Clinical utility of an array comparative genomic hybridization analysis for Williams syndrome.

To reveal the relation between intellectual disability and the deleted intervals in Williams syndrome, we performed an array comparative genomic hybridization analysis and standardized developmental testing for 11 patients diagnosed as having Williams syndrome based on fluorescent in situ hybridization testing. One patient had a large 4.2-Mb deletion spanning distally beyond the common 1.5-Mb intervals observed in 10/11 patients. We formulated a linear equation describing the developmental age of the 10 patients with the common deletion; the developmental age of the patient with the 4.2-Mb deletion was significantly below the expectation (developmental age = 0.51 × chronological age). The large deletion may account for the severe intellectual disability; therefore, the use of array comparative genomic hybridization may provide practical information regarding individuals with Williams syndrome.

Neural correlates of infant accent discrimination: an fNIRS study.

The present study investigated the neural correlates of infant discrimination of very similar linguistic varieties (Quebecois and Parisian French) using functional Near InfraRed Spectroscopy. In line with previous behavioral and electrophysiological data, there was no evidence that 3-month-olds discriminated the two regional accents, whereas 5-month-olds did, with the locus of discrimination in left anterior perisylvian regions. These neuroimaging results suggest that a developing language network relying crucially on left perisylvian cortices sustains infants' discrimination of similar linguistic varieties within this early period of infancy.

An online database of infant functional near infrared spectroscopy studies: a community-augmented systematic review.

Until recently, imaging the infant brain was very challenging. Functional Near InfraRed Spectroscopy (fNIRS) is a promising, relatively novel technique, whose use is rapidly expanding. As an emergent field, it is particularly important to share methodological knowledge to ensure replicable and robust results. In this paper, we present a community-augmented database which will facilitate precisely this exchange. We tabulated articles and theses reporting empirical fNIRS research carried out on infants below three years of age along several methodological variables. The resulting spreadsheet has been uploaded in a format allowing individuals to continue adding new results, and download the most recent version of the table. Thus, this database is ideal to carry out systematic reviews. We illustrate its academic utility by focusing on the factors affecting three key variables: infant attrition, the reliability of oxygenated and deoxygenated responses, and signal-to-noise ratios. We then discuss strengths and weaknesses of the DBIfNIRS, and conclude by suggesting a set of simple guidelines aimed to facilitate methodological convergence through the standardization of reports.

Insights on NIRS Sensitivity from a Cross-Linguistic Study on the Emergence of Phonological Grammar.

Each language has a unique set of phonemic categories and phonotactic rules which determine permissible sound sequences in that language. Behavioral research demonstrates that one's native language shapes the perception of both sound categories and sound sequences in adults, and neuroimaging results further indicate that the processing of native phonemes and phonotactics involves a left-dominant perisylvian brain network. Recent work using a novel technique, functional Near InfraRed Spectroscopy (NIRS), has suggested that a left-dominant network becomes evident toward the end of the first year of life as infants process phonemic contrasts. The present research project attempted to assess whether the same pattern would be seen for native phonotactics. We measured brain responses in Japanese- and French-learning infants to two contrasts: Abuna vs. Abna (a phonotactic contrast that is native in French, but not in Japanese) and Abuna vs. Abuuna (a vowel length contrast that is native in Japanese, but not in French). Results did not show a significant response to either contrast in either group, unlike both previous behavioral research on phonotactic processing and NIRS work on phonemic processing. To understand these null results, we performed similar NIRS experiments with Japanese adult participants. These data suggest that the infant null results arise from an interaction of multiple factors, involving the suitability of the experimental paradigm for NIRS measurements and stimulus perceptibility. We discuss the challenges facing this novel technique, particularly focusing on the optimal stimulus presentation which could yield strong enough hemodynamic responses when using the change detection paradigm.

[Current status and future perspectives of near-infrared spectroscopy: clinical applications and neurocognitive findings].

Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging tool that can measure local hemodynamic changes in the brain. Over the past decade, the technical advantage offered by multichannel NIRS has provided various new findings on higher cerebral function of the human brain. These findings have improved our knowledge of cognitive neuroscience, neurology, psychiatric medicine, rehabilitation medicine, and pharmacology. The present review illustrates such new findings and introduces a general trend of studies with NIRS and its clinical applications. In particular, new findings on early brain development and the organization of connectivity associated with language acquisition in the first year of life have been highlighted. Finally, some issues and concerns mostly stemming from the technical limitations of NIRS have been pointed out and discussed in view of current progress, so that future NIRS studies are more fruitful and reliable.

Reading speed, comprehension and eye movements while reading Japanese novels: evidence from untrained readers and cases of speed-reading trainees.

BACKGROUND: A growing body of evidence suggests that meditative training enhances perception and cognition. In Japan, the Park-Sasaki method of speed-reading involves organized visual training while forming both a relaxed and concentrated state of mind, as in meditation. The present study examined relationships between reading speed, sentence comprehension, and eye movements while reading short Japanese novels. In addition to normal untrained readers, three middle-level trainees and one high-level expert on this method were included for the two case studies. METHODOLOGY/PRINCIPAL FINDINGS: In Study 1, three of 17 participants were middle-level trainees on the speed-reading method. Immediately after reading each story once on a computer monitor, participants answered true or false questions regarding the content of the novel. Eye movements while reading were recorded using an eye-tracking system. Results revealed higher reading speed and lower comprehension scores in the trainees than in the untrained participants. Furthermore, eye-tracking data by untrained participants revealed multiple correlations between reading speed, accuracy and eye-movement measures, with faster readers showing shorter fixation durations and larger saccades in X than slower readers. In Study 2, participants included a high-level expert and 14 untrained students. The expert showed higher reading speed and statistically comparable, although numerically lower, comprehension scores compared with the untrained participants. During test sessions this expert moved her eyes along a nearly straight horizontal line as a first pass, without moving her eyes over the whole sentence display as did the untrained students. CONCLUSIONS/SIGNIFICANCE: In addition to revealing correlations between speed, comprehension and eye movements in reading Japanese contemporary novels by untrained readers, we describe cases of speed-reading trainees regarding relationships between these variables. The trainees overall tended to show poor performance influenced by the speed-accuracy trade-off, although this trade-off may be reduced in the case of at least one high-level expert.

Cerebral responses to infant-directed speech and the effect of talker familiarity.

A number of behavioral studies suggest that infant-directed speech (IDS) plays a more important role in facilitating both: a) speech perception, and b) adult-infant social interactions than does adult-directed speech (ADS), and hence that IDS contributes to subsequent social and language development. However neural substrates that may underlie these IDS functions have not been examined. The present study examined cerebral hemodynamic responses to IDS in 48 infants (4-13 months of age) using near-infrared spectroscopy (NIRS). Japanese sentences uttered by the infants' own mothers and by unfamiliar mothers were used to record activations in temporal and frontal area separately. Increased activations were observed predominantly in infants' left and right temporal areas when they listened to IDS rather than to ADS when both involved voices of their own and unfamiliar mothers. In contrast, significantly greater activations were observed in the frontal area when infants listened to IDS produced by their own mothers, not when IDS arose from unfamiliar mothers. Furthermore, the present results indicate that responses to IDS do vary as a function of the infant's age and the talker familiarity. These findings suggest a differential function for frontal and temporal areas in processing infant-directed speech by the different speakers.

Functional hemispheric specialization in processing phonemic and prosodic auditory changes in neonates.

This study focuses on the early cerebral base of speech perception by examining functional lateralization in neonates for processing segmental and suprasegmental features of speech. For this purpose, auditory evoked responses of full-term neonates to phonemic and prosodic contrasts were measured in their temporal area and part of the frontal and parietal areas using near-infrared spectroscopy (NIRS). Stimuli used here were phonemic contrast /itta/ and /itte/ and prosodic contrast of declarative and interrogative forms /itta/ and /itta?/. The results showed clear hemodynamic responses to both phonemic and prosodic changes in the temporal areas and part of the parietal and frontal regions. In particular, significantly higher hemoglobin (Hb) changes were observed for the prosodic change in the right temporal area than for that in the left one, whereas Hb responses to the vowel change were similarly elicited in bilateral temporal areas. However, Hb responses to the vowel contrast were asymmetrical in the parietal area (around supra marginal gyrus), with stronger activation in the left. These results suggest a specialized function of the right hemisphere in prosody processing, which is already present in neonates. The parietal activities during phonemic processing were discussed in relation to verbal-auditory short-term memory. On the basis of this study and previous studies on older infants, the developmental process of functional lateralization from birth to 2 years of age for vowel and prosody was summarized.

