Kozo Funase’s research while affiliated with Hiroshima University and other places

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Publications (94)


a Schematic illustration of the CoIT task. Panels 1–4 show each phase of the CoIT task, which was displayed on a computer monitor. A ball was released at a constant speed 300–400 ms after the appearance of a warning signal. The subjects were instructed to hit the ball so that it “landed” in a target area (located between the two red bars), regardless of the swing speed of the bat. b Schematic illustration of the experimental protocol. The upper and central panels show the procedure in cond F (faster swing perturbation) and cond S (slower swing perturbation), respectively. The lower panel illustrates the procedure in cond R (randomized perturbation). The experiment was composed of five stages, which are represented by thick black lines, i.e., the baseline, early learning stage, late learning stage, post 1 washout stage, and post 2 washout stage. We measured CBI at three timepoints, i.e., before, during, and after adaptive learning. The measurements are represented by inverted triangles. During the learning stage, the bat swing speed was changed abruptly so that it became faster (F) or slower (S). In condition R, the bat swing speed changed unpredictably to the speed employed in cond F, cond S, or ctrl. After the practice session, no visual feedback regarding the subjects’ bat swing movements was provided. Each block consisted of 10 task trials
Trial to trial changes in the CT (ms) (a, b) and CE (degrees) (c, d) seen in each experimental stage in groups F (left side) and S (right side). The thick black lines represent each stage (the baseline, the early and late learning stages, and the post 1 and post 2 washout stages). The horizontal axes indicate the number of blocks. The mean (lines) and SE (shaded areas) values obtained in the faster (cond F), slower (cond S), and random (cond R) perturbation conditions are represented in green, blue, and red, respectively. Negative CT and CE values indicated an earlier swing at the ball, which would result in the ball being hit to the left. The opposite was true for positive values
Changes in the mean (± SE) CT (ms) (a, b), CE (degrees) (c, d), and the success count (e, f) in each experimental stage in groups F (left side) and S (right side). Values were obtained by analyzing binned data. The success count represents the number of trials in which the AE was ≤ 5°. Cond F, cond S, and cond R are represented by green, blue, and red bars, respectively. The daggers (cond F and S) and hashes (cond R) indicate significant differences compared with the baseline. The asterisks indicate significant differences between the stages
a, b Typical examples of averaged MEP waveforms (n = 10) recorded at the baseline or during the early or late learning stages. The MEPs were recorded after the delivery of a TS alone over the left M1 (black line) or after the delivery of a CS over the right cerebellum and a TS over the left M1 (green line: cond F, blue line: cond S, red line: cond R) in one subject each from groups F (a) and S (b). Changes in the mean (± SE) CBI ratio between the baseline and the early or late learning stages in groups F (c) and S (d). Cond F, cond S, and cond R are represented by green, blue, and red bars, respectively. The asterisks indicate significant differences between the stages
The relationships between the changes in CBI and the changes in the CT (a, c, e) or CE (b, d, f) during adaptive learning in cond F (green circles), cond S (blue circles), or cond R (red circles) in group F

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Modulation of cerebellar brain inhibition during temporal adaptive learning in a coincident timing task
  • Article
  • Publisher preview available

January 2021

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74 Reads

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2 Citations

Experimental Brain Research

Shin-ya Tanaka

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Masato Hirano

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Kozo Funase

In the present study, we examined the role of the cerebellum in temporal adaptive learning during a coincident timing task, i.e., a baseball-like hitting task involving a moving ball presented on a computer monitor. The subjects were required to change the timing of their responses based on imposed temporal perturbations. Using paired-pulse transcranial magnetic stimulation, we measured cerebellar brain inhibition (CBI) before, during, and after the temporal adaptive learning. Reductions in CBI only occurred during and after the temporal adaptive learning, regardless of the direction of the temporal perturbations. In addition, the changes in CBI were correlated with the magnitude of the adaptation. Here, we showed that the cerebellum is essential for learning about and controlling the timing of movements during temporal adaptation. Furthermore, changes in cerebellar-primary motor cortex connectivity occurred during temporal adaptation, as has been previously reported for spatial adaptation.

