Hitoshi Uchiyama

Smaller insula and inferior frontal volumes in young adults with pervasive developmental disorders

Enlarged head circumference and increased brain weight have been reported in infants with pervasive developmental disorders (PDD), and volumetric studies suggest that children with PDD have abnormally enlarged brain volumes. However, little is known about brain volume abnormalities in young adults with PDD. We explored gray matter (GM) volume in young adults with PDD. T1-weighted volumetric images were acquired with a 3-T magnetic resonance scanner from 32 males with high-functioning PDD (23.8+/-4.2 years; Full Scale Intelligence Quotient [FSIQ]=101.6+/-15.6) and 40 age-matched normal male control subjects (22.5+/-4.3 years; FSIQ=109.7+/-7.9). Regional GM volumes were compared between the two groups using voxel-based morphometry (VBM) with the Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL). Compared with the control group, the high-functioning PDD group showed significantly less GM in the right insula, the right inferior frontal gyrus, and the right inferior parietal lobule. A conservative threshold confirmed considerably smaller volumes in the right insula and inferior frontal gyrus. In these areas, negative correlations were found between Autism Spectrum Quotient scores and GM volume, although no significant correlations were found between each subjects FSIQ and GM volume. No regions showed greater GM volumes in the high-functioning PDD group. The insular cortex, which works as a relay area for multiple neurocognitive systems, may be one of the key regions underlying the complex clinical features of PDD. These smaller GM volumes in high-functioning PDD subjects may reflect the clinical features of PDD itself, rather than FSIQ.

“Stay Tuned”: Inter-Individual Neural Synchronization During Mutual Gaze and Joint Attention

Eye contact provides a communicative link between humans, prompting joint attention. As spontaneous brain activity might have an important role in the coordination of neuronal processing within the brain, their inter-subject synchronization might occur during eye contact. To test this, we conducted simultaneous functional MRI in pairs of adults. Eye contact was maintained at baseline while the subjects engaged in real-time gaze exchange in a joint attention task. Averted gaze activated the bilateral occipital pole extending to the right posterior superior temporal sulcus, the dorso-medial prefrontal cortex, and the bilateral inferior frontal gyrus. Following a partners gaze toward an object activated the left intraparietal sulcus. After all the task-related effects were modeled out, inter-individual correlation analysis of residual time-courses was performed. Paired subjects showed more prominent correlations than non-paired subjects in the right inferior frontal gyrus, suggesting that this region is involved in sharing intention during eye contact that provides the context for joint attention.

Neural substrates of sarcasm: A functional magnetic-resonance imaging study

The understanding of sarcasm reflects a complex process, which involves recognizing the beliefs of the speaker. There is a clear association between deficits in mentalizing, which is the ability to understand other peoples behavior in terms of their mental state, and the understanding of sarcasm in individuals with autistic spectrum disorders. This suggests that mentalizing is important in pragmatic non-literal language comprehension. To highlight the neural substrates of sarcasm, 20 normal adult volunteers underwent functional magnetic-resonance imaging. We used scenario-reading tasks, in which sentences describing a certain situation were presented, followed by the protagonists comments regarding that situation. Depending on the situation, the semantic content of the comments was classified as sarcastic, non-sarcastic, or contextually unconnected. As the combination of the first and second sentences represented discourse-level information that was not encoded in the individual sentences, sarcasm detection was represented as the differential activation induced by the second sentences. Sarcasm detection activated the left temporal pole, the superior temporal sulcus, the medial prefrontal cortex, and the inferior frontal gyrus (Brodmanns area [BA] 47). The left BA 47 was activated more prominently by sarcasm detection than by the first sentence. These findings indicate that the detection of sarcasm recruits the medial prefrontal cortex, which is part of the mentalizing system, as well as the neural substrates involved in reading sentences. The left BA 47 might therefore be where mentalizing and language processes interact during sarcasm detection.

Distinction between the literal and intended meanings of sentences: A functional magnetic resonance imaging study of metaphor and sarcasm

To comprehend figurative utterances such as metaphor or sarcasm, a listener must both judge the literal meaning of the statement and infer the speakers intended meaning (mentalizing; Amodio and Frith, 2006). To delineate the neural substrates of pragmatic comprehension, we conducted functional magnetic resonance imaging (fMRI) with 20 normal adult volunteers. Participants read short stories followed by a target sentence. Depending on the context provided by the preceding stories, the target sentences were classified as follows: (1) metaphor versus literally coherent; (2) metaphor versus literally incoherent; (3) sarcasm versus literally coherent; and (4) sarcasm versus literally incoherent. For each task pair, we directly compared the activations evoked by the same target sentences in the different contexts. The contrast images were incorporated into a 2 (metaphor and sarcasm)×2 (literal coherency and incoherency) design. Metaphor-specific activation was found in the head of the caudate, which might be involved in associating statements with potential meanings, and restricting sentence meanings within a set of possible candidates for what the speaker intended. Sarcasm-specific activation was found in the left amygdala, which is an important component of the neural substrates of social behavior. Conjunction analysis revealed that both metaphor and sarcasm activated the anterior rostral medial frontal cortex (arMFC), which is a key node of mentalizing. A distinct literal coherency effect was found in the orbital MFC, which is thought to be involved in monitoring. These mesial frontal areas are jointly involved in monitoring literal coherency and mentalizing within social contexts in order to comprehend the pragmatic meanings of utterances.

