ヒト二足歩行の神経制御機序 : 大脳皮質と脊髄神経回路の役割

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 中澤 公孝, 東京大学准教授 柳原 大, 東京大学准教授 工藤 和俊, 東京大学准教授 吉岡 伸輔, 上武大学教授 関口 浩文University of Tokyo(東京大学

Comparative functional analysis of CYP71AV1 natural variants reveals an important residue for the successive oxidation of amorpha-4,11-diene

AbstractArtemisinin is an antimalarial sesquiterpenoid isolated from the aerial parts of the plant Artemisia annua. CYP71AV1, a cytochrome P450 monooxygenase was identified in the artemisinin biosynthetic pathway. CYP71AV1 catalyzes three successive oxidation steps at the C12 position of amorpha-4,11-diene to produce artemisinic acid. In this study, we isolated putative CYP71AV1 orthologs in different species of Artemisia. Comparative functional analysis of CYP71AV1 and its putative orthologs, together with homology modeling, enabled us to identify an amino acid residue (Ser479) critical for the second oxidation reaction catalyzed by CYP71AV1. Our results clearly show that a comparative study of natural variants is useful to investigate the structure–function relationships of CYP71AV1

Wavefield characterization of nearly diffraction-limited focused hard x-ray beam with size less than 10 nm

In situ wavefront compensation is a promising method to realize a focus size of only a few nanometers for x-ray beams. However, precise compensation requires evaluation of the wavefront with an accuracy much shorter than the wavelength. Here, we characterized a one-dimensionally focused beam with a width of 7 nm at 20 keV using a multilayer mirror. We demonstrate that the wavefront can be determined precisely from multiple intensity profiles measured around the beamwaist. We compare the phase profiles recovered from intensity profiles measured under the same mirror condition but with three different aperture sizes and find that the accuracy of phase retrieval is as small as 12. © 2010 American Institute of Physics.Takashi Kimura, Hidekazu Mimura, Soichiro Handa, Hirokatsu Yumoto, Hikaru Yokoyama, Shota Imai, Satoshi Matsuyama, Yasuhisa Sano, Kenji Tamasaku, Yoshiki Komura, Yoshinori Nishino, Makina Yabashi, Tetsuya Ishikawa, and Kazuto Yamauchi , "Wavefield characterization of nearly diffraction-limited focused hard x-ray beam with size less than 10 nm", Review of Scientific Instruments 81(12), 123704 (2010) https://doi.org/10.1063/1.3509384

Effects of time-compressed speech training on multiple functional and structural neural mechanisms involving the left superior temporal gyrus

Time-compressed speech is an artificial form of rapidly presented speech. Training with time-compressed speech (TCSSL) in a second language leads to adaptation toward TCSSL. Here, we newly investigated the effects of 4 weeks of training with TCSSL on diverse cognitive functions and neural systems using the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), resting-state functional connectivity (RSFC) with the left superior temporal gyrus (STG), fractional anisotropy (FA), and regional gray matter volume (rGMV) of young adults by magnetic resonance imaging. There were no significant differences in change of performance of measures of cognitive functions or second language skills after training with TCSSL compared with that of the active control group. However, compared with the active control group, training with TCSSL was associated with increased fALFF, RSFC, and FA and decreased rGMV involving areas in the left STG. These results lacked evidence of a far transfer effect of time-compressed speech training on a wide range of cognitive functions and second language skills in young adults. However, these results demonstrated effects of time-compressed speech training on gray and white matter structures as well as on resting-state intrinsic activity and connectivity involving the left STG, which plays a key role in listening comprehension

A comprehensive analysis of the correlations between resting-state oscillations in multiple-frequency bands and big five traits

Recently, the association between human personality traits and resting-state brain activity has gained interest in neuroimaging studies. However, it remains unclear if Big Five personality traits are represented in frequency bands (~0.25 Hz) of resting-state functional magnetic resonance imaging (fMRI) activity. Based on earlier neurophysiological studies, we investigated the correlation between the five personality traits assessed by the NEO Five-Factor Inventory (NEO-FFI), and the fractional amplitude of low-frequency fluctuation (fALFF) at four distinct frequency bands (slow-5 (0.01–0.027 Hz), slow-4 (0.027–0.073 Hz), slow-3 (0.073–0.198 Hz) and slow-2 (0.198–0.25 Hz)). We enrolled 835 young subjects and calculated the correlations of resting-state fMRI signals using a multiple regression analysis. We found a significant and consistent correlation between fALFF and the personality trait of extraversion at all frequency bands. Furthermore, significant correlations were detected in distinct brain regions for each frequency band. This finding supports the frequency-specific spatial representations of personality traits as previously suggested. In conclusion, our data highlight an association between human personality traits and fALFF at four distinct frequency bands

Effects of time-compressed speech training on multiple functional and structural neural mechanisms involving the left superior temporal gyrus