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Reorganization of finger covariation patterns represented in the corticospinal system by learning of a novel movement irrelevant to common daily movements

October 2019

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32 Reads

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2 Citations

Journal of Neurophysiology

How dexterous finger movements are acquired by the nervous system is a fundamental question in the neuroscience field. Previous studies have demonstrated that finger movements can be decomposed into finger covariation patterns, and these patterns are represented in the corticospinal system. However, it remains unclear how such covariation patterns represented in the corticospinal system develop during the acquisition of novel finger movements. In this study, each subject learned to perform a novel finger movement, which was mapped to a region outside of the movement subspace spanned by common finger movements seen in daily life, through a custom task. After practicing the task, we detected changes in the finger covariation patterns derived from artificially (transcranial magnetic stimulation) evoked finger joint movements. The artificially evoked movement-derived patterns seen after the training period were associated with both the novel and common finger movements. Regarding the patterns extracted from the artificially evoked movements, the number required to explain most of the variance in the data was unchanged after the training period. Our results indicate that novel finger movements are acquired through the reorganization of pre-existing finger covariation patterns represented in the corticospinal system, rather than the development of new patterns. These findings might have implications for the basic mechanism responsible for the development of movement repertories in the nervous system.


Acquisition of motor memory determines the inter-individual variability of learning-induced plasticity in the primary motor cortex

July 2018

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59 Reads

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3 Citations

Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology

Acquisition of new motor skills induces plastic reorganization in the primary motor cortex (M1). Previous studies have demonstrated the increases in the M1 excitability through motor skill learning. However, this M1 reorganization is highly variable between individuals even though they improve their skill performance through the same training protocol. To reveal the source of this inter-individual variability, we examined the relationship between an acquisition of memory-guided feedforward movements and the learning-induced increases in the M1 excitability. Twenty-eight subjects participated in experiment 1. We asked subjects to learn a visuomotor tracking task. The subjects controlled a cursor on a PC monitor to pursue a target line by performing ankle dorsiflexion and plantar flexion. In experiment 1, we removed the online visual feedback provided by the cursor movement once every 6 trials, which enabled us to assess whether the subjects could perform accurate memory-guided movements. Motor evoked potentials (MEP) were elicited in the tibialis anterior muscle by transcranial magnetic stimulation of the relevant M1 before and after the learning of the visuomotor tracking task and after half the trials. We found that the MEP amplitude was increased along with the improvement in memory-guided movements. In experiment 2 (n=10), we confirmed this relationship by examining whether the improvement in memory-guided movements induces increases in MEP amplitude. The results of this study indicate that the plastic reorganization of the M1 induced by the learning of a visuomotor skill is associated with the acquisition of memory-guided movements.



Relationship between the changes in M1 excitability after motor learning and arousal state as assessed by short-latency afferent inhibition

May 2017

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34 Reads

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10 Citations

Behavioural Brain Research

To examine the factors that influence the inter-individual differences in the changes in primary motor cortex (M1) excitability seen after motor learning, we investigated the relationship between the amplitude of transcranial magnetic stimulation-induced motor evoked potentials (MEP) and short-latency afferent inhibition (SAI) after motor learning, based on the working hypothesis that SAI can be used to evaluate cortical acetylcholine (ACh) activity. To confirm this working hypothesis, we manipulated the arousal state of the subjects using a vigilance task, the outcomes of which might be correlated with cortical ACh activity, and investigated the effects of arousal state on SAI. As a result, we showed that SAI was significantly affected by arousal state. Consequently, we concluded that the subjects’ arousal state during motor learning tasks is one of factors to influence on inter-individual differences in the changes in M1 excitability seen after motor learning tasks.


P247 Reorganization of modular architectures in the corticospinal neuromuscular system by implicit and explicit learning

March 2017

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10 Reads

Clinical Neurophysiology

Introduction A large number of researches have investigated the mechanisms of implicit and explicit motor sequence learning. The functional changes in motor circuits, which involve the primary motor cortex (M1), are thought to play an important role in memory formation of implicit knowledge. However, it is unclear what functions in the motor circuits contribute to formation of implicit knowledge in the M1. The corticospinal neuromuscular system organizes the modular architectures for generating a variety of movements. Therefore, we hypothesized that performance improvement through implicit learning results from reorganization of the modular architectures. Objectives We used transcranial magnetic stimulation (TMS), data-grove system, and principal component analysis (PCA) to test the hypothesis. Materials and methods Seventeen healthy subjects learned a sequence of serial reaction time task (SRTT) implicitly, and explicitly. Before and after a training session, both TMS-evoked finger joint movements and voluntary finger joint movements during the SRTT were recorded. Results PCA extracted a set of principal components (PCs) from TMS-evoked finger joint movements before (pre-PCs) and after (post-PCs) the training session, respectively. To test an idea that post-PCs contain large amount of information on the learned task, we reconstructed the voluntary movements during SRTT in post-training session by linear combination of a selected subset of the PCs. We found that the quality of the movements reconstructed by the post-PCs was superior to that of the pre-PCs in the implicit condition. By contrast, in the explicit condition, there was no significant difference in the reconstruction quality between the pre-PCs and post-PCs. Conclusion Our results suggest that the implicit knowledge is acquired through learning-specific reorganization of the modular architectures in the corticospinal neuromuscular system. On the other hand, the reorganization of the modular architectures does not relate to acquiring the explicit knowledge.


