TOPポスター
 
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C. 感覚系と運動系
C. Sensory and Motor Systems
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-298
重力方向の外乱が到達把持運動に及ぼす短期・長期的な影響
Short- and long-term effects of gravitational perturbations on the trajectory height of reach-to-grasp movements.

*安藤 瑠称(1)、板口 典弘(2)
1. 静岡大学、2. 慶應義塾大学
*Luna Ando(1), Yoshihiro Itaguchi(2)
1. Shizuoka University, 2. Keio University

Keyword: grasping, load, adaptation, perturbation

Reach-to-grasp movements against gravity are often experienced in our everyday activities. Although most of previous studies have investigated adaptation processes to horizontal perturbations, the effects of gravitational perturbations on kinematics of reach-to-grasp movements are still unclear. This topic is of great importance because gravitational effects on reach-to-grasp movements are perhaps overlearned, which clearly differs from the horizontal perturbation that participants have never experienced. To address this issue, we investigated the adaptation processes to gravitational perturbation in reach-to-grasp kinematics, simply by adding a weight to participants’ forearm. Based on the results of Experiment 1 using a short-term (10 trials) adaptation paradigm, we argued that participants optimize their movement trajectories by raising the height to reduce disturbances due to signal-dependent noises caused by the forearm weight load. To verify this hypothesis, we then used a longer-term adaptation paradigm to induce the increase of signal-dependent noises caused by muscle fatigue in addition to the weight load itself. In the Experiment 2, participants performed 400 trials of reach-to-grasp movements on a desk each for 0 g, 200 g, and 400 g weight conditions. Under 200 and 400 g weight conditions, they performed the movement with 200 or 400 g weight in the middle 300 trials. We predicted that trajectory height would increase with 200 and 400 g weight. In addition, due to the increase in signal-dependent noises with fatigue, we also predicted that the height would continue to increase only in 400 g weight condition. The results showed that trajectory height more increased in the trials with 200 and 400 g weights than the baseline. Furthermore, the trajectory height continued to increase only in the 400 g condition. The SD of max height (larger noises) in the last 50 trials with a weight was negatively correlated with the participants' BMI (which may be related to muscle endurance) and positively correlated with the regression slope of max height in the 300 trials with a weight. In addition, a computational simulation replicated the behavioral results that the movement trajectories increased as a function of the amplitude of signal-dependent noises regardless of their causes (weight loads and muscle fatigue). These results support our hypothesis and suggest that even overlearned movement would be changed adaptively to minimize the effects of noises.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-299
An anatomical investigation on the vestibulospinal projections to the tail motoneurons in mice
*Salvatore Andrea Lacava(1), Marylka Yoe Uusisaari(1)
1. OIST

Keyword: Spinal cord, Vestibular , Balance, Tail Motoneurons

Studies in mice have suggested that the tail is important for balance (Buck et al, 1925). However, we know very little on the neuronal control of the mouse tail during balancing. Animals with a spinal cord transection cannot produce corrective movement in response to a balance perturbation (Chvatal et al., 2013), indicating a critical role for descending supraspinal projections. The lateral vestibular nuclei (LVN) give rise to descending spinal pathway (the lateral vestibulospinal tract, LVST) that play a key role in the maintenance of balance. LVST neurons are also known to project to motoneurons from the cervical to the sacral spinal cord. Because of their role in balancing reflexes and their known anatomical projections, we hypothesized that LVST neurons project directly to tail motoneurons in the spinal cord. Here we aimed to 1) locate the tail motoneuron pool within the spinal cord, and 2) characterize the vestibulospinal input to the tail motoneurons. To locate tail motoneurons within the spinal cord we injected a retrograde virus expressing a green fluorophore (AAV2-retro.CAG.eGFP) or with cholera toxin b-subunit (CTB), a more efficient anatomical tracer for motoneurons , in the lateral muscle of the tail to reveal the tail-controlling motoneurons in the sacro-coccygeal spinal cord. To test whether LVST projected to the these tail motoneurons, a double-virus approach was used. AAV virus expressing a red fluorophore (AAV9.hsyn.tdTomato) was injected in the LVN, and AAVrg.CAG.eGFP in the tail as previously. With this method we could confirm presence of axonal terminals located on the tail motoneurons . Surprisingly, we found the LVN-originating synaptic boutons not only on the dendrites but also on the soma of the tail motoneurons, suggesting that LVST input should have a strong excitatory effect on the tail motoneurons. These results pave the way to future functional studies investigating the role of the vestibulospinal input to the motor control of the tail in the context of balance.
Bibliography
C. W. Buck, N. Tolman, and W. Tolman, The Tail as a Balancing Organ in Mice, American Society of Mammalogists 6 (1925).
Chvatal, S.A., Macpherson, J.M., Torres-Oviedo, G., and Ting, L.H. (2013). Absence of postural muscle synergies for balance after spinal cord transec- tion. J. Neurophysiol. 110, 1301–1310.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-300
閉口筋および開口筋運動ニューロンへの興奮性・抑制性シナプス入力の生後発達機構
Distinct developmental features of excitatory and inhibitory input to motoneurons innervating jaw-closing and jaw-opening muscles

*中村 史朗(1)、野口 毅(1,2)、梶原 里紗(1,3)、中山 希世美(1)、望月 文子(1)、壇辻 昌典(1)、Sarkar Avijite(1)、井上 富雄(1)
1. 昭和大学歯学部口腔生理学講座、2. 昭和大学歯学部スペシャルニーズ口腔医学講座口腔リハビリテーション医学部門、3. 昭和大学歯学部全身管理歯科学講座歯科麻酔科学部門
*Shiro Nakamura(1), Tsuyoshi Noguchi(1,2), Risa Kajiwara(1,3), Kiyomi Nakayama(1), Ayako Mochizuki(1), Masanori Dantsuji(1), Avijite Kumer Sarkar(1), Tomio Inoue(1)
1. Dept Oral Physiol, Showa Univ Sch Dent, Tokyo, Japan, 2. Dept Special Needs Dent, Div Oral Rehab Med, Showa Univ Sch Dent, Tokyo, Japan, 3. Dept Perioperative Med, Div Anesthesiol, Showa Univ Sch Dent, Tokyo, Japan

Keyword: feeding behavior, postnatal development, excitatory postsynaptic currents, inhibitory postsynaptic currents

Motoneurons that innervate the jaw-closing and -opening muscles receive a number of excitatory and inhibitory synaptic inputs from glutamatergic, GABAergic, and glycinergic premotor neurons, which have an important role in orofacial functions including mastication, suckling, and swallowing. The input properties of jaw-closing and -opening motoneurons change along with postnatal development, during which feeding behavior shifts from suckling to chewing. However, details related to the developmental patterns of synaptic input to these neurons remain to be elucidated. This study was conducted to examine the developmental characteristics of excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) evoked in rat masseter (jaw-closing) and digastric (jaw-opening) motoneurons during three postnatal time windows; postnatal day (P)2–5, 9–12, and 14–17, which cover the suckling period before and after tooth eruption, and immature chewing period, respectively. Among the three time periods, the properties of miniature EPSCs (mEPSCs) mediated by non-NMDA receptors remained unchanged in masseter motoneurons, whereas NMDA receptor-mediated mEPSCs were predominantly evoked in masseter motoneurons during P2–5, as compared to P9–12 and P14–17. Furthermore, the proportion of stimulation-evoked NMDA/non-NMDA EPSCs in masseter motoneurons was also remarkably higher in P2–5 than in P9–12 and P14–17. In contrast, digastric motoneurons showed unaltered features in non-NMDA and NMDA EPSCs during the examined time periods. GABAergic mIPSCs were predominant in masseter motoneurons during P2–5 as compared to P9–12 and P14–17, whereas those in digastric motoneurons remained unchanged throughout the examined periods. Also, glycinergic mIPSCs in both masseter and digastric motoneurons showed increased amplitude and frequency in association with age, whereas frequency was markedly higher in masseter motoneurons than digastric motoneurons during each of the postnatal periods examined. These distinct developmental trajectories of glutamatergic, GABAergic, and glycinergic input characteristics in jaw-closing and -opening motoneurons may be responsible for maturation of neural circuits that regulate the respective masticatory muscle activities as they change during development of feeding behavior.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-301
人参養栄湯と麻痺側集中使用の併用が内包出血後の運動機能と骨格筋に与える影響
Changes in fast twitch muscle are related to the functional recover by combination treatment of Ninjin’yoeito and rehabilitative training after internal capsule hemorrhage in rats

*田尻 直輝(1)、上野 新也(1)、清水 健史(1)、西村 柚(1)、羽田 栄輔(2)、水野 景太(2)、飛田 秀樹(1)
1. 名古屋市立大学 、2. 株式会社ツムラ
*Naoki Tajiri(1), Shinya Ueno(1), Takeshi Shimizu(1), Yu Nishimura(1), Eisuke Haneda(2), Keita Mizuno(2), Hideki Hida(1)
1. Nagoya City University, 2. Tsumura Kampo Research Laboratories, Tsumura and Co

Keyword: Intracerebral hemorrhage, Kampo medicines, Rehabilitation, Behavioral recovery

Rehabilitative training of forced limb use (FLU) after internal capsule hemorrhage (ICH) is due to a causal relationship between the cortico-rubral tract and the functional recovery. As the interests of Kampo medicine on rehabilitative training are recently increasing, Ninjin’yoeito (NYT) that acts on the muscle (sarcopenia) and the brain (cognitive dysfunction) was investigated in the effect on rehabilitation. We first investigate whether the combination of FLU and NYT can promote motor function after ICH, and then try to know the mechanism of NYT in rehabilitative training. ICH model was made by the injection of Type IV collagenase (15 units/ml, 1.4µl) into the left internal capsule of male rats. FLU was given from 1 day after the lesion (D1) for 7 days with the oral administration of 1% NYT until D56. Motor deficit score and horizontal ladder test were used for behavioral assessment at D28. We revealed that FLU + NYT group showed significantly better functional recovery in both tests, showing that the effect of NYT administration is additive to the effect of rehabilitative training FLU. To know the mechanism in the recovery by FLU + NYT, the changes in the muscle was investigated: gastrocnemius and soleus was stained with antibodies for MHC I (a marker of slow twitch), MHC IIb (a marker of fast twitch) and MHC IIa (a marker of mixed type). We revealed that ICH caused in significant decrease of all types of muscle in the ipsilateral side. Interestingly, fast twitch muscle (type 2 fiber) was preserved on FLU + NYT group in the gastrocnemius. These data suggest that combination therapy of FLU + NYT has a potency to improve deteriorated motor function in the rat ICH model, and the alteration of expression pattern of fast twitch muscle by FLU + NYT, at least in part, could be related to the improvement of the motor function in ICH.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-302
脊髄灰白質内を吻尾側方向に髄節間を越えて投射する体性感覚野由来の皮質脊髄線維
Rostro-caudal and intersegmental projections of the corticospinal fibers from the somatosensory cortex through the spinal gray matter

*村部 直之(1)、岩澤 凜(1)、林 俊宏(1)、桜井 正樹(1)
1. 帝京大学医学部生理
*Naoyuki Murabe(1), Rin Iwasawa(1), Toshihiro Hayashi(1), Masaki Sakurai(1)
1. Dept Physiol Teikyo Univ Sch Med, Tokyo, Japan

Keyword: Projections, Intersectional labeling, Arborization, AAV2-retro

Corticospinal (CS) neurons directly connect the cerebral cortices to the spinal cord and are distributed in not only the motor but also the somatosensory areas. When adeno-associated virus (AAV) encoding fluorescent proteins was injected into these areas, labeled CS fibers from the primary sensory (CS-S fibers) and the primary motor areas (CS-M fibers) projected to the dorsal and ventral horns of the cervical spinal cord, respectively. Recently, we found that CS-S and CS-M fibers in the gray matter showed strikingly different orientations: the CS-S fibers dominantly runs parallel to the rostro-caudal axis through the lamina III of the spinal cord, while CS-M fibers runs parallel to the transverse plane. In the present study, we investigated longitudinal axonal arbors of the CS-S fibers in detail. To sparsely and retrogradely label the CS-S fibers innervating the cervical spinal cord, we injected AAV encoding Cre with a low titer into the seventh cervical spinal cord. Thereafter, AAV bearing a Cre reporter was injected into a lateral part of the somatosensory cortex to label exclusively CS-S neurons. Then, we traced individual CS-S fibers in the cervical gray matter. Most of the CS-S fibers initially entered the gray matter to perpendicular to the rostro-caudal axis, reaching the dorsal horn. Then, the fibers made a sharp bend almost at right angles, further extending along the rostro-caudal axis. Some fibers went rostrally, some caudally, and some others bifurcated toward both directions. A considerable number of the fibers elongated beyond the segmental border. Distal part of fibers showed multiple branches with dense varicosities. Varicosities were also found along proximal part of the fibers running rostro-caudally with less density, suggesting the presence of en-passant type of synapses aligned longitudinally. These results indicate that mode of innervation of CS-S neurons exhibit a marked contrast to that of CS-M neurons.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-303
脊髄損傷は大脳皮質運動野における神経活動を変化させる
Spinal cord injury induces dynamic neural activity changes in the motor cortex

*山内 一平(1)、加藤 大輔(1)、大石 遼太郎(1)、中島 宏彰(1)、今釜 史郎(1)、和氣 弘明(1)
1. 名古屋大学大学院医学系研究科
*Ippei Yamauchi(1), Daisuke Kato(1), Ryotaro Ooishi(1), Hiroaki Nakashima(1), Shiro Imagama(1), Hiroaki Wake(1)
1. Grad Sch Med, Univ of Nagoya, Aichi, Japan

Keyword: Spinal Cord Injury, neural activity, two photon imaging, motor cortex

Spinal cord injury (SCI) damages the sensorimotor pathway, resulting in loss of motor, sensory and autonomic function. Several studies have shown that after SCI, free radical damage, excitotoxicity, Fas-tumor necrosis factor-α cause neural death or apoptosis occurred in spinal cord. In addition, it is known that the deafferentation leads not only to changes in electrophysiological properties of spinal cord neurons, but also to the disruption of functional connectivity between multi cortical brain regions. However, it remains unclear how the activity patterns of multi cortical neurons change during SCI remains unclear. To address this questions, we assessed neural activity and motor function in primary motor cortex (M1) and see correlation with (modified Basso, Beattie, and Bresnahan (BBB) locomotor scale and Basso mouse scale (BMS) locomotor scale) before and after SCI. We first developed a mouse model of SCI in which T10 of the spinal cord was injured by 70 kdyn with the Infinite Horizon impactor to evaluate its behavior. All SCI mice became paralyzed, whereas the sham-operated mice did not show any paralysis. The locomotor activity in SCI mice was almost unrecoverable after SCI. We further analyzed the neuronal activity in multi cortical brain regions by c-fos immuno-staining to quantify brain regions that are activated after SCI. We found that the protein expression level of c-fos was increased in motor associated cortex at 1 d after SCI, indicating that SCI dynamically alters neural activity in the brain. Furthermore, we visualized the neural activity in the left L2/3 motor cortex of SCI model mouse over time (the day before and 1d, 2d, 4d, 7d, 14d, 21d after the SCI) using in vivo two photon microscope. We found a transient decrease in synchronization of neural activity on the first day after SCI, and no significant change in power of Ca2+ transient over time. These results suggested that SCI may induce a transient increase in activity of inhibitory neurons. Now we are trying to identify the changes in neuronal activity caused by SCI in a cell type-specific manner, and examine whether manipulating the transient decrease in synchronized neural activity using Designer Receptors Exclusively Activated by Designer Drugs or GABA-A antagonist will change the pathological time course of SCI.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-304
リゾホスホリパーゼPNPLA6およびPNPLA7は中枢神経系において運動ニューロンの維持と恒常性に必要である
The lysophospholipases PNPLA6 and PNPLA7 are required for the maintenance and homeostasis of motor neurons in the CNS

*川口 舞(1,2)、笠原 浩二(1)、村上 誠(2)、平林 哲也(1)
1. 東京都医学総合研究所細胞膜研究室、2. 東京大学大学院医学系研究科健康環境医工学部門
*Mai Kawaguchi(1,2), Kohji Kasahara(1), Makoto Murakami(2), Tetsuya Hirabayashi(1)
1. Lab of Biomembrane, Tokyo Metro Inst of Med Sci, Tokyo, Japan, 2. Lab of Microenvironmental Metabolic Health Sciences, Grad Sch Med, Univ of Tokyo, Tokyo, Japan

Keyword: NEURODEGENERATION, MUSCLE ATROPHY, PHOSPHOLIPID, LYSOPHOSPHOLIPASE

Dysregulated phospholipid metabolism often causes neurodegenerative diseases with a diverse array of pathologic consequences. Autosomal recessive mutations in several genes encoding enzymes with phospholipase A2 (PLA2) and/or lysophospholipase activities in the PNPLA (patatin-like phospholipase domain containing)/iPLA2 (Ca2+-independent PLA2) family have been associated with various types of inherited neuronal diseases as follows: PNPLA6 with hereditary spastic paraplegia (SPG39), cerebellar ataxia, and pigmentary degeneration of the retina; PNPLA9/iPLA2beta/PLA2G6 with infantile neuroaxonal dystrophy (INAD), neurodegeneration with brain iron accumulation (NBIA) and young-onset dystonia–parkinsonism (PARK14); and PNPLA8/iPLA2gamma with mitochondrial myopathy with lactic acidosis. Among these enzymes, PNPLA6 and its paralog PNPLA7 are structurally most related, exhibit strong lysophosholipase activity, and are abundantly expressed in the central nervous system (CNS). As both enzymes can be functionally redundant and global Pnpla6-deficient mice show embryonic lethality, we generated and analyzed CNS-specific Pnpla6; Pnpla7 double knockout mice (6/7 dcKO) carrying the Nestin-Cre transgene to elucidate the physiological significance and roles of PNPLA6 and PNPLA7 in the CNS. These mice appeared normal until 2 weeks after birth, but subsequently showed more severe phenotypes than single mutant mice lacking each of these genes. The characteristic phenotypes in 6/7 dcKO included growth failure, short life span, muscle weakness and atrophy, and broad neurodegeneration with gliosis and motor neuron loss. The neuromuscular junction (NMJ) in the quadriceps of 6/7 dcKO mice exhibited the age-related detachment of nerve terminals, as revealed by immunohistochemistry. These results indicate that the lysophospholipases PNPLA6 and PNPLA7 have a critical role in the maintenance and homeostasis of motor neurons and possibly other neurons in the CNS.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-305
後根神経節および脊髄におけるセレべリンファミリーの局在
Localization of Cerebellin family proteins in dorsal root ganglion and spinal cord

*高杉 聡(1)、松田 恵子(1)、三浦 絵里子(1)、柚崎 通介(1)
1. 慶應義塾大学医学部医学研究科
*So Takasugi(1), Keiko Matsuda(1), Eriko Miura(1), Michisuke Yuzaki(1)
1. Keio University, School of Medicine

Keyword: synaptic organizer, dorasal root ganglion, spinal cord, somatosensory system

Cbln1 is a unique bidirectional synaptic organizer that simultaneously binds pre-and post-synaptic receptors to regulate synapse function. There are four members in Cbln families (Cbln1-4), which are all secreted glycoproteins. Cbln1 exists as a hexamer, a dimer of globular domains linked by the cysteine-rich regions (CRR) at the N-terminus. Cbln1 simultaneously binds to presynaptic neurexin (Nrx) via CRR and “orphan glutamate receptor” GluD2 on Purkinje cells via globular domain. This Nxn-Cbln1-GluD2 triad induces the differentiation of both pre-and post-synaptic sites. Cbln1 also binds to GluD1, the most related protein to GluD2, promoting synapse formation. Cbln2 and Cbln4 are widely expressed in whole brain regions. Cbln2 binds to GluD1, GluD2, and Nrx, and it is also involved in synaptic differentiation. In contrast, Cbln4 possesses a weaker binding ability to GluD1, GluD2, and Nrx, which instead binds to the Netrin-1 receptor, DCC (deleted in Colon Cancer).
Interestingly, Cbln1, Cbln2, and Cbln4 mRNAs are expressed in the dorsal root ganglion (DRG) and distinct populations of neurons in the spinal cord. However, whether and how Cbln proteins are involved in the integration of somatosensory information in the spinal cord and the DRG has remained largely unclear. As a first step to address this question, we investigated the localization of Cbln family proteins in the DRG and the spinal cord. To detect endogenous Cbln proteins in a highly sensitive and specific manner, we generated knock-in mice in which a hemagglutinin (HA) epitope was inserted in the Cbln genes. We would like to share our preliminary results and discuss the functional roles of Cbln proteins in neuronal circuits of the spinal cord.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-306
様々な種類の予測誤差により引き起こされる行動適応の神経機構を調べるための行動課題の確立
Establishment of a behavioral task to study neural mechanisms of various types of prediction error driven behavioral adaptations

*村上 誠祥(1)、石丸 知輝(1)、喜多村 和郎(1)
1. 山梨大学医学域
*Masayoshi Murakami(1), Tomoki Ishimaru(1), Kazuo Kitamura(1)
1. Div Med, Univ of Yamanashi, Yamanashi, Japan

Keyword: cerebellum, behavioral adaptation, prediction error, two-photon imaging

According to Marr-Albus-Ito theory, climbing fiber inputs to the cerebellum serve as a teaching signal that induces synaptic plasticity in the cerebellum and allows an organism to adapt to a new sensorimotor context. In line with this theory, climbing fiber inputs are activated by a prediction error, a mismatch between predicted and actual outcomes of our behavior. There are different types of prediction errors, such as prediction errors for spatial and temporal components of sensory inputs, and reward prediction errors. But how these different types of errors are represented in a population of climbing fibers is not known. Especially, we do not know whether and how these different types of errors map onto the known anatomical organization of climbing fiber inputs to the cerebellar cortex.

