Language：English   Publishing type：Research paper (scientific journal)  

Sensory prediction is considered an important element of mismatch negativity (MMN) whose reduction is well known in patients with schizophrenia. Omission MMN is a variant of the MMN which is elicited by the absence of a tone previously sequentially presented. Omission MMN can eliminate the effects of sound differences in typical oddball paradigms and affords the opportunity to identify prediction-related signals in the brain. Auditory predictions are thought to reflect bottom-up and top-down processing within hierarchically organized auditory areas. However, the communications between the various subregions of the auditory cortex and the prefrontal cortex that generate and communicate sensory prediction-related signals remain poorly understood. To explore how the frontal and temporal cortices communicate for the generation and propagation of such signals, we investigated the response in the omission paradigm using electrocorticogram (ECoG) electrodes implanted in the temporal, lateral prefrontal, and orbitofrontal cortices of macaque monkeys. We recorded ECoG data from three monkeys during the omission paradigm and examined the functional connectivity between the temporal and frontal cortices by calculating phase-locking values (PLVs). This revealed that theta- (4-8 Hz), alpha- (8-12 Hz), and low-beta- (12-25 Hz) band synchronization increased at tone onset between the higher auditory cortex and the frontal pole where an early omission response was observed in the event-related potential (ERP). These synchronizations were absent when the tone was omitted. Conversely, low-beta-band (12-25 Hz) oscillation then became stronger for tone omission than for tone presentation approximately 200 ms after tone onset. The results suggest that auditory input is propagated to the frontal pole via the higher auditory cortex and that a reciprocal network may be involved in the generation of auditory prediction and prediction error. As impairments of prediction may underlie MMN reduction in patients with schizophrenia, an aberrant hierarchical temporal-frontal network might be related to this pathological condition.

DOI： 10.3389/fpsyt.2022.557954

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Language：English   Publisher：Japanese Society for Medical and Biological Engineering  

<p>The rhythm of vocalizing a written language depends on a merge process that combines meaningless linguistic units into a meaningful lexical unit, word, or Bunsetsu in Japanese. However, in most previous studies, written language was presented to the participants in lexical units (word-by-word) with explicit inter-word (or inter-Bunsetsu) marks or spacing. Therefore, it has been difficult to conduct psychophysical assessment of the participants' own speed in segmenting meaningful units from unstructured written language when reading. Here, we hypothesized that the spontaneous reading speed of Japanese readers reflects their own punctuation process, even when sentences are written without punctuation marks or spaces. To test this hypothesis, we developed a new "self-paced sequential letterstring reading task," which visually presents sentences letter-by-letter. The task required participants to push a button to proceed to the next letter at their own pace, hence allowing evaluation of the reaction time (RT) to individual letters. We found that the average RT decreased parametrically as the position of the letter approached the end of a Bunsetsu. Moreover, the RT increased drastically at the last letter completing the Bunsetsu. Participants were not shown any punctuation marks and not instructed to explicitly recognize the punctuations during reading. Therefore, these effects strongly suggest that the implicit and spontaneous punctuation is the origin of the rhythm in reading. These results show that spontaneous punctuation of letterstring affects the reading speed. The task we have developed is a promising tool for revealing the temporal dynamics of natural reading, which opens a way to shape the fluency of script-to-speech human interfaces.</p>

DOI： 10.14326/abe.10.26

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The ability to infer others' mental states is essential to social interactions. This ability, critically evaluated by testing whether one attributes false beliefs (FBs) to others, has been considered to be uniquely hominid and to accompany the activation of a distributed brain network. We challenge the taxon specificity of this ability and identify the causal brain locus by introducing an anticipatory-looking FB paradigm combined with chemogenetic neuronal manipulation in macaque monkeys. We find spontaneous gaze bias of macaques implicitly anticipating others' FB-driven actions. Silencing of the medial prefrontal neuronal activity with inhibitory designer receptor exclusively activated by designer drugs (DREADDs) specifically eliminates the implicit gaze bias while leaving the animals' visually guided and memory-guided tracking abilities intact. Thus, neuronal activity in the medial prefrontal cortex could have a causal role in FB-attribution-like behaviors in the primate lineage, emphasizing the importance of probing the neuronal mechanisms underlying theory of mind with relevant macaque animal models.