Different Effects of Implicit and Explicit Motor Sequence Learning on Latency of Motor Evoked Potential Evoked by Transcranial Magnetic Stimulation on the Primary Motor Cortex

January 2017

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466 Reads

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23 Citations

Motor training induces plastic changes in the primary motor cortex (M1). However, it is unclear whether and how the latency of motor-evoked potentials (MEP) and MEP amplitude are affected by implicit and/or explicit motor learning. Here, we investigated the changes in M1 excitability and MEP latency induced by implicit and explicit motor learning. The subjects performed a serial reaction time task (SRTT) with their five fingers. In this task, visual cues were lit up sequentially along with a predetermined order. Through training, the subjects learned the order of sequence implicitly and explicitly. Before and after the SRTT, we recorded MEP at 25 stimulation points around the hot spot for the flexor pollicis brevis (FPB) muscle. Although no changes in MEP amplitude were observed in either session, we found increases in MEP latency and changes in histogram of MEP latency after implicit learning. Our results suggest that reorganization across the motor cortices occurs during the acquisition of implicit knowledge. In contrast, acquisition of explicit knowledge does not appear to induce the reorganization based on the measures we recorded. The fact that the above mentioned increases in MEP latency occurred without any alterations in MEP amplitude suggests that learning has different effects on different physiological signals. In conclusion, our results propose that analyzing a combination of some indices of M1 excitability, such as MEP amplitude and MEP latency, is encouraged in order to understand plasticity across motor cortices.


Changes in the Spinal Neural Circuits are Dependent on the Movement Speed of the Visuomotor Task

December 2015

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77 Reads

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3 Citations

Previous studies have shown that spinal neural circuits are modulated by motor skill training. However, the effects of task movement speed on changes in spinal neural circuits have not been clarified. The aim of this research was to investigate whether spinal neural circuits were affected by task movement speed. Thirty-eight healthy subjects participated in this study. In experiment 1, the effects of task movement speed on the spinal neural circuits were examined. Eighteen subjects performed a visuomotor task involving ankle muscle slow (nine subjects) or fast (nine subjects) movement speed. Another nine subjects performed a non-visuomotor task (controls) in fast movement speed. The motor task training lasted for 20 min. The amounts of D1 inhibition and reciprocal Ia inhibition were measured using H-relfex condition-test paradigm and recorded before, and at 5, 15, and 30 min after the training session. In experiment 2, using transcranial magnetic stimulation (TMS), the effects of corticospinal descending inputs on the presynaptic inhibitory pathway were examined before and after performing either a visuomotor (eight subjects) or a control task (eight subjects). All measurements were taken under resting conditions. The amount of D1 inhibition increased after the visuomotor task irrespective of movement speed (P < 0.01). The amount of reciprocal Ia inhibition increased with fast movement speed conditioning (P < 0.01), but was unchanged by slow movement speed conditioning. These changes lasted up to 15 min in D1 inhibition and 5 min in reciprocal Ia inhibition after the training session. The control task did not induce changes in D1 inhibition and reciprocal Ia inhibition. The TMS conditioned inhibitory effects of presynaptic inhibitory pathways decreased following visuomotor tasks (P < 0.01). The size of test H-reflex was almost the same size throughout experiments. The results suggest that supraspinal descending inputs for controlling joint movement are responsible for changes in the spinal neural circuits, and that task movement speed is one of the critical factors for inducing plastic changes in reciprocal Ia inhibition.


Interactions Among Learning Stage, Retention, and Primary Motor Cortex Excitability in Motor Skill Learning

