医学博士, 北海道大学医学研究科

大脳基底核

淡蒼球外節

黒質網様部

視床下核

線条体

前頭前野

前頭葉内側部

非ヒト霊長類

neurophysiology

neuroradiology

ライフサイエンス, 放射線科学, MRI 画像解析

ライフサイエンス, 神経科学一般

2021年10月, National Eye Institute (National Institutes of Health), Best Scientific Presentation on 2021 Focus on Fellows
Runner-up (2nd winner)

2015年11月, 10th Asian Oceanian Congress of Neuroradiology, Magna Cum Laude
吉田 篤司

2013年11月, 第3回社会神経科学研究会, 優秀ポスター賞
吉田 篤司

2013年02月, 第42回日本神経放射線学会, 優秀ポスター賞
吉田 篤司

2007年07月, 北海道大学医学研究科医学部, 音羽博次賞
吉田 篤司

Beyond the brake: The subthalamic nucleus predominantly facilitates action in non-human primates
Atsushi Yoshida; Richard J. Krauzlis; Okihide Hikosaka
Progress in Neurobiology, 262, 102921, 102921, Elsevier BV, 2026年07月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）

Development of a 24-channel 3T phased-array coil for fMRI in awake monkeys: Mitigating spatiotemporal artifacts in ferumoxytol-weighted functional connectivity estimation.
Joonas A Autio; Atsushi Yoshida; Yoshihiko Kawabata; Masahiro Ohno; Kantaro Nishigori; Takayuki Ose; Stephen M Smith; David C Van Essen; Matthew F Glasser; Takuya Hayashi
Imaging neuroscience (Cambridge, Mass.), 4, 2026年, ［国際誌］
英語, 研究論文（学術雑誌）, Functional magnetic resonance imaging (fMRI) of awake macaque monkeys holds promise for advancing our understanding of primate brain organization, including humans. However, estimating functional connectivity in awake animals is challenging due to the limited duration of imaging sessions and the relatively low sensitivity to neural activity. To overcome these challenges, we developed a 24-channel 3T receive radiofrequency (RF) coil optimized for parallel imaging of awake macaques. This enabled the acquisition of cross-plane and in-plane accelerated ferumoxytol-weighted resting-state fMRI. The Human Connectome Project-style data processing pipelines were adapted to address the unique preprocessing demands of cerebral blood volume-weighted (CBVw) imaging, including motion correction, functional-to-structural image co-registration, and training a multi-run independent component analysis-based X-noiseifier (ICA-FIX) classifier for removal of structured artifacts. Our CBVw fMRI approach resulted in an elevated contrast-to-noise ratio compared with blood oxygenation level-dependent (BOLD) imaging in anesthetized macaques. However, structured imaging artifacts still contributed more variance to the functional timeseries than neural activity. By applying the ICA-FIX classifier, we achieved highly reproducible parcellated functional connectivity at the single-subject level, with test-retest matrix correlations and subject identification accuracy comparable with those observed in humans. At the group level, we identified dense functional networks with spatial features homologous to those observed in humans. The developed RF receive coil, image acquisition protocols, and data analysis pipelines are publicly available, providing the broader scientific community with tools to leverage these advances for further research.

Excitatory drive to the globus pallidus external segment facilitates action initiation in non-human primates.
Atsushi Yoshida; Okihide Hikosaka
Current biology : CB, 2025年08月04日, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, The external segment of the globus pallidus (GPe) has been conventionally regarded as a key relay in the indirect pathway of the basal ganglia, primarily mediating movement suppression. However, recent studies in rodents suggest a more complex role, including active facilitation of actions. Here, we investigated whether the primate GPe exhibits similar functional diversity by recording single-unit activity in two macaque monkeys performing a novel sequential choice task. This task separated the process of action initiation and suppression by requiring the monkeys to either accept a "good" object for reward or reject a "bad" object using one of multiple strategies. We identified three distinct neuronal clusters based on their firing patterns. Clusters 1 and 2 were linked to action facilitation: cluster 1 increased activity for saccades to both object types, while cluster 2 was selectively active for good-object saccades and suppressed during rejections-similar to cluster 3, which showed suppression during bad-object rejection. Local pharmacological blockade of glutamate receptors within the caudal dorsal GPe prolonged saccade latencies and reduced the frequency of rejection saccades, confirming a causal role for excitatory drive in saccade facilitation. These findings expand the traditional view of the GPe beyond a purely inhibitory station, indicating that in primates, it simultaneously mediates both motor facilitation and proactive suppression. Our results emphasize the importance of characterizing circuit-specific and cell-type-specific roles of the GPe within basal ganglia networks, with implications for normal motor function and movement disorder pathophysiology under complex reward-based decision processes in non-human primates.

