　　　
董 冬, 細見 晃一, 清水 豪士, 岡田 研一, 角野 喜則, 森 信彦, 堀 祐樹, 八幡 憲明, 平林 敏行, 貴島 晴彦, 齋藤 洋一
臨床神経生理学, 2023年10月, (一社)日本臨床神経生理学会, 日本語
2023年10月 - 2023年10月

皮質−線条体経路の信号伝達はサルの適応行動に伴い柔軟に変化する　　　　　　　　　　　　　　　
岡田 研一, 田中 真樹
第46回日本神経科学大会, 2023年08月02日

リズミカルな視覚刺激の時間予測に関わる小脳プルキンエ細胞の活動　　　　　　　　　　　　　　　
リ リ, 岡田 研一, 田中 真樹
第46回日本神経科学大会, 2023年08月02日

小脳は行動エラーに関連した信号を内側前頭葉に送る　　　　　　　　　　　　　　　
安部 楓, 岡田 研一, 田中 真樹
第46回日本神経科学大会, 2023年08月01日

聴覚オドボール課題中にみられた視覚誘発電位の周期的変化　　　　　　　　　　　　　　　
杉尾 凌虎, 岡田 研一, 田中 真樹
第46回日本神経科学大会, 2023年08月01日

Rapid changes in cortico-striatal signal transmission during adaptive behavior in monkeys　　　　　　　　　　　　　　　
岡田研一, 田中真樹
Gordon Research Conference, Eye Movements, 2023, 2023年07月12日

行動上のエラー検出における小脳と内側前頭葉の機能連関　　　　　　　　　　　　　　　
安部 楓, 岡田 研一, 田中 真樹
第100回日本生理学会大会, 2023年03月14日

サルの適応行動に伴う皮質−線条体経路の信号伝達の素早い変化　　　　　　　　　　　　　　　
岡田 研一, 田中 真樹
第100回日本生理学会大会, 2023年03月14日

Efficacy of corticostriatal signaling changes rapidly during adaptive behavior in monkeys　　　　　　　　　　　　　　　
岡田研一, 田中真樹
International Symposium on Chronogenesis: How the Mind Generates Time, 2022年11月23日

Rapid changes in the efficacy of corticostriatal signal transmission during adaptive behavior in monkeys　　　　　　　　　　　　　　　
岡田研一, 田中真樹
Japan and Norway United in Brain, Educations and Therapeutics (JANUBET) Symposium 2022 "Tools and the Study of Brain Systems: New Vistas!", 2022年09月22日

覚醒サルfMRIのための完全非侵襲な頭部固定法　　　　　　　　　　　　　　　
渡邉 慶, 田中 澪士, 番 浩志, 岡田 研一, 北澤 茂
第44回日本神経科学大会, 2021年07月28日

同期眼球運動の実行における小脳歯状核の役割　　　　　　　　　　　　　　　
岡田 研一, 竹谷 隆司, 田中 真樹
第44回日本神経科学大会, 2021年07月28日

パーキンソン病患者の眼球運動制御に反復経頭蓋磁気刺激が与える影響　　　　　　　　　　　　　　　
岡田 研一, 高比良 みずき, 眞野 智生, 細見 晃一, 齋藤 洋一
第43回日本神経科学大会, 2020年07月31日

自由視課題における眼球運動の時空間的特徴から見る統合失調症患者の復帰抑制不全　　　　　　　　　　　　　　　
岡田 研一, 三浦 健一郎, 藤本 美智子, 森田 健太郎, 山森 英長, 安田 由華, 稲垣 未来男, 篠崎 隆志, 藤田 一郎, 橋本 亮太
第41回日本神経科学大会, 2018年07月28日

中枢性脳卒中後疼痛モデルマカクに対する反復経頭蓋磁気刺激の効果と神経回路への影響　　　　　　　　　　　　　　　
角野 喜則, 細見 晃一, 岡田 研一, 平石 幹, 高口 圭吾, 劉 国相, 黄田 育宏, 上口 貴志, 齋藤 洋一, 小林 康
第41回日本神経科学大会, 2018年07月27日