DOI： 10.1016/j.celrep.2020.03.013

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Language：Japanese   Publisher：(一社)日本生理学会  

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Language：Japanese   Publisher：(一社)日本生理学会  

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Language：Japanese   Publisher：(一社)日本生理学会  

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Language：Japanese   Publisher：(一社)日本生理学会  

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Language：Japanese   Publisher：(一社)日本生理学会  

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Language：Japanese   Publisher：(一社)日本小児精神神経学会  

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Language：Japanese   Publisher：(公社)日本精神神経学会  

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DOI： 10.1109/BIBM47256.2019.8983029

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Other Link： https://dblp.uni-trier.de/db/conf/bibm/bibm2019.html#DateKHO19

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Nature Publishing Group  

Propagation of oscillatory spike firing activity at specific frequencies plays an important role in distributed cortical networks. However, there is limited evidence for how such frequency-specific signals are induced or how the signal spectra of the propagating signals are modulated during across-layer (radial) and inter-areal (tangential) neuronal interactions. To directly evaluate the direction specificity of spectral changes in a spiking cortical network, we selectively photostimulated infragranular excitatory neurons in the rat primary visual cortex (V1) at a supra-threshold level with various frequencies, and recorded local field potentials (LFPs) at the infragranular stimulation site, the cortical surface site immediately above the stimulation site in V1, and cortical surface sites outside V1. We found a significant reduction of LFP powers during radial propagation, especially at high-frequency stimulation conditions. Moreover, low-gamma-band dominant rhythms were transiently induced during radial propagation. Contrastingly, inter-areal LFP propagation, directed to specific cortical sites, accompanied no significant signal reduction nor gamma-band power induction. We propose an anisotropic mechanism for signal processing in the spiking cortical network, in which the neuronal rhythms are locally induced/modulated along the radial direction, and then propagate without distortion via intrinsic horizontal connections for spatiotemporally precise, inter-areal communication.

DOI： 10.1038/s41598-018-26054-8

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The inferior temporal cortex (ITC) contains neurons selective to multiple levels of visual categories. However, the mechanisms by which these neurons collectively construct hierarchical category percepts remain unclear. By comparing decoding accuracy with simultaneously acquired electrocorticogram (ECoG), local field potentials (LFPs), and multi-unit activity in the macaque ITC, we show that low-frequency LFPs/ECoG in the early evoked visual response phase contain sufficient coarse category (e.g., face) information, which is homogeneous and enhanced by spatial summation of up to several millimeters. Late-induced high-frequency LFPs additionally carry spike-coupled finer category (e.g., species, view, and identity of the face) information, which is heterogeneous and reduced by spatial summation. Face-encoding neural activity forms a cluster in similar cortical locations regardless of whether it is defined by early evoked low-frequency signals or late-induced high-gamma signals. By contrast, facial subcategory-encoding activity is distributed, not confined to the face cluster, and dynamically increases its heterogeneity from the early evoked to late-induced phases. These findings support a view that, in contrast to the homogeneous and static coarse category-encoding neural cluster, finer category-encoding clusters are heterogeneously distributed even outside their parent category cluster and dynamically increase heterogeneity along with the local cortical processing in the ITC.

DOI： 10.1093/cercor/bhx342

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Language：English   Publisher：ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Highly localized neuronal spikes in primate temporal cortex can encode associative memory; however, whether memory formation involves area-wide reorganization of ensemble activity, which often accompanies rhythmicity, or just local microcircuit-level plasticity, remains elusive. Using high-density electrocorticography, we capture local-field potentials spanning the monkey temporal lobes, and show that the visual pair-association (PA) memory is encoded in spatial patterns of theta activity in areas TE, 36, and, partially, in the parahippocampal cortex, but not in the entorhinal cortex. The theta patterns elicited by learned paired associates are distinct between pairs, but similar within pairs. This pattern similarity, emerging through novel PA learning, allows a machine-learning decoder trained on theta patterns elicited by a particular visual item to correctly predict the identity of those elicited by its paired associate. Our results suggest that the formation and sharing of widespread cortical theta patterns via learning-induced reorganization are involved in the mechanisms of associative memory representation.

DOI： 10.1038/ncomms11827

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

Recognition of faces and written words is associated with category-specific brain activation in the ventral occipitotemporal cortex (vOT). However, topological and functional relationships between face-selective and word-selective vOT regions remain unclear. In this study, we collected data from patients with intractable epilepsy who underwent high-density recording of surface field potentials in the vOT. "Faces" and "letterstrings" induced outstanding category-selective responses among the 24 visual categories tested, particularly in high-gamma band powers. Strikingly, within-hemispheric analysis revealed alternation of face-selective and letterstring-selective zones within the vOT. Two distinct face-selective zones located anterior and posterior portions of the mid-fusiform sulcus whereas letterstring-selective zones alternated between and outside of these 2 face-selective zones. Further, a classification analysis indicated that activity patterns of these zones mostly represent dedicated categories. Functional connectivity analysis using Granger causality indicated asymmetrically directed causal influences from face-selective to letterstring-selective regions. These results challenge the prevailing view that different categories are represented in distinct contiguous regions in the vOT.

