日加シンポジウム「脳画像技術の進歩と精神機能およびその障害の研究への応用」 5th Japan-Canada Symposium on Innovations in Neuroscience: Progress in neuroimaging techniques and its application to human mental function and dysfunction
S3-2-3-1 マルチモーダル分子イメージング：モデル動物と人間の双方向の橋渡し Multimodal molecular imaging; bidirectional-translation between model animal and human ○須原哲也1 ○Tetsuya Suhara1 放射線医学総合研究所1 Molecular Neuroimaging Program, National Institute of Radiological Sciences, Molecular Imaging Center1 Neurons express various receptors and transporters and those can be a specific target of the imaging. The functions of those molecules can be examined in human and various types of pharmacologically modified animal models. Dopamine is one of the key neurotransmitters in the brain function such as psychosis and addiction. The role of dopamine in personal trait or motivation has been studied using positron emission tomography and functional MRI. The neuromolecular basis for cognitive bias such as “superiority illusion” can be illustrated by an interrelationship between dopamine neurotransmission and fronto-striatal resting-state functional connectivity. Regarding dopamine receptor, D1 receptor binding in the ventral striatum is related the nicotine addiction and risk taking behavior. For the validation of molecular mechanism of human behavior, nonhuman primate is useful to analyze the direct relation between neurotransmission and behavior. Using a monkey model of hypothyroidism, which is associated with symptoms of low motivation characterized by instrumental task performance, the performance of goal-directed action was affected by dopaminergic manipulations. PET revealed the change in dopamine D2 receptor in the ventromedial prefrontal cortex of the model monkey. The multimodal imagings provide the different aspects of the brain function and using nonhuman primate we can investigate circuit specific neural transmission.	S3-2-3-2 PET receptor imaging in Parkinson's Disease ○Strafella P. Antonio Dept. Neurology University of Toronto1 Motor and non-motor symptoms like cognitive dysfunction, impulse control disorders and visual hallucinations are increasingly been reported in Parkinson’s disease (PD) patients. Given the social implications, these symptoms represent a cause of significant distress not only for the patients but mostly their families. To date, the mechanisms underlying motor, cognitive and behavioral complications in PD are poorly understood. Proposed mechanisms include abnormal functioning of different neural networks resulting in dysregulation of various neurotransmitters. In this presentation, we will address how PET receptor imaging is helping us to understand the pathophysiology of PD.
S3-2-3-3 機能的磁気共鳴画像法によって描出される記憶想起の神経機構 Neural mechanism of memory retrieval revealed by fMRI ○小西清貴 ○Seiki Konishi 東京大学医学系研究科統合生理学教室1 Dept Physiology, The University of Tokyo School of Medicine1 It is most often held that memory encoded into the medial temporal lobe (MTL) including the hippocampus, after some time period, is to be consolidated in the temporal neocortex and is independent of the MTL during retrieval. The neural mechanisms underlying the MTL-neocortex interaction that support memory formation and retrieval remain largely unknown. Our recent work using functional MRI revealed the large-scale inter-regional interaction in the human temporal lobe during retrieval of recent and remote memory: The hippocampus interacted with the posterior temporal neocortex during consolidation of recent memory, and the posterior temporal neocortex interacted with the anterior temporal neocortex during retrieval of remote memory. The hippocampal-posterior temporal cortical interaction was modality specific, whereas the posterior temporal-anterior temporal interaction was modality general. In this talk our new model of memory formation and retrieval will be presented and discussed.	S3-2-3-4 Using Neuroimaging to Detect Consciousness ○Adrian M. Owen1 Brain and Mind Institute, Psychology, Western University1 How can we ever know, unequivocally, that another person is aware? Notwithstanding deeper philosophical considerations about the nature of consciousness itself, the only reliable method we have for detecting awareness in others is by eliciting a predicted response to an external prompt or command. Logically therefore, our ability to detect awareness in others is determined, not by whether they are aware or not, but by their ability to communicate that fact through a recognized behavioural response. This problem exposes a central conundrum in the study of awareness in general, and in particular, how it relates to the vegetative state, anesthetic sedation and other altered states of consciousness. From this perspective, I will discuss various solutions to this conundrum using functional neuroimaging. In particular, I will contrast those circumstances in which imaging data can be used to infer awareness in the absence of a reliable behavioural response, with those circumstances in which it cannot. This distinction is fundamental for understanding and interpreting patterns of brain activity in various states of consciousness (including anesthesia), and has profound implications for clinical care, diagnosis, prognosis and medical-legal decision-making after severe brain injury. It also sheds light on more basic scientific questions about how consciousness is measured and the neural representation of our own thoughts and intentions.