Parkinson病患者の運動障害と眼球運動障害に対する反復経頭蓋磁気刺激の効果　　　　　　　　　　　　　　　
眞野 智生, 岡田 研一, 細見 晃一, 小林 康, 齋藤 洋一
第41回日本神経科学大会, 2018年07月26日

rTMSを用いたパーキンソン病の脳内メカニズムの解明研究 (第57回日本定位・機能神経外科学会優秀演題)
眞野 智生, 岡田 研一, 細見 晃一, 後藤 雄子, 小林 康, 貴島 晴彦, 齋藤 洋一
機能的脳神経外科 : 日本定位・機能神経外科学会機関誌 = Functional neurosurgery : official journal of the Japan Society for Stereotactic and Functional Neurosurgery, 2018年, 日本定位・機能神経外科学会事務局, 日本語
2018年 - 2018年

パーキンソン病患者における反復経頭蓋磁気刺激治療前後の眼球運動評価　　　　　　　　　　　　　　　
宇賀 太一, 船本万里, 森風美加, 平石幹, 岡田研一, 小林康, 眞野智生, 齋藤 洋一
第40回日本神経科学大会, 2017年07月20日

サル脚橋被害核のLFPとスパイク活動の解析　　　　　　　　　　　　　　　
岡田 研一, 小林 康
第40回日本神経科学大会, 2017年07月20日

サルM1繰り返し経頭蓋磁気刺激の脚橋被蓋核神経活動への影響　　　　　　　　　　　　　　　
小林 康, 岡田 研一
第39回日本神経科学大会, 2016年07月22日

覚醒サルにおける情動計測システムの開発　　　　　　　　　　　　　　　
安田 正治, 中村 晋也, 岡田 研一, 飯島 敏夫, 小林 康, 筒井 健一郎, 中村 加枝
第38回日本神経科学大会, 2015年07月29日

パーキンソン病患者における注視時微小眼球運動の解析　　　　　　　　　　　　　　　
浜咲 雄太, 船本 万里, 浅原 舜平, 田中 文哲, 岡田 研一, 小林 康, Michael MacAskill, Leslie Livingston, Tim Anderson, 渡邊 雅之
第38回日本神経科学大会, 2015年07月28日

多発性硬化症患者における注視時微小眼球運動の解析　　　　　　　　　　　　　　　
船本 万里, 浜咲 雄太, 浅原 舜平, 田中 文哲, 岡田研一, 小林 康, Sridhar Alla, Michael MacAskill, Deborah Mason, Tim Anderson, 渡邊 雅之
第38回日本神経科学大会, 2015年07月28日

サル繰り返し経頭蓋磁気刺激の眼球運動への影響　　　　　　　　　　　　　　　
小林 康, 岡田 研一
第38回日本神経科学大会, 2015年07月28日

Analysis of eye movements after repetitive transcranial magnetic stimulation on behaving monkeys.　　　　　　　　　　　　　　　
Okada K, Kobayashi Y
The 45th Annual Meeting of the Society for Neuroscience, 2015年

経頭蓋磁気刺激法の逆橋渡し研究
中村加枝, 小林康, 筒井健一郎, 安田正治, 岡田研一, 中村晋也
日本神経精神薬理学会プログラム・抄録集, 2015年, 日本語

サル脚橋被蓋核における周期的ニューロン活動　　　　　　　　　　　　　　　
岡田 研一, 小林 康
第37回日本神経科学大会, 2014年09月12日

随意、不随意まばたきとその前後で起こる眼球運動の解析　　　　　　　　　　　　　　　
田中 文哲, 浜咲 雄太, 浅原 舜平, 岡田 研一, 喜多村 祐里, 渡邊 雅之, 小林 康
第37回日本神経科学大会, 2014年09月11日

ヒトマイクロサッケードは疲れを反映する　　　　　　　　　　　　　　　
浅原 舜平, 田中 文哲, 浜咲 雄太, 岡田 研一, 喜多村 祐里, 渡邊 雅之, 小林 康
第37回日本神経科学大会, 2014年09月11日