Contribution of glutamatergic projections to neurons in the nonhuman primate substantia nigra pars reticulata for reactive inhibition.
Atsushi Yoshida; Okihide Hikosaka
Proceedings of the National Academy of Sciences of the United States of America, 122, 26, e2427032122, 2025年07月, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, The basal ganglia play a crucial role in action selection by facilitating desired movements and suppressing unwanted ones. The substantia nigra pars reticulata (SNr), a key output nucleus, facilitates movement through disinhibition of the superior colliculus (SC). However, its role in action suppression, particularly in primates, remains less clear. We investigated whether individual SNr neurons in three male macaque monkeys bidirectionally modulate their activity to both facilitate and suppress actions and examined the role of glutamatergic inputs in suppression. Monkeys performed a sequential choice task, selecting or rejecting visually presented targets. Electrophysiological recordings showed that SNr neurons decreased firing rates during target selection and increased firing rates during rejection, demonstrating bidirectional modulation. Pharmacological blockade of glutamatergic inputs to the lateral SNr disrupted saccadic control and impaired suppression of reflexive saccades, providing causal evidence for the role of excitatory input in behavioral inhibition. These findings suggest that glutamatergic projections, potentially originating from sources including the subthalamic nucleus, contribute to the increased SNr activity during action suppression. Our results highlight conserved basal ganglia mechanisms across species and offer insights into the neural substrates of action selection and suppression in primates, with implications for understanding disorders such as Parkinson's disease.

Involvement of neurons in the non-human primate anterior striatum in proactive inhibition.
Atsushi Yoshida; Okihide Hikosaka
The Journal of neuroscience : the official journal of the Society for Neuroscience, 44, 49, 2024年11月04日, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, Behaving as desired requires selecting the appropriate behavior and inhibiting the selection of inappropriate behavior. This inhibitory function involves multiple processes, such as reactive and proactive inhibition, instead of a single process. In this study, two male macaque monkeys were required to perform a task in which they had to sequentially select (accept) or refuse (reject) a choice. Neural activity was recorded from the anterior striatum, which is considered to be involved in behavioral inhibition, focusing on the distinction between proactive and reactive inhibitions. We identified neurons with significant activity changes during the rejection of bad objects. Cluster analysis revealed three distinct groups, of which only one showed increased activity during object rejection, suggesting its involvement in proactive inhibition. This activity pattern was consistent irrespective of the rejection method, indicating a role beyond saccadic suppression. Furthermore, minimal activity changes during the fixation task indicated that these neurons were not primarily involved in reactive inhibition. In conclusion, these findings suggest that the anterior striatum plays a crucial role in cognitive control and orchestrates goal-directed behavior through proactive inhibition, which may be critical in understanding the mechanisms of behavioral inhibition dysfunction that occur in patients with basal ganglia disease.Significance statement This study revealed a group of neurons in the anterior striatum that plays a crucial role in cognitive control by actively participating in the rejection of unfavorable choices. Contrary to previous belief, these neurons were involved in proactive inhibition (i.e., the process of discarding unnecessary options), instead of suppressing automatic responses, to achieve a goal. This distinction is vital for understanding the mechanisms by which the brain makes decisions and may have implications for addressing neurological disorders associated with impaired decision-making and inhibitory control. Our findings provide new insights into the neural mechanisms underlying goal-directed behavior and highlight the importance of the anterior striatum in orchestrating complex cognitive functions.

Visualization of iron-rich subcortical structures in non-human primates in vivo by Quantitative Susceptibility Mapping at 3T MRI.
Atsushi Yoshida; Frank Q Ye; David K Yu; David A Leopold; Okihide Hikosaka
NeuroImage, 241, 118429, 118429, 2021年07月23日, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, Magnetic resonance imaging (MRI) is now an essential tool in the field of neuroscience involving non-human primates (NHP). Structural MRI scanning using T1-weighted (T1w) or T2-weighted (T2w) images provides anatomical information, particularly for experiments involving deep structures such as the basal ganglia and cerebellum. However, for certain subcortical structures, T1w and T2w image contrasts are insufficient for their detection of important anatomical details. To better visualize such structures in the macaque brain, we applied a relatively new method called quantitative susceptibility mapping (QSM), which enhances tissue contrast based on the local tissue magnetic susceptibility. The QSM significantly improved the visualization of important structures, including the ventral pallidum (VP), globus pallidus external and internal segments (GPe and GPi), substantia nigra (SN), subthalamic nucleus (STN) in the basal ganglia and the dentate nucleus (DN) in the cerebellum. We quantified this the contrast enhancement by systematically comparing of contrast-to-noise ratios (CNRs) of QSM images relative to the corresponding T1w and T2w images. In addition, QSM values of some structures were correlated to the age of the macaque subjects. These results identify the QSM method as a straightforward and useful tool for clearly visualizing details of subcortical structures that are invisible with more traditional scanning sequences.