To address this question, we developed a behavioral task in which head-fixed mice experienced different types of prediction errors, including spatial and temporal sensory prediction errors and reward prediction errors.

In this task, a tone was played at the beginning of a trial. After a 0.5 second delay from the onset of the tone, a water spout started to move and was presented in front of the mouse. If licking behavior was detected within a response window (1.0 second from the end of the delay), a water reward was delivered from the spout.

Once mice learned to perform this standard task, we introduced various types of non-standard trials to evoke sensory prediction errors or reward prediction errors. The position or timing of spout presentation was changed to evoke spatial or temporal sensory prediction errors, respectively. To evoke reward prediction errors, a reward was omitted. These different types of non-standard trials were presented in a block-wise manner interleaved with blocks of standard trials. Preliminary results showed that mice quickly and adaptively changed their anticipatory licking behavior in response to these various types of prediction errors.

We are currently investigating how climbing fiber inputs to the cerebellar cortex represent different types of prediction errors, as well as sensory, motor and cognitive variables, using two-photon calcium imaging of cerebellar Purkinje cells from mice performing this task.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-307
Modulation of Dendritic Voltage Signaling in Purkinje Neurons by Inhibitory Inputs in Awake Mice
*Soumen Jana(1), Christopher Roome(1), Bernd Kuhn(1)
1. Optical Neuroimaging Unit, OIST, Okinawa, Japan

Keyword: Dendritic Integration, Pre and Post-Synaptic Recording , Voltage Imaging , Purkinje Neuron

Understanding dendritic integration in relation to its excitatory and inhibitory inputs is critical to deciphering neuronal data processing, which is fundamental to understanding how the brain works. The cerebellar Purkinje neuron (PN) receives sensory-motor data from a single excitatory climbing fiber (CF), thousands of excitatory parallel fibers (PFs), and inhibitory molecular layer interneurons (MLIs). All these inputs are integrated at the PN dendrite, then passed on to soma to generate output at the axon hillock. This study aims to understand the dendritic integration of air puff-induced sensory-motor inputs to PNs in awake mice, emphasizing the inhibitory input of MLIs. We simultaneously imaged calcium in presynaptic MLI axons and voltage in the corresponding postsynaptic PN dendrite with 2P microscopy at 1kHz frame rate. At rest, the MLI calcium activity is constant while the dendritic voltage shows complex spikes and fluctuations of baseline membrane potential due to excitatory inputs as described before (Roome and Kuhn 2018). The administration of the GABAA receptor antagonist SR 95531 increases MLI calcium responses, while the GABAB receptor antagonist CGP 35348 reduces MLI calcium responses and PN hyperpolarizing responses. Dendritic hyperpolarization in PNs coincides with MLI calcium signals. Additionally, we detect spatiotemporal maps of excitatory and inhibitory inputs in PN dendrites, their local integration upon sensory stimulation, and alteration of integration map upon drug applications in the awake animal. We find that the dendrites show different spatiotemporal patterns of responses composed of excitatory and inhibitory inputs upon sensory stimulation. Interestingly, the magnitude and type of dendritic voltage signal varies spatially: while some parts of the dendrites get inhibited, others get excited, and this balance is altered with the dendritic depth. Summarizing, this study delivers insights into local circuit dynamics, including dendritic integration in awake, behaving animals on a millisecond and micrometer scale. It provides crucial insights to close the gap between our knowledge of synaptic transmission in vitro and the study of population activity in vivo.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-308
The diverse effect of cerebellar nuclei input on inferior olive neurons
*Guo Da(1)、Uusisaari Marylka(1)
*Da Guo(1), Marylka Yoe Uusisaari(1)
1. Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan

Keyword: inferior olive, cerebellar nuclei, calcium imaging, in vivo

Inferior olive (IO) is a nucleus in the ventral area of brainstem medulla. IO neurons receive input from cerebellar nuclei (CN) and project to cerebellar cortex Purkinje neurons (PN). Together, these three brain regions form the olivo-cerebellar system crucial for motor function. Damage to this system causes movement disorders, such as decomposition of movement, tremor, deficits in motor learning, etc. Previous investigations led to various hypotheses for the mechanism of the olivo-cerebellar system. The activity of IO neurons is in the center of most of them. However, our understanding of the role of IO in olivo-cerebellar system is far from complete. For example, there is little investigation on the nucleo-olivary (NO) pathway, which is from CN to IO, due to the difficulty in the direct recording of IO neurons and specific stimulation of NO neurons in vivo. Although the NO neurons are exclusively GABAergic according to literature, the efficacy of the inhibition is questioned since they terminate close to gap junctions among IO neurons instead of IO neuron somas. Here we present results of NO effect on IO in anesthetized mice using our newly established method. Gradient-index optics (GRIN) was used to approach IO from the ventral side of mice for calcium imaging of IO neurons and optogenetics stimulation of local NO input. Air-puff to the eye was applied to examine the NO effect on the sensory stimulation generated IO activity. We found that optogenetics stimulation of NO terminals could significantly reduce the calcium spike frequency in IO neurons showing the inhibitory effect of NO pathway, though this was not observed in all the cells. The air-puff triggered IO activity can be also suppressed by optogenetics stimulation in the NO-inhibited IO neurons. Surprisingly, NO input induced excitation was also observed in some IO neurons, suggesting NO neurons are not exclusively GABAergic.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-309
Bidirectional associated changes in synchronization and climbing fiber responses of cerebellar Purkinje-cell dependent on compartments along with auditory discrimination go/no-go learning
*Hoang Thien Huu(1), Shinichiro Tsutsumi(2), Mitsuo Kawato(4), Kazuo Kitamura(3), Keisuke Toyama(1)
1. ATR Neural Information Analysis Laboratories, Japan, 2. RIKEN Center for Brain Science, Japan, 3. Graduate School of Interdisciplinary Research, Yamanashi University, Japan, 4. ATR Computational Neuroscience Laboratories, Japan

Keyword: complex spike, Aldolase C, synchronization, auditory go/no-go

Cerebellar climbing fiber activity is known to convey motor and reward signals. However, how these signals are organized during learning, in the presence of compartmental structure of the cerebellar cortex, remains largely unclear. By utilizing two-photon calcium imaging data from Purkinje cell dendrites in mice learning a go/no-go auditory discrimination task, we reconstructed the complex spikes activity of about six-thousand Purkinje cells by the hyperacuity algorithm, which increases temporal precision 10-fold higher than the original sampling rate of two-photon imaging. Tensor component analysis demonstrated three neuron populations that may represent reward-related signals and motor commands. Compartmental distributions of these three populations were mainly based on lateral and medial hemispheres at the early learning stage, but became complicated combinations of the two hemispheres and Aldolase C positive and negative compartments at the later learning stages. In addition, changes in response of those components as learning progressed were closely paralleled with changes in synchronization of the complex spikes. These bidirectional and associated response-synchronization changes dependent on different compartments of the cerebellar cortex suggest that synchronization is an essential mechanism for learning.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-310
Single axon morphology of the cerebellar mossy fiber projection from the nucleus reticularis tegmenti pontis (NRTP)
*Yuhan Chao(1), Mohammad Shahangir Biswas(1,3), Yuanjun Luo(1), Izumi Sugihara(1,2)
1. Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan, 2. Center for Brain Integration Research, Tokyo Medical and Dental University, Tokyo, Japan, 3. Department of Biochemistry and Biotechnology, Khwaja Yunus Ali University, Enayetpur, Bangladesh

Keyword: cerebellar cortex, zebrin stripes, biotinylated dextran amine

The nucleus reticularis tegmenti pontis (NRTP) is one of the major sources of the cerebellar mossy fiber inputs and is presumed to be involved in oculomotor function. However, their projection patterns in the cerebellum have not been much clarified compared with the projection patterns of other major sources of the cerebellar mossy fibers. Here we studied the morphology of single axons of NRTP neurons in the mouse and compared it with other mossy fiber sources. Single axons were labeled with biotinylated dextran amine injected into various areas within the NRTP. A total of twenty-four axons were reconstructed in five mice, and soma identified in 11 axons. Generally, they ascend the middle cerebellar peduncle, either ipsilateral (n=13/24) or contralateral (11/24) to the origin. And they terminated in the cerebellar cortex in bilateral (n=17/24), ipsilateral (n=5/24), or contralateral (n=2/24) to the origin with 11-204 mossy fiber terminals. Nine axons out of 24 had collaterals terminating in the cerebellar nuclei. No collaterals terminated outside the cerebellum. Most mossy fiber terminals were located in hemispheric areas of the simple lobule, crus I, crus II, paramedian lobule, and paraflocculus. Terminals were more frequently located in zebrin-positive stripes than in zebrin-negative stripes, similar to pontine nucleus axons. The axons origin and target suggest a topographic organization within the NRTP, similar to the pontine nucleus.
As a whole, the morphological characteristics of NRTP mossy fiber axons have high similarity to those of pontine nucleus mossy fiber axons in many aspects. However, there were some noticeable differences such as frequency of the nuclear collaterals (more frequent in NRTP axons), laterality of axonal path (more frequent ipsilateral path), and major target lobules (more specific to particular lobules). Their target lobules suggest that the NRTP axons send required visuomotor, oculomotor, and cognitive information to the cerebellum and cerebellar nuclei.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-311
Long-term depression-inductive stimulation causes long-term potentiation in mouse Purkinje cells expressing a dominant-negative thyroid hormone receptor
*Ayane Kate Ninomiya(1), Izuki Amano(1), Michifumi Kokubo(1), Yusuke Takatsuru(2), Sumiyasu Ishii(1), Hirokazu Hirai(1), Nobutake Hosoi(1), Noriyuki Koibuchi(1)
1. Grad Sch Med, Gunma Univ, Gunma, Japan, 2. Toyo Univ, Gunma, Japan

Keyword: Cerebellum, Thyroid hormone, Motor coordination, Long-term depression

Thyroid hormones (THs) regulate gene expression by binding to nuclear TH receptors (TRs). Because THs are essential for brain development, congenital TH deficiency causes brain dysfunction that can persist into adulthood. However, little is known about the effects of congenital hypothyroidism in adulthood. Here we report specific TH effects on functional development of the cerebellum using transgenic mice (Mf-1) expressing a dominant-negative TR specifically in cerebellar Purkinje cells (PCs). We identified impaired motor coordination in adult Mf-1 mice, suggesting the functional attenuation of PCs. Then we examined the change in long-term depression (LTD) of plasticity at parallel fiber – PC synapses, which is proposed to control cerebellar motor coordination and learning. Surprisingly, the LTD-inductive stimulation caused long-term potentiation in Mf-1 PCs. Whereas the LTD induction requires a high calcium concentration in PCs, Mf-1 PCs displayed the low level of calcium signals due to the suppression of the inositol trisphosphate receptor type 1 (IP3R1)-mediated internal calcium release from the endoplasmic reticulum. A single Mf-1 PC contained a significantly lower level of IP3R1 mRNA. Such changes were not observed in the adult-onset Mf-1 mouse model. Taken together, these results suggest an important role for TH in maintaining cerebellar function via modulation of internal calcium release in PCs. The present study gives insight into the cellular and molecular mechanisms underlying congenital hypothyroidism-induced cerebellar dysfunction.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-312
学習依存的に変化する小脳外側部の神経活動
Learning dependent activity in the lateral cerebellum during reinforcement learning

*秋山 祐輔(1)、山田 洋(2)、松本 正幸(2)、國松 淳(2)
1. 筑波大学大学院、2. 筑波大学医学医療系
*Yusuke Akiyama(1), Hiroshi Yamada(2), Masayuki Matsumoto(2), Jun Kunimatsu(2)
1. Graduate school of comprehensive human sciences, University of Tsukuba, Tsukuba, Japan, 2. Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Keyword: CEREBELLUM, REINFORCEMENT LEARNING, EVE MOVEMENT, MONKEY

It has recently been shown that the lateral part of the cerebellum is involved in the higher cognitive functions rather than the adjustment of movement parameters (e.g. Kunimatsu et al., 2016, 2018). Particularly imaging studies reported an increase in activity in this region during visuomotor learning, although it remains unclear what information are encoded by the activity.
To answer this question, we recorded single neuron activity in the cerebellar dentate nucleus (DN) while monkeys performed a reinforcement learning task. In this task, one of two fractal objects (A or B) was presented in the center of the monitor. After the delay period (600-1200 ms), the fractal object was disappeared, then two identical saccade target points were presented on left and right hemifields. If the monkeys made a saccade to one of the directions that associated with the fractal object (e.g. A-right, B-left), they got a liquid reward. The monkeys had to learn, by trial and error, an association between the two objects and the two possible responses.
We recorded the activity of 280 DN neurons in two conditions: learning condition in which novel fractal objects were used and over-trained condition in which well-learned fractal objects were used. We first found that 42 of the 280 neurons (15%) showed an increase in activity during a visual and/or delay periods, and it was greater in the learning condition than in the over-trained condition. Many neurons changed the visual- and delay-period activity depending on the saccade direction in the learning condition. Notably, the direction selectivity of the delay-period activity was modulated by learning. That is, the direction selectivity was enhanced as the monkeys progressively learned the association between novel objects and rewarded saccade directions. This direction selectivity disappeared in the over-trained condition.
Our results suggest that the delay-period activity of DN neurons is involved in reinforcement learning, but not to retention or retrieval. Through the direct and indirect connections, their signals may be sent to the prefrontal cortex and the basal ganglia. The neuronal circuit constituted of these regions might be essential for the acquirement of visuomotor skills.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-313
健常者における予測可条件での重り負荷課題を用いた運動学習の評価および感覚情報の関与について
Assessment of motor learning and the contribution of sensory information using a predictable loading task in healthy volunteers

*太田 哲生(1)、菊池 ゆひ(1)、網谷 郁美(2)、少作 隆子(1)、小池 康晴(3)、米田 貢(1)
1. 金沢大学医薬保健研究域保健学系、2. 浅ノ川総合病院リハビリテーションセンター、3. 東京工業大学科学技術創成研究院
*Tetsuo Ota(1), Yui Kikuchi(1), Ikumi Amiya(2), Takako Ohno-Shosaku(1), Yasuharu Koike(3), Mitsugu Yoneda(1)
1. Fac. Health Sci. Kanazawa univ., Kanazawa, Japan, 2. Cent. Rehab., Asanogawa General Hospital, Kanazawa, Japan, 3. Inst. Innov. Res., Tokyo Institute of Technology, Yokohama, Japan

Keyword: Motor learning, Feedforward motor control, training effect, Upper limb loading task

The cerebellum is involved not only in motor functions but also in cognitive functions. Therefore, the assessment of cerebellar function is clinically important. The cerebellum-dependent motor learning process has been studied by using various tasks, in which conditions were artificially changed and the process to adjust motor commands to the new condition was monitored (e.g., prism adaptation task). However, artificial changes in conditions can be stressful for patients. In the present study, using the Space Interface Device for Artificial Reality (SPIDAR) we examined whether the motor learning process can be evaluated with a simple loading task without any artificial changes in conditions, and if so what type of sensory information is important for motor learning. Twenty-one healthy right-handed females (20-23 years old, 21.4 ± 0.9) participated in this study. When the subject pressed the Enter button on the keyboard a constant downward force of 4.9 N was applied to the subject’s hand (predictable loading), and the vertical movement of the hand was recorded. The deflection of the hand from the initial position was displayed on a computer screen for visual feedback information. The subject was instructed to keep the initial position during loading. The loading task was repeated 90 times with eyes open (open-eye condition), or repeated 10 times with eyes open, 70 times with eyes closed, and 10 times with eyes open (closed-eye condition). We found that the repeated training lowered the time constant of upward movement just before loading (anticipatory response) and reduced the amplitude and time-to-peak of downward movement after loading. These training effects were maintained into the next day. There was no significant difference in learning effects between open-eye and closed-eye conditions. These results indicate that the motor learning process can be evaluated with a simple loading task without any artificial changes in conditions, which is clinically useful for patients with various disorders. In addition, our data suggest that this learning process depends on proprioceptive feedback information from muscles and joints rather than visual information.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-314
脳出血後の麻痺側前肢集中使用による機能回復における小脳赤核路の関与
Involvement of cerebello-rubral pathway in the functional recovery by intensive use of the paralyzed forelimb after cerebral hemorrhage

