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1.  Altered brain activity for phonological manipulation in dyslexic Japanese children 
Brain  2013;136(12):3696-3708.
Because of unique linguistic characteristics, the prevalence rate of developmental dyslexia is relatively low in the Japanese language. Paradoxically, Japanese children have serious difficulty analysing phonological processes when they have dyslexia. Neurobiological deficits in Japanese dyslexia remain unclear and need to be identified, and may lead to better understanding of the commonality and diversity in the disorder among different linguistic systems. The present study investigated brain activity that underlies deficits in phonological awareness in Japanese dyslexic children using functional magnetic resonance imaging. We developed and conducted a phonological manipulation task to extract phonological processing skills and to minimize the influence of auditory working memory on healthy adults, typically developing children, and dyslexic children. Current experiments revealed that several brain regions participated in manipulating the phonological information including left inferior and middle frontal gyrus, left superior temporal gyrus, and bilateral basal ganglia. Moreover, dyslexic children showed altered activity in two brain regions. They showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found, suggesting difficulty in composing and processing phonological information. The altered brain activity shares similarity with those of dyslexic children in countries speaking alphabetical languages, but disparity also occurs between these two populations. These are initial findings concerning the neurobiological impairments in dyslexic Japanese children.
doi:10.1093/brain/awt248
PMCID: PMC3916739  PMID: 24052613
developmental dyslexia; phonological awareness; functional magnetic resonance imaging; basal ganglia; Japanese language
2.  Activation of the Prefrontal Cortex While Performing a Task at Preferred Slow Pace and Metronome Slow Pace: A Functional Near-Infrared Spectroscopy Study 
Neural Plasticity  2014;2014:269120.
Individuals have a preferred pace at which they perform voluntary repetitive movements. Previous studies have reported that greater activation of the prefrontal cortex was observed during self-initiated movements than during externally triggered movements. The purpose of the present study is to compare the activation of the prefrontal cortex induced when the subjects performed a peg-board task at their preferred slow pace (PSP, the self-initiated condition) with that induced when they performed the same task at metronome slow pace (MSP, the externally triggered condition) using functional near-infrared spectroscopy. Healthy subjects performed the task while sitting in a chair. By assessing the activated channels individually, we confirmed that all of the prefrontal regions of interest were activated by both tasks. In the second-level analyses, we found that the activation detected in the frontopolar cortex (FPPFC; Brodmann area 10) was higher during the PSP task than during the MSP task. The FPPFC is known to be at the top of prefrontal hierarchy, and specifically involved in evaluating self-generated information. In addition, the FPPFC plays a role in coordinating lateral prefrontal cortex. In the present study, the subjects evaluated and managed the internally generated PSP by coordinating the activity of other lower level prefrontal regions.
doi:10.1155/2014/269120
PMCID: PMC4243132  PMID: 25436155
3.  Sleepiness induced by sleep-debt enhanced amygdala activity for subliminal signals of fear 
BMC Neuroscience  2014;15(1):97.
Background
Emotional information is frequently processed below the level of consciousness, where subcortical regions of the brain are thought to play an important role. In the absence of conscious visual experience, patients with visual cortex damage discriminate the valence of emotional expression. Even in healthy individuals, a subliminal mechanism can be utilized to compensate for a functional decline in visual cognition of various causes such as strong sleepiness. In this study, sleep deprivation was simulated in healthy individuals to investigate functional alterations in the subliminal processing of emotional information caused by reduced conscious visual cognition and attention due to an increase in subjective sleepiness. Fourteen healthy adult men participated in a within-subject crossover study consisting of a 5-day session of sleep debt (SD, 4-h sleep) and a 5-day session of sleep control (SC, 8-h sleep). On the last day of each session, participants performed an emotional face-viewing task that included backward masking of nonconscious presentations during magnetic resonance scanning.
Results
Finally, data from eleven participants who were unaware of nonconscious face presentations were analyzed. In fear contrasts, subjective sleepiness was significantly positively correlated with activity in the amygdala, ventromedial prefrontal cortex, hippocampus, and insular cortex, and was significantly negatively correlated with the secondary and tertiary visual areas and the fusiform face area. In fear-neutral contrasts, subjective sleepiness was significantly positively correlated with activity of the bilateral amygdala. Further, changes in subjective sleepiness (the difference between the SC and SD sessions) were correlated with both changes in amygdala activity and functional connectivity between the amygdala and superior colliculus in response to subliminal fearful faces.