DOI： 10.1093/cercor/bht319

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

How visual object categories are represented in the brain is one of the key questions in neuroscience. Studies on low-level visual features have shown that relative timings or phases of neural activity between multiple brain locations encode information. However, whether such temporal patterns of neural activity are used in the representation of visual objects is unknown. Here, we examined whether and how visual object categories could be predicted (or decoded) from temporal patterns of electrocorticographic (ECoG) signals from the temporal cortex in five patients with epilepsy. We used temporal correlations between electrodes as input features, and compared the decoding performance with features defined by spectral power and phase from individual electrodes. While using power or phase alone, the decoding accuracy was significantly better than chance, correlations alone or those combined with power outperformed other features. Decoding performance with correlations was degraded by shuffling the order of trials of the same category in each electrode, indicating that the relative time series between electrodes in each trial is critical. Analysis using a sliding time window revealed that decoding performance with correlations began to rise earlier than that with power. This earlier increase in performance was replicated by a model using phase differences to encode categories. These results suggest that activity patterns arising from interactions between multiple neuronal units carry additional information on visual object categories. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.neuroimage.2013.12.020

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Language：English   Publisher：PION LTD  

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

In order to realize a low-invasive and high accuracy Brain-Machine Interface (BMI) system for clinical applications, a super multi-channel recording system was developed in which 4096 channels of Electrocorticogram (ECoG) signal can be amplified and transmitted to outside the body by using an Ultra Wide Band (UWB) wireless system. Also, a high density, flexible electrode array made by using a Parylene-C substrate was developed that is composed of units of 32-ch recording arrays. We have succeeded in an evaluation test of UWB wireless transmitting using a body phantom system.

DOI： 10.1109/EMBC.2014.6944799

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: There has been growing interest in clinical single-neuron recording to better understand epileptogenicity and brain function. It is crucial to compare this new information, single-neuronal activity, with that obtained from conventional intracranial electroencephalography during simultaneous recording. However, it is difficult to implant microwires and subdural electrodes during a single surgical operation because the stereotactic frame hampers flexible craniotomy.
OBJECTIVE: To describe newly designed electrodes and surgical techniques for implanting them with subdural electrodes that enable simultaneous recording from hippocampal neurons and broad areas of the cortical surface.
METHODS: We designed a depth electrode that does not protrude into the dura and pulsates naturally with the brain. The length and tract of the depth electrode were determined preoperatively between the lateral subiculum and the lateral surface of the temporal lobe. A frameless navigation system was used to insert the depth electrode. Surface grids and ventral strips were placed before and after the insertion of the depth electrodes, respectively. Finally, a microwire bundle was inserted into the lumen of the depth electrode. We evaluated the precision of implantation, the recording stability, and the recording rate with microwire electrodes.
RESULTS: Depth-microwire electrodes were placed with a precision of 3.6 mm. The mean successful recording rate of single-or multiple-unit activity was 14.8%, which was maintained throughout the entire recording period.
CONCLUSION: We achieved simultaneous implantation of microwires, depth electrodes, and broad-area subdural electrodes. Our method enabled simultaneous and stable recording of hippocampal single-neuron activities and multichannel intracranial electroencephalography.

DOI： 10.1227/01.neu.0000430327.48387.e1

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Electrocorticogram (ECoG) is an electrophysiological brain activity recording technique that has been widely revisited in recent years, not only for clinical monitoring, but also for prosthetic applications. However, the extent and limitations of the technique are poorly understood. Higher areas of human and macaque ventral visual cortices are known to have functional domain structures that are selective to certain categories, and population vectors that have been derived from visually evoked single-unit activity (SUA) recording in this region have been shown to form category clusters. How can visually evoked potentials recorded with ECoG from the same region be exploited to extract category information? To answer this question, the development of a simultaneous ECoG and SUA recording device by the modification of a previously reported flexible mesh ECoG probe with a microelectromechanical system has been promising (Toda et al., 2011). Indeed, Toda et al. conducted simultaneous recordings and reported that mesh ECoG signals exhibited comparable or better signal variabilities compared to conventional methods in the rat visual cortex. With this approach, we conducted intensive simultaneous ECoG and SUA recordings from the macaque anterior inferior temporal (IT) cortex. We compared how basic visual category and fine information is decoded from different recording modalities. Our preliminary results indicated that ECoG signals from the IT cortex may be a useful source for reading out certain levels of category information from visual input.

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Language：English   Publisher：Japanese Society for Medical and Biological Engineering  

DOI： 10.11239/jsmbe.51.M-2

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A sensation of depth can arise from two-dimensional (2D) movies without any stereoscopic depth cue. Depth perception in three-dimensional (3D) space depends on the stability of stereoscopic gaze by vergence - coordinated movement of the two eyes in opposite directions - compensating the misalignment of the retinal images from the two eyes (i.e. binocular disparity) [1]. On the other hand, the oculomotor mechanisms that stabilize stereoscopic gaze and depth perception in 2D movie space remain unclear [2]. Here, we propose a hypothesis that vergence eye movements signifying 3D depth perception persist during prolonged 20 movie presentation without binocular disparity cues. By measuring eye positions while the subject viewed moving random-dot video stimuli, we show that sustained vergence is induced during 30-s exposure to radially expanding 2D optic flow. Moreover, a 2D video movie showing a passenger's view of a roller coaster induces continuously changing vergence. In the absence of binocular disparity cues, the pictorial depth information within a 50 x 50 gaze window and optic flow in the movie simultaneously and independently influence vergence. The pictorial gaze-area depth information affects vergence mainly in the virtual far space, whereas optic flow robustly affects vergence irrespective of the nearness. These findings demonstrate that vergence serves as a reliable marker signifying 3D depth perception from 2D movies, imposing critical constraints on creation of an effective and safe virtual reality. 0 2011 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.displa.2011.11.001