*上野 新也(1)、清水 健史(1)、小林 憲太(2)、田尻 直輝(1)、飛田 秀樹(1)
1. 名古屋市立大学大学院医学研究科脳神経生理学、2. 生理学研究所ウィルスベクター開発室
*Shinya Ueno(1), Takeshi Shimizu(1), Kenta Kobayashi(2), Naoki Tajiri(1), Hideki Hida(1)
1. Neurophysiol & Brain Sci, Grad Sch Med, Nagoya City Univ, Nagoya, Japan, 2. Sec Viral Vector Develop, NIPS, Okazaki, Japan

Keyword: INTRACEREBRAL HEMORRHAGE, CEREBELLO-RUBRAL TRACT, REHABILITATION, DREADD

Motor function of the paralyzed forelimb is recovered by rehabilitative training of intensive use of the limb after intracerebral hemorrhage, showing a causal relationship between the cortico-rubral tract and the functional recovery (J Neurosci 36:455-67, 2016). However, the contribution of motor regulatory system in the recovery of upper limb function by the rehabilitative training remains unclear. In order to analyze the changes in motor regulatory system caused by the rehabilitative training, we focused on the cerebellar output system in the cerebellar lateral nucleus to the parvocellular red nucleus (cerebello-rubral tract), evaluating upper limb motor function under inhibition of cerebello-rubral tract with DREADD system. To block the cerebello-rubural tract, AAV-DJ-EF1a-DIO-hM4D(Gi)-mCherry and FuG-E-MSCV-Cre were injected into the cerebellar lateral nucleus and the parvocellular red nucleus, respectively. This model was intensively forced to use the paralyzed upper limb for 1 week from 1 day after hemorrhage (D1), and the upper limb function was evaluated by single pellet reaching test until D28. Success rate of the reaching test was improved in the rehabilitation group compared with the non-rehabilitation group. Interestingly, the blockade of cerebello-rubral tract with clozapine-N-oxide (CNO) significantly resulted in the reduction of the success rate, suggesting that the cerebello-rubral tract are involved in the improvement of impaired motor function by intensive use of the upper limb in rats. To confirm the involvement of the cerebello-rubral tract in the changes of motor regulatory system by rehabilitative training, we are now challenging electrophysiological studies in the tract. We can success to detecting the signals from the parvocellular red nucleus in response to the electrical stimulation of the cerebellar lateral nucleus. We hope to present the electrophysiological results of the blockade of cerebello-rubral pathway with CNO.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-315
Dendritic voltage changes of Cerebellar Purkinje Neurons during Associative Learning
*Lina M. Koronfel(1), Christopher J. Roome(1), Bernd Kuhn(1)
1. Okinawa Institute of Science and Technology, Okinawa, JAPAN

Keyword: Eyeblink Conditioning, Voltage sensitive dye, Purkinje neurons, Motor Learning

The cerebellar cortex is critical for many forms of associative learning, such as the timing of delay eyeblink conditioning. Here, we use two-photon voltage imaging of Purkinje neuron (PN) dendrites on a trial-to-trial basis in habituated, awake mice to study dendritic activity during an associative motor learning task: At first, we image the dendritic voltage changes during the presentation of a novel stimulus, an unfamiliar blue LED light stimulus; then, we image the dendritic voltage changes when this novel stimulus is associated with an unconditioned stimulus, such as an aversive air puff during delay eyeblink conditioning; finally, we image the dendritic voltage changes when the association between the two stimuli is unlearned. This was done with minimal disruption to the neuronal circuits involved: PNs expressing the genetically encoded Ca2+ sensor GCaMP6f after AAV injection were selected for the experiment if they repeatedly responded with a Ca2+ transient to an air puff stimulus to the eye. To allow for voltage imaging, the selected PNs were loaded with the voltage-sensitive dye ANNINE-6plus via post-surgical electroporation through a silicon access port designed in the cranial glass window. By selectively customizing the data acquisition software ScanImage, we were able to track the excitatory and inhibitory postsynaptic voltage responses in each dendrite of up to two PNs per animal, with 0.5 millisecond temporal precision, repeatedly over several weeks while maintaining high signal to noise ratio throughout the experimental sessions. In some experiments, we simultaneously imaged voltage and calcium changes. Results are acquired by comparing the two-photon voltage imaging data with behavioral data recorded at high speed by analyzing trial-to-trial short term changes during each session as well as long term changes between sessions.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-316
ドーパミン受容体D1とD2の発現が偏る尾側線条体の腹側領域は、黒質外側部に投射する
The caudal striatum expressing dopamine receptor D1 and D2 unevenly projects to substantia nigra pars lateralis

*苅部 冬紀(1)、緒方 久実子(2)、角野 風子(1)、平井 康治(1)、高田 昌彦(3)、井上 謙一(3)、藤山 文乃(1)
1. 北海道大学大学院医学研究院、2. 同志社大学脳科学研究科、3. 京都大学霊長類研究所
*Fuyuki Karube(1), Kumiko Ogata(2), Fuko Kadono(1), Yasuharu Hirai(1), Masahiko Takada(3), Ken-ichi Inoue(3), Fumino Fujiyama(1)
1. Grad Sch Med, Hokkaido Univ, Sapporo, Japan, 2. Grad Sch Brain Sci, Doshisha Univ, Kyotanabe, Japan, 3. Primate Research Institute, Inuyama, Japan

Keyword: striatum, dopamine receptor, substantia nigra pars lateralis, direct pathway

The striatum is composed of two types of projection neurons: the direct and indirect pathway medium spiny neurons (MSNs). The direct pathway MSNs (dMSNs) express dopamine receptor D1 (D1R), and directly project to the output nuclei of the basal ganglia. In contrast, the indirect pathway MSNs (iMSNs) express dopamine receptor D2 (D2R), and project to the globus pallidus external segment (GP). In most of the striatal area, dMSNs and iMSNs are randomly and uniformly distributed. On the other hand, recent studies discovered a unique striatal region in the ventral part of caudal striatum (cvStr). The region contains two distinguishable zones in which expression of D1R and D2R is highly biased. A conventional model of the striatum has been based on even distribution and complementary role of dMSNs and iMSNs; therefore, it will be necessary to uncover neural circuitries of the atypical striatal zones. First, we quantified cell type composition of the cvStr, and found DARPP32-positive neurons, namely MSNs, occupied over 92% of total neurons, similar to the rostral or dorsal striatum. As reported earlier, D2R-expressing MSNs were few (3.6% of total neurons) in the medial part of the cvStr, whereas D1R-expressing neurons were poor (12.2% of total neurons) in the laterally adjoining zone. These zones were named as D2R-poor zone and D1R-poor zone, respectively. Retrograde tracer injection into the output nuclei of the basal ganglia labeled more than four-fold density of neurons in D2R-poor zone than in D1R-poor zone. Fine scale anterograde labeling clarified that cvStr projected to substantia nigra pars lateralis (SNpl), similar to the caudo-dorsal striatum (cdStr), while cvStr including poor zones projected to the dorsal part of SNpl more densely than cdStr. The result was confirmed by retrograde tracer injection into SNpl, where the caudal GP also projected to. In addition, we confirmed D1R- and D2R- poor zones were stably present from postnatal-day-8 to over two years. Finally, the poor zones existed not only in mice, but in rats and even marmosets. The unique zones are innervated by the visual and auditory striatum, thus, may contribute to processing of sensory information.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-317
ゼブラフィッシュ淡蒼球内節推定部位における神経細胞タイプの同定
Identification of putative globus pallidus internus (dEN) neuronal cell types in zebrafish

*柿沼 久哉(1)、谷本 悠生(1)、白木 利幸(1)、青木 亮(2)、岡本 仁(1)
1. 理研CBS 意思決定回路動態研究チーム、2. 理研CBS 視覚意思決定研究チーム
*Hisaya Kakinuma(1), Yuki Tanimoto(1), Toshiyuki Shiraki(1), Ryo Aoki(2), Hitoshi Okamoto(1)
1. Lab for Neural Circuit Dynamics of Decision Making, RIKEN, CBS, Japan, 2. Lab for Neural Circuits and Behavior, RIKEN, CBS, Japan

Keyword: zebrafish, basal ganglia, scRNA-seq

An increasing number of comparative neuroanatomical and behavioral analyses have revealed that the basic structures and functions of brain are conserved between teleosts and mammals. Our laboratory has been focusing on a cortico-basal ganglia-thalamic circuit in zebrafish, which is implicated in behavior selection. Previously we examined the connectivity of dorsal entopeduncular nucleus dEN (globus pallidus internus GPi)-central posterior nucleus CP (thalamus)-dorsal pallium (cortex) in zebrafish. Our data suggested that CP receives inputs from neuropeptide-Y (npy)-negative and/or GABAergic dEN neurons and projects to the dorsal pallium as shown in the basal ganglia-thalamus-cortex circuit in lamprey and mammals. In the present study, to dissect the dEN (GPi)-CP (thalamus) projection and manipulate them genetically, we searched for marker genes expressed in npy-negative and /or GABAergic dEN neurons with single-cell-RNA-sequencing (scRNA-seq) analysis. We dissected dEN and its surrounding regions of the adult brains of TgBAC(npy:GAL4VP16)(UAS:GFP). Then we removed cell debris and dead cells by FACS. We used droplet-based 3’ end scRNA-seq provided by 10x Chromium and obtained data from 3381 cells. After single-cell sequencing, we performed unbiased clustering by Seurat software. Of the 18 clusters identified by our analysis, six clusters were dEN neuronal cell types that expressed GABergic neuronal markers and pallidum developmental precursor markers. Moreover, the other five clusters were glutamatergic neuronal cell types including the ventral entopeduncular nucleus (vEN). We also checked expression of mammalian GPi markers, somatostatin (sst) for habenula-projecting neurons and parvalbumin (pv) for thalamus-projecting neurons. All the six dEN clusters expressed sst, and none of them expressed pv. This data suggested that sst and pv were not suitable markers for distinguishing subpopulation in the dEN neurons which project to the different brain areas. Furthermore, to determine whether six dEN clusters corresponding to the thalamic-projecting neuronal cell types, we identified markers of npy-negative and gad67-positive neurons in each cluster. Now we are selecting candidate markers by their expression patterns in the dEN.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-318
Intragastric administration of low dose rotenone post colitis accelerate brain neuropathology and motor impairment in Parkinson’s disease
*Sharma Nishant(1)、khairnar Amit(1)
*Nishant Sharma(1), Amit khairnar(1)
1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat, India

Keyword: Parkinson's disease, Enteric Nervous system, Alpha-synuclein, Inflammation

Objective: The contribution of gastrointestinal (GI) inflammation and local exposure of neurotoxin in the gut, offers most in-depth explanation of Parkinson’s disease (PD) etiopathogenesis through abnormal accumulation and spreading of alpha-synuclein (αSyn) aggregates from the gut to the brain. This study was therefore designed to assess the exacerbation of proinflammatory intestinal milieu in progressive mouse model of PD. Methods: To induce chronic colitis, 10 months old C57BL/6 mice were treated with 1% Dextran Sodium Sulphate (DSS). After colitis-induction, animals received low dose of intragastric rotenone (which was undetectable in systemic blood or brain) for the next 8 weeks, followed by testing for Parkinsonian behavior and GI phenotypes of inflammation. At the end of 8th week, intestine, brain stem, and midbrain tissue were isolated and analyzed for the presence of misfolded α-Syn, inflammatory markers, and dopaminergic neuronal loss in substantia nigra, enteric neurons, and dorsal motor nucleus of vagus (DMV). Results: We found that intragastric administration of rotenone after colitis significantly decreased colon length as well as increased expression of inflammatory markers (CCl2, TNF-α, IL-1β, IL-6) in the colon and striatum. Gut inflammation in a mouse model of PD also disrupted GI architecture and caused loss of tight junction proteins (ZO-1, claudin1, occludin) in the colon compared to control mice. Gut inflammation accelerated the onset of motor dysfunction and significantly increased the expression of GFAP, phosphorylated α-syn in the cortex, and striatum. Conclusions: Our findings suggest a critical role of intestinal inflammation in the initiation and progression of PD.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-319
線条体と小脳の時間予測に関連した活動における効果器特異性の比較
Temporal prediction signals in the striatum but not in the cerebellum are effector specific

*亀田 将史(1)、田中 真樹(1)
1. 北海道大学
*Masashi Kameda(1), Masaki Tanaka(1)
1. Hokkaido University

Keyword: Basal Ganglia, Cerebellum, Temporal processing, Nonhuman primate

Both the cerebellum and basal ganglia are essential for the perception and production of rhythms. We recently found that neurons in the cerebellar dentate nucleus (Ohmae et al., 2013) and the caudate nucleus (Kameda et al., 2019) exhibited periodic firing modulation in monkeys performing the omission oddball detection task, in which the animals predicted the timing of each repetitive stimulus. Neurons in both structures appeared to be involved in rhythm processing, but only caudate neurons altered their activity depending on the direction of forthcoming eye movements, suggesting a role in periodic motor preparation. To clarify this, we trained three monkeys to report the stimulus omission by making a saccade or hand movement.
So far, we have recorded from 52 dentate and 24 caudate neurons exhibiting periodic activity during the task. When comparing the magnitude of periodic activity across three types of behavioral response (button release, ipsilateral and contralateral saccades), approximately 60% of neurons in both structures showed a significant difference (32/52 and 14/24, ANOVA, p<0.05). However, the degree of effector specificity was greater in the caudate than the dentate nucleus (unpaired t-test, p<10-4), and only caudate neurons showed a strong preference for contralateral rather than ipsilateral saccades (paired t-test, p=0.015), consistent with the previous studies. In contrast, dentate neurons showed a weak preference for saccade than hand movement (Tukey, p<0.05). This difference might reflect the difference in behavioral strategy (or attentional demand) between trials with eye and hand movements, even though the visual stimuli in these tasks were exactly the same. In fact, trials with no response (miss) were more frequently observed in hand than saccade trials (15 vs. 4%, Fisher's exact test, p<10−42), while those with premature response (false alarm) showed an opposite trend (4 vs. 14%, p<10−17). To test if the periodic activity reflected motor preparation, we additionally introduced the color change detection task that did not require temporal prediction. The magnitude of periodic activity in both structures significantly decreased during the task, and the effector-specific bias found in the cerebellum disappeared (ANOVA, p=0.98). These results suggest that striatal neurons may represent effector-specific, periodic motor preparation during rhythm processing, while the cerebellum might be involved in sensory prediction or temporal attention.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-320
尾状核ニューロンは網膜座標系以外でもサッケードのゴールを符号化している : 探索的課題における強化学習への示唆
Caudate neurons encode the saccade goal in non-retinocentric coordinate frame : implication for reinforcement learning in an exploratory task

*加藤 利佳子(1,2)、坂東 宏樹(1)、伊佐 正(1,2)
1. 京都大学大学院 医学研究科、2. 京都大学 高等研究院 ヒト生物学高等研究拠点
*Rikako Kato(1,2), Hiroki Bando(1), Isa Tadashi(1,2)
1. Graduate School of Medicine, Kyoto University, Kyoto, Japan, 2. Institute for the Advanced Study of Human Biology, Kyoto University, Kyoto, Japan

Keyword: caudate nucleus, reinforcement learning, saccades

Recently we examined reinforcement learning during a task to find a hidden area (HA) located within the blank monitor screen using visual cue in macaque monkeys. If their gaze moved into the HA, the visual cue was presented at an edge of the monitor. The visual cue did not indicate the location of HA, but informed the monkeys just the fact that they discovered the HA. If their gaze remained in the HA for few hundred ms, reward (a drop of water) was given two seconds later. Search in each trial was started randomly from a one of the 9 – 12 possible positions within the monitor, but interestingly, the final saccades entering the HA tended to converge on one or two vectors in each learning session. Thus, in this task,the monkeys appeared to have learnt both the non-retinocentric (non-RC) location of the start position of final saccades and its retinocentric (RC) vector to the HA. To enable this kind of learning, there must be a neural code of saccade goal in non-RC coordinates in brain regions relevant to reinforcement learning. To search for such neural code, we recorded neural activities from the caudate nucleus (CN), which is considered to play a critical role in the learning process in this type of exploratory task. In previous literature, neural activity related with the RC saccadic eye movements has been frequently examined in the CN. However, neural code o saccade goal in the non-RC coordinates has not been reported. To test this hypothesis, we simultaneously recorded spike activity from 13 – 30 neurons using multipolar electrode while the monkeys performed the search task. Saccade direction and the end points were classified into four quadrants on each RC and non-RC coordinated plane. We applied Bayesian inference methods to decode neural activity into those two components of the saccade. In three of the 5 cases, saccade direction and end points were decoded with a significantly above chance level of the decoding performance. Eight of the 116 CN neurons contributed to decoding performance for the saccade direction, while 9 of the 116 CN neurons contributed to decoding of the saccade endpoint. To confirm the encoding of saccadic end points in more detail, we recorded the CN neural activity during a memory guided saccade task with five different starting points on the monitor. The activity associated with the end point of the saccade was observed in 4 out of 69 CN neurons. Additionally, reward signal and visual cue signals related with the reward were also encoded in the CN. Those results suggested that the CN prepares broad signals, which might be the basis for the flexible combination of different signals in the CN to generate the novel signals necessary for learning.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-321
ゼブラフィッシュの大脳基底核における目標指向行動のための価値情報の機能的分離と統合
Functional segregation and integration by two anatomically different output pathways from the basal ganglia to the cortex for goal-directed behavior of adult zebrafish

*谷本 悠生(1)、鳥越 万紀夫(1)、イスラム タンビル(1)、青木 亮(2)、白木 利幸(1)、柿沼 久哉(1)、岡本 仁(1)
1. 理化学研究所 脳神経科学研究センター 意思決定回路動態研究チーム、2. 理化学研究所 脳神経科学研究センター 視覚意思決定研究チーム
*Yuki Tanimoto(1), Makio Torigoe(1), Tanvir Islam(1), Ryo Aoki(2), Toshiyuki Shiraki(1), Hisaya Kakinuma(1), Hitoshi Okamoto(1)
1. Laboratory for Neural Circuit Dynamics of Decision Making, RIKEN Center for Brain Science, Saitama, Japan, 2. Laboratory for Neural Circuits and Behavior, RIKEN Center for Brain Science, Saitama, Japan

