ワーキングメモリ・実行機能 Working Memory and Executive Function
P3-2-41 幸福感の神経基盤 Neural substrates associated with happiness ○松永昌宏1, 川道拓東1, 小池耕彦1, 吉原一文1, 吉田優美子1, 高橋陽香1, 中川恵理1, 定藤規弘1 ○Masahiro Matsunaga1, Hiroaki Kawamichi1, Takahiko Koike1, Kazufumi Yoshihara1, Yumiko Yoshida1, Haruka K. Takahashi1, Eri Nakagawa1, Norihiro Sadato1 生理学研究所　心理生理学研究部門1 Division of Cerebral Integration, National Institute for Physiological Sciences, Aichi, Japan1 How happiness is generated by brain mechanisms? Unfortunately, the neuroscience of happiness has not been established yet. In this study, we recognized happiness as the positive feelings generated when we perceive that everything is going well according to our own planning, and hypothesized that activation in the medial prefrontal cortex (mPFC), which evaluate goal-directed activities and outcomes, may represent the degree of transient happy feelings. Furthermore, we also hypothesized that the gray matter volume in the mPFC may represent trait-like prolonged happy feelings (perceived happiness). In order to demonstrate these two hypotheses, we conducted functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM) in the present study. The conjunction analysis in the fMRI revealed that the neural networks including the mPFC were significantly activated regardless of conditions (positive, negative, and neutral). Subtraction analysis indicated that the perigenual part of the mPFC (pmPFC) was significantly activated in the positive condition and self-rating of happy feelings was positively correlated with its activation. Furthermore, the VBM analysis revealed that there was a significant positive correlation between perceived happiness level and the gray matter volume in the pmPFC. These results suggested that the pmPFC function might represent the degree of happiness we experienced.	P3-2-42 プロスタノイド受容体DP2を欠損したマウスで認められる認知機能の変化 Altered cognitive function in mice lacking prostanoid receptor DP2 ○尾中勇祐1, 叶拓也1, 新谷紀人1, 武永理沙1, 羽場亮太1, 早田敦子1,2, 笠井淳司1,3, 平井博之4, 永田欽也5, 中村正孝5, 馬場明道6, 橋本均1,2 ○Yusuke Onaka1, Takuya Kanoh1, Norihito Shintani1, Risa Takenaga1, Ryota Haba1, Atsuko Hyata1,2, Atsushi Kasai1,3, Hiroyuki Hirai4, Kinya Nagata5, Masataka Nakamura5, Akemichi Baba6, Hitoshi Hashimoto1,21,2 大阪大院・薬・神経薬理学1, 大阪大院・連合小児発達・子どものこころセ2, 大阪大・未来戦略3, 株式会社 BML4, 東京医科歯科大・疾患遺伝子実験セ5, 兵庫医療大・薬・薬理6 Lab. Mol. Neuropharmacol., Grad. Sch. Pharmaceut. Sci., Osaka Univ.1, Mol. Res. Cent. Child Ment. Dev., United Grad. Sch. of Child Dev., Osaka Univ.2, Institute for Academic Initiatives, Osaka Univ.3, Dept. Advanced Med. and Dev., BML., Inc.4, Hum. Gene Sci. Cent., Tokyo Med. and Dent. Univ.5, Pharmaceut. Sci., Hyogo Univ. of Health Sci.6 DP2 is one of the prostaglandin D2 receptor subtypes and plays a proinflammatory role in allergic diseases. We recently demonstrated that DP2-deficient mice are resistant to peripheral inflammation-induced decrease in novel-object exploration, suggesting possible roles of DP2 in the emotional and/or cognitive regulation. Here, we examined the impacts of DP2 gene deficiency on the cognitive function in mice. DP2-deficient mice exhibited normal behavioral performances in the Y-maze and novel object recognition (NOR) tests. However, MK-801-induced decreases in the spontaneous alternation in the Y-maze test and the exploratory behaviors toward novel object in the NOR test were completely absent in DP2-deficient mice. Since mice injected with MK-801 are considered to be an animal model of schizophrenia, the present results suggest that DP2 signaling is involved in the cognitive dysfunction associated with psychiatric conditions.