July 2015

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59 Reads

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30 Citations

Brain Stimulation

Previous studies have shown that primary motor cortex (M1) excitability is modulated by motor skill learning and that the M1 plays a crucial role in motor memory. However, the following questions remain: 1) At what stage do changes in M1 excitability occur? 2) Are learning-induced changes in leg M1 excitability associated with motor memory? Here, we did two experiments to answer these questions. In experiment 1, subjects learned a visuomotor tracking task over two consecutive days. Before and after the task in Day 1, we recorded input-output curves of the motor evoked potentials (I-O curve) produced in the tibialis anterior muscle by transcranial magnetic stimulation. We found that the changes in M1 excitability were affected by learning stage. In addition, the changes in M1 excitability in Day 1 were correlated with the retention. In experiment 2, we recorded I-O curves before learning, after the fast-learning stage, and after learning. We found no changes in M1 excitability immediately after the fast-learning stage. Furthermore, a significant relationship between the length of slow-learning stage and the changes in M1 excitability was detected. Previous studies have suggested that optimal motor commands are repeatedly used during the slow-learning stage. Therefore, present results indicate that changes in M1 excitability occur during the slow-learning stage and that such changes are proportional to motor skill retention because use-dependent plasticity occur by repetitive use of same motor commands during the slow-learning stage. Copyright © 2015 Elsevier Inc. All rights reserved.


Effect of tactile stimulation on primary motor cortex excitability during action observation combined with motor imagery

May 2015

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73 Reads

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9 Citations

Neuroscience Letters

We aimed to investigate the effects of the tactile stimulation to an observer's fingertips at the moment that they saw an object being pinched by another person on the excitability of observer's primary motor cortex (M1) using transcranial magnetic stimulation (TMS). In addition, the above effects were also examined during action observation combined with the motor imagery. Motor evoked potentials (MEP) were evoked from the subjects' right first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. Electrical stimulation (ES) inducing tactile sensation was delivered to the subjects' first and second fingertips at the moment of pinching action performed by another person. Although neither the ES nor action observation alone had significant effects on the MEP amplitude of the FDI or ADM, the FDI MEP amplitude which acts as the prime mover during pinching was reduced when ES and action observation were combined; however, no such changes were seen in the ADM. Conversely, that reduced FDI MEP amplitude was increased during the motor imagery. These results indicated that the M1 excitability during the action observation of pinching action combined with motor imagery could be enhanced by the tactile stimulation delivered to the observer's fingertips at the moment corresponding to the pinching being observed. Copyright © 2015. Published by Elsevier Ireland Ltd.


Citations (58)


... The (lateral) cerebellum was most often targeted at a point either (1) 3 cm lateral (Daskalakis et al. 2004;Hardwick et al. 2014;Jayaram et al. 2011;Kassavetis et al. 2011;Pinto and Chen 2001;Schlerf et al. 2012Schlerf et al. , 2015Spampinato et al. , 2020aTanaka et al. 2021) or (2) 3 cm lateral and 1 cm inferior relative to the inion on the line joining the external auditory meatus (Fernandez et al. 2018b;Hardwick et al. 2014;Panyakaew et al. 2016;Tanaka et al. 2018). The latter target location corresponds to the cerebellar hand representation in lobule V and VIII which has been verified with MRI-based neuronavigation (Hardwick et al. 2014). ...

Reference:

Dual-site TMS as a tool to probe effective interactions within the motor network: a review
Modulation of cerebellar brain inhibition during temporal adaptive learning in a coincident timing task

Experimental Brain Research

... The experimental evidence from human studies suggests that the hand grasp synergies can be decoded from invasive and noninvasive neural recordings [9][10][11]. Transcranial magnetic stimulation (TMS) research has revealed that Sensors 2022, 22, 5349 2 of 16 rather than the development of new patterns, the evoked finger movements were reorganized with pre-existing primitive patterns represented in the corticospinal system [12]. The study on current source (CS) signals derived from electroencephalography (EEG) has shown that the primary motor cortex is the primary area for controlling finger movement, and characteristic differences between various finger movements were reflected in CS synergies patterns [13]. ...

Reorganization of finger covariation patterns represented in the corticospinal system by learning of a novel movement irrelevant to common daily movements
  • Citing Article
  • October 2019

Journal of Neurophysiology

... The direct current component was subtracted from the EMG data, and the peak-to-peak amplitudes of the motor-evoked potentials (MEPs) within this 0.02-0.1 s window from TMS onset were evaluated and averaged offline. Furthermore, the common peroneal nerve was stimulated with supramaximal stimuli (1-ms rectangular pulse) using a constant voltage stimulator (SS-104; Nihon Kohden, Tokyo, Japan) controlled by a pulse-regulating system (SEN7202; Nihon Kohden) to obtain the maximum M-wave (M max ) in the PL muscle and to normalize the MEPs (Hirano et al. 2018;Suzuki et al. 2022;Tazoe et al. 2007). ...

