Effects of Fast Simple Numerical Calculation Training on Neural Systems.

Cognitive training, including fast simple numerical calculation (FSNC), has been shown to improve performance on untrained processing speed and executive function tasks in the elderly. However, the effects of FSNC training on cognitive functions in the young and on neural mechanisms remain unknown. We investigated the effects of 1-week intensive FSNC training on cognitive function, regional gray matter volume (rGMV), and regional cerebral blood flow at rest (resting rCBF) in healthy young adults. FSNC training was associated with improvements in performance on simple processing speed, speeded executive functioning, and simple and complex arithmetic tasks. FSNC training was associated with a reduction in rGMV and an increase in resting rCBF in the frontopolar areas and a weak but widespread increase in resting rCBF in an anatomical cluster in the posterior region. These results provide direct evidence that FSNC training alone can improve performance on processing speed and executive function tasks as well as plasticity of brain structures and perfusion. Our results also indicate that changes in neural systems in the frontopolar areas may underlie these cognitive improvements.

Degree centrality and fractional amplitude of low-frequency oscillations associated with Stroop interference.

Stroop paradigms are commonly used as an index of attention deficits and a tool for investigating functions of the frontal lobes and other associated structures. Here we investigated the correlation between resting-state functional magnetic imaging (fMRI) measures [degree centrality (DC)/fractional amplitude of low frequency fluctuations (fALFFs)] and Stroop interference. We examined this relationship in the brains of 958 healthy young adults. DC reflects the number of instantaneous functional connections between a region and the rest of the brain within the entire connectivity matrix of the brain (connectome), and thus how much of the node influences the entire brain areas, while fALFF is an indicator of the intensity of regional brain spontaneous activity. Reduced Stroop interference was associated with larger DC in the left lateral prefrontal cortex, left IFJ, and left inferior parietal lobule as well as larger fALFF in the areas of the dorsal attention network and the precuneus. These findings suggest that Stroop performance is reflected in resting state functional properties of these areas and the network. In addition, default brain activity of the dorsal attention network and precuneus as well as higher cognitive processes represented there, and default stronger global influence of the areas critical in executive functioning underlie better Stroop performance.

Mean diffusivity of globus pallidus associated with verbal creativity measured by divergent thinking and creativity-related temperaments in young healthy adults.

Recent investigations revealed mean diffusivity (MD) in gray matter and white matter areas is correlated with individual cognitive differences in healthy subjects and show unique properties and sensitivity that other neuroimaging tools donot have. In this study, we tested the hypothesis that the MD in the dopaminergic system is associated with individual differences in verbal creativity measured by divergent thinking (VCDT) and novelty seeking based on prior studies suggesting associations between these and dopaminergic functions. We examined this issue in a large sample of right-handed healthy young adults. We used analyses of MD and a psychological measure of VCDT, as well as personality measures of the Temperament and Character Inventory (TCI). Our results revealed associations between higher VCDT and lower MD in the bilateral globus pallidus. Furthermore, not only higher novelty seeking, but also lower harm avoidance, higher self-directedness, and higher self-transcendence were robustly associated with lower MD in the right globus pallidus, whereas higher persistence was associated with lower MD in the left globus pallidus. These personality variables were also associated with VCDT. The globus pallidus receives the dopaminergic input from the substantia nigra and plays a key role in motivation which is critically linked to dopamine. These results suggested the MD in the globus pallidus, underlie the association between VCDT and multiple personalities in TCI including novelty seeking.

The Associations between Regional Gray Matter Structural Changes and Changes of Cognitive Performance in Control Groups of Intervention Studies.