サル脚橋被蓋核における注視中のマイクロサッケードに関連したニューロン活動　　　　　　　　　　　　　　　
小林 康, 岡田 研一
第37回日本神経科学大会, 2014年09月11日

Fixational-saccade related and periodic activity of the pedunculopontine tegmental nucleus neurons in behaving monkeys　　　　　　　　　　　　　　　
Y. KOBAYASHI, K. OKADA
The 44th Annual Meeting of the Society for Neuroscience, 2014年

ヒトマイクロサッケードと随意まばたき運動の準備状態との関係　　　　　　　　　　　　　　　
浅原 舜平, 田中 文哲, 松尾 有華, 査 凌, 岡田 研一, 渡邊 雅之, 小林 康
第36回日本神経科学大会・第56回日本神経化会大会・第23回日本神経回路学会大会合同大会, 2013年06月22日

脚橋被蓋核におけるニューロン活動の増加・減少による報酬価値予測の表現　　　　　　　　　　　　　　　
岡田 研一, 小林 康
第36回日本神経科学大会・第56回日本神経化会大会・第23回日本神経回路学会大会合同大会, 2013年06月21日

Microsaccade-related activity of pedunculopontine tegmental nucleus neurons in behaving monkeys.　　　　　　　　　　　　　　　
Okada K, Kobayashi Y
The 43rd Annual Meeting of the Society for Neuroscience, 2013年

サル脚橋被蓋核ニューロンにおけるサッカード抑制応答　　　　　　　　　　　　　　　
岡田 研一, 小林 康
第35回日本神経科学大会, 2012年09月18日

Sustained tonic excitation and suppression of activity on pedunculopontine tegmental nucleus neurons in behaving monkeys.　　　　　　　　　　　　　　　
Okada K, Kobayashi Y
The 42nd Annual Meeting of the Society for Neuroscience, 2012年

Saccade-related modulation of rhythmic firing pattern on pedunculopontine tegmental nucleus neurons in behaving monkeys.　　　　　　　　　　　　　　　
Okada K, Kobayashi Y
The 41st annual meeting of the society for neuroscience, 2011年

The pedunculopontine tegmental nucleus neurons encode predicted reward signal by tonic regular firing and given reward signal phasically
Kobayashi Yasushi, Okada Ken-ichi
NEUROSCIENCE RESEARCH, 2011年

Context-dependent firing regularity of pedunculopontine tegmental nucleus neurons in behaving monkeys.　　　　　　　　　　　　　　　
Okada K, Kobayashi Y
The 40th Annual Meeting of the Society for Neuroscience, 2010年

The pedunculopontine tegmental nucleus neurons relay predicted and actual reward and context dependent visuomotor information
Kobayashi Yasushi, Okada Ken-ichi
NEUROSCIENCE RESEARCH, 2010年

Rhythmic firing of pedunculopontine tegmental nucleus neurons in behaving monkeys
Okada Ken-ichi, Kobayashi Yasushi
NEUROSCIENCE RESEARCH, 2010年

Analyses of the time course of neuronal activity of the pedunculopontine tegmental nucleus in monkeys for reward conditioned saccade task.　　　　　　　　　　　　　　　
Okada K, Kobayashi Y
The 39th Annual Meeting of the Society for Neuroscience,, 2009年

Computational mechanism of reward prediction error by the Pedunculopontine tegmental nucleus neurons
Kobayashi Yasushi, Okada Ken-ichi
NEUROSCIENCE RESEARCH, 2009年

Relation of pedunculopontine tegmental nucleus neurons in monkeys to reward prediction and behavior
Okada Ken-Ichi, Kobayashi Yasushi
NEUROSCIENCE RESEARCH, 2009年

Neural correlates of task performance of the visually guided saccade tasks in the primate pedunculopontine tegmental nucleus.　　　　　　　　　　　　　　　
Okada K, Kobayashi Y
The 38th Annual Meeting of the Society for Neuroscience, 2008年

Neural correlates of task performance in the primate pedunculopontine tegmental nucleus　　　　　　　　　　　　　　　
Okada Ken-ichi, Kobayashi Yasushi
NEUROSCIENCE RESEARCH, 2008年