Time-compressed speech is an artificial form of rapidly presented speech. Training with time compressed speech in a second language leads to adaptation toward time-compressed speech in a second language and toward time compressed speech in different languages. However, the effects of training with time-compressed speech of a second language (TCSSL) on diverse cognitive functions and neural mechanisms beyond time compressed speech-related activation are unknown. We investigated the effects of 4 weeks of training with TCSSL on the fractional amplitude of spontaneous low-frequency fluctuations (fALFF) of 0.01–0.08 Hz, resting-state functional connectivity (RSFC) with the left superior temporal gyrus (STG), fractional anisotropy (FA), and regional gray matter volume (rGMV) of young adults by magnetic resonance imaging. There were no significant differences in change of performance of measures of cognitive functions or second language skills after training with TCSSL compared with that of the active control group. However, compared with the active control group, training with TCSSL was associated with increased fALFF, RSFC, and FA and decreased rGMV involving areas in the left STG. These results lacked evidence of a far transfer effect of time compressed speech training on a wide range of cognitive functions and second language skills in young adults. However, these results demonstrated effects of time compressed speech training on gray and white matter structures as well as on resting-state intrinsic activity and connectivity involving the left STG, which plays a key role in listening comprehension

Lenticular nucleus correlates of general self-efficacy in young adults

General self-efficacy (GSE) is an important factor in education, social participation, and medical treatment. However, the only study that has investigated the direct association between GSE and a neural correlate did not identify specific brain regions, rather only assessed brain structures, and included older adult subjects. GSE is related to motivation, physical activity, learning, the willingness to initiate behaviour and expend effort, and adjustment. Thus, it was hypothesized in the present study that the neural correlates of GSE might be related to changes in the basal ganglia, which is a region related to the abovementioned self-efficacy factors. This study aimed to identify the brain structures associated with GSE in healthy young adults (n = 1204, 691 males and 513 females, age 20.7 ± 1.8 years) using regional grey matter density and volume (rGMD and rGMV), fractional anisotropy (FA) and mean diffusivity (MD) analyses of magnetic resonance imaging (MRI) data. The findings showed that scores on the GSE Scale (GSES) were associated with a lower MD value in regions from the right putamen to the globus pallidum; however, there were no significant association between GSES scores and regional brain structures using the other analyses (rGMD, rGMV, and FA). Thus, the present findings indicated that the lenticular nucleus is a neural correlate of GSE

Regional homogeneity, resting-state functional connectivity and amplitude of low frequency fluctuation associated with creativity measured by divergent thinking in a sex-specific manner

Brain connectivity is traditionally thought to be important for creativity. Here we investigated the associations of creativity measured by divergent thinking (CMDT) with resting-state functional magnetic imaging (fMRI) measures and their sex differences. We examined these relationships in the brains of 1277 healthy young adults. Whole-brain analyses revealed a significant interaction between verbal CMDT and sex on (a) regional homogeneity within an area from the left anterior temporal lobe (b) on the resting state functional connectivity (RSFC) between the mPFC and the left inferior frontal gyrus and (c) on fractional amplitude of low frequency fluctuations (fALFF) in several distinct areas, including the precuneus and middle cingulate gyrus, left middle temporal gyrus, right middle frontal gyrus, and cerebellum. These interactions were mediated by positive correlations in females and negative correlations in males. These findings suggest that greater CMDT in females is reflected by (a) regional coherence (regional homogeneity) of brain areas responsible for representing and combining concepts as well as (b) the efficient functional connection (RSFC) between the key areas for the default state of cognitive activity and speech production, and (c) greater spontaneous neural activity (fALFF) during the resting of brain areas involved in frontal lobe functions, default cognitive activities, and language functions. Furthermore, these findings suggest that the associations between creativity and resting state brain connectivity patterns are different between males and females

Cerebral Blood Flow during Rest Associates with General Intelligence and Creativity

Recently, much scientific attention has been focused on resting brain activity and its investigation through such methods as the analysis of functional connectivity during rest (the temporal correlation of brain activities in different regions). However, investigation of the magnitude of brain activity during rest has focused on the relative decrease of brain activity during a task, rather than on the absolute resting brain activity. It is thus necessary to investigate the association between cognitive factors and measures of absolute resting brain activity, such as cerebral blood flow (CBF), during rest (rest-CBF). In this study, we examined this association using multiple regression analyses. Rest-CBF was the dependent variable and the independent variables included two essential components of cognitive functions, psychometric general intelligence and creativity. CBF was measured using arterial spin labeling and there were three analyses for rest-CBF; namely mean gray matter rest-CBF, mean white matter rest-CBF, and regional rest-CBF. The results showed that mean gray and white matter rest-CBF were significantly and positively correlated with individual psychometric intelligence. Furthermore, mean white matter rest-CBF was significantly and positively correlated with creativity. After correcting the effect of mean gray matter rest-CBF the significant and positive correlation between regional rest-CBF in the perisylvian anatomical cluster that includes the left superior temporal gyrus and insula and individual psychometric intelligence was found. Also, regional rest-CBF in the precuneus was significantly and negatively correlated with individual creativity. Significance of these results of regional rest-CBF did not change when the effect of regional gray matter density was corrected. The findings showed mean and regional rest-CBF in healthy young subjects to be correlated with cognitive functions. The findings also suggest that, even in young cognitively intact subjects, resting brain activity (possibly underlain by default cognitive activity or metabolic demand from developed brain structures) is associated with cognitive functions