Conclusion
Sleepiness induced functional decline in the brain areas involved in conscious visual cognition of facial expressions, but also enhanced subliminal emotional processing via superior colliculus as represented by activity in the amygdala. These findings suggest that an evolutionally old and auxiliary subliminal hazard perception system is activated as a compensatory mechanism when conscious visual cognition is impaired. In addition, enhancement of subliminal emotional processing might cause involuntary emotional instability during sleep debt through changes in emotional response to or emotional evaluation of external stimuli.
doi:10.1186/1471-2202-15-97
PMCID: PMC4143558  PMID: 25134639
Sleepiness; Nonconscious; Unconscious; Subliminal; Emotion; Fearful face; Amygdala
4.  Anterior insular cortex mediates bodily sensibility and social anxiety 
Studies in psychiatry and cognitive neuroscience have reported an important relationship between individual interoceptive accuracy and anxiety level. This indicates that greater attention to one’s bodily state may contribute to the development of intense negative emotions and anxiety disorders. We hypothesized that reactivity in the anterior insular cortex underlies the intensity of interoceptive awareness and anxiety. To elucidate this triadic mechanism, we conducted functional magnetic resonance imaging (fMRI) and mediation analyses to examine the relationship between emotional disposition and activation in the anterior insular cortex while participants evaluated their own emotional and bodily states. Our results indicated that right anterior insular activation was positively correlated with individual levels of social anxiety and neuroticism and negatively correlated with agreeableness and extraversion. The results of the mediation analyses revealed that activity in the right anterior insula mediated the activity of neural correlates of interoceptive sensibility and social fear. Our findings suggest that attention to interoceptive sensation affects personality traits through how we feel emotion subjectively in various situations.
doi:10.1093/scan/nss108
PMCID: PMC3594729  PMID: 22977199
interoception; anxiety; neuroticism; body; emotion
5.  Correction: Sleep Debt Elicits Negative Emotional Reaction through Diminished Amygdala-Anterior Cingulate Functional Connectivity 
PLoS ONE  2013;8(10):10.1371/annotation/5970fff3-0a1c-4056-9396-408d76165c4d.
doi:10.1371/annotation/5970fff3-0a1c-4056-9396-408d76165c4d
PMCID: PMC3806906
6.  States of mind: Emotions, body feelings, and thoughts share distributed neural networks 
NeuroImage  2012;62(3):2110-2128.
Scientists have traditionally assumed that different kinds of mental states (e.g., fear, disgust, love, memory, planning, concentration, etc.) correspond to different psychological faculties that have domain-specific correlates in the brain. Yet, growing evidence points to the constructionist hypothesis that mental states emerge from the combination of domain-general psychological processes that map to large-scale distributed brain networks. In this paper, we report a novel study testing a constructionist model of the mind in which participants generated three kinds of mental states (emotions, body feelings, or thoughts) while we measured activity within large-scale distributed brain networks using fMRI. We examined the similarity and differences in the pattern of network activity across these three classes of mental states. Consistent with a constructionist hypothesis, a combination of large-scale distributed networks contributed to emotions, thoughts, and body feelings, although these mental states differed in the relative contribution of those networks. Implications for a constructionist functional architecture of diverse mental states are discussed.
doi:10.1016/j.neuroimage.2012.05.079
PMCID: PMC3453527  PMID: 22677148
constructionist; emotion; thought; body feelings; intrinsic networks
7.  In vitro circadian period is associated with circadian/sleep preference 
Scientific Reports  2013;3:2074.
Evaluation of circadian phenotypes is crucial for understanding the pathophysiology of diseases associated with disturbed biological rhythms such as circadian rhythm sleep disorders (CRSDs). We measured clock gene expression in fibroblasts from individual subjects and observed circadian rhythms in the cells (in vitro rhythms). Period length of the in vitro rhythm (in vitro period) was compared with the intrinsic circadian period, τ, measured under a forced desynchrony protocol (in vivo period) and circadian/sleep parameters evaluated by questionnaires, sleep log, and actigraphy. Although no significant correlation was observed between the in vitro and in vivo periods, the in vitro period was correlated with chronotype, habitual sleep time, and preferred sleep time. Our data demonstrate that the in vitro period is significantly correlated with circadian/sleep preference. The findings suggest that fibroblasts from individual patients can be utilized for in vitro screening of therapeutic agents to provide personalized therapeutic regimens for CRSD patients.