P3-2-43 背内側線条体コリン作動性介在ニューロンは行動の柔軟性を抑制する Behavioral flexibility inhibited by cholinergic interneurons in the dorsomedial striatum ○岡田佳奈1, 西澤佳代2, 甲斐信行2, 深堀良二2, 塩田明3, 上田正次3, 筒井雄二4, 松下夏樹5, 小林和人2,6 ○Kana Okada1, Kayo Nishizawa2, Nobuyuki Kai2, Ryoji Fukabori2, Akira Shiota3, Masatsugu Ueda3, Yuji Tsutsui4, Natsuki Matsushita5, Kazuto Kobayashi2,6 広島大・総合科学・行動科学1, 福島県立医大・医・生体機能2, フェニックスバイオ(株)3, 福島大・共生理工・人間支援4, 愛媛大・プロテオ医セ5 Dept Behav Sci, Grad Sch of Integrated Arts & Sci, Hiroshima Univ, Higashihiroshima1, Dept Mol Genet, Fukushima Medical Univ, Fukushima, Japan2, PhenixBio, Co., Ltd, Hiroshima, Japan3, Dept Human Support System, Fukushima Univ, Fukushima, Japan4, Ehime Univ Proteo-Medicine Res Ctr, Ehime, Japan5, CREST, JST, Tokyo, Japan6 Searching for the neural mechanisms underlying learning and its flexibility has focused on the prefrontal cortex-basal ganglia circuit over the last decade. Previous studies showed that the dorsomedial striatum (DMS) and their neuromodulative actions should be involved in behavioral flexibility. But their neuropsychological mechanisms are poorly understood. Cholinergic interneurons, regarded as the tonically active neurons, in the striatum are speculated to play a critical role in behavioral flexibility. The authors investigated the role of striatal cholinergic interneurons in simple behavioral flexibility which is represented by reversal and extinction learning. Selective elimination of the interneurons conducted by the immunotoxin-mediated cell targeting resulted in the amelioration of reversal/extinction learning, persisting normally the acquisition of place learning. The enhancement of reversal/extinctions learning was found to be caused by cholinergic cell ablations especially in the DMS and reversed by the infusion of non-selective muscarinic receptor agonist into the DMS either during the acquisition or reversal/extinction learning phase. Our data provided the evidence that cholinergic interneurons in the DMS are involved in the inhibition of switching processes to the different pattern of reward contingencies, suggesting that the cholinergic interneurons play an important role in the maintenance of the animals' balanced state between flexibility and stability.	P3-2-44 前頭前野におけるドーパミンとグルタミン酸の相互作用 Dopamine-glutamate interactions in the laterodorsal prefrontal area of the monkey ○児玉亨1, 彦坂和雄1,2, 小島崇1, 本多芳子1, 渡邊正孝1 ○Tohru Kodama1, Kazuo Hikosaka1,2, Takashi Kojima1, Yoshiko Honda1, Masataka Watanabe1 東京都医学総合研究所・生理心理1, 川崎医療福祉大学・感覚矯正学科2 Dept Physiological Psychology, Tokyo Metropolitan Institute of Medical Science1, Dept Sensory Science, Kawasaki University of Medical Welfare2 It has been well documented that the prefrontal cortex (PFC) is essential for learning and performance of working memory tasks. Furthermore, dopamine and glutamate in the PFC plays important roles for working memory task performance both in the rat and in the monkey. We previously reported that there is a double dissociation in changes in glutamate and dopamine between sensory guided tasks (SGT) and delayed alternation task (DALT). We observed an increase in glutamate but no change in dopamine during SGT period, whereas we observed a significant increase in dopamine but no change in glutamate during the DALT period. In order to clarify the mechanism of this dissociation, we examined dopamine-glutamate interaction in PFC under the semi-chronic unanesthetized condition. The monkeys were implanted with the guide cannulae for microdialysis probes into PFC. Using reverse dialysis method, a D1 dopamine agonist (SKF38393, 0.1, 1.0 mM) and/or a D2 dopamine agonist (Quinulorane, 0.1, 1.0 mM) were applied to PFC during resting state (conscious but without tasks). Simultaneously dialysates were collected every 10 min and amino acids concentrations in the perfusates were analyzed using a HPLC system. The co-application of 1mM D1 and D2 agonist induced a significant decrease (p = 0.019, n = 8), whose amount was almost the same as 1 mM dopamine application itself did (p = 0.049, n = 8), in glutamate concentrations in the PFC. With a Quinulorane application, a dose dependent decrease of glutamate was observed . Furthermore, the decrease of glutamate with Quinulorane was not antagonized by co-application of 0.5 mM muscimol(a GABAA receptor agonist). On the other hand, SKF38393 application resulted in a slight increase in glutamate concentration (p = 0.06, n = 8). These results indicate that the disfacilitatory mechanism through D2 receptor in PFC is important for working memory task performance.