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Publishing type：Research paper (international conference proceedings)   Publisher：IEEE Computer Society  

DOI： 10.1109/PRNI.2012.17

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Viral vector-mediated gene transfer has become increasingly valuable for primate brain research, in particular for application of genetic methods (e.g. optogenetics) to study neuronal circuit functions. Neuronal cell tropisms and infection patterns are viable options for obtaining viral vector-mediated transgene delivery that is selective for particular neuronal pathways. For example, several types of viral vectors can infect axon terminals (retrograde infections), which enables targeted transgene delivery to neurons that directly project to a particular viral injection region. Although recent studies in rodents have demonstrated that adeno-associated virus serotype 8 (AAV8) and 9 (AAV9) efficiently transduce neurons, the tropisms and infection patterns remain poorly understood in primate brains. Here, we constructed recombinant AAV8 or AAV9, which expressed an enhanced green fluorescent protein (EGFP) gene driven by a ubiquitous promoter (AAV8-EGFP and AAV9-EGFP, respectively), and stereotaxically injected it into several brain regions in marmosets and macaque monkeys. Immunohistochemical analyses revealed almost exclusive colocalization of EGFP fluorescence via AAV9-mediated gene transfer with a neuron-specific marker, indicating endogenous neuronal tropism of AAV9, which was consistent with our previous results utilizing AAV8. Injections of either AAV8-EGFP or AAV9-EGFP into the marmoset striatum resulted in EGFP expression in local striatal neurons as a result of local infection, as well as expression in dopaminergic neurons of the substantia nigra via retrograde transport along nigrostriatal axonal projections. Retrograde infections were also observed in the frontal cortex and thalamus, which are known to have direct projections to the striatum. These local and retrograde gene transfers were further demonstrated in the geniculocortical pathway of the marmoset visual system. These findings indicate promising capabilities of AAV8 and AAV9 to deliver molecular tools into a range of primate neural systems in pathway-specific manners through their neuronal tropisms and infection patterns. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuroscience.2011.06.080

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Electrocorticography (ECoG), multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate's brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems (MEMS) technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the whole brain. © 2011 Matsuo, Kawasaki, Osada, Sawahata, Suzuki, Shibata, Miyakawa, Nakahara, Iijima, Sato, Kawai, Saito and Hasegawa.

DOI： 10.3389/fnsys.2011.00034

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Electrocorticogram (ECoG) is a well-balanced methodology for stably mapping brain surface local field potentials (LFPs) over a wide cortical region with high signal fidelity and minimal invasiveness to the brain tissue. To directly compare surface ECoG signals with intracortical neuronal activity immediately underneath, we fabricated a flexible multichannel electrode array with mesh-form structure using micro-electro-mechanical systems. A Parylene-C-based "electrode-mesh" for rats contained a 6 x 6 gold electrode array with 1-mm interval. Specifically, the probe had 800 x 800 mu m(2) fenestrae in interelectrode spaces, through which simultaneous penetration of microelectrode was capable. This electrode-mesh was placed acutely or chronically on the dural/pial surface of the visual cortex of Long Evans rats for up to 2 weeks. We obtained reliable trial-wise profiles of visually evoked ECoG signals through individual eye stimulation. Visually evoked ECoG signals from the electrode-mesh exhibited as well or larger signal amplitudes as intracortical LFPs and less across-trial variability than conventional silver-ball ECoG. Ocular selectivity of ECoG responses was correlated with that of intracortical spike/LFP activities. Moreover, single-trial ECoG signals carried sufficient information for predicting the stimulated eye with a correct performance approaching 90%, and the decoding was significantly generalized across sessions over 6 hours. Electrode impedance or signal quality did not obviously deteriorate for 2 weeks following implantation. These findings open up a methodology to directly explore ECoG signals with reference to intracortical neuronal sources and would provide a key to developing minimally invasive next-generation brain machine interfaces. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.neuroimage.2010.08.003

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DOI： 10.1016/j.neures.2011.07.1710

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Language：Japanese   Publisher：Japanese Society for Medical and Biological Engineering  

We investigated an effective method for evaluating chronic stress in humans by using pupillary responses to visual motion stimuli. Nine subjects watched movies including 18 short video movies (duration:10s in each). The pupil diameter responding to the movies were measured with a video oculography and calculated the difference between the maximum and minimum pupil diameters responded to the stimuli was highly correlated with the salivary α-amylase (R=-0.76, <i>p</i>=0.018) activities. The sympathetic nervous system is activated by a stress and secretes the salivary amylase. We found that there were some autonomic different responses in the stress subject from pupillary and salivary observations. These phenomena were clearly observed under the visual movie stimulation which was able to reveal the steady pupillary responses.