doi:10.1038/srep02074
PMCID: PMC3691610  PMID: 23797865
8.  Neuroimaging studies of alexithymia: physical, affective, and social perspectives 
Alexithymia refers to difficulty in identifying and expressing one’s emotions, and it is related to disturbed emotional regulation. It was originally proposed as a personality trait that plays a central role in psychosomatic diseases. This review of neuroimaging studies on alexithymia suggests that alexithymia is associated with reduced neural responses to emotional stimuli from the external environment, as well as with reduced activity during imagery, in the limbic and paralimbic areas (i.e., amygdala, insula, anterior/posterior cingulate cortex). In contrast, alexithymia is also known to be associated with enhanced neural activity in somatosensory and sensorimotor regions, including the insula. Moreover, neural activity in the medial, prefrontal, and insula cortex was lowered when people with alexithymia were involved in social tasks. Because most neuroimaging studies have been based on sampling by self-reported questionnaires, the contrasted features of neural activities in response to internal and external emotional stimuli need to be elucidated. The social and emotional responses of people with alexithymia are discussed and recommendations for future research are presented.
doi:10.1186/1751-0759-7-8
PMCID: PMC3621096  PMID: 23537323
Alexithymia; fMRI; PET; Neuroimaging study; Interoception; Psychosomatic medicine; Emotional awareness
9.  Sleep Debt Elicits Negative Emotional Reaction through Diminished Amygdala-Anterior Cingulate Functional Connectivity 
PLoS ONE  2013;8(2):e56578.
Objectives
Sleep debt reportedly increases emotional instability, such as anxiety and confusion, in addition to sleepiness and psychomotor impairment. However, the neural basis of emotional instability due to sleep debt has yet to be elucidated. This study investigated changes in emotional responses that are elicited by the simulation of short-term sleep loss and the brain regions responsible for these changes.
Subjects and Methods
Fourteen healthy adult men aged 24.1±3.3 years (range, 20–32 years) participated in a within-subject crossover study consisting of 5-day sessions of both sleep debt (4 h for time in bed) and sleep control (8 h for time in bed). On the last day of each session, participants underwent polysomnography and completed the State-Trait Anxiety Inventory and Profile of Mood States questionnaires. In addition, functional magnetic resonance imaging was conducted while performing an emotional face viewing task.
Results
Restricted sleep over the 5-day period increased the activity of the left amygdala in response to the facial expression of fear, whereas a happy facial expression did not change the activity. Restricted sleep also resulted in a significant decrease in the functional connectivity between the amygdala and the ventral anterior cingulate cortex (vACC) in proportion to the degree of sleep debt (as indicated by the percentage of slow wave sleep and δ wave power). This decrease was significantly correlated with activation of the left amygdala and deterioration of subjective mood state.
Conclusion
The results of this study suggest that continuous and accumulating sleep debt that can be experienced in everyday life can downregulate the functional suppression of the amygdala by the vACC and consequently enhance the response of the amygdala to negative emotional stimuli. Such functional alteration in emotional control may, in part, be attributed to the neural basis of emotional instability during sleep debt.
doi:10.1371/journal.pone.0056578
PMCID: PMC3572063  PMID: 23418586
10.  Neural Network Development in Late Adolescents during Observation of Risk-Taking Action 
PLoS ONE  2012;7(6):e39527.
Emotional maturity and social awareness are important for adolescents, particularly college students beginning to face the challenges and risks of the adult world. However, there has been relatively little research into personality maturation and psychological development during late adolescence and the neural changes underlying this development. We investigated the correlation between psychological properties (neuroticism, extraversion, anxiety, and depression) and age among late adolescents (n = 25, from 18 years and 1 month to 22 years and 8 months). The results revealed that late adolescents became less neurotic, less anxious, less depressive and more extraverted as they aged. Participants then observed video clips depicting hand movements with and without a risk of harm (risk-taking or safe actions) during functional magnetic resonance imaging (fMRI). The results revealed that risk-taking actions elicited significantly stronger activation in the bilateral inferior parietal lobule, temporal visual regions (superior/middle temporal areas), and parieto-occipital visual areas (cuneus, middle occipital gyri, precuneus). We found positive correlations of age and extraversion with neural activation in the insula, middle temporal gyrus, lingual gyrus, and precuneus. We also found a negative correlation of age and anxiety with activation in the angular gyrus, precentral gyrus, and red nucleus/substantia nigra. Moreover, we found that insula activation mediated the relationship between age and extraversion. Overall, our results indicate that late adolescents become less anxious and more extraverted with age, a process involving functional neural changes in brain networks related to social cognition and emotional processing. The possible neural mechanisms of psychological and social maturation during late adolescence are discussed.