Cortico-Subcortical Functional Connectivity Profiles of Resting-State Networks in Marmosets and Humans.
Yuki Hori; David J Schaeffer; Atsushi Yoshida; Justine C Cléry; Lauren K Hayrynen; Joseph S Gati; Ravi S Menon; Stefan Everling
The Journal of neuroscience : the official journal of the Society for Neuroscience, 40, 48, 9236, 9249, 2020年11月25日, ［国際誌］
英語, 研究論文（学術雑誌）, Understanding the similarity of cortico-subcortical networks topologies between humans and nonhuman primate species is critical to study the origin of network alternations underlying human neurologic and neuropsychiatric diseases. The New World common marmoset (Callithrix jacchus) has become popular as a nonhuman primate model for human brain function. Most marmoset connectomic research, however, has exclusively focused on cortical areas, with connectivity to subcortical networks less extensively explored. Here, we aimed to first isolate patterns of subcortical connectivity with cortical resting-state networks in awake marmosets using resting-state fMRI, then to compare these networks with those in humans using connectivity fingerprinting. In this study, we used 5 marmosets (4 males, 1 female). While we could match several marmoset and human resting-state networks based on their functional fingerprints, we also found a few striking differences, for example, strong functional connectivity of the default mode network with the superior colliculus in marmosets that was much weaker in humans. Together, these findings demonstrate that many of the core cortico-subcortical networks in humans are also present in marmosets, but that small, potentially functionally relevant differences exist.SIGNIFICANCE STATEMENT The common marmoset is becoming increasingly popular as an additional preclinical nonhuman primate model for human brain function. Here we compared the functional organization of cortico-subcortical networks in marmosets and humans using ultra-high field fMRI. We isolated the patterns of subcortical connectivity with cortical resting-state networks (RSNs) in awake marmosets using resting-state fMRI and then compared these networks with those in humans using connectivity fingerprinting. While we could match several marmoset and human RSNs based on their functional fingerprints, we also found several striking differences. Together, these findings demonstrate that many of the core cortico-subcortical RSNs in humans are also present in marmosets, but that small, potentially functionally relevant differences exist.

Towards HCP-Style macaque connectomes: 24-Channel 3T multi-array coil, MRI sequences and preprocessing.
Joonas A Autio; Matthew F Glasser; Takayuki Ose; Chad J Donahue; Matteo Bastiani; Masahiro Ohno; Yoshihiko Kawabata; Yuta Urushibata; Katsutoshi Murata; Kantaro Nishigori; Masataka Yamaguchi; Yuki Hori; Atsushi Yoshida; Yasuhiro Go; Timothy S Coalson; Saad Jbabdi; Stamatios N Sotiropoulos; Henry Kennedy; Stephen Smith; David C Van Essen; Takuya Hayashi
NeuroImage, 215, 116800, 116800, 2020年07月15日, ［国際誌］
英語, 研究論文（学術雑誌）, Macaque monkeys are an important animal model where invasive investigations can lead to a better understanding of the cortical organization of primates including humans. However, the tools and methods for noninvasive image acquisition (e.g. MRI RF coils and pulse sequence protocols) and image data preprocessing have lagged behind those developed for humans. To resolve the structural and functional characteristics of the smaller macaque brain, high spatial, temporal, and angular resolutions combined with high signal-to-noise ratio are required to ensure good image quality. To address these challenges, we developed a macaque 24-channel receive coil for 3-T MRI with parallel imaging capabilities. This coil enables adaptation of the Human Connectome Project (HCP) image acquisition protocols to the in-vivo macaque brain. In addition, we adapted HCP preprocessing methods to the macaque brain, including spatial minimal preprocessing of structural, functional MRI (fMRI), and diffusion MRI (dMRI). The coil provides the necessary high signal-to-noise ratio and high efficiency in data acquisition, allowing four- and five-fold accelerations for dMRI and fMRI. Automated FreeSurfer segmentation of cortex, reconstruction of cortical surface, removal of artefacts and nuisance signals in fMRI, and distortion correction of dMRI all performed well, and the overall quality of basic neurobiological measures was comparable with those for the HCP. Analyses of functional connectivity in fMRI revealed high sensitivity as compared with those from publicly shared datasets. Tractography-based connectivity estimates correlated with tracer connectivity similarly to that achieved using ex-vivo dMRI. The resulting HCP-style in vivo macaque MRI data show considerable promise for analyzing cortical architecture and functional and structural connectivity using advanced methods that have previously only been available in studies of the human brain.