Keyword: zebrafish, calcium imaging, basal ganglia

The adult zebrafish telencephalon contains evolutionary homologs of the mammalian striatum, pallidum and cortex, providing a compact model for functional study of this circuit. For this, we established a closed-loop virtual-reality system for 2-photon Ca2+ imaging of the zebrafish cortex in Go/No-go tasks, where fish needs to escape from blue-region in Go trials and stay in red-region in No-go trials to avoid electrical shock (Torigoe et al., 2021). During this, we observed emergence of multiple neural ensembles encoding danger for blue-cue, safety for red-cue, and prediction error of current situations from ideal situations. Here, we report anatomy of the zebrafish striatum (Vc/Vd) and pallidum (Vl/dEN) and their roles for learning. The Vc/Vd expresses mammalian direct- and indirect-pathway neuron markers Tac1 and Penk. Synaptic tracing by transgenically expressed wheat germ agglutinin (WGA) with Penk promoter resulted in higher WGA transfer to the Vl, while WGA expression by Tac1 promoter resulted in higher WGA transfer to dEN, suggesting that the Vl and dEN are evolutionary homologs of mammalian globus pallidus externus and internus, respectively. To our surprise, a majority of the dEN neurons were immunoreactive to Npy and directly projected to the entire cortex, while Npy negative dEN neurons projected to the thalamus (Kakinuma et al., this meeting). This result indicates that fish has a shortcut pathway from the pallidum to the cortex in addition to the evolutionarily conserved pallido-thalamic tract. We further recorded activity of the Vc/Vd striatal neurons in Go/No-go task. We observed enlargement of cluster-like neural ensembles in Penk+ indirect pathway neurons during Go cue-evoked escape behavior after learning, while Tac1+ direct pathway neurons rather showed shrink of such clusters in a majority of fishes. Such learning-dependent activity changes suggest focused disinhibition of specific cortical neurons by the direct pathway, and broad inhibition of unwanted cortical neurons by the indirect pathway. In contrast, the Npy+ shortcut pathway was uniformly activated by dangerous blue-cue after learning, which was enhanced by prediction error of an ideal sensory state. Based on the results, we will discuss a hypothesis that the pallido-thalamic tract provides focused output encoding prediction of a specific ideal sensory state, and the shortcut pathway provides uniform output encoding subjective evaluation of danger to promote the escape behavior.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-323
マカクサルにおける運動の実行と中止に関わる視床下核ニューロンの活動様式
Subthalamic activity in motor execution and cancellation in monkeys

*畑中 伸彦(1)、Zlata Polyakova(2)、知見 聡美(1)、南部 篤(1)
1. 生理学研究所・生体システム、2. 北海道大学 人間知・脳・AI研究教育センター
*Nobuhiko Hatanaka(1), Zlata Polyakova(2), Satomi Chiken(1), Atsushi Nambu(1)
1. Division of System Neurophysiology, National Institute for Physiological Sciences, 2. Center for Human Nature, Artificial Intelligence, and Neuroscience, Hokkaido University,

Keyword: Subthalamic nucleus, Motor cancelation, Monkey, Limb movement

The subthalamic nucleus (STN) has a crucial role in motor control. There have been increasing evidences for the various functions of the STN, such as monitoring of ongoing activity during action performance. This has been fueled by the clinical relevance of the STN as an effective target of stereotactic surgery for Parkinson's disease. Here we address the functional significance of the STN in voluntary movements. We examined STN neuronal activity in two Japanese monkeys (Macaca fuscata) during the performance of goal-directed reaching task with a delay that includes Go, Stop, and NoGo trials. This task paradigm allows us to examine and compare neuronal activity during motor planning, execution, cancellation, and planned action suppression. We recorded neuronal activity in the dorsal somatomotor region of the STN. Stimulation of the primary motor cortex and/or supplementary motor area induced early excitation and late excitation, which are mediated by the hyperdirect and indirect pathways, respectively. These STN neurons showed a complicated firing pattern during tasks, which varied in different task conditions and targets. They showed activity changes during not only Go trials but also Stop trials. Some STN neurons increased discharge rate during a delay period. These results suggest that the STN neuron has different functions in combination of execution, cancellation, and preparation of actions and that these STN activity may be mediated by the hyperdirect and indirect pathways.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-324
淡蒼球外節尾側領域での聴覚応答に関わる脳領域の探索
The brain regions associating with the auditory receptive caudal portion of the rat globus pallidus

*平井 康治(1)、藤山 文乃(1)
1. 北海道大学・医学研究院・組織細胞学
*Yasuharu Hirai(1), Fumino Fujiyama(1)
1. Histology and Cytology, Fac of Med, Hokkaido Univ, Sapporo, Japan

Keyword: basal ganglia, globus pallidus, auditory, rat

The globus pallidus externalis (GPe, or simply GP in rodents) is one of the inhibitory nuclei in the basal ganglia, which distributes their axons to whole basal ganglia structures and serves as the center of the functional basal ganglia neural pathway, the “indirect pathway”. In the classical basal ganglia scheme, GP neurons only receive inhibitory inputs from the GABAergic medium spiny neurons of the striatum, and disinhibition of the basal ganglia output nuclei by the GP efferent counterbalance to the alternative striatum to output nucleus inhibitory projection, the “direct pathway”. However, a number of research successively indicated that the GP anatomy and its functional role are more complicated and significant. Previously, we demonstrated that the GP neurons responded to the acoustic stimulus most excitatory, which is contrary to the classical scheme but corresponds to the recent findings that elucidated the existence of the direct excitatory synaptic inputs from the cortical pyramidal cells. However, it’s direct cortico-pallidal pathways were revealed in the somatomotor regions of the rostral GP. It remains unclear if the case can be applied in the auditory receptive caudal portion of the GP, and whether there are other candidates conveying the auditory information to the GP especially with excitation. To explore the afferent origins of the auditory input recipient region of the GP, we injected retrograde tracers into the caudal part of the rat GP. The results indicated that many cortical inputs were originated not only from auditory related area but also limbic area including insular and parahippocampal cortices. In addition, retrogradely labeled cells were found in posterior paralaminar thalamic nuclei. Further studies based on this anatomical finding might elucidate the role of the GP neurons for sensory processing.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-325
上肢到達運動の制御過程に小脳を起点とし筋肉に至る神経経路が関与する
Neural pathway originating from the cerebellum to muscles contributes to controlling forelimb reaching movement in monkeys

*中山 義久(1)、佐野 暢哉(1)、知見 聡美(2,3)、南部 篤(2,3)、西村 幸男(1)
1. 東京都医学総合研究所、2. 生理学研究所、3. 総合研究大学院大学生命科学研究科
*Yoshihisa Nakayama(1), Nobuya Sano(1), Satomi Chiken(2,3), Atsushi Nambu(2,3), Yukio Nishimura(1)
1. Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan, 2. National Institute for Physiological Sciences, Okazaki, Japan, 3. Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Hayama, Japan

Keyword: CEREBELLUM, PRIMARY MOTOR CORTEX, CORTICOMOTONEURONAL CELL, ELECTROMYOGRAPHY

Dysfunction of the cerebellum (Cb) causes motor deficits. Anatomical studies have demonstrated that the Cb projects to the primary motor cortex (M1) through the motor thalamus. In addition, the M1 projects monosynaptically to motoneurons in the spinal cord, which control muscle activity. Therefore, outputs from the Cb should eventually reach the muscles and manifest motor deficits. However, how this neural pathway contributes to muscle activity has not been examined. In the present study, we addressed this issue by examining the responses of M1 neurons to Cb stimulation and observing electromyographic (EMG) activity of the forelimb muscles following a single spike of M1 neurons using monkeys (Macaca fuscata). First, we recorded M1 neuronal activity and performed electrical stimulation of the Cb dentate nucleus. The majority of M1 neurons either increased or decreased their neuronal firings in response to Cb stimulation, indicating that most M1 neurons receive information from the Cb. We then recorded EMG activity as well as M1 neuronal activity simultaneously while monkeys performed an arm-reaching task. By averaging EMG activity triggered by single spikes in the M1, we successfully identified corticomotoneuronal (CM) cells in the M1, which have monosynaptic connections with motoneurons in the spinal cord. In addition, these CM cells exhibited movement-related neuronal activity. Moreover, they responded to Cb stimulation. These results provide direct evidence of the pathway from the Cb to the forelimb muscles through the M1 by which the Cb controls muscle activity. Altogether, the present findings suggest that the network originating from the Cb through the M1 to the muscles plays an important role in the realization of motor behavior.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-326
N-back課題中の前頭連合野ニューロンの神経活動
Neuronal activity in the primate prefrontal cortex during the oculomotor n-back task

*澤頭 亮(1,2)、田中 真樹(1)
1. 北海道大学大学院医学院 神経生理学教室、2. 北海道大学大学院医学院 精神医学教室
*Ryo Sawagashira(1,2), Masaki Tanaka(1)
1. Dept of Physiology, Grad Sch Med, Hokkaido University, Japan, 2. Dept of Psychiatry, Grad Sch Med, Hokkaido University, Japan

Keyword: Working memory, Prefrontal cortex, Primate, Central executive

Working memory (WM) consists of multiple components including the storages of short-term memory and the central executive system managing them (Baddeley and Hitch, 1974). Although many previous studies have demonstrated neural correlates of short-term memory, the underlying mechanism of the central executive system remains largely unknown. Here we explored neuronal activity in the lateral prefrontal cortex in monkeys performing the oculomotor version of the n-back task.
During central fixation, two to four peripheral visual cues were sequentially presented with a short delay (800 ms). In response to the offset of the fixation target, monkeys made a memory-guided saccade to one of the cue locations. When the fixation target was either a red triangle or a white cross (1-back condition), animals were required to make a saccade to the most recent cue location. When the fixation target was either a blue square or a white star (2-back condition), they needed to make a saccade to the location of the two previous cue. We found three types of prefrontal neurons (n = 119) in three monkeys that were well trained for the task (correct rate > 80%). Visual neurons (n = 37) exhibited a transient activity as the cue appeared in the receptive field. Memory neurons (n = 37) displayed sustained activity following the cue that lasted for one (1-back) or two (2-back) delay intervals. Extinction neurons (n = 31) showed an increase in activity when the memory of a specific cue location became no longer necessary. Thus, along with neuronal correlates of short-term memory, we first found extinction neurons that represent the central executive function. A generalized linear model applied to the delay period activity showed that 57, 28, and 39% of neurons exhibited visual, memory, and extinction signals, respectively. Extinction neurons tended to be localized in the ventral part of the lateral prefrontal cortex and memory neurons in the dorsal part, but more data is needed to situate the two different WM systems. We plan to examine how these signals are causally related to animal behavior by manipulating neuronal activity at the recording sites in future studies.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-327
モルモットの予見的運動時間で見られる量子的タイミング生成
Quantal timing generation in internal estimation of prospective sub-second time for actions in guinea pigs

*西村 方孝(1)、宋 文杰(1,2)
*Masataka Nishimura(1), Wen-Jie Song(1,2)
1. Faculty of Life Sciences, Kumamoto Univ, Kumamoto, Japan, 2. Program for Leading Graduate Schools HIGO Program, Kumamoto Univ, Kumamoto, Japan

Keyword: INTERNAL TIMER, TIMING, TIME PRODUCTION

Mammals can estimate both retrospective and prospective time. How time is measured in the brain is still an issue of debate. In general, there are two possible timers for counting time; one is continuous, and the other is quantal. The prevailing scalar expectancy theory proposes a quantal timer for timing generation, and previous human studies have suggested the existence of quantal timer in the brain for sub-second time measurement. Yet no direct evidence showing quantized timings has been demonstrated. In previous studies on estimation of prospective time, animals are trained to wait for a certain period in response to a sensory cue, before starting an action to obtain a reward; and time of action from the cue onset (action time) has been taken as the time measured internally by the animal. Action times observed around a timing determined by the animal, however, typically show large variance and include the time required for sensory processing and motor control, in addition to the time produced with the internal timer. Here, we designed a self-initiated training protocol to control dynamically the reward time window (Rw) for reducing the variance, and to eliminate the time required for sensory processing and motor control with two cues. One cue had a Rw around 300 ms, and the other was 600 ms. Action timings for each cue were estimated with medians of 20 neighboring action times within 15 minutes. Momentary difference in action timings to these cues is referred to as iT. Histograms of iTs showed quasi-periodic peaks in multiple test sessions, in all three examined guinea pigs. Monte Carlo simulations revealed non-random nature of the peaks. Since iT reflects the timing difference determined by the internal timer for the actions, these results suggest quantal timing generation in estimation of prospective sub-second time for actions in guinea pigs.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-328
化学遺伝学的手法による下行性運動路の活性化は筋活動を高める
Chemogenetic activation of descending motor pathways in non-human primates

*鈴木 迪諒(1)、小林 憲太(2)、西村 幸男(1)
1. 東京都医学総合研究所脳機能再建プロジェクト、2. 生理学研究所ウイルスベクター開発室
*Michiaki Suzuki(1), Kenta Kobayashi(2), Yukio Nishimura(1)
1. Neural Prosthetics Project, Tokyo Metropolitan Institute of Medical Science, 2. Section of Viral Vector Development, National Institute for Physiological Sciences

Keyword: DREADDs, motor control, corticospinal tract

Descending motor pathways to the spinal cord originate from diverse cortical areas and subcortical, and serve a wide range of motor functions. Damage of these descending motor pathways induces motor paralysis. The amount of remaining descending motor pathway is associated with residual motor function after spinal cord injury. Thus, the activation of the preserved descending motor pathways may have potential ability to facilitate functional recovery. One of the feasible tools activating supraspinal neurons of origins simultaneously is the chemogenetic technology, designer receptors exclusively activated by designer drugs (DREADDs) which afford remotely reversible control of neuronal activity. In order to establish the selective activation method of descending motor pathways using DREADDs, we injected AAV2-retro-hSyn-hM3D(Gq)-mCherry was unilaterally injected to a part of the cervical enlargement [C7-C8 (3.0 or 3.6 µl)] in two macaque monkeys. Histological results showed efficient transduction of supraspinal populations which innervates cervical enlargements, especially in the primary motor cortex (M1). Retrograde labeling was also found in dorsal premotor cortex, supplementary motor area, red nucleus, and reticular formation. The chemogenetic activation was investigated in one monkey. Under anesthesia by intubation with isoflurane, we recorded muscle activity from ipsilateral forelimb muscles to the spinal injection side, and compared spontaneous muscle activity and evoked muscle responses induced by the electrical stimulation of the contralateral M1 before and after intramuscular injection of selective agonist deschloroclozapine (DCZ) for muscarinic-based DREADDs. After DCZ injection, spontaneous activation was observed in several muscles. In addition, evoked muscle responses induced by the M1 stimulation were larger than those before injection. These increased excitability in descending motor pathways were not observed after vehicle injection. Thus, the chemogenectic activation facilitates descending motor pathways. These results suggest its potential application to enhance motor functions and accelerate functional recovery after spinal cord injury.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-329
運動企図に起因した時間知覚のバイアス:計算論的モデル解析.
Biased temporal perception caused by actor's own intention: Computational model analysis.

*望月 圭(1)、村田 哲(2)、稲瀬 正彦(2)
1. 岩手医科大学 医学部 生理学講座 統合生理学分野、2. 近畿大学 医学部 生理学教室
*Kei Mochizuki(1), Akira Murata(2), Masahiko Inase(2)
1. Dept Physiol, Sch Med, Iwate Medical Univ, 2. Dept Physiol, Facult Med, Kindai Univ

Keyword: BRAIN

In order to achieve temporally coordinated body movements, temporal perception of own action and resulting external events is crucial. However, human subjects are known to possess a cognitive bias to underrate temporal interval between own action and its consequence. For instance, the sound of the doorbell is perceived to be highly time-locked to the button press, although there is an inevitable physical delay until the bell actually rings. This skewed tendency in time perception is called "intentional binding", and is well accepted as a human's innate cognitive bias to temporally associate ("bind") own action to the consequence.
To investigate this phenomenon in animal experiments, we established a behavioral task suitable for macaque monkeys. The monkey judged the temporal interval between a pair of tones as short or long, compared with the predetermined criterion. To evaluate the influence of animal's action intention on temporal perception, the tones were presented either contingent on monkey's voluntary button press or just passively. The interval between tones was varied from 100 to 600 ms and changed in each trial. For each session (experimental day), we randomly used different set of intervals and a criterion.
Although the discrimination criterion randomly changed in each session, the monkey generally performed the task well by learning the current criterion. To evaluate this learning process, we applied several computational models to the monkey's choice sequence. We formulated the learning process as updates of internal criterion for short/long judgments on each occasion of trials and errors. Among the models tested, some updated the criterion depending solely on objective task conditions such as physical intervals. Other models also distinguished voluntary/passive presentation conditions which should have been ideally independent of temporal discrimination. Of those, the latter models with distinct account for voluntary presentation suited better to the monkey's behavior. This implies that non-human primates have a cognitive bias in temporal perception similar to humans, and opened future advances of this psychological discipline in animal experiments.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-330
能動・受動運動時の感覚入力ゲーティング計測手法の確立
Sensory gating during active and passive movements: A new methodology using EEG and a haptic device

*小澤 勇介(1)、上原 一将(2,3)、関 和彦(4)、吉村 奈津江(5,6,7,8)
1. 東京工業大学工学院、2. 生理学研究所システム脳科学研究領域神経ダイナミクス研究部門、3. 総合研究大学院大学生命科学研究科生理科学専攻、4. 国立精神・神経医療研究センター神経研究所、5. 東京工業大学科学技術創成研究院、6. 科学技術振興機構戦略的創造研究推進事業(さきがけ)、7. ATR脳情報研究所計算脳イメージング研究室、8. 国立精神・神経医療研究センター脳病態統合イメージングセンター
*Yusuke Ozawa(1), Uehara Kazumasa(2,3), Kazuhiko Seki(4), Natsue Yoshimura(5,6,7,8)
1. School of Engineering, Tokyo institute of technology, Yokohama, Kanagawa, Japan, 2. Division of Neural Dynamics, Department of System Neuroscience, National Institute for Physiological Sciences, Okazaki, Aichi, Japan, 3. Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi, Japan, 4. Department of Neurophysiology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, 5. Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan, 6. Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan, 7. Department of Computational Brain Imaging, ATR Brain Information Communication Research Laboratory Group, Soraku-gun, Kyoto, Japan, 8. Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan

Keyword: Sensory gating, Somatosensory Evoked Potentials, Voluntary movement

Sensory information is essential for us to recognize objects. Sensations perceived on the skin are input as sensory signals by receptors and ascend from skin to the spinal cord and cortex. It has been shown that the sensation of peripheral stimulation to the skin and muscle is suppressed and becomes difficult to perceive during movement, resulting in a phenomenon called "sensory gating". In sensory gating studies, somatosensory evoked potentials (SEPs), which are potentials evoked in the spinal cord and cortex by stimulation of peripheral nerves, are often used through electroencephalography (EEG) recordings. Especially, N20/P25 components are considered to reflect activation in the primary somatosensory cortex (S1), and their amplitudes have been used to confirm modulation by sensory gating. Most of the sensory gating studies based on SEPs have used signals recorded at single or a few EEG electrodes over the sensory motor area, and no study has confirmed whether or not modulation actually occurs in S1.
In this study, therefore, we recorded EEG signals using 64-channel electrodes according to the extended international 10-20 method to investigate whether SEPs at current dipoles that were isolated using independent component analysis (ICA) and localized in S1 are modulated according to motor command differences. We have developed an experimental paradigm that realizes active and passive finger movements using a haptic device called SPIDAR. Twenty participants repeatedly performed a task of pushing a vertically fixed spring back with their index finger (i.e., Active condition), during which they received electrical stimulation of the median nerve in the right wrist at randomized frequencies between 2.5~3.5 Hz. Since the participant’s finger movement positions were recorded and reproduced by SPIDAR, the participants can achieve exactly the same passive movements without pushing the spring and receive electrical stimulation at exactly the same finger movement timing as active (i.e., Passive condition).
As a result, it was confirmed that the both Active and Passive conditions caused sensory gating in the signals recorded from the EEG electrodes, and that the degree of gating was greater in the Active condition than in the Passive condition. Furthermore, dipole fitting following ICA identified independent components in S1 that showed sensory gating in several participants. Our results demonstrate that the establishment of an experimental system can reproduce differences in sensory gating between active and passive movements, as have been shown in a previous monkey study using cortical local field potentials (Seki et al, 2003). In addition, the use of ICA together with the system might allow us to discuss SEP modulation in brain regions rather than at the EEG sensor level.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-331
脳性麻痺動物モデルにおける全身運動に関連したコネクトーム変化
Connectome changes associated with whole-body exercise in cerebral palsy animal model