P3-2-45 視覚性対連合学習におけるサル前頭連合野のニューロン活動 Primate prefrontal activities in visual paired association performances ○船橋新太郎1,2 ○Shintaro Funahashi1,2, Jorge M. Andreau2 京都大・こころの未来研究センター1, 京都大院・人間・環境学・認知行動科学2 Kokoro Res Ctr, Kyoto University, Kyoto1, Dept Cog Behav Sci, Grad Sch Human & Environmental Std, Kyoto Univ, Kyoto2 The prefrontal cortex (PFC) has been known as an important brain structure for executive control. To conduct executive control, the PFC requires monitoring the operations in other brain structures and controlling them by sending control signals named top-down signals. It has been shown that top-down signals of the PFC are used to retrieve specific information stored in long-term memory and that top-down signals play a role to produce pair-recall activity in inferotemporal (IT) neurons, which reflects retrieval of a paired associate while monkeys performed a pair-association task (Sakai & Miyashita 1991). Although studies indicate that the PFC sends top-down signals to the posterior cortices, neural correlate of the top-down signal is not yet known. Therefore, in the present study, we used a paired association task with 12 pairs of visual stimuli to examine neural correlates of top-down signals in the PFC. PFC neurons with visual response exhibited stimulus selectivity and pair selectivity. Comparison of these selectivity with IT neurons revealed that PFC neurons had broader stimulus selectivity but similar values of pair selectivity. Further, PFC neurons with delay-period activity also exhibited stimulus selectivity and pair selectivity. Indices showing the strength of stimulus and pair selectivity were similar between visual activities and delay-period activities. However, the strength of pair selectivity of delay-period activity was increased with a progress of the delay period. These results indicate that pair-selective activity observed in PFC neurons could be neural correlates of top-down signals that the PFC provides to the IT cortex during pair association performances.	P3-2-46 統合失調症におけるCued switching課題遂行時の事象関連電位の異常 Impairment of cued switching task in Schizophrenia: an ERP study ○豊巻敦人1, 橋本直樹1, 久住一郎1 ○Atsuhito Toyomaki1, Naoki Hashimoto1, Ichiro Kusumi1 北海道大学大学院医学研究科精神医学分野1 Department of Psychiatry, Hokkaido University, Sapporo1 [Objectives] Executive function has been regarded as one of core deficits of cognitive dysfunction in schizophrenia. Neuropsychological test(e.g. Wisconsin Card Sorting Test) indicate that "rule shifting/generating" processes are dysfunctional in schizophrenia patient. However neural substrate of "rule shifting/generating" has not been investigated in schizophrenia. In particular, it is important to compare exogenous rule shifting and endogenous shifting. We made novel cued switching tasks and configured cue stimuli in order to induce two patterns of rule switching: exogenous (bottom-up) rule shifting and endogenous (top-down) rule shifting. In each task cue stimulus was configured in order to induce switching or maintaining rule. In order to investigate and compare neural response of these rule shifting processes, we measured event related brain potentials and neural oscillation. [Methods] Eleven schizophrenia patients and 16 normal subjects performed modified cued switching task. An electroencephalogram was recorded from 55 electrodes according to the international 10-10 system. [Results] In exogenous switching tasks, late positive deflection (P300 like component) was larger in the switch rule condition than in the maintain rule condition. There was no significant difference between schizophrenia patients and normal control. However, in endogenous switching tasks amplitude of late positive deflection wad declined in schizophrenia patients. [Conclusions] These results indicate that exogenous rule switching is explicit stimulus-driven processes and intact in schizophrenia. Whereas endogenous rule switching is a kind of volitional process and dysfunctional in schizophrenia.