doi:10.1371/journal.pone.0039527
PMCID: PMC3387168  PMID: 22768085
11.  Differential Hemodynamic Response in Affective Circuitry with Aging: An fMRI Study of Novelty, Valence, and Arousal 
Journal of cognitive neuroscience  2010;23(5):1027-1041.
Emerging evidence indicates that stimulus novelty is affectively potent and reliably engages the amygdala and other portions of the affective workspace in the brain. Using fMRI, we examined whether novel stimuli remain affectively salient across the lifespan, and therefore, whether novelty processing—a potentially survival-relevant function—is preserved with aging. Nineteen young and 22 older healthy adults were scanned during observing novel and familiar affective pictures while estimating their own subjectively experienced aroused levels. We investigated age-related difference of magnitude of activation, hemodynamic time course, and functional connectivity of BOLD responses in the amygdala. Although there were no age-related differences in the peak response of the amygdala to novelty, older individuals showed a narrower, sharper (i.e., “peakier”) hemodynamic time course in response to novel stimuli, as well as decreased connectivity between the left amygdala and the affective areas including orbito-frontal regions. These findings have relevance for understanding age-related differences in memory and affect regulation.
doi:10.1162/jocn.2010.21527
PMCID: PMC3141584  PMID: 20521849
12.  The reliability and validity of the Japanese version of the Levels of Emotional Awareness Scale (LEAS-J) 
Background
The Levels of Emotional Awareness Scale (LEAS) was developed to assess five levels of emotional awareness: bodily sensations, action tendencies, single emotions, blends of emotion, and combinations of blends. It is a paper and pencil performance questionnaire that presents 20 emotion-evoking scenes. We developed a Japanese version of the LEAS (LEAS-J), and its reliability and validity were examined.
Methods
The LEAS-J level was independently assessed by two researchers who scored each response according to the LEAS scoring manual. High inter-rater reliability and internal consistency were obtained for the LEAS-J. Measures were socioeconomic status, LEAS-J, Toronto Alexithymia Scale-20 (TAS-20), Interpersonal Reactivity Index (IRI), and NEO Five-Factor Inventory (NEO-FFI). TAS-20, IRI and NEO-FFI were the measures used to explore the construct validity of LEAS-J, as it was predicted that higher scores on the LEAS-J would be related to fewer alexithymic features, greater empathetic ability, and a greater sense of cooperation with others. Questionnaires were completed by 344 university students.
Results
The criterion-referenced validity was determined: a significant negative relationship was found with the externally-oriented thinking scores of TAS-20, and positive relationships were found with fantasy, perspective taking, and empathic concern on IRI and with extraversion, openness to experience, and agreeableness on NEO-FFI.
Conclusions
Consistent with our expectations, the findings provide evidence that the LEAS-J has good reliability and validity. In addition, women had significantly higher scores than men on LEAS-J, showing that the gender difference identified in the original LEAS was cross-culturally consistent.
doi:10.1186/1751-0759-5-2
PMCID: PMC3042374  PMID: 21281491
13.  Validity issues in the assessment of alexithymia related to the developmental stages of emotional cognition and language 
Objective
We examined developmental aspects of the emotional awareness of adolescents by evaluating their responses to a self-reported questionnaire based on the Toronto Alexithymia Scale-20 (TAS-20).
Methods
The items of the TAS-20 were modified to make them more understandable by adolescents, and nine new items related to a limited capacity for imagination were added. The Japanese Linguistic Ability Test and the multi-dimensional empathy scale for adolescents were administered to examine concurrent validity. Two hundred and two normative young adolescents and thirty-two adolescent patients with psychosomatic and/or behavioral problems participated in the study. Eighty junior high school students also participated in a separate examination of test-retest reliability.