Direct and indirect pathways for choosing objects and actions.
Hikosaka, O; Kim, H. F; Amita, H; Yasuda, M; Isoda, M; Tachibana, Y; Yoshida, A
Eur J Neuroscience, 2019年03月, ［査読有り］

Advanced diffusion models in head and neck squamous cell carcinoma patients: Goodness of fit, relationships among diffusion parameters and comparison with dynamic contrast-enhanced perfusion
Noriyuki Fujima; Tomohiro Sakashita; Akihiro Homma; Yukie Shimizu; Atsushi Yoshida; Taisuke Harada; Khin Khin Tha; Kohsuke Kudo; Hiroki Shirato
MAGNETIC RESONANCE IMAGING, 36, 16, 23, 2017年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Utility of noncontrast-enhanced time-resolved four-dimensional MR angiography with a vessel-selective technique for intracranial arteriovenous malformations
Noriyuki Fujima; Toshiya Osanai; Yukie Shimizu; Atsushi Yoshida; Taisuke Harada; Naoki Nakayama; Kohsuke Kudo; Kiyohiro Houkin; Hiroki Shirato
JOURNAL OF MAGNETIC RESONANCE IMAGING, 44, 4, 834, 845, 2016年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Two Types of Neurons in the Primate Globus Pallidus External Segment Play Distinct Roles in Antisaccade Generation.
Atsushi Yoshida; Masaki Tanaka
Cerebral cortex (New York, N.Y. : 1991), 26, 3, 1187, 99, 2016年03月, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）

Isolated posterior fossa involvement in posterior reversible encephalopathy syndrome.
Yukie Shimizu; Khin Khin Tha; Akihiro Iguchi; Yuko Cho; Atsushi Yoshida; Noriyuki Fujima; Akiko Tsukahara; Hiroki Shirato; Satoshi Terae
The neuroradiology journal, 26, 5, 514, 9, 2013年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Posterior reversible encephalopathy syndrome (PRES) is characterized by reversible vasogenic edema affecting the subcortical white matter of bilateral occipital and parietal lobes. We describe a case of isolated posterior fossa involvement of PRES which occurred during remission induction chemotherapy for T-cell acute lymphoblastic leukemia. Both the brainstem and cerebellum were extensively involved, but the supratentorial structures were completely spared. The follow-up magnetic resonance images revealed reversibility of most lesions. The knowledge of atypical radiological features of PRES is essential for prompt diagnosis.

Detection of Brain Metastases by 3-Dimensional Magnetic Resonance Imaging at 3 T: Comparison Between T1-Weighted Volume Isotropic Turbo Spin Echo Acquisition and 3-Dimensional T1-Weighted Fluid-Attenuated Inversion Recovery Imaging
Atsushi Yoshida; Khin Khin Tha; Noriyuki Fujima; Yuri Zaitsu; Daisuke Yoshida; Akiko Tsukahara; Shunsuke Onodera; Hiroki Shirato; Satoshi Terae
JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY, 37, 1, 84, 90, 2013年01月, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）

Neuronal activity in the primate globus pallidus during smooth pursuit eye movements.
Atsushi Yoshida; Masaki Tanaka
Neuroreport, 20, 2, 121, 5, 2009年01月28日, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）

Enhanced modulation of neuronal activity during antisaccades in the primate globus pallidus.
Atsushi Yoshida; Masaki Tanaka
Cerebral cortex (New York, N.Y. : 1991), 19, 1, 206, 17, 2009年01月, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）

