学位論文の要旨(和文) 一致タイミング課題の時間的適応学習における小脳の役割
論 文 題 目 ( 英 文 ) The role of the cerebellum during temporal adaptive
learning in a coincident timing task
広島大学大学院総合科学研究科
総合科学専攻学生番号 D184286
氏

名 田中 新也

論文の要旨
Chapter 1: General Introduction
Time and space are fundamental factors in our daily lives, or sports scenes.
To show sports skills, spatio-temporal control and perception is essential. For
example, fastball sports like baseball, table tennis, and tennis demand us to beable to treat hand tools, such as a bat or a racket, as freely as their own body, andprecise spatio-temporal control under severe time constraints to hit high-speed or
braking ball. How does our brain process these external information and enable
us to move smoothly?
The cerebellum has been shown to play an important role in error-basedlearning, e.g., it contributed to spatial adaptive learning in a visuomotor reachingtask (Schlerf et al. 2012; Spampinato et al. 2017). In these studies, changes incerebellar–M1 connectivity have been detected after motor learning in humans
using paired-pulse TMS. In these studies, the cerebellum was stimulated bydelivering a conditioning stimulus (CS) to a location 3 cm lateral to the inion, on
the line joining the inion and the external auditory meatus (Ugawa et al. 1995;
Pinto and Chen 2001). Stimulating this site leads to the activation of Purkinje cells(PCs), probably in the cerebellar lobules V, VII and VIII (Hardwick et al. 2014;
Spampinato and Celnik 2020). Compared with MEPs elicited by the delivery of aTS alone, those seen after the delivery of a CS to the cerebellum followed by thedelivery of a TS to the contralateral M1 were suppressed. This suppression, i.e.,cerebellar brain inhibition (CBI), has been suggested to reflect the activation ofcerebellar PCs (Celnik 2015; Fernandez et al. 2018). The CBI technique is usefulfor assessing how cerebellar–M1 connectivity is affected by spatial adaptive
learning (Schlerf et al. 2012), and the changes in CBI found following visuomotor
adaptation were found to occur in a somatotopic-specific manner (Spampinato etal. 2017).

In general, timing is functionally classified into four dimensions, i.e., explicit
vs. implicit, and motor vs. perception (Coull and Nobre 2008). The interceptiontasks used in previous studies (Bares et al. 2007, 2010, 2011; Markova et al. 2020)
and the Coincident timing task (CoIT task) used in this thesis are considered to be
implicit motor timing tasks. Previous studies showed that the CoIT task has been
useful to explore the function of cerebellum, involving patients with cerebellar
damage or baseball players (Bares et al. 2007, 2010, 2011; Marcova et al. 2020).
They also indicated that this task required for better performance both theaccurate perception of target information (Merchant et al. 2003) and a precise
predictive motor response (Caljouw et al. 2004). These cognitive and motor
responses are important for movement skills seen in everyday lives or sports, suchas catching, riding a motorbike, shooting, or playing fastball sports (Causer et al.
2011; Davoodi et al. 2012; Iacoboni 2001). However, so far, no studies haveinvestigated the physiological mechanism of the cerebellum in temporal adaptive
learning. In this thesis, I carried out two experiments using CoIT task, andtranscranial magnetic stimulation (TMS) to evaluate the relationship the functionof cerebellum and CoIT performance.
Chapter 2: Modulation of cerebellar brain inhibition during temporal adaptive
learning in a coincident timing task
The aim of this chapter was to investigate the role of the cerebellum in
temporal adaptive learning. We hypothesized that the cerebellum also plays animportant role in temporal adaptive learning, as was reported for various otherkinds of adaptation in previous studies (Donchin et al. 2012; Izawa et al. 2012;
Morton and Bastian 2006; Prsa and Their 2011; Rabe et al. 2009; Schlerf et al.
2012; Schlerf et al. 2013; Spampinato et al. 2017). To examine this hypothesis, weused the paired-pulse TMS paradigm to assess the changes in cerebellar–M1
connectivity that occur before, during, and after temporal adaptive learning.
I programmed a CoIT task, i.e., a baseball-like hitting task involving a movingball presented on a computer monitor. The subjects were required to change the timingof 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 onlyoccurred during and after the temporal adaptive learning, regardless of the directionof the temporal perturbations. In addition, the changes in CBI were correlated withthe 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.

Chapter 3: Role of the cerebellum for adapting the change of target velocity in acoincident timing task
The tasks that rely on implicit motor timing have showed central role for thecerebellum (Bares et al. 2019). Interception task, considered to be similar to CoIT
task used in this thesis, has been used in previous studies (Bares et al. 2007, 2010,2011). They demonstrated that cerebellum may have internal models of predictive
motor behavior. If the models exist in the cerebellum, training involving predictionof future state of the circumstances would improve the CoIT skill. Another study(Markova et al. 2020) showed baseball players showed significantly higherquantitative, not qualitative, performance than control subjects. They pointed outthat the result of their experiment reflected the possibility that same cerebellar
mechanism as non-athletes selectively refined due to athletes’ rigorous training
over years. Based on these findings, I modified CoIT task to investigate basic
timing skill in more realistic conditions, i.e. the subjects, not trained, wererequired to adapt the changes of velocity of a moving target. Previous fMRI
research indicated that the high activation in the cerebellum associated withincreasing speed occurred (Filip et al. 2016). Using same paired-pulse TMS
technique in chapter 2, I investigated whether the changes of the cerebellar-M1
connectivity with adaptive learning occurred under the condition abovementioned.
The reduction of cerebellar-M1 connectivity occurred despite no improvement ofthe CoIT performance. In addition, Similar changes were observed in a random
condition. There were some differences from previous researches, but these resultsindicated that the cerebellum played an important role for integrating incoming visual
information with timely adjusted motor output in conditions, similar to the actual
sports scenes.

Chapter 4: General discussion and conclusion
Timing control, of course, doesn’t only depend on the cerebellum. The cerebellum
is a part of timing network (basal ganglia, supplementary motor area, and the rightinferior frontal gyrus, etc.). However, many previous researches have indicated thatthe cerebellum has an essential role for timing control (Raghavan et al. 2016). In thisresearch, it demonstrated that cerebellum plays an essential role for integrating visual
information with timely motor output, and even in an experimental environment thatis as close to actual sports scenes as possible, it is possible to investigate the neuralmechanism of CoIT task using TMS paradigm. I hope this research will be an
important basis for future researches.