DOI： 10.11239/jsmbe.49.946

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DOI： 10.1016/j.neures.2011.07.1118

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DOI： 10.1016/j.neures.2011.07.881

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DOI： 10.1016/j.neures.2011.07.877

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DOI： 10.1016/j.neures.2011.07.415

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DOI： 10.1016/j.neures.2011.07.1812

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Language：English   Publisher：日本神経化学会  

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Language：English   Publisher：日本神経化学会  

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Language：English   Publisher：日本神経化学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim:
Somatoform pain disorder is characterized by persistent and chronic pain at one or more sites without an associated general medical condition and in which psychological factors are thought to play a role. This study aimed to investigate the pathological features of somatoform pain disorder localized to the oral region by single photon emission computed tomography (SPECT).
Methods:
Ten patients (nine females and one male; average age 55.0 +/- 14.4 years) having somatoform pain disorder with oral symptoms participated. SPECT was performed using N-isopropyl-4-[123I] iodoamphetamine intravenous injections, and regional cerebral blood flow (rCBF) was assessed by three-dimensional stereotactic surface projections. We also selected 12 healthy individuals (seven females and five males; average age 61.8 +/- 13.2 years) to act as controls.
Results:
Both the patient and control groups showed no atrophy or infarction on CT or magnetic resonance imaging. The patient group showed higher rCBF in the subcortical area, especially in the thalamus and cingulate gyri, than the control group. In contrast, the patient group showed lower rCBF in the bilateral frontal and occipital lobes as well as in the left temporal lobe.
Conclusions:
These results suggest that the biological process involved in somatoform pain disorder of the oral region is characterized by changes in limbic and cortical functions. The finding that somatoform pain disorder with oral symptoms is associated with brain functional changes will help to develop treatment regimes for this disorder and clarify the underlying pathology.

DOI： 10.1111/j.1440-1819.2010.02119.x

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DOI： 10.1016/j.neures.2010.07.1445

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DOI： 10.1016/j.neures.2010.07.2370

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DOI： 10.1016/j.neures.2010.07.1446

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DOI： 10.1016/j.neures.2010.07.132

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DOI： 10.1016/j.neures.2010.07.202

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Language：English   Publisher：SPRINGER TOKYO  

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DOI： 10.1016/j.neures.2009.09.967

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DOI： 10.1016/j.neures.2009.09.170

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ENDOCRINE SOC  

Cyclic Cushing's disease is a rare clinical entity that is defined as a periodic excessive production of adrenocorticotropic hormone (ACTH) and cortisol. Only 42 cases with cyclic Cushing's disease have been reported in the literature. The diagnosis is very difficult because of the fluctuating secretion of ACTH and cortisol. We report a 78-year-old woman with a pituitary adenoma presenting with cyclic Cushing's disease. In the present case, several interesting issues are pointed out: 1) MRI study detected the presence of an adenoma and selective venous sampling in the cavernous sinus disclosed the hypersecretion of ACTH from a pituitary adenoma. These neuroimaging and endocrinological studies were helpful for the diagnosis, even in the remission phase. 2) The disease was in the long-term remission phase after transsphenoidal Surgery despite the high recurrence rate in this clinical entity, although it recurred four years later. Even in the remission phase of cyclic Cushing's disease, meticulous endocrinological and neuroimaging examinations can reveal the presence of a pituitary adenoma, which should be treated surgically.

DOI： 10.1507/endocrj.K06-218

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

We examined prefrontal neuronal activity while monkeys performed a sequential target-shift task, in which, after a positional cue indicated the initial saccade target among 8 peripheral positions, the monkeys were required to internally shift the target by one position on every flash of a target-shift cue. The target-shift cue appeared in the center 0 to 3 times within a single trial and was always the same in shape, size, and color. We found selective neuronal activity related to the target position: when the target-shift cue implied the target shift to particular peripheral positions, neurons exhibited early-dominant and late-dominant activity during the following delay period. The early-dominant target-selective activity emerged early in the delay just after the presentation of the target-shift cue, whereas the late-dominant activity gradually built up toward the end of the delay. Because the target-shift cue was not related to any specific target location, the early-dominant target-selective activity could not be a mere visual response to the target-shift cue. We suggest that the early-dominant activity reflects the transitory representation for the saccade target that was triggered by the nonspatial target-shift cue, whereas the late-dominant activity reflects the target representation in the spatial working memory or the preparatory set for the possible impending saccade, being repeatedly updated during sequential target shifts.