「眼と精神」彦坂興秀 著 （医学書院）
吉田 篤司, 北大100人に聞く、人生を変えた一冊, 2026年10月

Parallel basal ganglia and frontal cortical outputs differentially encode context-dependent evaluation and categorical commitment during choice
Atsushi Yoshida; Richard Krauzlis; Okihide Hikosaka, bioRxiv : the preprint server for biology, 2026年06月18日, ［筆頭著者, 責任著者］
Adaptive choice requires transforming the evaluation of available options into commitment to a specific action but understanding how this transformation is implemented across neural circuits remains a central challenge. Here we recorded well-isolated neurons in the substantia nigra pars reticulata (SNr) and frontal eye field (FEF), which send parallel projections to the superior colliculus for driving the eye movement choice, while monkeys performed a sequential-offer choice task designed to partially dissociate scene-defined ordinal rank from the categorical commitment. Before target onset, SNr displayed stronger scene-related modulation than FEF. During target evaluation, SNr activity showed ordered modulation across behavioral outcomes dominated by ordinal rank, whereas FEF activity categorically separated acceptance from rejection and strongly encoded target direction. Behavioral model decomposition revealed that ordinal rank alone best explained SNr activity, outperforming both reward magnitude and even a composite acceptability measure that incorporated rank together with reward, scene context, and waiting cost, whereas FEF activity was best explained by categorical commitment. This dissociation was consistent across multivariable modeling, single-neuron response patterns, and all three monkeys. Together, these findings support a division of labor in which context-dependent evaluation and categorical commitment are distributed across parallel basal ganglia and frontal cortical output pathways to efficiently guide voluntary choices., openRxiv

Beyond the Brake: the Subthalamic Nucleus Predominantly Facilitates Action in Non-human Primates
Atsushi Yoshida; Richard J Krauzlis; Okihide Hikosaka, bioRxiv : the preprint server for biology, 2025年12月12日, ［筆頭著者, 責任著者］
The subthalamic nucleus (STN) is traditionally viewed as a brake on motor output. Challenging this model, we investigated its role in value-based decision-making by recording single-neuron activity from the primate STN during a choice task. Our findings reveal that the STN contains functionally distinct clusters of neurons and, contrary to its classical role, the vast majority of task-related neurons (approximately 89%) exhibited activity consistent with action facilitation. Two of the clusters contained facilitative neurons that increased their firing for rewarded choices, and critically, their response latency predicted saccadic reaction times on a trial-by-trial basis. Population-level analyses further demonstrated that these facilitative neurons robustly encode the upcoming choice. A smaller third cluster of neurons showed activity consistent with action suppression. These results indicate a dual function of the STN, suggesting it plays a predominant role in actively facilitating desired actions, rather than simply suppressing unwanted ones., openRxiv

Excitatory drive to the globus pallidus external segment facilitates action initiation in non-human primates.
Atsushi Yoshida; Okihide Hikosaka, bioRxiv : the preprint server for biology, 2025年04月21日, ［筆頭著者, 責任著者］, ［国際誌］
The external segment of the globus pallidus (GPe) has conventionally been regarded as a key relay in the indirect pathway of the basal ganglia, primarily mediating movement suppression; however, recent studies in rodents suggest a more complex role, including active facilitation of actions. Therefore, we investigated whether the primate GPe exhibits similar functional diversity by recording single-unit activity in two macaque monkeys performing a sequential choice task. This task separated processes of action initiation and suppression by requiring the monkeys to either accept a "good" object for reward or reject a "bad" object using one of multiple strategies. We identified three distinct neuronal clusters based on their firing patterns. Clusters 1 and 2 displayed elevated activity preceding contralateral saccades toward good objects, strongly correlating with shorter reaction times, suggesting a facilitative contribution. In contrast, Clusters 2 and 3 showed decreased activity during rejection of bad objects, reflecting proactive inhibition. Local pharmacological blockade of glutamate receptors within the caudodorsal GPe prolonged saccade latencies and reduced the frequency of rejection saccades, suggesting a causal role for excitatory drive in saccade facilitation. These findings expand the traditional view of the GPe beyond a purely inhibitory station, indicating that in primates it may simultaneously mediate both motor facilitation and proactive suppression. Our results emphasize the importance of characterizing circuit-specific and cell-type-specific roles of the GPe within basal ganglia networks, with implications for normal motor function and movement disorder pathophysiology under complex reward-based decision processes in non-human primates., 英語

Development of a 24-Channel 3T Phased-Array Coil for fMRI in Awake Monkeys - Mitigating Spatiotemporal Artifacts in Ferumoxytol-Weighted Functional Connectivity Estimation
Joonas A. Autio; Atsushi Yoshida; Yoshihiko Kawabata; Masahiro Ohno; Kantaro Nishigori; Takayuki Ose; Stephen Smith; David C. Van Essen; Matthew F. Glasser; Takuya Hayashi, bioRxiv : the preprint server for biology, 4, 2025年04月20日, ［国際誌］
Abstract