In intervention studies of cognitive training, the challenging cognitive tests, which were used as outcome measures, are generally completed in more than a few hours. Here, utilizing the control groups' data from three 1-week intervention studies in which young healthy adult subjects underwent a wide range of cognitive tests and T1-weighted magnetic resonance imaging (MRI) before and after the intervention period, we investigated how regional gray matter (GM) density (rGMD) of the subjects changed through voxel-based morphometry (VBM). Statistically significant increases in rGMD were observed in the anatomical cluster that mainly spread around the bilateral dorsal anterior cingulate cortex (dACC) and the right superior frontal gyrus (rSFG). Moreover, mean rGMD within this cluster changes were significantly and positively correlated with performance changes in the Stroop task, and tended to positively correlate with performance changes in a divergent thinking task. Affected regions are considered to be associated with performance monitoring (dACC) and manipulation of the maintained information including generating associations (rSFG), and both are relevant to the cognitive functions measured in the cognitive tests. Thus, the results suggest that even in the groups of the typical "control group" in intervention studies including those of the passive one, experimental or non-experimental factors can result in an increase in the regional GM structure and form the association between such neural changes and improvements related to these cognitive tests. These results suggest caution toward the experimental study designs without control groups.

Association between resting-state functional connectivity and empathizing/systemizing.

Empathizing is the drive to identify the mental status of other individuals and respond to it with an appropriate emotion; systemizing is the drive to analyze a system. Previously, we have shown that structures associated with the default mode network (DMN) and external attention system (EAS) are associated with empathizing and systemizing, respectively. Here we investigated the association between resting-state functional connectivity (RSFC) and empathizing/systemizing in 248 healthy young adults. We considered the medial prefrontal cortex (mPFC) and bilateral dorsolateral prefrontal cortices (DLPFCs), which are key nodes of DMN and EAS, as seed regions, and investigated correlations across subjects between individual empathizing/systemizing and RSFC between each seed region and other brain regions. We found that higher empathizing was associated with larger RSFC between the mPFC and areas in (a) the dorsal anterior cingulate cortex (dACC), (b) precuneus, and (c) left superior temporal sulcus (STS). Furthermore, there was an interaction effect between sex and systemizing on RSFC between the left DLPFC and dACC: males showed positive correlations between this RSFC and systemizing, whereas females showed the opposite tendency. Thus, empathizing was associated with increased positive functional coupling with the key node and other nodes of DMN, as well as the area associated with feeling another's pain. Systemizing was associated with increased positive functional coupling between the key nodes of EAS in males. These findings provide further support for the concept of an association between DMN/EAS and empathizing/systemizing.

Associations among imaging measures (2): the association between gray matter concentration and task-induced activation changes.

The association between functional activation and gray matter (GM) structure has been revealed in clinical studies and studies of aging involving a small number of subjects. The purpose of this study was to investigate the association between functional activation maps and GM structures in young adults who do not show apparent GM atrophy and to investigate in detail the nature of this association using a large number of subjects. We used voxel-by-voxel regression analyses to investigate voxel-by-voxel associations between GM concentration (GMC) and contrast estimate images of brain activity during n-back working memory tasks. Associations were assessed for each voxel after regressing out the effects of age, sex, and mean signal intensity during functional magnetic resonance imaging scanning at each voxel using data from 248 normal, right-handed, young adult subjects. In our study, the concept of "the greater the GMC, the greater the task-related activation increase/task-related activation decrease (or the greater the task-related activation change from baseline)" was true for a wide range of activated and deactivated areas. However, in some minor regions, the other pattern of "the greater the GMC, the smaller the task-related activation increase" was observed. The first pattern is often observed at the borders of GM structures. These findings may have to be taken into consideration when group/individual differences in functional activation are investigated.

Anatomical correlates of quality of life: evidence from voxel-based morphometry.