Acquisition of motor memory determines the inter-individual variability of learning-induced plasticity in the primary motor cortex
  • Citing Article
  • July 2018

Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology

... The phenomenon that movements of body parts induce concurrent movement of other body parts has been called enslaving (Zatsiorsky et al. 1998). In the case of chording, some chords may be harder to produce than others because of biomechanical and/or neural interactions between the neighboring fingers of one hand (Hirano et al. 2018;Lawrence and Hopkins 1976;Zatsiorsky et al. 2000). Those fingers may be enslaved biomechanically by the anatomical connection of tendons across fingers, and neurally by the synchronized activity of motor units in different compartments of the multi-tendoned flexors and extensor of the digits (Leijnse et al. 1993) and by the overlapping representations of individual fingers in the motor cortex (Furuya et al. 2014). ...

The acquisition of skilled finger movements is accompanied by the reorganization of the corticospinal system
  • Citing Article
  • November 2017

Journal of Neurophysiology

... SAI is assessed within the paired associative stimulation paradigm as the percent decrease of the single-pulse transcranial magnetic stimulation (TMS)-induced motor evoked potential (MEP) amplitude when TMS is preceded by a single-pulse electrical median nerve stimulation at the wrist 20-30 ms prior [25]. SAI is known to be mediated at the level of the motor cortex [25] via suppression of I2 and I3 waves [26] through cholinergic circuits [27], which is necessary for experience-dependent plasticity [28,29]. Thus, SAI represents responsiveness of the primary motor cortex (M1) to sensory input from the primary sensory cortex (S1) [30]. ...

Relationship between the changes in M1 excitability after motor learning and arousal state as assessed by short-latency afferent inhibition
  • Citing Article
  • May 2017

Behavioural Brain Research

... By extension, activation of premotor cortex by FFB signals deemed to be self-owned (i.e. internally generated/ interoceptive) may nevertheless predispose to re exive movement and thus recruit motor inhibitory pathways, including those connecting contralateral premotor and ipsilateral motor cortices [49][50][51]. ...

Contribution of ipsilateral primary motor cortex activity to the execution of voluntary movements in humans: A review of recent studies
  • Citing Article
  • July 2014

The Journal of Physical Fitness and Sports Medicine

... It is widely believed that the two phenomena have a common physiological substrate, such as a modulation of synaptic efficacy involved in motor skill learning [8][9][10][11][12][13][14][15][16][17][18] . While there is ample evidence that various interventions with electric and magnetic stimulation can modulate plasticity in M1 19 , human behavioral studies have not shown a consistent effect of motor skill learning on MEPs 18,[20][21][22][23][24][25][26][27][28][29] . Studies on the effects of tDCS on motor skill learning have given mixed results [30][31][32][33] , and there is skepticism around reproducibility of MEP effects of tDCS 34,35 . ...

Different Effects of Implicit and Explicit Motor Sequence Learning on Latency of Motor Evoked Potential Evoked by Transcranial Magnetic Stimulation on the Primary Motor Cortex

... Six studies (Bakker et al. 2021;Hirano et al. 2015Hirano et al. , 2018Kubota et al. 2015;Tatemoto et al. 2019) were assessed, with strong evidence that a single session of lower limb motor skill training improved motor performance. The magnitudes of the intervention effect were moderate to large, with an effect size ranging between 0.71 and 3.00 (Fig. 3b). ...

Changes in the Spinal Neural Circuits are Dependent on the Movement Speed of the Visuomotor Task

... Our results show that early-phase learning is marked by activation in the PFC and PMC, while this activation decreases in the later phase. Neurologically, this indicates a shift from early motor decision-making and high attention demands to the automatic execution of movement sequences with reduced attention in the late phase, which aligns with the views of Ohuchida [21] and Hirano [37]. During the early learning phase, cognitive and action sequence regulation are required, whereas, in the late phase, effective cognitive and action sequence arrangements have already formed, resulting in higher brain functional efficiency and reduced demands. ...

Interactions Among Learning Stage, Retention, and Primary Motor Cortex Excitability in Motor Skill Learning

Brain Stimulation

... Apart from high immersion of VR-based paradigms, the multisensory stimulation is also an effective approach to improve visual guided MI. Previous research found that visuo-tactile stimulation could significantly enhance visual guided MI in healthy participants [26][27][28], comparing to the condition without synchronous visuo-tactile stimulation [29]. It is worth noting that the multisensory stimulation would form or improve SOO over target limb (or body), which is carried out by several illusion paradigms, including rubber hand illusion (RHI) [30], virtual hand illusion (VHI) [31], and full body illusion [32]. ...

Effect of tactile stimulation on primary motor cortex excitability during action observation combined with motor imagery
  • Citing Article
  • May 2015

Neuroscience Letters