Functional magnetic resonance imaging (fMRI) of awake macaque monkeys holds promise for advancing our understanding of primate brain organization, including humans. However, estimating functional connectivity in awake animals is challenging due to the limited duration of imaging sessions and the relatively low sensitivity to neural activity. To overcome these challenges, we developed a 24-channel 3T receive radiofrequency (RF) coil optimized for parallel imaging of awake macaques. This enabled the acquisition of multiband and GRAPPA-accelerated ferumoxytol-weighted resting-state fMRI. The Human Connectome Project-style data processing pipelines were adapted to address the unique preprocessing demands of cerebral blood volume-weighted (CBVw) imaging, including motion correction, functional-to-structural image co-registration, and training a multi-run independent component analysis-based X-noiseifier (ICA-FIX) classifier for removal of structured artifacts. Our CBVw fMRI approach resulted in an elevated contrast-to-noise ratio compared to blood oxygenation level dependent (BOLD) imaging in anesthetized macaques. However, structured imaging artifacts still contributed more variance to the functional timeseries than neural activity. By applying the ICA-FIX classifier, we achieved highly reproducible parcellated functional connectivity at the single-subject level. At the group-level, we identified dense functional networks with spatial features homologous to those observed in humans. The developed RF receive coil, image acquisition protocols, and data analysis pipelines are publicly available, providing the broader scientific community with tools to leverage these advances for further research., Cold Spring Harbor Laboratory, 英語

Contribution of glutamatergic projections to neurons in the nonhuman primate lateral substantia nigra pars reticulata for the reactive inhibition.
Atsushi Yoshida; Okihide Hikosaka, bioRxiv : the preprint server for biology, 2024年12月25日, ［筆頭著者, 責任著者］, ［国際誌］
The basal ganglia play a crucial role in action selection by facilitating desired movements and suppressing unwanted ones. The substantia nigra pars reticulata (SNr), a key output nucleus, facilitates movement through disinhibition of the superior colliculus (SC). However, its role in action suppression, particularly in primates, remains less clear. We investigated whether individual SNr neurons in three male macaque monkeys bidirectionally modulate their activity to both facilitate and suppress actions and examined the role of glutamatergic inputs in suppression. Monkeys performed a sequential choice task, selecting or rejecting visually presented targets. Electrophysiological recordings showed SNr neurons decreased firing rates during target selection and increased firing rates during rejection, demonstrating bidirectional modulation. Pharmacological blockade of glutamatergic inputs to the lateral SNr disrupted saccadic control and impaired suppression of reflexive saccades, providing causal evidence for the role of excitatory input in behavioral inhibition. These findings suggest that glutamatergic projections, most likely from the subthalamic nucleus, drive the increased SNr activity during action suppression. Our results highlight conserved basal ganglia mechanisms across species and offer insights into the neural substrates of action selection and suppression in primates, with implications for understanding disorders such as Parkinson's disease., 英語

Involvement of neurons in the non-human primate anterior striatum in proactive inhibition.
Atsushi Yoshida; Okihide Hikosaka, bioRxiv : the preprint server for biology, 2024年04月28日, ［筆頭著者, 責任著者］, ［国際誌］
Behaving as desired requires selecting the appropriate behavior and inhibiting the selection of inappropriate behavior. This inhibitory function involves multiple processes, such as reactive and proactive inhibition, instead of a single process. In this study, macaque monkeys were required to perform a task in which they had to sequentially select (accept) or refuse (reject) a choice. Neural activity was recorded from the anterior striatum, which is considered to be involved in behavioral inhibition, focusing on the distinction between proactive and reactive inhibitions. We identified neurons with significant activity changes during the rejection of bad objects. Cluster analysis revealed three distinct groups, of which one showed obviously increased activity during object rejection, suggesting its involvement in proactive inhibition. This activity pattern was consistent irrespective of the rejection method, indicating a role beyond mere saccadic suppression. Furthermore, minimal activity changes during the fixation task indicated that these neurons were not primarily involved in reactive inhibition. In conclusion, these findings suggest that the anterior striatum plays a crucial role in cognitive control and orchestrates goal-directed behavior through proactive inhibition, which may be critical in understanding the mechanisms of behavioral inhibition dysfunction that occur in patients with basal ganglia disease., 英語