Incidental Findings of Brain Magnetic Resonance Imaging Study in a Pediatric Cohort in Japan and Recommendation for a Model Management Protocol

Background The increasing use of magnetic resonance imaging (MRI) in brain researches has led to growing concern over incidental findings (IFs). To establish a practical management protocol for IFs, it is useful to know the actual prevalence and problems of IF management. In the present study, we report the prevalence proportion and some handling problems of IFs in healthy Japanese children, and suggest a management protocol from ethical and practical standpoints. Methods Between 2006 and 2008, 120 healthy children aged 5–8 years participated in a structural MRI study conducted in a pediatric cohort in Japan. All MRI images were reviewed by a pediatric neurologist, and detected IFs were classified into 4 categories. Results IFs of all categories were detected in 40 of the 110 participants (36.4%) for whom T2-weighted or 3D-T1-weighted images were available. Findings of sinusitis and/or otitis media were most frequent (26.4%). Excluding these findings, the prevalence of IFs was still 10.9% (12 findings): 9 findings were categorized as “no referral” (8.2%), 2 as “routine referral” (1.8%), 1 as “urgent referral” (0.9%), and 0 as “immediate referral” (0.0%). In “routine referral” category, only one participant was referred for further examinations. Conclusions Although the prevalence of IFs was high, the proportion of those requiring further examination was low. This result revealed a fairly high false-positive rate and suggested that evaluating equivocal findings was the most difficult part of IF management. A management protocol needs to include a process to properly assess the clinical importance of findings.

Reading ability and phonological awareness in Japanese children with dyslexia

UNLABELLED In alphabetic languages, the deficit of the phonological awareness is considered as the core deficit in developmental dyslexia. However, the role of phonological awareness in the acquisition of reading Japanese kana, the transparent, mora-based phonogram, has not been understood completely. We examine the abilities of Japanese dyslexic children on different types of Japanese phonological tasks, and discussed which tasks significantly account for each aspect of reading ability. METHODS Fifteen dyslexic children (9.53+/-1.52 years old), and 15 children with normal reading ability (9.17+/-0.90 years old) participated in this study. They performed three types of phonological awareness tasks. The mora counting task and the mora reversal task of words require phonological awareness at the mora level. The letter rhyming task, which resembles the task in English language, requires phonological awareness at the phoneme level. We evaluated the reading ability by the reading speed, the reading errors, and the number of pauses while reading sentences aloud. RESULTS The task performances of the dyslexic group on all three phonological awareness tasks were significantly lower than those of the control group. Stepwise multiple regression analysis revealed that the mora counting task and the rhyming letter task most significantly explained the reading speed and number of reading pauses. The mora reversal task of words, together with the antegraded digit span, significantly explained the reading errors. CONCLUSIONS Japanese dyslexics showed deficits of phonological awareness both at the mora and the phoneme levels. Phonological awareness must be crucial for acquiring the ability of decoding phonograms, including Japanese kana.

Altered brain activity for phonological manipulation in dyslexic Japanese children

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.

A study of the standard brain in Japanese children: Morphological comparison with the MNI template

Functional magnetic resonance imaging (MRI) studies involve normalization so that the brains of different subjects can be described using the same coordinate system. However, standard brain templates, including the Montreal Neurological Institute (MNI) template that is most frequently used at present, were created based on the brains of Western adults. Because morphological characteristics of the brain differ by race and ethnicity and between adults and children, errors are likely to occur when data from the brains of non-Western individuals are processed using these templates. Therefore, this study was conducted to collect basic data for the creation of a Japanese pediatric standard brain. Participants in this study were 45 healthy children (contributing 65 brain images) between the ages of 6 and 9 years, who had nothing notable in their perinatal and other histories and neurological findings, had normal physical findings and cognitive function, exhibited no behavioral abnormalities, and provided analyzable MR images. 3D-T1-weighted images were obtained using a 1.5-T MRI device, and images from each child were adjusted to the reference image by affine transformation using SPM8. The lengths were measured and compared with those of the MNI template. The Western adult standard brain and the Japanese pediatric standard brain obtained in this study differed greatly in size, particularly along the anteroposterior diameter and in height, suggesting that the correction rates are high, and that errors are likely to occur in the normalization of pediatric brain images. We propose that the use of the Japanese pediatric standard brain created in this study will improve the accuracy of identification of brain regions in functional brain imaging studies involving children.

Sleep is associated with offline improvement of motor sequence skill in children

In adults, sleep is necessary for the offline improvement of certain skills, such as sequential finger tapping, but whether children show a similar effect is still debatable. Here, we tested whether sleep is associated with offline performance improvement in children. Nine- and 11-year-old children trained on an explicit sequential finger tapping task. On the night following training, their parents observed and recorded the duration of each child’s sleep. The following day, all children performed a surprise retest session on the previously trained sequence. In both 9- and 11-year-old children, skill performance was significantly improved during the first retest session relative to the end of training on the previous day, confirming the offline improvement in performance. There was a significant correlation between the degree of improvement and sleep duration the night after training, suggesting that in children, as in adults, sleep is associated with offline skill enhancement.

Dyslexia: advances in clinical and imaging studies.

The aim of this report is to describe the characteristics of Japanese dyslexia, and to demonstrate several of our studies about the extraction of these characteristic and their neurophysiological and neuroimaging abnormalities, as well as advanced studies of phonological awareness and the underlying neural substrate. Based on these results, we have proposed a 2-step approach for remedial education (e-learning web site: http://www.dyslexia-koeda.jp/). The first step is decoding, which decreases reading errors, and the second is vocabulary learning, which improves reading fluency. This 2-step approach is designed to serve first grade children. In addition, we propose the RTI (response to intervention) model as a desirable system for remedial education.