DOI： 10.1152/jn.00306.2003

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CELL PRESS  

The frontal and parietal eye fields serve as functional landmarks of the primate brain, although their correspondences between humans and macaque monkeys remain unclear. We conducted fMRI at 4.7 T in monkeys performing visually-guided saccade tasks and compared brain activations with those in humans using identical paradigms. Among multiple parietal activations, the dorsal lateral intraparietal area in monkeys and an area in the posterior superior parietal lobule in humans exhibited the highest selectivity to saccade directions. In the frontal cortex, the selectivity was highest at the junction of the precentral and superior frontal sulci in humans and in the frontal eye field (FEF) in monkeys. BOLD activation peaks were also found in premotor areas (BA6) in monkeys, which suggests that the apparent discrepancy in location between putative human FEF (BA6, suggested by imaging studies) and monkey FEF (BA8, identified by microstimulation studies) partly arose from methodological differences.

DOI： 10.1016/S0896-6273(04)00047-9

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In a Nature paper, Sigala and Logothetis record from infero- temporal cortex after monkeys learn a categorization task, and find increased sensitivity to features critical for the task.

DOI： 10.1038/nn0202-90

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：FREUND & PETTMAN PUBLISHERS  

In the primate brain, long-term memory is stored in the neocortical association area which is also engaged in sensory perception. The coded representation of memory is retrieved via interactions of hierarchically different cortical areas along bottom-up and top-down anatomical connections. The functional significance of the fronto-cortical top-down neuronal projections has been relevantly assessed in a new experimental paradigm using posterior-split-brain monkeys, When the splenium of the corpus callosum and the anterior commissure were selectively split, the bottom-up visual signal originating from the unilateral striate cortex could not reach the contralateral visual cortical areas. In this preparation, long-term memory acquired through visual stimulus-stimulus association learning was prevented from transferring across hemispheres, Nonetheless, following the presentation of a visual cue to one hemisphere, the prefrontal cortex could instruct the contralateral hemisphere to retrieve: the correct stimulus specified by the cue. These results support the hypothesis that the prefrontal cortex can regulate memory recall in the absence of bottom-up sensory input, In humans, functional neuroimaging studies have revealed activation of a distributed neural network, including the prefrontal cortex, during memory retrieval tasks, Thus, the prefrontal cortex is consistently involved in retrieval of long-term memory in primates.

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Language：English   Publisher：ROYAL SOC MEDICINE PRESS LTD  

Memory retrieval is a process wherein a distributed neural network reactivates the brain's representation of past experiences. Sensory long-term memory is represented among: a population of neurones in the modality-specific posterior association cortex. The coded representation of memory earn be retrieved by interactions of hierarchically different cortical areas along bottom-up and top-down anatomical connections. We examined the function of the prefrontal cortex in memory retrieval by two different approaches. Firstly, a meta-analysis of brain imaging studies revealed that the prefrontal cortex is reliably activated by memory retrieval in humans. Secondly, in order to determine the causal relationship between the prefrontal activations and memory retrieval, we designed a new experimental paradigm using posterior-split-brain monkeys. Following section of the splenium of the corpus callosum and the anterior commissure, visual stimulus-stimulus association learning within one hemisphere did nor transfer to the other. Nevertheless, when a visual cue was presented to one hemisphere, the prefrontal cortex could instruct the contralateral hemisphere to retrieve the correct stimulus specified by the cue. These findings suggest that the prefrontal cortex can regulate the recall of long-term memory in the absence of bottom-up sensory inputs.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MACMILLAN MAGAZINES LTD  

Knowledge or experience is voluntarily recalled from memory by reactivation of the neural representations in the cerebral association cortex(1-4). In inferior temporal cortex, which serves as the storehouse of visual long-term memory(5-8), activation of mnemonic engrams through electric stimulation results in imagery recall in humans(9), and neurons can be dynamically activated by the necessity for memory recall in monkeys(10,11). Neuropsychological studies(12) and previous split-brain experiments(13) predicted that prefrontal cortex exerts executive control upon inferior temporal cortex in memory retrieval; however, no neuronal correlate of this process has ever been detected. Here we show evidence of the top-down signal from prefrontal cortex. In the absence of bottom-up visual inputs, single inferior temporal neurons were activated by the top-down signal, which conveyed information on semantic categorization imposed by visual stimulus-stimulus association. Behavioural performance was severely impaired with loss of the top-down signal. Control experiments confirmed that the signal was transmitted not through a subcortical but through a frontotemporal cortical pathway. Thus, feedback projections from prefrontal cortex to the posterior association cortex(2,3,14) appear to serve the executive control of voluntary recall.