Opposing functions of glutamatergic inputs between the globus pallidus external segment and substantia nigra pars reticulata.
Atsushi Yoshida; Okihide Hikosaka, bioRxiv : the preprint server for biology, 2023年07月28日, ［筆頭著者, 責任著者］, ［国際誌］
The indirect pathway of the basal ganglia, including the subthalamic nucleus (STN) and globus pallidus external segment (GPe), is believed to play a crucial role in suppressing involuntary movements. However, recent evidence suggests the STN and GPe also facilitate voluntary movements. This study hypothesized that excitatory inputs from the STN to the GPe contribute to this facilitation, and that excitatory projections to the substantia nigra pars reticulata (SNr) are involved in the inhibition. To disrupt the STN-GPe or STN-SNr projections in monkeys during choice and fixation tasks, glutamate receptor inhibitors were injected into the GPe or SNr, which induced delayed saccade latencies toward good choices in the choice task (GPe) and caused frequent reflexive saccades to objects in the fixation task (SNr). Our findings suggest excitatory inputs to the GPe and SNr work in opposing manners, providing new insights that redefine our understanding of the functions of basal ganglia pathways., 英語

拡散尖度画像と定量的磁化率画像を用いた多系統萎縮症の診断
吉田 篤司; 工藤; 與亮, 神経内科, 2015年, ［招待有り］
記事・総説・解説・論説等（学術雑誌）

脳の拡散強調画像と灌流強調画像
吉田 篤司; 藤間; 憲幸; 工藤 與亮, medicina, 2014年, ［招待有り］

QSMの原理と臨床応用
吉田 篤司; 工藤; 與亮, Innervision, 2014年, ［招待有り］
記事・総説・解説・論説等（学術雑誌）

3T装置での脳転移スクリーニング用の造影3D‐MRIの撮像法の検討:T1‐VISTA法とT1‐FLAIR法との比較
吉田篤司; THA Khin Khin; 塚原亜希子; 吉田大介; 曽山武士; 原田慶一; 財津有里; 藤間憲幸; 寺江聡; 白土博樹, 日本医学放射線学会総会抄録集, 70th, S243, S243, 2011年02月28日
(公社)日本医学放射線学会, 日本語

まっすぐじゃなくていい ―医師・神経科学者になるまで遠回りした私の話―
吉田 篤司
立命館慶祥中学校講演会, 2026年09月25日

生成AIを用いた論文作成の第1歩
吉田 篤司
北大脊椎脊髄外科セミナー 2026, 2026年07月02日
［招待講演］

生成AIの研究活動への利用法 2026 update
吉田 篤司
北海道大学呼吸器内科学教室, 2026年06月17日

研究活動におけるAIの適切な利用法
吉田 篤司
北海道大学大学院医学研究院研究戦略室研修会, 2026年06月15日

生成AIを研究活動にどう「うまく、正しく」使うか
吉田 篤司
北海道大学統合病理学教室 第15回統合病理学教室セミナー, 2026年05月11日

生成AIを研究活動、日々の雑用にどう活かすか
北海道大学皮膚科学教室, 2026年03月04日

相対的価値に基づく意思決定から行動実行への変換メカニズム
量子医科学研究所脳機能イメージング研究センター Neuroscience Seminor, 2026年02月03日

AIを用いた論文作成・テータ解析の初歩
北海道大学耳鼻咽喉科頭頸部外科教室, 2026年01月07日

AIを用いた論文作成の初歩
北海道大学整形外科教室, 2025年12月01日

AIを用いた論文作成入門
北海道大学精神医学教室, 2025年11月26日

URAによる研究支援
北海道大学呼吸器内科学教室, 2025年10月29日

Relative value representation in the macaque substantia nigra pars reticulata (SNr) and frontal eye field (FEF)
Atsushi Yoshida
International Mini-symposium on Brain Science, 2024年03月14日
［招待講演］

脳損傷後機能回復に関与する脳可塑性システムの解明
基盤研究(C)
2017年04月 - 2020年03月
吉田 篤司
日本学術振興会, 研究代表者, 競争的資金

磁気共鳴画像法を用いた大脳皮質-基底核新経路の存在証明と大脳基底核機能概念の再構築
基礎科学特別研究員研究費
2017年04月 - 2020年03月
吉田 篤司
理化学研究所, 研究代表者, 競争的資金

精神疾患MRI画像診断法の確立に向けた覚醒マカクサル実験用のMRI受信コイルの開発
2017年度技術交流助成研修プログラム（海外研修）
2018年02月 - 2018年03月
吉田 篤司
中谷医工計測技術振興財団, 研究代表者, 競争的資金