Different groups of pedunculopontine tegmental nucleus neurons signal the expected and actual task reward　　　　　　　　　　　　　　　
Y. KOBAYASHI, K. OKADA, K. TOYAMA, T. ISA
The 37th Annual Meeting of the Society for Neuroscience, 2007年

Phasic responses of the pedunculopontine tegmental nucleus in primates
Okada Ken-Ichi, Inoue Yuka, Isa Tadashi, Kobayashi Yasushi
NEUROSCIENCE RESEARCH, 2007年

Different groups of pedunculopontine tegmental nucleus neurons signal the expected and actual task reward
Kobayashi Yasushi, Okada Ken-ichi
NEUROSCIENCE RESEARCH, 2007年

サル脚橋被蓋核ニューロンの視覚運動関連活動に報酬や課題状況が及ぼす影響の解析
岡田 研一, 井上 由香, 伊佐 正, 小林 康
日本生理学会大会発表要旨集, 2007年
The cholinergic pedunculopontine tegmental nucleus (PPTN) in the brainstem is thought to associated with reward-related behaviors by integrating polymodal signals related to the motivational state of animal, sensory information, motor control and reward. Here, we examined the effect of behavioral and reward context on neuronal activity of the pedunculopontine tegmental nucleus (PPTN) in primates during visually guided saccade tasks. About half of movement-related activities occurred for only the saccades to the saccade target in the task, but they did not occur for the saccades outside the task. On the other hand, for the other half of neurons, movement-related activities occurred for every saccade regardless of the task condition. For visual responses, some neurons responded either the initial fixation point or saccade target, and others responded equally to both stimuli. We further analyzed mutual relationship among modulation timing, preferred direction, effect of reward expectation and this context dependency of the activities, and discussed the visuo-motor processing of PPTN. [J Physiol Sci. 2007;57 Suppl:S161]

Influences of reward prediction on neuronal activity of the pedunculopontine tegmental nucleus during visually guided saccade tasks in monkeys.　　　　　　　　　　　　　　　
Okada K, Inoue Y, Isa T, Kobayashi Y
The 36th Annual Meeting of the Society for Neuroscience, 2006年

Context dependent property of visuomotor activities of pedunculopontine tegmental nucleus in primates　　　　　　　　　　　　　　　
Okada Ken-ichi, Inoue Yuka, Isa Tadashi, Kobayashi Yasushi
NEUROSCIENCE RESEARCH, 2006年

Neuronal activities sufficient for reward prediction error computation in the pedunculopontine tegmental nucleus during visually guided saccade tasks in monkeys　　　　　　　　　　　　　　　
Kobayashi Yasushi, Okada Kenich, Isa Tadashi, Inoue Yuka
NEUROSCIENCE RESEARCH, 2006年

線条体の柔軟な神経活動を制御するメカニズムの解明
科学研究費助成事業 基盤研究(C)
2021年04月01日 - 2024年03月31日
岡田 研一
状況に合わせた行動の選択・抑制に大脳基底核の線条体が重要な役割を果たしており、大脳皮質－基底核ネットワークの状態変化によって、線条体の神経活動が動的に制御されていると考えられる。試行毎のルールに応じて行動を切り替えるような短い時間スケールでの行動選択における大脳皮質－基底核ネットワークの状態変化の役割を明らかにすべく、研究を行った。
短い時間スケールでの状況適応的な行動の制御機構を調べるために、試行毎に示される指示（CUE）に従って、（i）突然現れる視覚刺激にそのままサッカードするか、（ii）視覚刺激への反射的なサッカードを抑制し反対方向にサッカードするかを選択するアンチサッカード課題を２頭のサルに習得させた。それぞれのサルにおいて、MRI画像と機能マッピングにより線条体と大脳皮質の補足眼野を同定した。試行毎の大脳皮質－基底核ネットワークのダイナミックな状態変化を調べるためにアンチサッカード課題中のLFPを単一電極により記録し、CUEの呈示から視覚刺激の呈示までの期間において試行毎のルールに応じてLFPのβ成分が減弱することを確認した。
更に当初の予定を上回った成果として、皮質線条体経路の機能結合の変化を調べるために、補足眼野への微小電流刺激に対する線条体での短潜時応答を記録した。補足眼野への刺激は、新たに開発した複数本の単一電極を短期間埋め込む手法と、同心円型双極電極を用いて局所的に刺激する手法で行った。線条体に刺入した単一電極を用いて、同側・対側の補足眼野への微小電流刺激に対する応答を記録したところ、線条体LFPの刺激誘発応答のみならず、線条体ニューロンの短潜時の刺激誘発スパイクの計測に成功した。これらのLFP・スパイク応答が、課題のルールや刺激前のLFPのβ成分の強さや位相に応じてどのように変化するか、解析を進めている。
日本学術振興会, 基盤研究(C), 北海道大学, 21K06418