DOI： 10.1038/44372

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Functional magnetic resonance imaging (fMRI) in macaque monkeys is emerging as a potent candidate to bridge the gap between data from human fMRI studies and data from anatomy, electrophysiology and lesion studies in monkeys. The primary (SI) and secondary (SII) somatosensory cortices are the principal regions for somatosensory information processing and contain systematic representations of the body surface map (somatotopy). To examine the functional organization of the somatosensory cortices in anaesthetized macaque monkeys with fMRI, we asked whether focal and differential activation could be observed in SI and SII in response to tactile stimulation with two parameters: body sides (right and left) and body regions (hand and face). We found that changes in stimulus parameters elicited differential focal activation in both SI and SII in two ways. First, the hand and face stimulation activated SI and SII in the contralateral, but not in the ipsilateral, hemisphere. Second, the hand and face stimulation differentially activated two adjacent regions in both SI and SII. These fMRI results appear to correlate with previous mapping studies by other methods in the macaque somatosensory cortices. This study shows the feasibility of fMRI studies in mapping multiple sensory areas in monkeys by which we can distinguish between adjacent functionally distinct regions.

DOI： 10.1046/j.1460-9568.1999.00892.x

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Other Link： http://orcid.org/0000-0003-4362-7439

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC ADVANCEMENT SCIENCE  

A perceptual image can be recalled from memory without sensory stimulation. However, the neural origin of memory retrieval remains unsettled. To examine whether memory retrieval can be regulated by top-down processes originating from the prefrontal cortex, a visual associative memory task was introduced into the partial split-brain paradigm in monkeys. Long-term memory acquired through stimulus-stimulus association did not transfer via the anterior corpus callosum, a key part interconnecting prefrontal cortices. Nonetheless, when a visual cue was presented to one hemisphere, the anterior callosum could instruct the other hemisphere to retrieve the correct stimulus specified by the cue. Thus, although visual Long-term memory is stored in the temporal cortex, memory retrieval is under the executive control of the prefrontal cortex.

DOI： 10.1126/science.281.5378.814

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC  

Neuropsychological theories have proposed a critical role for the interaction between the medial temporal lobe and the neocortex in the formation of long-term memory for facts and events, which has often been tested by learning of a series of paired words or figures in humans. We have examined neural mechanisms underlying the memory "consolidation" process by single-unit recording and molecular biological methods in an animal model of a visual pair-association task in monkeys. In our previous studies, we found that long-term associative representations of visual objects are acquired through learning in the neural network of the anterior inferior temporal (IT) cortex. In this article, we propose the hypothesis that limbic neurons undergo rapid modification of synaptic connectivity and provide backward signals that guide the reorganization of neocortical neural circuits. Two experiments tested this hypothesis: (1) we examined the role of the backward connections from the medial temporal lobe to the IT cortex by injecting ibotenic acid into the entorhinal and perirhinal cortices, which provided massive backward projections ipsilaterally to the IT cortex. We found that the limbic lesion disrupted the associative code of the IT neurons between the paired associates, without impairing the visual response to each stimulus. (2) We then tested the first half of this hypothesis by detecting the expression of immediate-early genes in the monkey temporal cortex. We found specific expression of zif268 during the learning of a new set of paired associates in the pair-association task, most intensively in area 36 of the perirhinal cortex. All these results with the visual pair-association task support our hypothesis and demonstrate that the consolidation process, which was first proposed on the basis of clinico-psychological evidence, can now be examined in primates using neurophysiolocical and molecular biological approaches. (C) 1998 Academic Press.

DOI： 10.1006/nlme.1998.3848

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：SEIWA SHOTEN PUBL LTD  

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Language：Japanese   Publisher：(株)中外医学社  

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Language：Japanese   Publisher：(一社)電子情報通信学会  

わたしたちは脳の表面に「網をかける」ように張りめぐらせて局所フィールド電位を多点記録する柔軟なメッシュ型の皮質脳波電極を設計し、さらにラットやマカクザルの動物モデルで、微小電極法との比較において、高密度のメッシュ型電極によって得られる信号の記録特性を検証する系を開発しました。マカクザルでは、メッシュ型電極を脳表のみならず脳溝に広範囲留置することも可能となりました。これらの手法を用いてマカクザル下側頭葉の神経活動を計測し、視覚刺激のカテゴリーを解読する技術が、次世代の脳と機械のインターフェイス(ブレイン・マシン・インターフェイス)の構築につながることが期待されます。(著者抄録)

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Language：Japanese   Publisher：新潟医学会  

