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Last Updated :2024/08/20
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- 【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 (有)科学評論社 100 (6) 563 - 571 2434-3285 2024/06
- Masaki Tanaka, Masashi Kameda, Ken-Ichi OkadaAdvances in experimental medicine and biology 1455 95 - 116 2024Temporal 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Clinical Neuroscience (株)中外医学社 41 (8) 1044 - 1047 0289-0585 2023/08
- Masashi Kameda, Koichiro Niikawa, Akiko Uematsu, Masaki TanakaProceedings of the National Academy of Sciences of the United States of America 120 (24) e2221641120 2023/06/13Both 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.
- Masaki Tanaka, Jun Kunimatsu, Tomoki W Suzuki, Masashi Kameda, Shogo Ohmae, Akiko Uematsu, Ryuji TakeyaNeuroscience 462 220 - 234 2021/05/10The 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.
- Masashi Kameda, Shogo Ohmae, Masaki TanakaeLife 8 2019/09/06Rhythmic 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.
- Masaki Tanaka, Tomoki W. Suzuki, Masashi Kameda, Ryuji TakeyaBrain and Nerve 69 (11) 1213 - 1222 1881-6096 2017/11/01 [Refereed][Not invited]
When waiting for a traffic light or dancing to a musical beat, we unconsciously keep track of elapsed time and precisely predict the timing of forthcoming sensory events. Temporal monitoring and prediction are integral to our daily life, and are regulated by neuronal processes through multiple global networks involving the frontoparietal cortices, the basal ganglia and the cerebellum. These processes are also known to be influenced by a variety of internal state and neuromodulators. Here, we review recent advance of research in the field. - Ryuji Takeya, Masashi Kameda, Aniruddh D Patel, Masaki TanakaScientific reports 7 (1) 6127 - 6127 2017/07/21Predictive and tempo-flexible synchronization to an auditory beat is a fundamental component of human music. To date, only certain vocal learning species show this behaviour spontaneously. Prior research training macaques (vocal non-learners) to tap to an auditory or visual metronome found their movements to be largely reactive, not predictive. Does this reflect the lack of capacity for predictive synchronization in monkeys, or lack of motivation to exhibit this behaviour? To discriminate these possibilities, we trained monkeys to make synchronized eye movements to a visual metronome. We found that monkeys could generate predictive saccades synchronized to periodic visual stimuli when an immediate reward was given for every predictive movement. This behaviour generalized to novel tempi, and the monkeys could maintain the tempo internally. Furthermore, monkeys could flexibly switch from predictive to reactive saccades when a reward was given for each reactive response. In contrast, when humans were asked to make a sequence of reactive saccades to a visual metronome, they often unintentionally generated predictive movements. These results suggest that even vocal non-learners may have the capacity for predictive and tempo-flexible synchronization to a beat, but that only certain vocal learning species are intrinsically motivated to do it.
Research Projects
- 日本学術振興会：科学研究費助成事業Date (from‐to) : 2018/04 -2021/03Author : 亀田 将史申請者は大脳基底核と小脳における周期的な時間予測に関連した神経活動の機能の違いを明らかにするために研究を行なってきた。研究内容の一部は昨年度に論文誌に発表し（Kameda et al., 2019）、当該年度もこれらを発展させた研究を進めている。大脳基底核と小脳の時間予測における感覚運動成分を比較するために従来の行動課題を一部改変した研究（申請書記載の研究１）に関しては、データ収集や解析をほぼ終わらせ論文の執筆を進めている。また、時間予測的活動の効果器特異性を調べるために課題への答え方を眼球運動と手指の運動に分けてた研究（申請書記載の研究２）においても、小脳と大脳基底核からそれぞれ多くのデータが収集できており、両部位間に興味深い違いを見出している。それぞれ１頭の個体（ニホンザル）から十分なデータを得ており、別の個体からも記録を進めている。また、論文化のために詳細な解析も進めている。