S3-2-3-5 “私たち”の神経科学：２個体同時計測fMRIによるアプローチ We-mode neuroscience using dual fMRI ○定藤規弘 ○Norihiro Sadato 自然科学研究機構生理学研究所心理生理学研究部門1 Dept. Cereb Research Natl Inst Physiol Sci1 Social cognition is embedded in real-time interaction across individuals. To depict its neural underpinning, we propose dual fMRI that enables to depict the neural activities of the two brains during the real time interaction. We treat the two brains as one unit to understand the neural substrates of “inter-subjectivity”, and to apply this “two-in-one” strategy to joint attention and eye contact. Eye contact provides a communicative link between humans, prompting joint attention. As spontaneous brain activity might have an important role in the coordination of neuronal processing within the brain, their inter-subject synchronization might occur during eye contact. To test this, we conducted dual fMRI in pairs of adults. Eye contact was maintained at baseline while the subjects engaged in real-time gaze exchange in a joint attention task. After all the task-related effects were modeled out, inter-individual correlation analysis of residual time-courses was performed. Paired subjects showed more prominent correlations than non-paired subjects in the right inferior frontal gyrus (IFG), suggesting that this region is involved in sharing intention during eye contact that provides the context for joint attention. Lack of joint attention and eye contact is an early signs of autism spectrum disorders (ASD). To depict its neural underpinning, identical protocol was applied to ASD subjects paired with normal subjects. Performance was not only impaired in ASD subjects, but also their paired normal subjects. Inter-brain coherence in the right IFG was significantly less prominent in the ASD – Normal pairs than Normal – Normal pairs. Thus the impairment of joint attention in ASD is partly related to difficulty in obtaining the shared intention through eye contact, represented by the reduced inter-subject synchronization of the right IFG. Our “two-in-one” strategy with dual fMRI will be an indispensable and ground-breaking method to open a new field of “we-mode” neuroscience.	S3-2-3-6 Dynamic functional connectivity in human and non-human primates. ○Ravi S. Menon Centre for Functional and Metabolic Mapping The University of Western Ontario, Canada1 The characterization of large-scale primate brain networks using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is usually based on the fundamental assumption that the network is stationary for the duration of the typical 5 minute scan. Recent studies in humans have cast this assumption in doubt by showing that intra-network functional connectivity fluctuates on the order of seconds to minutes. The time-varying activity of resting-state networks (RSNs) may relate to spontaneously shifting, electrophysiological network states and are could be of particular importance. Initial demonstrations of the dynamic nature of these RSNs utilized data from awake subjects, hence the fluctuating connectivity could reflect various forms of conscious brain processing such as passive mind wandering, active monitoring, memory formation, or changes in attention and arousal during image acquisition. We have characterized RSN dynamics of anesthetized macaques that control for these confounding factors, and compared them to awake human subjects. Focussing on one well defined network, we find that functional connectivity among nodes comprising the "oculomotor (OCM) network" strongly fluctuated over time during awake as well as anaesthetized states. For time dependent analysis with short windows (<60 s), periods of positive functional correlations alternated with prominent anticorrelations that were missed when utilizing longer time windows. Similarly, the analysis identified other network nodes that transiently linked to the OCM network but were not visualized in average RSN analysis. Furthermore, time-dependent analysis reliably revealed transient states of large-scale synchronization that spanned all seeds. The results illustrate that resting-state functional connectivity is not static and that RSNs can exhibit nonstationary, spontaneous relationships irrespective of conscious, cognitive processing. Our findings imply that potentially mechanistically important network information can be missed when using average functional connectivity as the single network measure.

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