非侵襲脳活動計測を用いた一次運動野刺激の疼痛認知抑制機構の解明
科学研究費助成事業 基盤研究(C)
2018年04月01日 - 2021年03月31日
細見 晃一, 齋藤 洋一, 眞野 智生, 岡田 研一
難治性神経障害性疼痛に対する一次運動野刺激療法(MCS)の除痛機序については、運動系の活動が疼痛の認知を抑制することが推定されるが、その詳細な脳内機序については不明な点が多い。本研究では、視床痛霊長類モデルおよび中枢性神経障害性疼痛患者を対象として、MCSによる脳内の運動・感覚関連領域の活動の変化を非侵襲的に計測する。
動物実験では、マカクサルを各課題へ馴化し、モデル作成前の評価を実施した。健常状態で、経頭蓋磁気刺激(TMS)によるMCSを実施し、行動評価とマルチモダル脳MRI撮影を実施し、TMS-MCSによる行動及び脳内変化を評価した。視床出血後疼痛モデルを作成し、行動実験及び脳MRI、TMS-MCSを行った。また、それぞれの脳MRIの解析手法を検討した。疼痛患者実験では、2018年度までに収集したデータをもとにMCSによる除痛や痛みに特異的な脳内の運動・感覚システムの変化を検討している。
日本学術振興会, 基盤研究(C), 大阪大学, 18K08993

霊長類視床痛モデルにおける中枢性疼痛メカニズムの解明
科学研究費助成事業 基盤研究(C)
2017年04月01日 - 2020年03月31日
齋藤 洋一, 小林 康, 細見 晃一, 眞野 智生, 岡田 研一
肥後博士の協力で、マカクサルの片側視床(VPL核)に微小な破壊を行いアロジニアを示す個体を作成した。その2頭のマカクサルの行動データ（温度刺激、触覚刺激）を検討。片側VPL核破壊後、数週間後からアロジニアが反対側に現れ数か月かけて減少していく傾向が見られた。VPL核破壊後の経時的な構造画像では1ヶ月ほどで破壊巣は小さくなった。拡散テンソル画像ではVPL核と一次感覚野を結ぶ神経束の密度が減少した。
経時的なrs-fMRIデータを解析したところ、アロジニアが発生後は、破壊と同側の視床(MD/Pf核)と扁桃体間の機能結合が上昇していた。rTMSを施行すると、MD/Pf核と扁桃体間の機能結合が低下した。
日本学術振興会, 基盤研究(C), 大阪大学, 17K10893

動物モデルを用いた中枢性脳卒中後疼痛の病態および神経刺激療法の除痛機序の解明
科学研究費助成事業 若手研究(B)
2015年04月01日 - 2018年03月31日
細見 晃一, 齋藤 洋一, 岡田 研一, 角野 喜則
霊長類中枢性脳卒中後疼痛(CPSP)モデルを作成し、行動評価および高磁場MRIを用いた脳機能評価を行った。疼痛発症後には、痛み関連領域内における領域間の機能的結合が増加していた。その疼痛モデルザルに一次運動野に対する反復経頭蓋磁気刺激(rTMS)を実施したところ、感覚過敏が改善すると共に、痛み関連領域内における領域間の機能的結合が減弱していた。CPSPの発症機序やrTMSの除痛機序に痛み関連領域内の領域間機能的結合が関与していることが示唆された。
日本学術振興会, 若手研究(B), 大阪大学, 15K21142