P3-2-47 健常高齢者と認知症高齢者の前頭前野における視覚作業記憶課題中の脳血流反応差について Differences in cerebral blood flow responses in the prefrontal cortex during visual working memory task between cognitively normal old subjects and dementia patients ○大星有美1,2, 菊知充3, 寺田達弘1, 清水良幸1,2,4, 吉川悦次4, 間賀田泰寛2, 尾内康臣1 ○Yumi Oboshi1,2, Mitsuru Kikuchi3, Tatsuhiro Terada1, Yoshiyuki Shimizu1,2,4, Etsuji Yoshikawa4, Yasuhiro Magata2, Yasuomi Ouchi1 浜松医大・生体機能イメージング1, 浜松医大・分子病態イメージング2, 金沢大・子供の発達研究セ3, 浜松ホトニクス・中研4 Dept Biofunct Imaging, Hamamatsu Univ. Med., Hamamatsu, Japan1, Dept Mol Imaging, Hamamatsu Univ. Med., Hamamatsu, Japan2, Ctr Child Mental Develop, Kanazawa Univ., Kanazawa, Japan3, Hamamatsu Photonics, Hamamatsu, Japan4 The purpose of this study was to examine the differences in working-memory induced prefrontal activation between the cognitively normal elderly and demented patients by a near-infrared spectroscopy in order to clarify the cognitive processing characteristic of dementia. Methods: Healthy 12 old (71.2 ± 6.7 yrs, MMSE: 26.7 ± 1.8) and 12 patients with dementia of Alzheimer's type (DAT) (63.8 ± 7.7 yrs, MMSE: 15.5 ± 4.4) participated in this study. With 16 channels NIRS system (OEG-16, Spectratech Inc.), we examined a change in oxygenated hemoglobin (oxy-Hb) as an indicator of regional CBF change. We calculated the time-averaged values of oxy-Hb change during the former half of a task period (14.4 sec; task 1), the latter half of a task period (14.4 sec; task 2) and post-task period (the former half of resting period, 14.4 sec) and analyzed the differences between two groups using SPSS. Results: Repeated measures ANOVA showed significant interaction between the time × group factors in channels 7/10/13/14 placed on the frontal pole area (p < 0.05). Unpaired T test revealed that oxy-Hb change in dementia patients was significantly lower than that of normal elderly subjects in channels 4/6/7/9/10/14 during the task 1 period (p < 0.05). Spearman rank correlation coefficient in all subjects of both groups showed significant positive correlation between time-averaged oxy-Hb change during the task 1 period and correct answer ratio in channels 4/6/7/9, and MMSE scores in channels 4/6/7/9/10/14 (p < 0.05). Conclusions: We found that the CBF response was delayed initially and remained elevated during the task in the frontal pole region in demented patients. This indicates that the delayed and prolonged frontal pole response may reflect the abnormal cognitive processing characteristic of DAT.

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