Quality of life (QOL) has been defined in many ways, and these definitions usually emphasize happiness and satisfaction with life. Health-related problems are known to cause lower QOL. However, the neural mechanisms underlying individual differences in QOL measured by questionnaire (QOLMQ) in young healthy subjects are unknown. QOL is essential to our well-being, and investigation of the neural mechanisms underlying QOL in uncompromised subjects is obviously of great scientific and social interest. We used voxel-based morphometry to investigate the association between regional gray matter volume (rGMV) and QOLMQ across the brain in healthy young adults (age, 21.4 ± 1.8 years) men (n = 88) and women (n = 68) in humans. We found significant negative relationships between QOLMQ and rGMV in a region in the left rostrolateral prefrontal cortex and regions in the dorsal part of the anterior cingulate gyrus and contingent cingulate regions. These findings show that structural variations in regions associated with processing of negative emotions such as fear and anger as well as those associated with evaluation of internally generated information are associated with QOLMQ. These findings suggest that these processes might be related to QOLMQ in healthy young adults.

Advanced nanocluster ion source based on high-power impulse magnetron sputtering and time-resolved measurements of nanocluster formation.

We developed a new nanocluster (NC) ion source based on the high-power impulse magnetron sputtering (HiPIMS) technique coupled with a gas flow cell reactor. Silver NC anions (Ag(n)(-)) with a maximum intensity of 5.5 nA (Ag11(-)) are generated with the size ranging from the atomic anion to the 70-mer, which is well-controlled by simply adjusting the peak power and repetition rate of the HiPIMS. By time-resolved density profiles of Ag(n)(-), we find that the ion beam generated by HiPIMS is characterized by individual 100 ms duration "bunches" below a repetition rate of 10 Hz, which is well-thermalized with a group velocity of 5 m/s. The high intensity of the NCs is attributable to the high ionization fraction by this HiPIMS ion source, while the underlying mechanism of the flexible size tuning of the ion source is understood by time-resolved mass spectrometry coupled with the sequential growth mechanism; the increment of the density of the target species in the bunches with the peak power and the overlapping of the bunches with the repetition rate cause the formation of large NCs.

Resting state functional connectivity associated with trait emotional intelligence.

Previous neuroimaging studies have suggested that trait emotional intelligence (TEI) is associated with components of the neural network involved in social cognition (SCN) and somatic marker circuitry (SMC). Our study is the first to investigate the association of TEI with resting-state functional connectivity (RSFC) between the key nodes of SCN and SMC [medial prefromtal cortex (mPFC) and bilateral anterior insula (AI), respectively] and other brain regions. We found that (a) the intrapersonal factor of TEI was negatively correlated with RSFC between mPFC and the anterior part of the right dorsolateral prefrontal cortex (DLPFC), (b) the TEI interpersonal factor score was positively correlated with RSFC between mPFC and the lingual gyrus, and (c) total TEI was positively correlated with RSFC between mPFC and the precuneus as well as (d) between the left AI and the middle part of the right DLPFC. Taken together with previous study findings, our findings can be comprehensively understood as neural mechanisms of SCN and SMC components are associated with TEI. In particular, the fluent interaction between SCN's two key nodes (mPFC and precuneus/PCC) [as well as between DMN's two key nodes] is suggested to be crucial for total TEI. Our study also indicated that (a) a clear functional separation between the two key nodes of the two major intrinsic networks, DMN and the task-positive network (mPFC and DLPFC), is important for higher intrapersonal TEI, (b) brain interactions involving vision-related areas (lingual gyrus) and the key node of SCN (mPFC) are important for interpersonal TEI, and (c) control of DLPFC over the key node of SMC (AI) is important for total TEI.

White matter structures associated with empathizing and systemizing in young adults.