Assessing signal-driven mechanisms in neonates: brain responses to temporally and spectrally different sounds.

Past studies have found that, in adults, the acoustic properties of sound signals (such as fast versus slow temporal features) differentially activate the left and right hemispheres, and some have hypothesized that left-lateralization for speech processing may follow from left-lateralization to rapidly changing signals. Here, we tested whether newborns' brains show some evidence of signal-specific lateralization responses using near-infrared spectroscopy (NIRS) and auditory stimuli that elicits lateralized responses in adults, composed of segments that vary in duration and spectral diversity. We found significantly greater bilateral responses of oxygenated hemoglobin (oxy-Hb) in the temporal areas for stimuli with a minimum segment duration of 21 ms, than stimuli with a minimum segment duration of 667 ms. However, we found no evidence for hemispheric asymmetries dependent on the stimulus characteristics. We hypothesize that acoustic-based functional brain asymmetries may develop throughout early infancy, and discuss their possible relationship with brain asymmetries for language.

Functional lateralization of speech processing in adults and children who stutter.

Developmental stuttering is a speech disorder in fluency characterized by repetitions, prolongations, and silent blocks, especially in the initial parts of utterances. Although their symptoms are motor related, people who stutter show abnormal patterns of cerebral hemispheric dominance in both anterior and posterior language areas. It is unknown whether the abnormal functional lateralization in the posterior language area starts during childhood or emerges as a consequence of many years of stuttering. In order to address this issue, we measured the lateralization of hemodynamic responses in the auditory cortex during auditory speech processing in adults and children who stutter, including preschoolers, with near-infrared spectroscopy. We used the analysis-resynthesis technique to prepare two types of stimuli: (i) a phonemic contrast embedded in Japanese spoken words (/itta/ vs. /itte/) and (ii) a prosodic contrast (/itta/ vs. /itta?/). In the baseline blocks, only /itta/ tokens were presented. In phonemic contrast blocks, /itta/ and /itte/ tokens were presented pseudo-randomly, and /itta/ and /itta?/ tokens in prosodic contrast blocks. In adults and children who do not stutter, there was a clear left-hemispheric advantage for the phonemic contrast compared to the prosodic contrast. Adults and children who stutter, however, showed no significant difference between the two stimulus conditions. A subject-by-subject analysis revealed that not a single subject who stutters showed a left advantage in the phonemic contrast over the prosodic contrast condition. These results indicate that the functional lateralization for auditory speech processing is in disarray among those who stutter, even at preschool age. These results shed light on the neural pathophysiology of developmental stuttering.

Two successive neurocognitive processes captured by near-infrared spectroscopy: prefrontal activation during a computerized plus-shaped maze task.

The present study using near-infrared spectroscopy (NIRS) examined prefrontal activation associated with maze-solving performance in adult humans. The participants were required to solve a plus-shaped maze, comparable to the one used for pigeons and human children to behaviorally assess planning processes, by moving a target square to a goal square presented on a touch-sensitive screen. The participants made incorrect responses toward a previous goal immediately after the goal jumped to the end of another arm, in parallel with but less frequently than previous participants, with shorter reaction times than when they correctly adjusted their responses. In these incorrect trials, relatively larger hemodynamic changes having two peaks were observed, especially in channels near the right inferior frontal cortex (IFC), suggesting use of additional cognitive resources for adjustment of responses after making errors. In addition to showing human adults' better behavioral inhibition than previous participants, the present NIRS data suggest a difference in prefrontal activation patterns according to whether inhibition of the forward plan was working well or not. The results also testify to the effective NIRS recording, while the participants were moving a computer-generated stimulus by actually making finger touches to the monitor.

Cerebral lateralization and early speech acquisition: a developmental scenario.