*後藤 太一(1,2)、釣木澤 朋和(3,4)、小牧 裕司(5)、髙島 一郎(1,2)、九里 信夫(2)
1. 筑波大学大学院人間総合科学学術院人間総合科学研究群ニューロサイエンス学位プログラム、2. 国立研究開発法人産業技術総合研究所人間情報インタラクション研究部門統合神経科学研究グループ、3. 国立研究開発法人産業技術総合研究所人間情報インタラクション研究部門心身機能・モデル化研究グループ、4. 筑波大学大学院理工情報生命学術院システム情報工学研究群知能機能システム学位プログラム、5. 公益財団法人実験動物中央研究所ライブイメージングセンター
*Taichi Goto(1,2), Tomokazu Tsurugizawa(3,4), Yuji Komaki(5), Ichiro Takashima(1,2), Nobuo Kunori(2)
1. Master's and Doctral Prog in Neurosci, Deg Prog in Comp Hum Sci, Grad Sch of Comp Hum Sci, Univ of Tsukuba, Japan, 2. Integ Neurosci Res Group, Hum Infor Inter Res Insti, AIST, Japan, 3. Mental and Physical Func Mod Group, Hum Infor and Inter Res Insti, AIST, Japan, 4. Master's and Doctral Prog in Intel and Mech Inter Sys, Deg Prog in Sys and Infor Engi, Grad Sch of Sci and Tech, Univ of Tsukuba, Japan, 5. Live Imaging Center, Cent Insti for Exp Ani, Japan

Keyword: cerebral palsy, sensorimotor function, connectome, DTI tractography

Neonatal hypoxic ischemia (HI) is the main cause of the cerebral palsy (CP) and often results in some dysfunctions (e.g. sensorimotor impairment, cognitive dysfunction and learning disorder). In medical fields, sensorimotor impairments in CP patients are often treated with rehabilitation although there is still no established treatment to promote functional recovery. It has been thought that the plastic changes in the sensorimotor areas can be important for CP patients to improve their motor functions. However, the change of whole-brain neural connectivity in CP patients resulting from the rehabilitation is not well-known. In this study, we aimed to investigate the effect of exercise on the white matter structure in HI rats. White matter structure was estimated by using ex vivo diffusion tensor imaging (DTI) tractography in neonatal HI animal model to compare between the HI animals with and without training exercise. Neonatal HI animal model was made by following procedures: neonatal rat pups on the PND7 (postnatal day 7) were subjected to ligate their unilateral common carotid artery, and then exposed to hypoxic condition (8% O2). From PND21, HI rats performed exercise training for three weeks with a rotarod apparatus as a rehabilitation to improve their sensorimotor function. The HI rats were sacrificed after the training and whole-brain was used for ex vivo DTI with 7.0 tesla MRI system. In DTI tractography, fractional anisotropy was calculated to estimate the white matter connectivity. During the training periods, motor impairments observed in the trained-HI rats was significantly improved than that in the untrained-HI rats, suggesting the effectiveness of exercise training. The DTI tractography analysis revealed that the intra-hemispheric connectivity among motor-related brain regions, including the motor cortex, sensory cortex, striatum, substantia nigra and thalamus was strengthened in the trained-HI rats. On the other hand, the trained-HI rats showed the weakened inter-hemispheric connectivity between the bilateral sensorimotor cortex and thalamus. These results suggest that exercise training after neonatal HI can induce different changes in white matter connectivity between inter- and intra- hemisphere. These changes derived from exercise training may be important to promote the improvement of motor performance in CP.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-332
加齢による脳機能結合柔軟性変化と運動誤差学習能力
Age-related changes in flexible brain networks: how network flexibility influences aging effects on error-based motor learning

*上原 一将(1,2)、萩原 淳(1,2)、北城 圭一(1,2)
1. 自然科学研究機構 生理学研究所 神経ダイナミクス研究部門、2. 総合研究大学院大学 生命科学研究科
*Kazumasa Uehara(1,2), Makoto Hagihara(1,2), Keiichi Kitajo(1,2)
1. Division of Neural Dynamics, National Institute for Physiological Sciences, Okazaki, Japan, 2. Department of Physiological Sciences, The Graduate University of Advanced Studies, Okazaki, Japan

Keyword: Flexible brain networks, Aging , Error-based motor learning, Electroencephalogram

Motor learning is a lifelong experience from early childhood through older age. In general, the ability to flexibly readjust motor output in response to sensory input is essential for better motor learning. To achieve this, the ability to flexibly reorganize brain networks is a requirement to update subsequent sensory inputs and motor outputs. However, a wealth of evidence has reported that aging-related changes in neuromuscular function disrupt a relationship between sensory input and motor output, resulting in a decrease in the capacity of motor learning. Throughout aging, the central nervous system must adapt continuously age-related changes in neuromuscular function. This sustained adaptation may lead to the induction of maladaptive brain plasticity. Based on this putative mechanism, we hypothesized that aging influences network flexibility due to maladaptive plasticity. If this is the case, the contributions of network flexibility to motor learning processes may differ between younger and older ages. To address this, we recorded cortical electroencephalogram (EEG) while younger- and older-aged participants learned a simple error-based visuomotor adaptation task. Fifty-four participants were recruited and divided into two groups of 27 participants, each based on younger- and older-aged groups. We asked participants to learn the error-based visuomotor adaptation task with their right fingers and recorded 63-channel cortical EEG data. Using the phase synchrony index to quantify phase synchrony of EEG signals from electrode pairs, temporal changes in functional connectivity of brain networks in the theta, alpha and beta frequency bands were assessed. Network flexibility in each frequency band was then extracted using the Louvain method for network community detection. We found that the whole brain network flexibility in the alpha band in the older group was significantly lower than that in the younger group. During the online learning period, the younger group showed a significantly longer-lasting decline in tracking error than the older group, even at the end of the learning period. Furthermore, LASSO regression analyses revealed that network flexibility in the alpha band during the motor preparation predicted the ability of the long-lasting learning as well as 10-min retention in the younger group, but not in the older group. In contrast, the older group exhibited that network flexibility in the beta band after presenting a binary feedback signal, which informs the participants of success or failure, predicted the ability of the long-lasting learning. Together, our study characterizes the decline in network flexibility with aging and suggests that distinct roles of network flexibility in error-based motor learning may exist between younger and older individuals in order to cope with the aging effects on neuromuscular function.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-333
ヒト同側皮質脊髄路の定量比較
Quantitative comparison of ipsilateral corticospinal tracts in humans

*臼田 升(1)、菅原 翔(1)、福山 博幸(2)、雨宮 きよみ(2)、西村 幸男(1)
1. 東京都医学総合研究所脳機能再建プロジェクト、2. 東京都立松沢病院診療放射線科
*Noboru Usuda(1), Sho K Sugawara(1), Hiroyuki Fukuyama(2), Kiyomi Amemiya(2), Yukio Nishimura(1)
1. Neural Prosthesis Project, Tokyo Metropolitan Institute of Medical Science, 2. Department of Radiology, Tokyo Metropolitan Matsuzawa Hospital

Keyword: Corticospinal tract, fiber tractography, humans, voluntary movements

The corticospinal tract (CST) has an important role to control skilled movements. Over 85% of CSTs cross at the pyramid, while 10–15% of CSTs are believed to project to the ipsilateral side in humans. Cortical stimulation induces movement not only in the contralateral limb but also in the ipsilateral limb to the stimulation. However, it remains obscure cortical origin of CSTs from the ipsilateral hemisphere in humans. The current study aimed to clarify the cortical origins and to estimate the proportion of ipsilateral CSTs (iCSTs) arising from each origin based on diffusion-weighted imaging (DWI).
Twenty-nine healthy volunteers participated in the 3T MRI experiment. T1-weighted image and DWI were measured covering through the whole brain to the cervical cord. Anatomical evidences showed that the damaged cortical areas induced degeneration of lateral funiculus which corresponds with CST on the ipsilateral spinal cord. Electrophysiological evidence showed the cortical areas where electrical stimulation elicits the motor responses of body on the ipsilateral side. Based on these evidences, Brodmann area (BA) 1-9, 24, 31, 32, 39, 40, 44, 45, and 46 were decided as the candidates for the origin of iCSTs. In addition, we defined BA10, frontal pole (FP) as a negative control. Streamlines were delineated from these candidate areas and reached to C1 segment on the lateral funiculus of the spinal cord on the ipsilateral side.
The densities of streamline from BA3-6 were significantly higher, while those of the posterior parietal area and medial wall were not different or lower than that of the FP. Therefore, BA3-6 were defined as the origin of iCSTs in humans which corresponded with contralateral CSTs. 50% of iCSTs arose from BA4 which refers to the primary motor cortex (M1), and 42% from the BA6 which refers to the premotor cortex (PM), and the rest from BA3 and 5. The present study identified the cortical origin of iCSTs in humans and quantified their cortical proportion non-invasively. Our present results may contribute to improving the prognosis prediction after spinal cord injury and brain damage, and to elucidating the mechanism of congenital mirror movements.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-334
運動能力の熟練における高次運動野から一次運動野への文脈依存的な集団神経活動の移行
Transition of distinct context-dependent ensembles from secondary to primary motor cortex facilitates skilled motor performance

*寺田 晋一郎(1)、松崎 政紀(1,2,3)
1. 東京大学大学院医学系研究科細胞分子生理学、2. 理化学研究所脳神経科学研究センター脳機能動態学連携研究チーム、3. 東京大学国際高等研究所ニューロインテリジェンス国際研究機構
*Shin-Ichiro Terada(1), Masanori Matsuzaki(1,2,3)
1. Dept of Physiolgoy, Grad Sch Med, Univ of Tokyo, Tokyo, Japan, 2. Brain Functional Dynamics Collab Lab, RIKEN CBS, Saitama, Japan, 3. WPI-IRCN, Univ of Tokyo, Tokyo, Japan

Keyword: MOTOR CORTEX, MULTI-AREA CALCIUM IMAGING, AXON IMAGING, SKILLED MOVEMENT

Voluntary movements can be either internally or externally triggered. The higher motor cortex (M2) is activated differently in these scenarios, even when the same motor outputs were produced. However, it is still poorly understood how and where the different context information converted into the same goal-directed motor output in the motor cortex. Here, we trained head-fixed mice to perform internally triggered (IT) and external-cue triggered (ET) lever-pull trials. To compare L2/3 neuronal activities between M2 and primary motor cortex (M1) and reveal their interactions at population and single-neuron levels, it is crucial to measure the activity of multiple neurons in the same trials, because trial-to-trial variability in behavior affects neuronal activity. Therefore, we used super-wide-field two-photon microscopy (Terada et al., 2018), which can sequentially image forelimb M2 and M1 that are 2 mm apart. To directly reveal the signal transmitted from M2 to M1, we imaged the activities of axons from M2 to M1. We also examined the pyramidal tract (PT) neurons in M1. M2 consistently showed different population activity between IT and ET trials, although forelimb movements were very similar. By contrast, the context dependency of M1 was lower than or equal to M2, and was variable. M2→M1 axons behaved like M1 L2/3 neurons, and M1 pyramidal tract neurons consistently showed low context dependency. The higher the context dependency in M2→M1 axons was, the better task performance was. High context dependency in M1 L2/3 was associated with improved task performance with fine-movement proficiency. These results suggest that emergence of distinct context-dependent ensembles in the M2→M1 channel and M1 L2/3 is required for the context-motor transformation that facilitates skilled motor performance.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-335
リーチング運動の誤差の補正における大細胞性赤核と小細胞性赤核の異なる機能
Distinct functions of the parvocellular and magnocellular divisions of red nucleus in compensating for the error in reaching

*井上 雅仁(1)、北澤 茂(1,2,3)
1. 大阪大学大学院生命機能研究科、2. 大阪大学大学院医学系研究科、3. 情報通信研究機構脳情報通信融合研究センター
*Masato Inoue(1), Shigeru Kitazawa(1,2,3)
1. Grad Sch Frontier Bioscience, Osaka University, Osaka,Japan, 2. Grad Sch Medicine, Osaka University, Osaka, Japan, 3. Center for Information and Neural Networks, National Institute of Information and Communications Technology, and Osaka University, Osaka, Japan

Keyword: Red Nucleus, monkey, Reaching

The primate red nucleus contains two regions, parvocellular (RNp) and magnocellular (RNm) divisions. RNm receive cortical input from the primary motor cortex and project to the contralateral spinal cord in the rubrospinal tract. RNp projects to the inferior olive, which give rise to the climbing fibers that synapse onto Purkinje cells in the cerebellar cortex. These difference input-output configurations suggest that RNm is involved in motor control but RNp is related to motor learning. To clarify distinctive roles of the two divisions in motor control and learning, we examined neuronal activities of RNp and RNm while two monkeys made rapid reaching movement toward a visual target. Not only RNp neurons (40%) but also RNm neuron (20%) encoded information on motor prediction error (MPE) during the movement, and/or visual apparent error (AE) after the end of movement. Repetitive paring of reaching movements with post-movement microstimulation to RNp, but not that to RNm, produced a gradual and significant increase of the end-point error opposite to the preferred direction of AE and MPE. Interestingly, RNm neurons in particular encoded information on AE of the previous reaching movement as well as information on MPE of the forthcoming reaching movement “before” the target presentation. These pre-target activities could reflect monkey’s motor bias to adapt the forthcoming reaching movement. These results suggest that RNp provide visual and non-visual error signals that drive trial-by-trial adaptation through modification of the cerebellum via the inferior olivary nucleus, and RNm contributes to the online modification of the forthcoming reaching movement based on the memory of the error in the previous trial.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-336
随意運動において下行性入力と感覚フィードバック信号は連続的に筋活動生成に寄与する
Sequential contribution of descending drive and afferent feedback to muscle activity during voluntary limb movements

*梅田 達也(1,2,3)、伊佐 正(1,3,4,5)、西村 幸男(3,4,5,6,7)
1. 京都大学大学院医学系研究科、2. 国立精神・神経医療センター、3. 生理学研究所、4. 京都大学ヒト生物学高等研究拠点、5. 総研大、6. 東京都医学総合研究所、7. JST
*Tatsuya Umeda(1,2,3), Tadashi Isa(1,3,4,5), Yukio Nishimura(3,4,5,6,7)
1. Grad Sch Med, Kyoto University, Kyoto, Japan, 2. National Center of Neurology and Psychiatry, Kodaira, Japan, 3. National Institute for Physiological Sciences, Okazaki, Japan, 4. WPI-ASHBi, Kyoto University, Kyoto, Japan, 5. Sch Life Sci, SOKENDAI, Hayama, Japan, 6. Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan, 7. PRESTO, JST, Kawaguchi, Japan

Keyword: MOTOR CORTEX, SPINAL REFLEX, DECODING, MONKEY

Descending drive and spinal reflexes play an important part in generating muscle activity during voluntary movement. However, since the role of these factors has been evaluated separately, we do not know the relative importance of these two inputs during voluntary limb movements. Therefore, the temporal impacts of these inputs on the spinal motoneurons should be clarified by comprehensively analyzing the movement control systems that incorporate the motor cortex (MCx) and the spinal reflex arc composed of muscles and peripheral afferents. In this study, we simultaneously recorded electrocorticogram signals from the MCx, including the primary motor and premotor cortices, the activity of a population of peripheral afferents by chronically implanting electrode arrays into cervical dorsal root ganglions, and electromyography of forelimb muscles (10, 12 muscles) of two monkeys during reaching and grasping movements. To examine how activities in both the MCx and peripheral afferents were converged in the spinal motoneurons, we built a linear model to explain muscle activity at time 0 from activities in the MCx (descending input) and peripheral afferents (afferent input) from -50 ms to -5 ms. Decomposition of the reconstructed muscle activity into each subcomponent indicated that muscle activity before movements could first be explained by ongoing descending input and that after movement onset by both descending and afferent inputs. While descending input has a facilitatory effect on all muscles, afferent input exhibited facilitatory or suppressive effects among muscles. The various impacts of afferent input were accounted for by the spinal reflex and reciprocal inhibition. Thus, descending input from the MCx drives the premovement activity of muscles to initiate voluntary movement, and the initial movement subsequently affects muscle activity through the spinal reflex arc. These results suggest that the MCx affects muscle activity by the sequential activation through descending and spinal reflex pathways in addition to direct activation through the descending pathway.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-337
脳卒中麻痺側手指の分離動作における定量評価法の開発
Development of a quantitative evaluation method for finger individuation on hemiparesis patients

*今村 彰吾(1,2)、武田 湖太郎(3)、大高 洋平(1,4)
1. 藤田医科大学病院 リハビリテーション部、2. 藤田医科大学大学院 保健学研究科、3. 藤田医科大学 保健衛生学部 リハビリテーション学科、4. 藤田医科大学医学部 リハビリテーション医学I講座
*Shogo Imamura(1,2), Kotaro Takeda(3), Yohei Otaka(1,4)
1. Department of Rehabilitation, Fujita Health Univ, Aichi, Japan, 2. Grad Sch Health Sci, Fujita Health Univ, Aichi, Japan, 3. Faculty of Rehabilitation, Sch of Health Sci, Fujita Health Univ, Aichi, Japan, 4. Department of Rehabilitation Med I, Sch of Med, Fujita Health Univ, Aichi, Japan.