Results
Thirteen items were extracted after exploratory and confirmatory factor analyses, and four core factors were identified in the resulting scale: Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), Externally-Oriented Thinking (EOT) and Constricted Imaginal Capacities (CIC). Interestingly, scores on the multi-dimensional empathy scale correlated positively with DIF and DDF, but negatively with EOT and CIC. Higher DDF scores were associated with higher Japanese linguistic abilities. DIF/DDF scores were higher for females than males, irrespective of linguistic ability. Test-retest reliability coefficients were significant. The patient group showed significantly higher DIF scores than the normative students.
Conclusion
The present findings indicated that subjective difficulties in identifying and describing feelings are associated with empathetic and linguistic abilities. The developmental aspect to emotional awareness herein described suggests that self-reported questionnaires for alexithymia must be carefully constructed and examined, even for adults.
doi:10.1186/1751-0759-3-12
PMCID: PMC2777913  PMID: 19886981
14.  Prospects of Psychosomatic Medicine 
doi:10.1186/1751-0759-3-1
PMCID: PMC2642858  PMID: 19161633
15.  The empathic brain and its dysfunction in psychiatric populations: implications for intervention across different clinical conditions 
Empathy is a concept central to psychiatry, psychotherapy and clinical psychology. The construct of empathy involves not only the affective experience of the other person's actual or inferred emotional state but also some minimal recognition and understanding of another's emotional state. It is proposed, in the light of multiple levels of analysis including social psychology, cognitive neuroscience and clinical neuropsychology, a model of empathy that involves both bottom-up and top-down information processing underpinned by parallel and distributed computational mechanisms. The predictive validity of this model is explored with reference to clinical conditions. As many psychiatric conditions are associated with deficits or even lack of empathy, we discuss a limited number of these disorders including psychopathy/antisocial personality disorders, borderline and narcissistic personality disorders, autistic spectrum disorders, and alexithymia. We argue that future clinical investigations of empathy disorders can only be informative if behavioral, dispositional and biological factors are combined.
doi:10.1186/1751-0759-1-22
PMCID: PMC2206036  PMID: 18021398
16.  Age and gender effect on alexithymia in large, Japanese community and clinical samples: a cross-validation study of the Toronto Alexithymia Scale (TAS-20) 
Background
The construct validity of alexithymia and its assessment using the 20-item Toronto Alexithymia Scale (TAS-20) in Japan is unknown. Low reliability has been found for the third factor of the TAS-20 in some cultures, and the factor structure for psychosomatic disorder patients has not been adequately investigated. Although alexithymia most likely has certain developmental aspects, this has infrequently been investigated.
Methods
The newly-developed Japanese TAS-20 was administered to a normative sample (n = 2,718; 14–84 y.o.), along with the NEO Five-Factor Inventory (NEO-FFI) for cross validation. Psychosomatic patients (n = 1,924, 12–87 y.o.) were tested to evaluate the factor structure in a clinical sample. College students (n = 196) were used for a test-retest study. Internal reliability and consistency were assessed, and the factorial structure was evaluated using confirmatory and exploratory factor analyses for both the normative and the clinical samples. The correlations between the TAS-20 and the NEO-FFI factor scores were evaluated. Age-related and gender differences in the TAS-20 were explored using analysis of variance in the normative sample.
Results
The original three-factor model of the TAS-20 was confirmed to be valid for these Japanese samples, although a 4-factor solution that included negatively keyed items (NKI) as an additional factor was more effective. Significant correlations of the TAS-20 with the NEO-FFI were found, as has been previously reported. Factor analyses of the normative and patient samples showed similar patterns. The TAS-20 total, difficulty in identifying feelings (DIF), and difficulty in describing feelings (DDF) scores were high for teenagers, decreased with age, and from 30s did not change significantly. In contrast, externally oriented thinking (EOT) scores showed an almost linear positive correlation with age. DIF scores were higher for females, while EOT scores were higher for males, without any interaction between gender and age differences.
Conclusion
The original three-factor concept of the TAS-20 was generally supported for practical use. Age-related differences in TAS-20 scores indicate developmental aspects of alexithymia. Alexithymia is made up of two components with different developmental paths: DIF/DDF and EOT.
doi:10.1186/1751-0759-1-7
PMCID: PMC1838425  PMID: 17371586

Results 1-16 (16)