During the past ten years, research using Near-infrared Spectroscopy (NIRS) to study the developing brain has provided groundbreaking evidence of brain functions in infants. This paper presents a theoretically oriented review of this wealth of evidence, summarizing recent NIRS data on language processing, without neglecting other neuroimaging or behavioral studies in infancy and adulthood. We review three competing classes of hypotheses (i.e. signal-driven, domain-driven, and learning biases hypotheses) regarding the causes of hemispheric specialization for speech processing. We assess the fit between each of these hypotheses and neuroimaging evidence in speech perception and show that none of the three hypotheses can account for the entire set of observations on its own. However, we argue that they provide a good fit when combined within a developmental perspective. According to our proposed scenario, lateralization for language emerges out of the interaction between pre-existing left-right biases in generic auditory processing (signal-driven hypothesis), and a left-hemisphere predominance of particular learning mechanisms (learning-biases hypothesis). As a result of this completed developmental process, the native language is represented in the left hemisphere predominantly. The integrated scenario enables to link infant and adult data, and points to many empirical avenues that need to be explored more systematically.

Optical brain imaging reveals general auditory and language-specific processing in early infant development.

This study uses near-infrared spectroscopy in young infants in order to elucidate the nature of functional cerebral processing for speech. Previous imaging studies of infants' speech perception revealed left-lateralized responses to native language. However, it is unclear if these activations were due to language per se rather than to some low-level acoustic correlate of spoken language. Here we compare native (L1) and non-native (L2) languages with 3 different nonspeech conditions including emotional voices, monkey calls, and phase scrambled sounds that provide more stringent controls. Hemodynamic responses to these stimuli were measured in the temporal areas of Japanese 4 month-olds. The results show clear left-lateralized responses to speech, prominently to L1, as opposed to various activation patterns in the nonspeech conditions. Furthermore, implementing a new analysis method designed for infants, we discovered a slower hemodynamic time course in awake infants. Our results are largely explained by signal-driven auditory processing. However, stronger activations to L1 than to L2 indicate a language-specific neural factor that modulates these responses. This study is the first to discover a significantly higher sensitivity to L1 in 4 month-olds and reveals a neural precursor of the functional specialization for the higher cognitive network.

Cerebral laterality for phonemic and prosodic cue decoding in children with autism.

This study examined the cerebral functional lateralization, from a phonological perspective, in children with autism spectrum disorder (ASD) and typically developing children (TDC). With near infrared spectroscopy, we measured auditory evoked-responses in the temporal areas to phonemic and prosodic contrasts in word contexts. The results of TDC showed stronger left-dominant and right-dominant responses to phonemic and prosodic differences, respectively. Furthermore, although ASD children displayed similar tendencies, the functional asymmetry for phonemic changes was relatively weak, suggesting less-specialized left-brain functions. The typical asymmetry for the prosodic condition was further discussed in terms of acoustic-physical perceptual ability of ASD children. The study revealed differential neural recruitment in decoding phonetic cues between ASD children and TDC and verified the applicability of near infrared spectroscopy as a suitable neuroimaging method for children with developmental disorders.

Prefrontal activation associated with social attachment: facial-emotion recognition in mothers and infants.

Attachment between mothers and infants is the most primitive and primary form of human social relationship. Many reports have suggested that the orbitofrontal cortex (OFC) plays a significant role in this attachment; however, only a select few provide experimental neurophysiological evidence. In the present study, to determine the neural substrates underlying the social and emotional attachment between mothers and infants, we measured their prefrontal activation by using near-infrared spectroscopy. We used movie stimuli that could robustly induce a positive affect, and the results for viewing own versus unfamiliar infants showed that own-infant viewing elicited increased activations around the anterior part of the orbitofrontal cortex (OFC) in the mothers. Their response magnitude in that area was also correlated with the behavioral rating of the pleasant mood of infants. Furthermore, our study revealed that the infants' prefrontal activation around the anterior OFC is specific to viewing their mothers' smile. These results suggest the OFC's role in regulating and encoding the affect in attachment system and also show that infants share similar neuronal functions with mothers, associated with their bonds at 1 year of age. We further discussed infants' prefrontal activations and their implications for the development of the social brain network.

Optical imaging of infants' neurocognitive development: recent advances and perspectives.