Keyword: Stroke, quantitatively and objectively, three-dimensional motion analysis

【Background and aims】 The impairment of finger individuation remains for a long term after stroke. Because the individuation is expressed in ordinal scales in clinical rehabilitation, it is difficult to detect the process of functional recovery in detail. In the present study, we proposed a method to evaluate the finger individuation quantitatively and objectively using three-dimensional motion analysis. 【Methods】 Forty right-handed healthy subjects and two stroke patients with different motor paralysis (case 1, Brunnstrom Recovery Stage of Hand, BRS-H, VI; case 2, BRS-H, V) were participated in the present study. The participants were asked to flex each finger of the paretic hand from full extension to a position to touch a ball which was placed on their palm. We measured three-dimensional coordinates of the fingertips using two CCD cameras. The obtained positions of the fingertips were normalized with the coordinates in full extension as 0 % and the those reaching the ball as 100 %. Because it is difficult for healthy people to fully flex only the target finger, the involuntary ranges of motion of the nontarget fingers were defined as the mean distance +2SD of healthy participants. In the measurement of patients, the amount of voluntary movement of the target finger without the involuntary movement of non-target finger beyond the healthy range was used as the individual index for each finger of the patients. 【Results】 In the case 1, the patient was able to move the thumb, index finger, and little finger independently within the range of involuntary movements of healthy participants (individuation index was 100 % for each). For the middle and ring fingers, the indexes were 66.6 and 98.7 % of the full trajectory, respectively. Involuntary movements of the thumb beyond the healthy range were detected in these conditions. In the case 2, involuntary movements of various non-target fingers were observed during all target finger movements. Consequently, the amount of each target finger that could be moved independently was 46.7, 67.9, 51.9, 72.0, and 20.5 %, in the order of thumb, index finger, middle finger, ring finger, and little finger, respectively. 【Discussion】 The percentage value for each target finger indicates the maximum flexion amount without involuntary movements of the non-target fingers which were defined using the range of the healthy participants. If the value is 100 %, it means that the target finger has the same individuation of the healthy population. Most of the indexes in case 1, whose BRS-H score was VI ("hand independence is maintained"), were high and closed to the healthy participants. On the other hand, the case 2 whose BRS-H score was V ("clumsy movement and limited functional use") showed lower individuation indexes for all fingers. In conclusion, therefore, the proposed method may be considered to detect the differences of the finger individuation objectively and quantitatively.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-338
感覚運動協調における時間的予測に関わる神経基盤の解明:7T fMRI研究
Neural correlates of temporal prediction during sensorimotor synchronization: a 7T fMRI study

*宮田 紘平(1,2)、山本 哲也(2)、福永 雅喜(2)、菅原 翔(2)、定藤 規弘(2)
1. 東京大学大学院総合文化研究科、2. 生理学研究所システム脳科学研究領域
*Kohei Miyata(1,2), Tetsuya Yamamoto(2), Masaki Fukunaga(2), Sho Sugawara(2), Norihiro Sadato(2)

Keyword: Sensorimotor synchronization, Temporal prediction, 7T fMRI, Dorsal premotor cortex

Movement synchronization with external rhythms (sensorimotor synchronization) is paramount for mesmerizing performances in music and dance. In order to achieve synchronization, the performers must anticipate the upcoming beats seamlessly. Temporal-prediction ability is vital for a comprehensive range of movement and performance skills; however, little is known regarding individual variation in temporal prediction ability and its neural correlates. This study aimed to determine the underlying neural correlates with temporal prediction, and the individual variation during auditory-motor synchronization. We hypothesized that the non-primary motor cortex, such as the premotor cortex and supplementary motor area, is the key brain region, which correlates individual variation in prediction ability. To test this hypothesis, we performed functional magnetic resonance imaging using 7T MRI with 18 healthy volunteers who tapped to three types of auditory metronome beats: isochronous, tempo change, and random. The inter-onset interval (IOI) was 500 ms through a trial in the isochronous condition. The IOI varied in range from 400 ms to 600 ms following a triangle wave in the tempo change condition. In the random condition, the IOI of the tempo change condition was randomly ordered. The prediction ability was evaluated using prediction/tracking ratios that were computed based on the lag-0 and lag-1 cross correlations between the IOI and the inter-tap interval in the tempo change trials. Participants with a higher prediction/tracking ratio (i.e., stronger predictive tendency) tapped to metronome beats more accurately and precisely. The prediction/tracking ratio positively correlated with the activity in the bilateral dorsal premotor cortex (PMd), suggesting that the bilateral PMd explains the individual variation in the prediction ability. These results indicate that the PMd is involved in generating a model for temporal prediction of auditory rhythm patterns, and its activity would reflect the model accuracy, which is critical for accurate and precise sensorimotor synchronization.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-339
時間知覚と生成におけるサル前頭前野と内側運動前野の機能連関
Functional linkage between prefrontal cortex and medial premotor areas of the monkey in time estimation and production

*千葉 惇(1)、守田 和紀(2)、生塩 研一(1)、稲瀬 正彦(1)
1. 近畿大学医学部生理学、2. 岩手医科大学医学部生理学
*Atsushi Chiba(1), Kazunori Morita(2), Ken-ichi Oshio(1), Masahiko Inase(1)
1. Dept Physiol., Facult Med., Kindai Univ., 2. Dept Physiol., Facult Med., Iwate Medical Univ.

Keyword: FUNCTIONAL LINKAGE, PREFRONTAL CORTEX, MEDIAL PREMOTOR AREAS, TIME ESTIMATION AND PRODUCTION

Time perception and generation are vitally important in sensory recognition and behavioral control. In the research on neural mechanism of interval timing, functional linkage between different cortical areas in duration estimation and production has not been clarified. To investigate this functional linkage, we examined neuronal activity in the dorsolateral prefrontal cortex (PFC) and the medial premotor areas (MPA) of monkeys during the task in which subjects estimated duration of a visual stimulus and produced duration in motor preparation. A trial started when subjects pressed the hold key. One sec later a green square (C1) was presented on the center of a monitor for 0.8, 1.6, or 3.2 sec. Following a 1 sec delay period, a red square (C2) was presented on the monitor and kept on until the release of the hold key. Subjects were required to keep pressing the hold key until the start of the allowed press interval, and to release it and to press a target button during that interval. The allowed press interval was indicated by the C1 duration. When the C1 was presented for 0.8 sec, the subject needed to keep pressing the hold key more than 3.2 sec and to press the target button within 4.8 sec after the start of the C2 presentation. When the C1 duration was 1.6 or 3.2 sec, the allowed press interval was 1.6 to 3.2 sec, or 0.8 to 1.6 sec after the C2 onset, respectively. Subjects behaved differently among the short, middle, and long C1 trials. Correct rates to the short C1 trials were lower than those to the other two types of trials. Retention times between the C2 onset and the hold key release were differentially distributed among the three types of trials. The retention times peaked steeply in 1.0-1.4 sec after the C2 onset for the long C1 trials, gently in 2.0-3.0 sec for the middle C1 trials, and 3.2-4.0 sec for the short C1 trials. Out of 297 recorded PFC neurons, 5, 18 and 60 neurons responded during the C1, delay, and retention periods, respectively. Among500 recorded MPA neurons, 5, 37, and 68 neurons responded during the C1, delay, and retention periods, respectively. C1-responsive PFC neurons showed build-up activity during the late part of the long C1 presentation. Delay-responsive PFC neurons showed phasic activity that changed depending on C1 duration. Delay-responsive MPA neurons also exhibited phasic activity that represented C1 duration. Retention-responsive MPA neurons showed build-up activity that were increasing toward the end of the retention period. The build-up activity was different after the three types of C1 presentation. So far, neurons related to both estimation of C1 duration and duration production have not been found either in PFC or MPA. These results suggest that PFC engaged more in duration estimation of a visual cue, and that the temporal information of the cue was sent from PFC to MPA. After that MPA was involved more in production of retention duration based on the cue information from PFC.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-340
外的なエラーに基づく潜在的な運動調節
Implicit motor adjustment based on errors caused by external sources

*松田 直祥(1)、阿部 匡樹(1)
1. 北海道大学教育学院
*Naoyoshi Matsuda(1), Moa O Abe(1)
1. Grad Sch Edu, Hokkaido Univ, Japan

Keyword: error-based learning, motor variability, sensorimotor adaptation, error sensitivity

To adapt to the changing environment, humans implicitly adjust their movement based on the generated error. Whereas the adjustment is effective for consistent environmental changes, we should not adjust our movement when the environment changes temporarily and infrequently, or when the intermittent occurrence of error is attributed to external sources rather than our movement. This study examined the impact of an intermittent error caused by an external source on the subsequent movement with a visuomotor rotation task. Participants performed a shooting movement without a direct vision of the hand and moved a cursor, representing online visual feedback, toward a target. The rotation between their hand location and the cursor location increased by 0.25° counterclockwise per trial until it reached 30°, and the 30° rotation lasted for 60 trials. Then, 200 trials were conducted in Exp 1, including 150 trials with 30° rotation and 50 trials with 46° rotation. During the 200 trials, following every shooting movement, the participants rated the extent to which they felt that the cursor was under their control to confirm their awareness of changes in the environment (that is, 16° increase in rotation). In Exp 2, the 46° rotation trial was replaced by clamped visual feedback that followed a fixed trajectory ignoring their hand movement. This trajectory was always offset from the target by 16° in this study. After, but not before, the movement, participants were able to know whether the clamp feedback was presented by the color of the cursor and auditory feedback. Notably, trials with the 46° rotation and clamp feedback always presented a large error even though they had adapted to the 30° rotation environment. In Exp 1, participants were able to attribute the occurrence of approximately 16° error to external sources, but immediately after the exposure to the large error, they slightly, but significantly, compensated the error. In Exp 2, they also corrected their movement in the next trial of clamped visual feedback. Furthermore, we observed a tendency that the greater the variability of the shooting movement under new environment with the 30° rotation, the greater was the sensitivity to the clamp feedback. The results indicated that humans could not completely ignore an error whose occurrence is not attributed to themselves and would adjust their movements unnecessarily based on the error. Moreover, the extent of the adjustment would depend on the motor variability.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-341
下肢への末梢感覚刺激による運動野および脊髄における短潜時・長潜時求心性抑制
Short- and long-latency afferent inhibition in the motor cortex and spinal cord by peripheral somatosensory stimulation in the lower limb

*加藤 辰弥(1,2)、佐々木 睦(1,2)、中澤 公孝(1)
1. 東京大学総合文化研究科、2. 日本学術振興会
*Tatsuya Kato(1,2), Atsushi Sasaki(1,2), Kimitaka Nakazawa(1)
1. Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan, 2. Japan Society for the Promotion of Science, Tokyo, Japan

Keyword: sensorimotor integration, transcranial magnetic stimulation, Hoffman reflex, afferent inhibition

The integration of peripheral afferent information and motor commands is essential for motor control. In humans, paired-pulse paradigms have been used to explore how sensory signals modulate the primary motor cortex. Preceding peripheral sensory stimulation inhibits motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS), which is called short-latency afferent inhibition (SAI) or long-latency afferent inhibition (LAI), depending on the length of inter-stimulus intervals (ISIs). Many previous studies have demonstrated that SAI and LAI of the upper limbs are evoked at ISI near 22 ms and 100 ms ~, respectively, but optimal ISIs and stimulus intensities of lower-limb SAI and LAI remain unclear. Here, we investigated MEP of the right soleus (SOL) muscle after right tibial nerve stimulation at the knee, using ISIs of 20-50, 100, 200, and 220 ms. When the stimulus intensity of peripheral sensory stimulation was set to a three-fold perceptual threshold, MEP amplitudes were significantly decreased at ISIs of 220 ms. However, when the stimulus intensity of peripheral sensory stimulation was set to H-reflex threshold minus 1 mA, MEP amplitudes were significantly decreased at ISIs of 30, 35, 100, and 200 ms. For the SAI at ISIs of 30 and 35 ms, shorter ISI to P30 latency of somatosensory evoked potentials (SEPs) resulted in greater inhibition of MEPs. We also measured the H-reflex of the SOL muscle to observe modulation at the spinal level after peripheral sensory stimulation, but H-reflex was unchanged at all ISIs. In addition, we tested at ISIs of 60-200 ms to explore the modulation at long latency in more detail. MEP amplitudes were significantly decreased at ISIs of 100 and 180 ms, while H-reflex was significantly decreased at ISIs of 120 ms. In summary, ISI of 30 and 35 ms may be most effective for SOL muscle SAI and induce MEP suppression at the cortical level. Given the conduction time from the periphery to the motor cortex via the somatosensory cortex, lower-limb SAI may involve a pathway from the periphery to M1 directly through the thalamus. MEPs were also suppressed at ISIs from 100 to 220 ms, which may be attributed to extensive cortical activities.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-342
Rewarding electric brain stimulations can induce positive emotion associated with 50-kHz ultrasonic vocalizations in rats even under a head-fixed condition
*Chinzorig Choijiljav(1,3), Jumpei Matsumoto(1,2), Hiroshi Nishimaru(1,2), Tsuyoshi Setogawa(1,2), Hisao Nishijo(1,2)
1. Dep SES, Grad Sch of Innovative life sci, Univ of Toyama, Toyama, Japan, 2. RC for Idling Brain sci, Univ of Toyama, Toyama, Japan, 3. Ins of Biomedical sci, Sch of Bio Med, MNUMS, Ulaanbaatar, Mongolia

Keyword: vocal-audio interaction, single-unit recording, ultrasonic vocalizations, auditory feedback

The auditory system is thought to receive feed-forward signals from the vocal-motor system conveying predictions about the auditory signals caused by own vocalization. To investigate neural mechanisms of such vocal-audio interaction, auditory feedback experiments, where feedback sounds of the subject’s vocalizations are modified via a ‘voice changer’, have been developed and used in various species such as humans, monkeys, and birds. Recently ultrasonic vocalizations (USVs) in rodents have been receiving attention as a new experimental model to study neural mechanism of vocalization. However, a method for the auditory feedback experiment for the rodents’ USVs has not been developed. In the auditory feedback experiment, the animal’s head is often required to be fixed, and its vocalization is recorded and played back from a microphone in front of its mouth and a headphone, respectively. So, as the first step to set up the feedback experimental system, in this study, we established the protocol to induce USVs under the head-fixed condition. We found that rewarding electric brain stimulations in ventral tegmental area (VTA) or lateral hypothalamus (LH) could induce 50-kHz USVs, which are reported to reflect positive emotion, even under the head-fixed condition with high reproducibility (USV frequency: 7.9 to 31.2 calls/min; four Wistar male rats were tested) after the rats were well acclimated. The USV frequency in the head-fixed conditions tended to be positively correlated with the one with the same electric stimulation in a freely moving condition (r = 0.91, p = 0.09), although the average USV frequency was smaller in the head-fixed condition (head-fixed: 17.3 ± 5.1 calls/min; freely moving: 42.6 ± 4.8 calls/min; p = 0.0013, paired t-test). By utilizing the established protocol, we also recorded neuronal activity of 28 neurons in the auditory cortex during USVs under the head-fixed condition. We found 4 neurons showing responses prior to the sound onset, which may be associated with the feedforward signal from the vocal-motor system. The results support that the present rat model would be useful for investigating vocal-audio interaction. Development of the methods for the auditory feedback experiment in rats based on the present findings should contribute to understanding of neural mechanisms of vocal-audio interaction and its possible dysfunctions in neuropsychiatric disorders, such as auditory hallucinations in schizophrenia.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-343
一致タイミング課題において複数の事前分布の汎化を妨げる要因の検証
Factors inhibiting generalization for multiple prior distributions in a coincidence timing task

*夏目 柊(1)、佐藤 良(1)、松村 圭貴(1)、James Heron(2)、Neil Roach(3)、宮崎 真(1)
1. 静岡大学大学院総合科学技術研究科、2. ブラッドフォード大学検眼・視覚科学部、3. ノッティンガム大学心理学部
*Shu Natsume(1), Ryo Sato(1), Yoshiki Matsumura(1), James Heron(2), Neil W. Roach(3), Makoto Miyazaki(1)
1. Grad Sch Integrated Sci & Tech, Shizuoka Univ, Hamamatsu, Japan,, 2. Sch of Optometry and Vision Sci, Univ of Bradford, Bradford, United Kingdom, 3. Sch of Psychology, Univ of Nottingham, Nottingham, United Kingdom

Keyword: Timing, Bayesian estimation, Prior, Generalization

The brain can acquire prior distributions of stimuli to optimize sensorimotor task performance. Real environments involve a variety of factors and events; thus, in daily life, the brain must deal with multiple prior distributions. In a duration reproduction task, when participants were subject to two prior distributions, short-time and long-time, they rapidly acquired a single prior by generalizing the two distributions (‘Generalization’, Roach et al. 2017, PNAS). In a coincidence timing task, however, the generalization did not occur; participants did not acquire a short-time prior, but instead selectively acquired the long-time prior (Matsumura et al. FENS2020). We hypothesized that the differences in results between the studies are due to differences in the availability of error feedback between the tasks. In coincidence timing tasks, it should be easier and more precise for participants to obtain feedback, as they can compare their motor responses to target stimuli in real time. In duration reproduction tasks, however, participants cannot compare their motor responses to target stimuli in real time. In the current study, we tested this hypothesis using a timing reproduction task that was designed by modifying the coincidence timing task (Matsumura et al. FENS2020). In the study by Matsumura et al., three sequential visual stimuli (S1, S2, and S3) were presented, and participants pressed a key to coincide with the onset of S3. In the current experiments, S3 was removed. Thus, two sequential visual stimuli (S1 and S2) were presented on the right and left sides of the fixation point. Participants pressed a key to make the time interval between S2 and the key press coincide with that between S1 and S2 (target interval) using only the dominant index finger, irrespective of the stimulus locations. Each participant performed 640 trials (40 trials/set × 16 sets) of the task. Target intervals were sampled from short-time (424–988 ms) or long-time (1129–1694 ms) prior distributions. Each of the two priors was assigned to one of the two stimulus locations. Consistent with the findings of Roach et al., we found that participants exhibited generalization in early sets but subsequently learned the two priors separately. These results demonstrate that the availability of error feedback can shape prior learning with multiple stimulus distributions.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-344
ヒトの脳における超適応:車いすレースのトップパラリンピアンでみられる一次運動野足領域の機能的・構造的変化
Hyper-adaptation in the Human Brain: Functional and structural changes in the foot section of the primary motor cortex in a top wheelchair racing Paralympian

*内藤 栄一(1,2)、守田 知代(1,2)、廣瀬 智士(3,1)
1. 情報通信研究機構、2. 大阪大学、3. 追手門学院大学
*Eiichi Naito(1,2), Tomoyo Morita(1,2), Satoshi Hirose(3,1)
1. National Institute of Information and Communications Technology, 2. Osaka University, 3. Otemon Gakuin University

Keyword: hyper-adaptation, magnetic resonance imaging, primary motor cortex, paraplegia

The human brain has a capacity to drastically change its somatotopic representations in response to congenital or acquired limb deficiencies and dysfunction. Main purpose of the present study was to elucidate such higher adaptability in the brain of an active top wheelchair racing Paralympian (participant P1), who had congenital paraplegia (dysfunction of bilateral lower limbs), and long-term wheelchair racing training using bilateral upper limbs, and has won a total of 19 medals in six consecutive summer Paralympic games by 2021. We examined the functional and structural changes in the foot section of the primary motor cortex (M1) in participant P1 when compared to able-bodied control participants. We also examined such functional and structural changes in other three individuals (participants P2, P3, and P4) with acquired paraplegia, who also had long-term non-use period of lower limbs and long-term wheelchair sports training (but not top athletes at the level of participant P1). In all participants, we measured brain activity using functional magnetic resonance imaging (MRI) when bimanual wrist extension-flexion movement was performed, and structural MRI images were collected. Compared to 37 control participants, participant P1 showed significantly greater activity in the M1 foot section during the bimanual task, and significant local GM expansion in the M1 foot section. The significantly greater activity in the M1 foot section was also observed in participant P4, but not in P2 and P3, and the significant local GM expansion was observed in participant P2, but not in P3 and P4. Thus, the functional or structural change identified in participant P1 was also observable even in an acquired paraplegic participant, but not always observable in all paraplegic participants. The functional and structural changes observed in participant P1 could be the results of brain’s adaptation to unusual physical conditon (paraplegia), in which a brain region (M1 foot section) has drastically changed (not temporary change) to become used for a function (hand sensory-motor processing) other than its original function (foot motor control) with its organic alteration, probably through long-term physical (wheelchair racing) training. In this light, one could argue that the functional and structural changes may represent extraordinary adaptability of the human brain, and thus we propose that these could be better called hyper-adaptation than normal adaption because these are rarely seen in normal people. The current study provided valuable insights for thinking about hyper-adaptation.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-345
dystonia musculorumマウスの運動異常における感覚運動回路の役割
Role of sensory-motor circuit in the movement disorders observed in dystonia musculorum mice.