Empathizing is defined as the drive to identify the mental states of others in order to predict their behavior and respond with an appropriate emotion. Systemizing is defined as the drive to analyze a system in terms of the rules that govern it to predict its behavior. We undertook voxel-by-voxel investigations of regional white matter volume (rWMV) and fractional anisotropy (FA) of diffusion tensor imaging to discover the WM structural correlates of empathizing, systemizing, and their difference (D score: systemizing-empathizing). Whole brain analyses of covariance revealed that across both sexes, the D score was negatively correlated with rWMV in the WM area in the bilateral temporal lobe, near the right inferior frontal gyrus, near the ventral medial prefrontal cortex, and near the posterior cingulate cortex and positively correlated with FA in an area involving the superior longitudinal fasciculus. Post-hoc analyses revealed that these associations were generally formed by both the correlation between WM structures and empathizing as well as the opposite correlation between WM structures and systemizing. A significant effect of interaction between sex and the D score on rWMV, which was mainly observed because of a positive correlation between rWMV and empathizing in females and a negative correlation between rWMV and systemizing in females, was found in an area close to the right inferior parietal lobule and temporoparietal junction. Our results suggest that WM structures involving the default mode network and the mirror neuron system support empathizing, and that a WM structure relating to the external attention system supports systemizing. Further, our results revealed an overlap between positive/negative WM structural correlates of empathizing and negative/positive WM structural correlates of systemizing despite little correlation between empathizing and systemizing, which supports the previously held idea that there is a trade-off between empathizing and systemizing in the brain.

White matter structures associated with emotional intelligence: evidence from diffusion tensor imaging.

Previous studies of brain lesions, functional activity, and gray matter structures have suggested that emotional intelligence (EI) is associated with regions involved in the network of social cognition (SCN) and in somatic marker circuitry (SMC). Our new study is the first to investigate the association between white matter (WM) integrity and EI. We examined this relationship in the brain of healthy young adult men [n = 74, mean age = 21.5 years, standard deviation (SD) = 1.6] and women (n = 44, mean age = 21.9 years, SD = 1.4). We performed a voxel-based analysis of fractional anisotropy, which is an indicator of WM integrity, using diffusion tensor imaging and used a questionnaire (EI Scale) for measuring EI to identify the correlation of WM integrity with individual EI factor (intrapersonal, interpersonal, and situation management factors). Our results showed that (a) the intrapersonal factor of EI was positively correlated with WM integrity in the right anterior insula, and (b) the interpersonal factor of EI was associated with WM integrity in a part of the right inferior longitudinal fasciculus (ILF). The right anterior insula is one of the important nodes of the SMC, whereas the ILF connects the visual cortex and areas related to SCN, and thus, is a part of the SCN. Our findings further support the notion that the brain regions involved in the SCN and in the SMC are associated with EI.

The association between resting functional connectivity and creativity.

The analysis of functional connectivity at rest (rFC) enables us to know how brain regions within and between networks interact. In this study, we used resting-state functional magnetic resonance imaging and a creativity test of divergent thinking (DT) to investigate the relationship between creativity measured by DT and rFC. We took the medial prefrontal cortex (mPFC) to be the seed region and investigated correlations across subjects between the score of the DT test and the strength of rFC between the mPFC and other brain regions. Our results showed that the strength of rFC with the mPFC significantly and positively correlated with creativity as measured by the DT test in the posterior cingulate cortex (PCC). These results showed that higher creativity measured by DT is associated with rFC between the mPFC and the PCC, the key nodes of the default mode network (DMN). Increased rFC between these regions is completely opposite from that is generally expected from the association between higher creativity and reduced deactivation in DMN during an externally directed attention-demanding task shown in our previous study but is similar to the pattern seen in relatives of schizophrenia. These findings are comparable to the previously reported psychological associations between schizotypy and creativity.

Regional gray and white matter volume associated with Stroop interference: evidence from voxel-based morphometry.

During Stroop tasks, subjects experience cognitive interference when they resolve interferences such as identifying the ink color of a printed word while ignoring the word's identity. Stroop paradigms are commonly used as an index of attention deficits and a tool for investigating the functions of the frontal lobes and other associated structures. Despite these uses and the vast amount of attention given to Stroop paradigms, the regional gray matter volume/regional white matter volume (rGMV/rWMV) correlates of Stroop interference have not yet been identified at the whole brain level in normal adults. We examined this issue using voxel-based morphometry in right-handed healthy young adults. We found significant negative relationships between the Stroop interference rate and rGMV in the anterior cingulate cortex (ACC), right inferior frontal gyrus, and cerebellum. Furthermore, we found relationships between the Stroop interference rate and rWMV in bilateral anatomical clusters that extended around extensive WM regions in the dorsal part of the frontal lobe. These findings are the first to reveal rGMV/rWMV that underlie the performance of the Stroop task, a widely used psychological paradigm at the whole brain level. Of note, our findings support the notion that ACC contributes to Stroop performance and show the involvement of regions that have been implicated in response inhibition and attention.