過去半世紀にわたり、金属微小電極による細胞外記録法は、中枢神経系機能の電気生理学的研究の王道であった。神経回路の素子である個々のニューロンの出力様式を明らかにすることにより、脳の情報処理の特徴や局所の機能構築が次々と解明されてきた。しかし、微小電極法は定点観測に過ぎない。個々のニューロンがどんな刺激に反応するかは調べられるが、逆にある刺激によって活性化されるニューロン集団の全体像を推測したり、広範囲の大脳ネットワークにおける興奮伝播の動態をミリ秒単位で可視化したりすることは難しい。この問題に対する有力なアプローチとして皮質脳波(Electrocorticogram:ECoG)法がある。ECoG法は、柔軟な電極アレイを脳に刺入せず、表面に置いただけで直接電気刺激/記録する臨床由来の手法である。近年、実験神経科学において極間距離1mm〜数mmの微小ECoGアレイを用いて局所フィールド電位(local field potential、LFP)を低侵襲的に記録しようとする機運が高まっている。わたしたちは、脳の表面に「網をかける」ように張りめぐらせられる柔軟な微小ECoG電極をマイクロマシン技術の応用により開発した。このECoGメッシュ法を用いたラットおよびマカクザルの動物モデル実験から、ヒト臨床研究までECoG法を軸に多元的に実験研究を進めている。まずECoGメッシュ法と微小電極法とを同一個体で同時記録する実験系を開発した。これにより、ECoGメッシュ法により得られる信号記録特性を微小電極法と直接比較しながら、技術的フィージビリティーが検証された。次にECoG電極をマカクザル大脳の脳表と脳溝に広範囲に留置する手術法を開発した。ヒトやサルなどの霊長類における物体視の高次中枢である下側頭葉からECoG記録を進め、物の形や視覚的イメージに選択的な神経活動が観測できることが明らかになりつつある。(著者抄録)

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：日本視覚学会  

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Publisher：Primate Society of Japan  

目的&lt;br&gt;ニホンザルにおいて2要素の組み合わせからなる複合図形と物体との関係を学習させ，それに基づいて複合図形の分解ができるかを調査した．また，物体のカテゴリー化を要素図形による複合図形の組み立てタスクによって回答できるかについても調査した．&lt;br&gt;&lt;br&gt;方法&lt;br&gt;2頭のニホンザル（&lt;i&gt;Macaca fuscata&lt;/i&gt;）に6組の複合図形と物体との関係を学習させた（Paired Association Training：PA）．複合図形は物体とは無関係の6つの要素図形の中の2つで構成した．PAを十分に学習したのち，物体をcueとして呈示し，choiceで複合図形そのものではなく要素図形を4つ呈示し，正しい2つを選択させるテストを行った（Articulation Test：AT）．更に，6組の複合図形－物体に対して，物体と同一カテゴリーの図形を順次加え，一組に7種類の図形を用いてカテゴリーを形成し，そのカテゴリーが汎化するかを，probe test としてtrial unique刺激を用いてATで検証した．&lt;br&gt;結果&lt;br&gt;PAを十分に学習した後のATのfirst trialは，2頭の平均正答率が62.3%で，16.7%のchance levelに比べて有意に正答を示した．また，trial unique刺激を用いてカテゴリーの汎化力を調べた結果，Probe trial（p =3.2*10^-15, binominal test），Prototype trial（p =1.6*10^-14）でともにchance levelの16.7%を有意に上回る成績だった．&lt;br&gt;考察・結論ニホンザルにおいて，基本セットの学習を行えば，それをもとに要素図形から複合図形を構成できることが分かった．これはcueとして与えられた物体画像を見ることが，対応する複合図形を見なくてもそれを想起させ，そのイメージを基に複合図形を構成したと考えられる．カテゴリーの汎化と合わせて，個々には意味を持たない図形要素の組み合わせから，意味のある図形を作り出す能力がニホンザルに存在すると考えられる．

DOI： 10.14907/primate.28.0_81

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Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

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Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：English   Publisher：日本神経化学会  

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Language：Japanese   Publisher：社団法人電子情報通信学会  

我々は実験動物に対する侵襲を低減し、頭部非固定による行動実験の実現を目指している。本研究では、松田ら(BPES2000他)が過去に開発した高速楕円近似アルゴリズムによるビデオ眼球運動解析システムを利用して、ヒトの眼球運動を頭部固定した場合及び頭部非固定の場合で計測をした。また、ニホンザルの頭部非固定での眼球運動の計測を試みた。それぞれの方法から得られたビデオ画像より瞳孔が検出される確度を検証し、頭部非固定の動物でビデオ方式による視線位置計測が可能か否か検討した。(著者抄録)

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わたしたちは脳の表面に「網をかける」ように張りめぐらせて局所フィールド電位を多点記録する柔軟なメッシュ型の皮質脳波電極を設計し、さらにラットやマカクザルの動物モデルで、微小電極法との比較において、高密度のメッシュ型電極によって得られる信号の記録特性を検証する系を開発しました。マカクザルでは、メッシュ型電極を脳表のみならず脳溝に広範囲留置することも可能となりました。これらの手法を用いてマカクザル下側頭葉の神経活動を計測し、視覚刺激のカテゴリーを解読する技術が、次世代の脳と機械のインターフェイス(ブレイン・マシン・インターフェイス)の構築につながることが期待されます。(著者抄録)

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Applicant：国立大学法人 新潟大学, 国立大学法人 東京大学

Application no：特願2009-178454  Date applied：2009.7

Announcement no：特開2011-030678  Date announced：2011.2

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Applicant：国立大学法人 新潟大学, 株式会社国際電気通信基礎技術研究所

Application no：特願2009-108467  Date applied：2009.4

Announcement no：特開2010-257343  Date announced：2010.11

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