*吉岡 望(1)、黒瀬 雅之(2)、佐野 裕美(3)、知見 聡美(3)、山村 健介(4)、南部 篤(3)、竹林 浩秀(1)
1. 新潟大学医学部脳機能形態学、2. 岩手医科大学歯学部病態生理学、3. 生理学研究所生体システム、4. 新潟大学歯学部口腔生理学
*Nozomu Yoshioka(1), Masayuki Kurose(2), Hiromi Sano(3), Satomi Chiken(3), Kensuke Yamamura(4), Atsushi Nambu(3), Hirohide Takebayashi(1)
1. Div of Neurobiol and Anat, Grad Sch of Med and Dent Sci, Niigata Univ., 2. Dep of Physiol, Sch of Dent, Iwate Med Univ., 3. Div of System Neurophysiol, Natl Inst for Physiol Sci., 4. Div of Oral Physiol, Grad Sch of Med and Dent Sci, Niigata Univ.

Keyword: Sensory-motor circuit, dystonin, heriditary neuropathy, conditional gene trap

Mutations in the dystonin (DST) gene encoding the cytoskeletal linker protein is causative for the hereditary sensory autonomic neuropathy VI (HSAN6) which is an inherited human disease of the peripheral nervous system (PNS). Original dystonia musculorum (dt) mice carrying mutations in the Dst locus have been characterized by naturally occurring ataxia and neuronal degeneration in dorsal root ganglion (DRG) sensory neurons. We had generated conditional/invertible Dst gene trap mice in which the Dst gene trap allele inverts from the mutant (DstGt) to functional (DstGt-inv) allele and from functional (DstGt-inv) to mutant (DstGt-DO) allele by Cre-mediated recombination. In the Dst gene trap allele, the conditional gene trap (cGT) construct was inserted in actin-binding domain at the N-terminus of neuronal Dst-a and muscular Dst-b isoforms. Homozygous mice carrying DstGt or DstGt-DO alleles showed ataxia and a deletion of Dst-a mRNA in the neural tissue, while homozygous mice carrying DstGt-inv alleles was phenotypically intact. To manipulate Dst expression in the PNS, Dst gene trap mice were crossed with Wnt1-Cre transgenic mice in which Cre recombinase is expressed in neural crest cells and the hindbrain during the embryonic stages. As expected, Cre-mediated inversion of the Dst gene trap allele was observed in DRG sensory neurons. Wnt1-Cre; Dst cGT mice exhibited ataxia and pathological alternations in DRG neurons including abnormal accumulation of neurofilament and up-regulation of the stress-inducible gene Atf3. In Wnt1-Cre; Dst conditional rescue (cRescue) mice, Dst-a mRNA restored in the nervous system and pathological remarks were ameliorated in DRG neurons. Wnt1-Cre; Dst cRes mice showed increased life span and recovered from ataxia, compared to DstGt homozygous. We found that abnormalities of sensory-motor circuit correlate with ataxic phenotype. These results revealed that abnormalities of sensory-motor circuit are crucial for movement disorder observed in dystonia musculorum mice.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-346
INTERPLAY BETWEEN ENTROPY AND INTEGRATION QUANTIFIES DRUG-INDUCED CHANGES IN MICE BEHAVIOURAL COMPLEXITY
*Keshmiri Soheil(1)、Ignatowska-Jankowska Bogna(1)、Gurkan-Ozer Aysen(1)、Kuck Alexander(2)、Niphakis Micah(2)、Ogasawara Daisuke(2)、Cravatt Benjamin(2)、Uusisaari Marylka(1)
*Soheil Keshmiri(1), Bogna Ignatowska-Jankowska(1), Aysen Gurkan-Ozer(1), Alexander Kuck(2), Micah Niphakis(2), Daisuke Ogasawara(2), Benjamin Cravatt(2), Marylka Yoe Uusisaari(1)
1. Okinawa Institute of Science and Technology Graduate School, 2. Department of Chemical Physiology, Scripps Research Institute

Keyword: endocannabinoid, Entropy, Mice, Behavioural Complexity

Organizational complexity of a system is characterized by the ability of its elements to process and integrate information. Here, we show that the same characteristic “integration of differential information” quantifies drug-induced alteration in behavioural complexity of freely moving mice.

To alter behaviour in C57BL/6 male mice (n=8), we used selective inhibitors of monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH): MJN110 and PF3845, respectively. MAGL and FAAH are enzymes responsible for the degradation of endogenous cannabinoids: 2-arachidonoylglycerol and anandamide, respectively. Systemic administration of MJN110 and PF3845 is known to selectively elevate signaling of these endocannabinoids in the brain. We recorded mouse locomotion during voluntary open field exploration and vertical climbing tasks by tracking the position of 10 markers that were placed on key locations of the body of the mouse. For this purpose, we used high-speed, high-resolution, marker-based 3D motion capture system (Qualisys, Sweden). We then quantified the locomotion complexity in terms of each marker’s entropy (differentiation) and their multi-information (integration).

Inhibition of endocannabinoid degradation resulted in distinct changes in locomotory information integration and differentiation. Mouse became more coordinated (reduced entropy and increased integration) in the open field after PF3845 administration while the effect of MJN110 was opposite (i.e., increased entropy and decreased integration). In vertical climbing task, PF3845 elevated complexity (increased entropy and integration) while MJN110 decreased entropy and increased integration. These results indicate that MJN110 and PF3845 induce different effects on mouse movement complexity, in line with our previous observations. This suggests that entropy and integration are useful analytical tools for quantification of animal behavior. Additionally, the precision of marker-based 3D motion capture in mice opens new avenues for introduction of pointwise information measures in behavioural research, thereby enabling fine-grained analysis of temporally emerging dynamical patterns in animal behaviour.

Acknowledgements: Research was supported by the Japan Society for Promotion of Science (JSPS).
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-347
サルにおける意識下の予期的プロセスが把持運動のフィードバック制御に与える影響
Feedback control of grasping influenced by subliminal prospective process in the macaque monkey

*村田 哲(1)、小高 泰(1)、望月 圭(2)、稲瀬 正彦(1)
1. 近畿大学医学部 生理学教室、2. 岩手医科大学医学部 生理学講座
*AKIRA MURATA(1), YASUSHI KODAKA(1), KEI MOCHIZUKI(2), MASAHIKO INASE(1)
1. Department of Physiology, Faculty of Medicine, Kindai University, 2. Department of Physiology, School of Medicine, Iwate Medical University

Keyword: hand manipulation, prieto-frontal network, subliminal priming, feedback control

The monkey can very well control hand manipulation movement using visual information of object and visual feedback. It is well known that the manipulative hand movement is controlled by parieto-premotor network (AIP and F5), that is core circuit for sensory motor transformation. Recently it has been revealed that the network for manipulative hand movement in the monkey also includes dorsolateral prefrontal cortex, which may contribute intentional control before movement onset. In the previous human experiments, decision for the hand action was influenced by subliminal priming stimuli, showing less reaction time when the actual target for the movement is congruent with the priming stimuli than incongruent. These studies also revealed that this fluency of movement sequence enhanced sense of agency. Furthermore, imaging study showed activity of prefrontal cortex correlated with reaction time in the task. However, it is still unknown how the subliminal prospective process of decision influence feedback control after the movement onset. In this study, we tried to investigate the monkey’s behavior to reveal correlation between subliminal priming and feedback control during reaching-grasping hand movement. We briefly presented a priming visual cue (subliminal or supraliminal) that was one of two objects to be grasped, then after some delay period, the monkey started reaching-grasping movement directed to the congruent or incongruent object with the priming cue. The actual object and visual feedback were presented at the movement onset or several hundred ms after that. In the task session that required the animal to grasp only congruent object with priming, the movement time was always consistent regardless of whether priming was visible consciously or not, even if we presented two objects randomly. Furthermore, when the monkey was required to grasp the congruent or incongruent object randomly, the movement time was longer for the incongruent object than congruent one both with subliminal and supraliminal priming. This means the monkey corrected grasping movement while grasping incongruent object independent of visibility of priming stimuli. The subliminal prospective process could also influence feedback control during reaching-grasping movement.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-348
視覚性二段階応答課題を用いたげっ歯類大脳皮質における感覚・運動変換関連領域の探索
Exploration of sensorimotor transformation-related rodent cerebral cortices using a visual two-step response task

*川端 政則(1)、リオス アライン(1)、坂入 朋美(1)、酒井 裕(2)、礒村 宜和(1,2)
1. 東京医科歯科大学、2. 玉川大学 脳科学研究所
*Masanori Kawabata(1), Alain Antonio Rios(1), Tomomi Sakairi(1), Yutaka Sakai(2), Yoshikazu Isomura(1,2)
1. Tokyo Medical and Dental University, 2. Brain Science Institute, Tamagawa University

Keyword: Sensorimotor transformation, Visual two-step response task, Cortex, Electrophysiology

When an animal performs a visual responsive lever pulling task, sensorimotor transformation occurs in the brain. However, it is unclear whether the transformation occurs in one local area or across multiple areas via intermediate processes. Our previous study (Kawabata et al., 2020) shows that neuronal representation largely changes from sensory to motor between primary visual cortex (V1) and posterior parietal cortex (PPC). In this study, we focused on higher order visual areas (HVA) located between V1 and PPC.
During a simple visual responsive task, rats predict the timing of next stimulation and pull the lever before stimulation (false alarm; FA). Confounding the prediction of stimulus timing may interfere with the quantification of the sensorimotor transformation process. Therefore, we established a visual two-step response task that required usually long hold time (LHT, >1500 ms, >70%) and sometimes short hold time (SHT, <1200 ms, <30%). In SHT trials, the stimulus intensity was weak or middle (response rate: 40% or 60%). If rats did not response to the weak or middle stimulus, strong stimulus was presented after 1200 ms. In this task, FA rate of SHT trials was low, because whole mean hold time was longer than 1200 ms. To explore the areas related to sensorimotor transformation, we focused on the period around middle stimulation that includes both of responded and non-responded trials.
We recorded neuronal activity in the cerebral cortex by using 32ch silicone probes during task performance. The recording sites were changed day-by-day as mapping the cortex around HVA. In preliminary results, HVA showed intermediate neuronal representation between V1 and PPC. It included ramping down neurons that had transient peak related to stimulus onset and long decay until response start. We also noticed that there were oscillating neurons in the visual areas. It may relate to gamma oscillation (Saleem et al., 2017) or beta oscillation (Kimura and Yoshimura, 2021) accompanied with visual stimulus. These results suggest that HVA plays an important role in sensorimotor transformation.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-349
Somatotopic reorganization of the sensorimotor cortex in macaque monkeys after accidental arm amputation
*Pimpimon Nondhalee(1,2), Nobuhiko Hatanaka(1,2), Atsushi Nambu(1,2)
1. Div. of System Neurophysiol, National Inst. for Physiological Sci., Okazaki, Japan, 2. Dep Physiol Sci, Sch Life Sci, Grad Univ Adv Stud (SOKENDAI), Okazaki, Japan

Keyword: M1, Somatotopy, Reorganization

The primary motor (M1) and primary somatosensory (S1) cortices show a somatotopic representation, which is a one-to-one correspondence of each body part to a small region of these cortices. The M1 is located in the precentral gyrus including the anterior bank of the central sulcus (CS), while the S1 is located in the post-central gyrus. The hindlimb, body trunk, forelimb, and orofacial regions are represented mediolaterally in the M1 and S1 along with the CS. The supplementary motor area (SMA), which is located in the mesial side of the hemisphere, is also somatotopically organized. The aim of this study is to investigate how such somatotopy is affected when the subjects lose their body parts. We trained two female Japanese monkeys (Macaca fuscata), who lost their left distal forelimbs below the elbows, to sit quietly in a monkey chair. After they were accustomed, under general anesthesia, they underwent surgery to fix two tubes on the skull for head fixation. Craniotomy was done over the M1/S1 of both sides and SMA, and plastic chambers were fixed on the skull. Electrical intra-cortical micro-stimulation (ICMS) mappings were started after a recovery period. Evoked body part movements by ICMS, threshold currents, and somatosensory responses to body parts were recorded in wide areas of the M1, S1, and SMA including hindlimb, forelimb, and orofacial regions under awake state. This precise ICMS electrophysiological mapping revealed that there was shrinkage of the distal forelimb region in the M1 in the affected side that required less than 10 microA. In the SMA, the stump region was lost or shrunk in the affected side. The mean threshold to evoke distal forelimb movements in the healthy side and that to evoke stump movements in the affected side were comparable in the M1 and SMA. On the other hand, only a little shrinkage of the S1 distal forelimb region was detected. The general arrangement of somatotopy, such as hindlimb, trunk, forelimb, and orofacial, was preserved in the M1, S1, and SMA. In this study, chronic recording in awake monkeys enabled us to obtain precise somatotopic mappings with lower thresholds than previous studies. The stump region previously representing the distal forelimb in the M1 and SMA shrank, while that in the S1 was rather preserved. The reorganization in the M1 and SMA may occur when they lost the body part to control, while the S1 may remain because somatosensory inputs from stumps still exist.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-350
運動状態によるコオロギ気流逃避行動の変化とその神経基盤
Motor-state-dependent changes in wind-elicited escape behavior and their neural basis

*小川 宏人(1)、木内 和秀(2)、設樂 久志(1,3)、岩谷 靖(4)
1. 北海道大学大学院理学研究院生物科学部門、2. 北海道大学大学院生命科学院生命システム科学コース、3. 三重大学大学院医学系研究科生化学講座、4. 弘前大学大学院理工学研究科機械科学コース
*Hiroto Ogawa(1), Kazuhide Kiuchi(2), Hisashi Shidara(1,3), Yasushi Iwatani(4)
1. Dept Bio Sci, Fac Sci, Hokkaido Univ, Hokkaido, Japan, 2. Biosystem Sci, Grad Sch Life Sci, Hokkaido Univ, Hokkaido, Japan, 3. Dept Biochem, Grad Sch Med, Mie Univ, Mie, Japan, 4. Dept Sci Tech, Grad Sch Sci Tech, Hirosaki Univ, Hirosaki, Japan

Keyword: INSECT, ESCAPE BEHAVIOR, LOCOMOTION, MECHANOSENSORY SYSTEM

Animals exhibit different behavioral responses to the identical stimuli, depending on their environments that include[YI1] the external environment and the internal state, such as whether the animal is stationary or in motion. The escape behavior, which determines survival, should be performed differentially according to the motor state when prey animals received threat signals suggesting predators. However, it is still unknown what effects the motor state has on the escape behavior of animals. We address this issue for the wind-elicited escape behavior of crickets. Crickets respond to a short airflow stimulus, which is detected as a signal suggesting the predator approach, and run or jump quickly in opposite direction to the stimulus. Previous studies reported that cricket changes their escape behavior by stimulus parameters and additional stimulus of different modality. In this study, we examined how crickets change their escape behavior by its motor state that is standing still or moving. We used a closed-looped servo-sphere treadmill system to keep the freely moving cricket in a specific location and orientation, which allowed us to provide an air puff from a specific direction[YI2] . Using a high-speed camera, we measured several behavioral parameters, such as response probability, behavioral choice (run or jump), reaction time, moving velocity, distance, and directional accuracy. Most of the moving crickets immediately paused upon receiving an airflow stimulus, and then started escape running or jumping. The stimulus threshold for pausing of the moving cricket during locomotion was lower than that for escape of the stationary cricket. The delay from the stimulus onset to the pausing in the moving crickets was much shorter than the reaction time in the stationary crickets. These results imply that the ascending projection neuron conveying the airflow signals from abdominal terminal ganglion, which is a primary center for airflow sensing system, to higher center may directly suppress the motor circuit located in thoracic ganglia not mediated by the brain. There was no difference in the choice of running or jumping between the moving and stationary animals. On the other hand, the running distance was shorter, and the control of escape direction was less accurate in the response of the moving crickets than that of the stationary cricket. It is supposed that the higher sensitivity for escape during locomotion might compensate the poor performance.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-351
マウス大脳皮質の重層的領野間回路の軸索投射パターンの比較解析
Comparative analysis on axon projection patterns of multi-layered inter-areal projections in the mouse cerebral cortex

*岡 雄一郎(1,2)、山本 拓都(3)、瀬木 健生(2,3)、Murtala Hamza Yahaya(2)、谷口 学(2)、黒瀬 建(4)、佐藤 真(1,2,4)
1. 大阪大学大学院連合小児発達学研究科、2. 大阪大学大学院医学系研究科神経機能形態学、3. 大阪大学医学部、4. 大阪大学大学院生命機能研究科
*Yuichiro Oka(1,2), Takuto Yamamoto(3), Kensei Seki(2,3), Murtala Hamza Yahaya(2), Manabu Taniguchi(2), Takeru Kurose(4), Makoto Sato(1,2,4)
1. United Grad Sch of Child Dev, Osaka Univ, Osaka, Japan, 2. Dept Anat and Neruosci, Grad Sch of Med, Osaka Univ, Osaka, Japan, 3. Fac of Med, Osaka Univ, Osaka, Japan, 4. Grad Sch of Front Biosci, Osaka Univ, Osaka, Japan

Keyword: Corticocortical projection, association projection, sensorimotor integration

Direct neuronal projections between cortical functional areas play pivotal roles in higher cortical functions including, but not limited to, multi-sensory integration and regulation of voluntary movements. A body of preceding studies proposed several cortical networks consisted of such inter-areal projections. The sensorimotor network is among them and includes connections between the primary and secondary somatosensory cortices (S1 and S2) and the primary and secondary motor cortices (M1 and M2). Reciprocal projections are reported for any two cortices among the four. Furthermore, these connections are multi-layered. For example, we and others reported that projections from S1 to M1 in mice originate from 3 layers in S1: layers 2/3, 5a, and 6b. As the neurons in different layers serve as different parts in the local circuit within S1, the M1-projecting neurons in different layers should convey different information to their common targeting area. The layer 2/3 neurons are the major recipient of feedforward inputs from layer 4 neurons, which are the direct interface to the sensory inputs from sensory thalamic nuclei (VPM/VPL). The recent studies revealed inputs from a higher order thalamic nucleus (POm) to the layer 5a neurons showed the synaptic plasticity during sensorimotor association learning. Taking it into account that layer 5 is a major branching zone of axons from layer 2/3 neurons, it is possible that M1-projecting neurons in layer 5a convey the sensory information modulated by experiences. A comprehensive retrograde trans-synaptic tracing study have shown that layer 6b neurons in S1 receive major inputs from M1, S2 and contralateral S1. In spite of the accumulating knowledges on neuronal inputs to the three layers containing M1-projecting neurons in S1, their axonal targets in M1 have not fully characterized. As a step towards understanding their circuit structure and functions, we analyzed axon projection patterns of M1-projecting neurons in different layers separately or in combination in a single mouse. We report our results possibly with those about the post-synaptic targets in M1.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-352
後頭皮質の経頭蓋磁気刺激は視覚障がい者の足運動を阻害する
Transcranial magnetic stimulation of the occipital cortex interferes with foot movements in blind individuals