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.

Effects of training of processing speed on neural systems.

Processing speed (PS) training improves performance on untrained PS tasks in the elderly. However, PS training's effects on the PS of young adults and on neural mechanisms are still unknown. In humans, we investigated this issue using psychological measures, voxel-based morphometry, the n-back task [a typical task for functional magnetic resonance imaging (fMRI) studies with conditions of 0-back (simple cognitive processes) and 2-back tasks (working memory; WM)], resting-state fMRI for the analysis of functional connectivity between brain regions during rest (resting-FC), and intensive adaptive training of PS. PS training was associated with (1) significant or substantial improvement in the performance of PS measures, (2) changes in the gray matter structures of the left superior temporal gyrus and the bilateral regions around the occipitotemporal junction, (3) changes in functional activity that are related to simple cognitive processes (but not those of WM) in the left perisylvian region, and (4) increased resting-FC between the left perisylvian area and the area that extends to the lingual gyrus and calcarine cortex. These results confirm the PS-training-induced plasticity in PS and the training-induced plasticity of functions and structures that are associated with speeded cognitive processes. The observed neural changes caused by PS training may give us new insights into how PS training, and possibly other cognitive training, can improve PS.

Failing to deactivate: the association between brain activity during a working memory task and creativity.

Working memory (WM) is an essential component for human higher order cognitive activities. Creativity has been essential to the development of human civilization. Previous studies from different fields have suggested creativity and capacity of WM have opposing characteristics possibly in terms of diffuse attention. However, despite a number of functional imaging studies on creativity, how creativity relates to brain activity during WM has never been investigated. In this functional magnetic resonance imaging (fMRI) study, we investigated this issue using an n-back WM paradigm and a psychometric measure of creativity (a divergent thinking test). A multiple regression analysis revealed that individual creativity was significantly and positively correlated with brain activity in the precuneus during the 2-back task (WM task), but not during the non-WM 0-back task. As the precuneus shows deactivation during cognitive tasks, our findings show that reduced task induced deactivation (TID) in the precuneus is associated with higher creativity measured by divergent thinking. The precuneus is included in the default mode network, which is deactivated during cognitive tasks. The magnitude of TID in the default mode network is considered to reflect the reallocation of cognitive resources from networks irrelevant to the performance of the task. Thus, our findings may indicate that individual creativity, as measured by the divergent thinking test, is related to the inefficient reallocation of attention, congruent with the idea that diffuse attention is associated with individual creativity.

Importance of the leader region of mRNA for translation initiation of ColE2 Rep protein.

Translation initiation of mRNA encoding the Rep protein of the ColE2 plasmid required for initiation of plasmid DNA replication is fairly efficient in Escherichia coli cells despite the absence of a canonical Shine-Dalgarno sequence. To define sequences and structural elements responsible for translation efficiency of the Rep mRNA, a series of rep-lacZalpha translational fusions bearing various mutations in the region encoding the leader region of the Rep mRNA was generated and tested for the translation activity by measuring the beta-galactosidase activity. We showed that the region rich in A and U between the stem-loop II structure and GA cluster sequence, formation of the stem-loop II structure, but not its sequence, and the region between the GA cluster sequence and initiation codon are important along with the GA cluster sequence for efficient translation of the Rep protein. The existence of these important regions in the leader region of the Rep mRNA may explain the mechanism of inhibition of the Rep protein translation by an antisense RNA (RNAI), which is complementary to the leader region.