Near-infrared spectroscopy (NIRS) provides a unique method of monitoring infant brain function by measuring the changes in the concentrations of oxygenated and deoxygenated hemoglobin. During the past 10 years, NIRS measurement of the developing brain has rapidly expanded. In this article, a brief discussion of the general principles of NIRS, including its technical advantages and limitations, is followed by a detailed review of the role played so far by NIRS in the study of infant perception and cognition, including language, and visual and auditory functions. Results have highlighted, in particular, the developmental changes of cerebral asymmetry associated with speech acquisition. Finally, suggestions for future studies of neurocognitive development using NIRS are presented. Although NIRS studies of the infant brain have yet to fulfill their potential, a review of the work done so far indicates that NIRS is likely to provide many unique insights in the field of developmental neuroscience.

Neural attunement processes in infants during the acquisition of a language-specific phonemic contrast.

To elucidate the developmental neural attunement process in the language-specific phonemic repertoire, cerebral hemodynamic responses to a Japanese durational vowel contrast were measured in Japanese infants using near-infrared spectroscopy. Because only relative durational information distinguishes this particular vowel contrast, both first and second language learners have difficulties in acquiring this phonemically crucial durational difference. Previous cross-linguistic studies conducted on adults showed that phoneme-specific, left-dominant neural responses were observed only for native Japanese listeners. Using the same stimuli, we show that a larger response to the across-category changes than to the within-category changes occurred transiently in the 6- to 7-month-old group before stabilizing in the groups older than 12 months. However, the left dominance of the phoneme-specific response in the auditory area was observed only in the groups of 13 months and above. Thus, the durational phonemic contrast is most likely processed first by a generic auditory circuit at 6-7 months as a result of early auditory experience. The neural processing of the contrast is then switched over to a more linguistic circuit after 12 months, this time with a left dominance similar to native adult listeners.

Motion illusion activates the visual motion area of the brain: a near-infrared spectroscopy (NIRS) study.

Near-infrared spectroscopy (NIRS) enables noninvasive measurement of concentration changes of oxy- and deoxy-hemoglobin. The present study investigated cerebral representations of motion illusion by NIRS and examined several experimental procedures to determine an efficient procedure that can shorten the experimental time. We compared hemodynamic responses to figures with and without motion illusion. The number of repetitions of the tasks in the experiments and other factors were also examined. Results showed significant responses around area MT/V5 to the motion illusion from the analyses of three cycles (blocks) of presentation of illusion induction stimulus. These findings indicate that motion illusion can be detected by NIRS, and we propose a concise and efficient procedure for NIRS.

Different brain strategies underlie the categorical perception of foreign and native phonemes.

The present study using near-infrared spectroscopy examined the neuronal correlates of Japanese long/short vowel contrast discrimination and its relationship with behavioral performance by comparing native Japanese (L1) subjects and Korean subjects learning Japanese as a second language (L2). Phoneme-specific responses were predominantly observed in the left auditory area only in the L1 subjects, although the behavioral scores of the L2 subjects indicated categorical perception (CP) that was indistinguishable from that of the L1 subjects. These inconsistent relationships were more evident in the correlation coefficients between the brain recording and behavior. However, slower reaction times and non-specific brain responses in the L2 listeners suggest differences in their cortical processes from those of the L1 subjects. These findings suggest that the CP of L2 phonemes as determined by behavioral scores alone does not always predict a language-specific neural processing as employed by the L1 listeners.

Differential cortical responses in second language learners to different vowel contrasts.

Near-infrared spectroscopy was used to measure hemodynamic responses in Korean subjects learning Japanese as a second-language to Japanese phonemic contrasts that are either phonologically distinctive or non-distinctive in their first-language. These results were compared with those of Japanese native listeners reported previously. Unlike the results observed in the Japanese subjects, the Korean subjects did not show category-specific neural responses to a durational contrast that is non-distinctive in their first-language. The /a-e/ contrast elicited the larger response in the left auditory area, consistent with the results of the Japanese. These phoneme-dependent responses imply that the neuronal networks subserving the first and second-languages are either shared or exclusive according to the mutual relationship between the phonemic properties of the first and second-languages.