*池上 剛(1,2)、平島 雅也(1,2)、内藤 栄一(1,2)、廣瀬 智士(1,3)
1. 情報通信研究機構 脳情報通信融合研究センター、2. 大阪大学 生命機能研究科、3. 追手門学院大学 心理学部
*Tsuyoshi Ikegami(1,2), Masaya Hirashima(1,2), Eiichi Naito(1,2), Satoshi Hirose(1,3)
1. Center for Information and Neural Networks(CiNet), National Institute of Information and Communications Technology, 2. Graduate School of Frontier Biosciences, Osaka University, 3. Faculty of Psychology, Otemon Gakuin University

Keyword: blind individuals, visual cortex, TMS, sensorimotor control

Sensory loss can lead to a dramatic reorganization of the brain. There is accumulating evidence that the visual cortex of blind individuals can be reorganized to contribute to nonvisual perception (e.g., sound localization or tactile spatial discrimination) and cognitive functions (e.g., verbal memory or mathematical processing). To our knowledge, however, no studies have directly examined its involvement in motor production, one of the essential brain functions. To test this question, we applied transcranial magnetic stimulation (TMS) to the occipital cortex of blind individuals, and examined interference effects of TMS on a foot movement task, which requires no visuomotor control. Twelve acquired blind participants and twelve blindfolded age-matched sighted controls made rhythmic and alternating foot movements. During the foot movement, we applied 20 single TMS pulses to one of 14 stimulation sites located over their occipital cortex, including the primary and secondary visual cortex (V1/V2), with random inter-stimulus-intervals (2–4s). The participants were instructed to make the movement frequency (1 Hz) as constant as possible. We quantified the effect of TMS on movement by assessing the variability of movement frequency with the coefficient of variation (CV) of the cycle duration. TMS to V1/V2 increased the CV in the acquired blind participants but not the sighted controls. An additional experiment revealed that this TMS effect was absent in congenitally blind participants. These results suggest that the visual cortex of blind individuals is involved in motor production, but its involvement requires prior visual experience. As far as we know, our study provides the first evidence suggesting that the visual cortex after visual loss is reorganized to participate in motor production. Our findings indicate that the plasticity of the human brain after sensory loss is more flexible than previously thought; functional repurposing of the lower sensory cortices may be not restricted to perception and cognitive functions but extended to motor function.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-353
健常成人におけるニューロフィードバック訓練は運動能力を向上させるか:系統的レビューとメタアナリシス
Neurofeedback training for motor performance improvements in healthy adults; a systematic review and meta-analysis

*武見 充晃(1)、女川 亮司(2)、村岡 慶人(1)、羽倉 信宏(3,4)
1. 慶應義塾大学大学院理工学研究科、2. 早稲田大学理工学術院総合研究所、3. 情報通信研究機構未来ICT研究所脳情報通信融合研究センター、4. 大阪大学大学院生命機能研究科
*Mitsuaki Takemi(1), Ryoji Onagawa(2), Yoshihito Muraoka(1), Nobuhiro Hagura(3,4)
1. Grad Sch Sci & Technol, Keio Univ, Yokohama, Japan, 2. Waseda Res Inst for Sci & Eng, Tokyo, Japan, 3. Ctr for Informat & Neural Netw, Natl Inst of Informat & Commun Technol, Osaka, Japan, 4. Grad Sch Front Biosci, Osaka Univ, Osaka, Japan

Keyword: Neurofeedback, Electroencephalogram (EEG), Athletic performance, Motor training

Neurofeedback training (NFT) refers to a training in which the participants voluntarily aim to manipulate their own brain activity using the abstract sensory input as feedback of their brain activity. NFT has been capturing attention in the field of motor learning for its potential to become an alternative or additional training method for conventional physical training. Here we assess the effectiveness of NFT on motor performance improvements in healthy adults by performing a narrative overview and meta-analysis on the NFT studies. A computerized search of Web of Science, Scopus, PubMed, JDreamIII, and Ichushi-Web was performed to identify relevant studies published between January 1st, 1990 to August 3rd, 2021. As a result, 34 studies for the narrative overview and 20 trials (428 subjects) for the meta-analysis were identified. The identified measurement techniques included EEG (27 studies), fMRI (3 studies), fNIRS (2 studies), and MEG (2 studies). In the studies using EEG, alpha (13 studies), theta (12 studies), beta (10 studies), and sensorimotor rhythm (9 studies) were the features of brain activity used for NFT. The identified outcome measures were shooting accuracy (9 studies), hand dexterity (9 studies), reaction time (8 studies), body balance maintenance (2 studies), and time to exhaustion (2 studies). The meta-analysis revealed significant effects of NFT for motor performance improvements at the timing right after the last NFT session (Standard mean differences (SMDs) = 0.77, 95% confidence intervals (CIs) = 0.38 to 1.03), but with substantial heterogeneity among the trials (I2 = 78%). Subsequent subgroup meta-analysis revealed that interventions longer than one week can induce significantly larger effects than the shorter interventions (p < 0.001). Furthermore, subgroup meta-analysis also showed reliable benefits when the NFT is performed longer than one week, particularly for reaction time measures (4 trials (78 subjects), SMDs = 0.57, 95% CI = 0.15 to 0.98, I2 = 0%). Effectiveness of NFT for other motor skills remained unclear due to high heterogeneity or small trial numbers. Only 5 out of 34 studies tested side effects associated with NFTs, and none of them reported the occurrence of serious adverse events. We conclude that the NFT longer than one week can be effective to reduce reaction times of the given motor task. Further accumulation of empirical NFT studies will be necessary to reduce the heterogeneity of studies, to robustly evaluate the NFT effect from different perspectives, and to safely incorporate NFT training into real-world settings.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-354
安静時脳活動は標的部位に依存しないfMRIニューロフィードバック適性を予測する
Resting-state brain activity predicts target-independent fMRI-neurofeedback training aptitude

*中野 高志(1,2)、高村 真広(3)、西村 春輝(4)、町澤 まろ(3)、市川 奈穂(3)、吉野 敦雄(5)、岡田 剛(5)、岡本 泰昌(5,3)、山脇 成人(3)、山田 真希子(4)、須原 哲也(4)、吉本 潤一郎(2)
1. 藤田医科大学医学部、2. 奈良先端科学技術大学院大学、3. 広島大学脳・こころ・感性科学研究センター、4. 量子科学技術研究開発機構、5. 広島大学大学院医系科学研究科
*Takashi Nakano(1,2), Masahiro Takamura(3), Haruki Nishimura(4), Maro Machizawa(3), Naho Ichikawa(3), Atsuo Yoshino(5), Go Okada(5), Yasumasa Okamoto(5,3), Shigeto Yamawaki(3), Makiko Yamada(4), Tetsuya Suhara(4), Junichiro Yoshimoto(2)
1. School of Medicine, Fujita Health University, Toyoake, Japan, 2. Nara Institute of Science and Technology, Nara, Japan, 3. Center for Brain, Mind and KANSEI Res Sci, Hiroshima Univ, Hiroshima, Japan, 4. Natl Inst Quant Radiol Sci Tech, Chiba, Japan, 5. Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan

Keyword: neurofeedback, machine learning, resting-state fMRI, functional connectivity

Neurofeedback (NF) training has been developed as a promising novel treatment of brain psychiatric disorders like major depressive disorder (MDD). However, NF aptitude, an individual’s ability to change brain activity through NF training, has been reported to vary significantly among different individuals. The prediction of individual NF aptitudes independent of NF-targeting brain regions is critical in clinical applications to screen patients suitable for NF treatment.
In the present study, we applied machine learning to resting-state functional magnetic resonance imaging (fMRI) data for the prediction of NF aptitude. We have collected the data from fMRI-NF studies targeting four different brain regions at two independent sites (obtained from 59 healthy adults and six patients with major depressive disorder). The resting-state fMRI data were associated with NF aptitude scores in subsequent fMRI-NF training. We extracted the resting-state functional brain connectivity (FC) as markers. We then trained the multiple regression models to predict the individual NF aptitude scores from the resting-state FC data using a discovery dataset from one site in an exhaustive manner.
As results, we identified six resting-state FCs that predicted NF aptitude and succeeded in the prediction of NF aptitude of the discovery dataset. Subsequently, the reproducibility of the prediction model was validated using independent test data from another site. The identified FCs predicted NF aptitude of the independent test data. The identified FC model revealed that the posterior cingulate cortex and posterior insular cortex were the functional hub among the brain regions and formed predictive resting-state FCs, suggesting that NF aptitude may be involved in the attentional mode-orientation modulation system’s characteristics in task-free resting-state brain activity.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-355
人工的な皮質脊髄路への適応に伴う脊髄損傷サルの一次運動野ニューロン群の同調
An ensemble tuning of the macaque primary motor cortex during adaptation to the artificial corticospinal pathway after spinal cord injury

*尾原 圭(1,2)、兼重 美希(1)、鈴木 迪諒(1)、田添 歳樹(1)、西村 幸男(1,2)
1. 東京都医学総合研究所、2. 新潟大学大学院医歯学総合研究科
*Kei Obara(1,2), Miki Kaneshige(1), Michiaki Suzuki(1), Toshiki Tazoe(1), Yukio Nishimura(1,2)
1. Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan, 2. Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan

Keyword: spinal cord injury, brain computer interface, primary motor cortex, spinal cord stimulation

Spinal cord injury (SCI) disrupts neural communications between the brain and the spinal circuits. We have demonstrated that bypassing the damaged pathway using brain-computer interface, which artificially-connects a preserved cortical site and spinal cord, restored volitional control of the impaired forelimb movements after SCI. However, it remains unclear how an ensemble of cortical neurons incorporates a novel artificial neural pathway into the volitional control of the paralyzed limb. Here, we employed a neural interface which connects a single neuron and a spinal site in the cervical enlargement beyond the lesion site at the mid cervical cord in monkeys. The ensemble of neurons was recorded with a multi-channel Utah array from the wrist region in the contralesional primary motor cortex. A single neuron was randomly selected to be directly linked to spinal stimulation (linked neuron). Firing rate of the linked neuron was transformed to the current intensity and the frequency of spinal stimulation with a linear converter optimized to generate wrist movements in real time. The remaining neurons were also recorded, but were not linked to the spinal stimulation (unlinked neurons). Spinal stimulation was achieved by a subdural array placing over the dorsal rootlets on C6-T1 spinal segments to generate the paralyzed wrist movements. Without the artificial pathway, the monkeys with SCI were unable to accomplish a wrist-torque-tracking task and most of neurons did not show task-related modulation. The monkeys succeeded the task using the artificial pathway with which the monkeys voluntarily adjusted the firing rate of the linked neuron to control spinal stimulation and generate targeted wrist-torque. 41% of unliked neurons also showed task-related activities. 17% and 24% of unlinked neurons were facilitated and suppressed their activities in relation to the task, respectively. Additionally, we found that the magnitude of task-related facilitation and suppression in the unlinked neurons varied in accordance with the required wrist-torque. These findings demonstrated that the monkeys tuned the activity in the ensemble of cortical neurons to incorporate an artificial pathway into the volitional limb control.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-356
脳磁界バイアス方式の革新的高精度非侵襲脳機能計測技術: 運動関連脳信号計測による実証
Novel Noninvasive Technique for Precise Measurement of Brain Signals with Magnetically Biased Fields: Verification by Measurement of Movement Related Cortical Signals

*樋脇 治(1)、松永 諒(1)
1. 広島市立大学
*Osamu Hiwaki(1), Ryo Matsunaga(1)
1. Hiroshima City University

Keyword: BRAIN-MACHINE INTERFACE, NONINVASIVE MEASUREMENT OF BRAIN FUNCTION , MOVEMENT RELATED CORTICAL SIGNAL, MAGNETICALLY BIASED FIELD

Noninvasive techniques for measurement of brain signals have been utilized for brain- machine interfaces as well as for understanding and diagnosis of the brain functions. Electroencephalography (EEG), magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) are commonly used as brain-imaging techniques. EEG and MEG signals associated with electrical neural activity are fast, but they are characterized by a poor signal-to-noise ratio and spatial resolution. Temporal resolution of fMRI and NIRS signals are limited by hemodynamic response time with a width of ~3s after the onset of a neural stimulus. We have developed a novel technique, called as MBF (magnetically biased field), achieving noninvasive measurement of brain activity with high spatial and temporal resolution. In the MBF technique, a magnetic field emitted from a coil located on the head surface passing through the cerebral cortex is used. We have found that the fast cortical signals can be detected as perturbation of the magnetic field according to the cortical activity by a magnetometer on the upper end of a coil. Here, we verify the effectiveness of the MBF by measurement of movement related signals. We tried to measure movement related signals with a 30-channel MBF system. Subjects sat in a magnetically shielded room and watched a clock hand rotating with a period of 6 s on a computer monitor. The start position of the clock hand was set randomly at each trial. Subjects were instructed to push a button with the index finger at the moment of the returning of the clock hand to the starting position after the rotation. The signals at 30 points with 5 lateral and 6 vertical points at 20mm intervals around Cz were measured simultaneously. The movement related signals were obtained by an average of 300 trials. As a result, clear movement related signals were successfully obtained by the MBF system. The signals preceding the onset by more than 1 sec were recorded in an extremely localized fashion exclusively from points in the vicinity of the precentral hand motor area. It is verified that the movement related signals representing the preparation of voluntary finger movements can be detected by the MBF with excellent spatiotemporal resolution.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-357
発声と行動に対するデコーディング貢献度の脳内マッピング
Brain mapping of contributions to vocal and behavioral decoding

*佐藤 元重(1)、小松 三佐子(2)、笹井 俊太朗(1)
1. 株式会社アラヤ、2. 理化学研究所 脳神経科学研究センター 高次脳機能分子解析チーム
*Motoshige Sato(1), Misako Komatsu(2), Shuntaro Sasai(1)
1. Araya, Inc., Tokyo, Japan, 2. Laboratory for Molecular Analysis of Higher Brain Functions, RIKEN Center for Brain Science, Saitama, Japan.

Keyword: decoding, behavioral and vocal, ECoG, Explainable AI

Brain computer interfaces (BCIs) enable patients with spinal cord injury or stroke who are unable to move their limbs or speak to use their own neural activity to move prosthetic limbs and communicate with other people. For BCIs to be more widely used, it is important to decode neural activity before the subjects’ action is generated from the minimum number of recording electrodes. It is little known whether there are common areas which highly contribute to both behavioral and vocal decoding. In this study, we developed Deep Neural Network decoders for vocalizations and behaviors from ECoG covering the left hemisphere of marmosets under free-moving condition, then compared spatio-temporal brain maps of contribution to inference of decoders. For vocalizations, five types of call patterns were identified by performing clustering of the audio waveforms. The decoder was trained to predict these five classes from the ECoG of the 1 sec immediately before each vocalization occurred. For behavior, 22 body markers were extracted using DeepLabCut, and the features of the patterns of these markers during 500 msec were computed. To obtain low dimensional features independent of body orientation, VAEs conditioned with direction vector of the spine were trained to reconstruct original dynamics of body markers from 10-dimensional latent variables. The decoders were trained to predict these 10-dimensional latent variables from ECoG of the 500 msec immediately before each behavioral window. As for the decoder architecture, a convolutional neural network which has the independent kernels in time and electrode axes was used for both vocal and behavioral decoding. To visualize the contribution to the decoding, Integrated Gradients were computed, which is the back propagated values from prediction scores for each class / feature to the inputs. As a result, the temporal association cortex and parietal cortex were found to be the regions that have large contribution to the decoding for both vocalization and behavior. The temporal association cortex is involved in higher-order audiovisual information processing, which may have a large influence on the future action. In addition, parietal cortex is known to be an information-rich region that is connected to many brain regions and works as a hub, therefore high contribution to decoding is anatomically explained. This study provides an insight into the development of efficient BCIs by targeting these areas.
2022年7月1日 11:00~12:00 宜野湾市民体育館 ポスター会場2
2P-358
自由行動下長時間計測のためのワイヤレス脳活動計測システムの開発
A lightweight, low-power, low-latency wireless headstage for freely-moving subjects

*海住 太郎(1,2)、井上 雅仁(1,2)、平田 雅之(3)、鈴木 隆文(1,2)
1. 情報通信研究機構 未来ICT研究所脳情報通信融合研究センター、2. 大阪大学大学院生命機能研究科、3. 大阪大学大学院医学系研究科 脳機能診断再建学共同研究講座
*Taro Kaiju(1,2), Masato Inoue(1,2), Masayuki Hirata(3), Takafumi Suzuki(1,2)
1. Center for Information and Neural Networks(CiNet), National Institute of Information and Communications Technology, and Osaka University, Osaka, Japan, 2. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan, 3. Department of Neurological Diagnosis and Restoration, Osaka University Graduate School of Medicine, Osaka, Japan

Keyword: Electrocorticography(ECoG), Wireless recording, Brain-computer interface, Electrophysiology

Background: Harnessing neuroplasticity is a crucial consideration in developing efficient rehabilitation techniques and neuroprosthetics. Recently, neurofeedback, a method to modulate neural activity by directly presenting one's own neural activity to the subject, has been actively investigated. However, its effectiveness when constantly applied over a prolonged period, such as several weeks or months, needs to be further investigated. This is because closed-loop experiments, including neurofeedback, require time-consuming training and simultaneous recording, but wired electrophysiology involves a limited duration of recording sessions. We developed a wireless system suitable for long-term recording from freely-moving subjects to overcome this issue.

Methods: By designing a device specifically to record signals below 500 Hz, we have simultaneously developed a compact and lightweight unit, extended battery life, and achieved low latency. We designed, developed, and bench-tested a device composed mainly of a 32-channel neural recording IC, 6-axis inertial measurement unit, and 2.4-GHz wireless module. We evaluated it upon a Japanese macaque through somatosensory evoked potentials (SEPs) recording and freely-moving recording.

Results: The unit was 25×16×4 mm3 (excluding the battery) in size. Its average power consumption was 50 mW (in operation) and 0.7 mW (in standby mode), and approximately 8 hours of continuous recording was achieved with a 3-gram, 100 mAh battery. By utilizing the remotely-controlled standby mode, we also achieved intermittent telemetry that consists of 2.5-hour session per day for three days. We verified that the latency from signal measurement to receiver operation was ~1 ms based on the arbitrary waveform input. Recorded SEPs had comparable quality with wired systems. In the freely-moving recording experiment, visual evoked potentials and potentials related to button-pressing could be captured.

Discussions and Conclusions: Reduced power consumption (approximately 20–25% that of commercial systems) makes it possible to achieve long-duration recording from freely-moving subjects, which is difficult with currently available systems. This system can be used with a wide range of subjects such as non-human primates, mice, rats, and marmosets, and can measure a wide variety of signals such as ECoG, LFP, EEG, and EMG. Therefore, it can be adopted in various neurophysiological studies as well as long-term neuroplasticity studies.