霊長類システム神経生理学と覚醒下MRI研究との融合による脳可塑性システムの解明
国際共同研究加速基金（国際共同研究強化）
2018年 - 2018年
吉田 篤司
ルールを学習することや技術を習熟することは日常生活や社会生活を効率的に、問題なく営む上で重要であり、これらは脳の可塑性により実現されると考えられている。また、脳卒中のように脳が損傷されたあとにリハビリテーションなどで機能が回復する際にも脳の可塑性が関与する。しかしながら脳可塑性のメカニズムについては依然として解明されていない部分が多い。申請者はヒトと相同の脳を持つマカクザルの脳損傷実験と麻酔下での磁気共鳴画像法(Magnetic Resonance Imaging: MRI)を組み合わせ、障害後の機能回復に関与する脳ネットワークの検出と脳可塑性メカニズムの解明を目的に研究を行っていた。しかし、麻酔下でのMRI撮像には麻酔薬の影響を除外できない、行動課題とMRI撮像を同時に行うことができず、機能欠落や機能回復時に脳内でどのような変化が起こっているか観察できない、といった問題点がある。
本課題ではまずMRI実験を行う前に、サルに複数のフラクタル図形を提示し、それぞれのフラクタル図形で報酬量が異なることを学習させ、眼球運動にて図形を選択させる課題を行った。学習後、大脳基底核淡蒼球外節に局所的に薬剤を注入し、同部への投射を局所的に遮断することでどのような行動変化が起こるか観察した。薬剤注入後サルの反応が遅延したことから同部が行動選択の促進に関与していることが示された。この研究結果は2019年度の北米神経学会にて発表を行う。
今後は学習過程に関与すると考えられる脳部位に対して薬剤を注入することにより学習が阻害されるかどうか、また学習過程や薬剤による不活化を行っている際にMRI撮像を行い、脳内でどのような変化が生じているかを観察する。これらの研究を行うためには更に時間を要するため、申請者は米国NIHに異動することとした。そのため本課題はやむなく廃止することとしたが、研究は発展的に継続する。
日本学術振興会, 国際共同研究加速基金(国際共同研究強化), 国立研究開発法人理化学研究所, 研究代表者, 競争的資金, 17KK0180

眼球運動課題を用いた大脳基底核機能の解明
科学研究費助成事業 特別研究員奨励費
2011年 - 2013年
吉田 篤司
大脳基底核各経路(直接路、間接路、ハイパー直接路)の機能を解明するために、これまで神経心理実験によく用いられている課題に加えて、新たな眼球運動課題を3頭のサルにトレーニングした。具体的には提示された視覚刺激に対して即座に視線を向ける眼球運動課題(Prosaccade課題)、視覚刺激に対して180°反対側へ視線を向ける眼球運動課題(Antisaccade課題)、視覚刺激へ視線を向けず、画面の中心を固視し続ける課題(NoGo課題)をサルに訓練した。また、事前にどのルールの課題かがわかるタイプと、ターゲットとなる視覚刺激が提示されると同時にルールが提示されるタイプの計6種類の課題を訓練した。十分にトレーニングを行い、大脳基底核の一つである淡蒼球外節から単一細胞外神経活動記録を開始した。以前報告した通り(Yoshida and Tanaka, 2009)、GPeには課題遂行中に神経活動を増加させるもの(increase-type neuron, n=117)と減少させるもの(decrease-type neuron, n=51)があった。Deliberate条件ではincrease-type neuron、decrease-type neuronともにantisaccadeで神経活動の変化が大きかった。それに対し、i㎜ediate条件ではニューロンタイプによって活動の変化に違いが認められた。Increase-type neuronでは、 antisaccadeに加えてprosaccadeでも大きな活動変化がみられ、特にantisaccadeでは神経活動と反応時間の間に負の相関を認めた。一方、decrease-type neuronではincrease-type neuronと異なり、NoGo課題でもantisaccadeと同様の神経活動の経時的変化を認めた。また、decrease-type neuronでは神経活動と反応時間の間に相関が認められなかった。以上の結果からはGPeが素早い行動選択へ関与していることが示唆され、大脳皮質から視床下核を介して興奮性の投射を受けていると考えられるincrease-type neuronは行動の促進に、線条体から抑制性の投射を受けていると考えられるdecrease-typeneuronは行動の抑制に関与している可能性があると考えられた。追加実験として視床下核からの興奮性の投射を抑えるためにグルタミン酸受容体拮抗薬をGPeに局所注入したところ、 antisaccadeおよびprosaccadeの反応時間は有意に遅くなったが、antisaccadeやNoGo時の抑制機能の障害は認められず、大脳皮質から視床下核を介して生成されると考えられるGPeのincrease-type neuronが即時性の行動選択に関与していることが示された。
日本学術振興会, 特別研究員奨励費, 北海道大学, 11J04606

2016年10月 - 2016年10月
日本学術振興会特別研究員(PD)内定
理化学研究所基礎科学特別研究員に採用されたため辞退

2016年09月 - 2016年09月
日本放射線学会放射線科診断専門医