Hama Watanabe

The right hemisphere of sleeping infant perceives sentential prosody

Behavioral studies proposed that prosodic information in speech sounds plays important roles for human infants to acquire their native languages. Here, we examined the neural basis of prosodic processing in 3-month-old infants. In order to obtain hemodynamic responses with high signal-to-noise ratio, we used near-infrared optical topography in the infants while they were in quiet sleep. First, we observed bilateral activation under each of the normal and flattened speech conditions. The flattened speech sound was created by eliminating changes in the pitch contours of the original utterance. In a direct comparison between the two conditions, the right temporoparietal region showed more prominent activation to normal speech sounds than to flattened speech sounds. This result demonstrates that the localized region of the right hemisphere in 3-month-old infant is involved in the processing of pitch contours. Our findings suggest that prosodic processing in the right hemisphere may facilitate the acquisition of lexical or syntactic knowledge in the early stages of language development.

Development of Global Cortical Networks in Early Infancy

Human cognition and behaviors are subserved by global networks of neural mechanisms. Although the organization of the brain is a subject of interest, the process of development of global cortical networks in early infancy has not yet been clarified. In the present study, we explored developmental changes in these networks from several days to 6 months after birth by examining spontaneous fluctuations in brain activity, using multichannel near-infrared spectroscopy. We set up 94 measurement channels over the frontal, temporal, parietal, and occipital regions of the infant brain. The obtained signals showed complex time-series properties, which were characterized as 1/f fluctuations. To reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of continuous signals between all the pairs of measurement channels. We found that the cortical network organization showed regional dependency and dynamic changes in the course of development. In the temporal, parietal, and occipital regions, connectivity increased between homologous regions in the two hemispheres and within hemispheres; in the frontal regions, it decreased progressively. Frontoposterior connectivity changed to a “U-shaped” pattern within 6 months: it decreases from the neonatal period to the age of 3 months and increases from the age of 3 months to the age of 6 months. We applied cluster analyses to the correlation coefficients and showed that the bilateral organization of the networks begins to emerge during the first 3 months of life. Our findings suggest that these developing networks, which form multiple clusters, are precursors of the functional cerebral architecture.

Prosodic processing in the developing brain.

Speech prosody is considered to be one of the most important sources of information for infants in acquiring their native language. Using multi-channel near-infrared spectroscopy in 10-month-old infants, we examined cortical activation when normal and flattened speech sounds were presented to the infants. The flattened speech sound was generated by eliminating changes in the pitch contours of the original utterance. We found bilateral activation under both speech conditions. In a direct comparison between the two conditions, the right temporal and temporoparietal regions, and bilateral prefrontal regions showed more prominent activation in response to flattened speech than to normal speech. These results demonstrate that the unfamiliar pitch contours of flattened speech induce additional processing in the cortical regions of 10-month-old infants, suggesting that 10-month-old infants already have neural mechanisms for the processing of at least a part of the prosodic structures in their native language. To investigate developmental changes in cortical activation patterns, we compared the present results with those of our previous study using the same paradigm with 3-month-old infants. We propose that speech processing in the infant brain develops from analyzing pitch information per se, to comparing and integrating information in input speech sounds with acquired prosodic structures.

Prefrontal Cortical Involvement in Young Infants’ Analysis of Novelty

Our knowledge of infant perception and cognition is primarily based on habituation and dishabituation, but the underlying neural mechanisms for these processes per se remain unclear. It has been argued that habituation is related to building internal representations of repeated stimuli in the central nervous system, whereas dishabituation is related to an increased attention to novel items and events. This leads to a hypothesis that a distributed network including the sensory, association and prefrontal cortical regions of young infants is involved in those processes, in contrast with the classical developmental view that onset of the functioning of the prefrontal cortex is delayed. Here we examined the time evolution of spatio-temporal hemodynamic responses related to the auditory habituation and dishabituation in the temporal and prefrontal regions of 3-month-old infants by using multichannel near-infrared spectroscopy. We found that the temporal regions remained activated by repetitive auditory stimuli; however, the prefrontal regions exhibited phasic activation in relation to novel stimuli. The dissociated activation pattern between the temporal and prefrontal regions suggests that distinct cortical regions play distinct functional roles in auditory habituation and dishabituation, and that the prefrontal cortex is involved in perceiving invariance or novelty of the immediate environment in early infancy.

A NIRS-fMRI study of resting state network

Resting state functional connectivity, which is defined as temporal correlation of spontaneous activity between diverse brain regions, has been reported to form resting state networks (RSNs), consisting of a specific set of brain regions, based on functional magnetic resonance imaging (fMRI). Recently, studies using near-infrared spectroscopy (NIRS) reported that NIRS signals also show temporal correlation between different brain regions. The local relationship between NIRS and fMRI signals has been examined by simultaneously recording these signals when participants perform tasks or respond to stimuli. However, the NIRS-fMRI signal relationship during the resting state has been reported only between NIRS signals obtained within limited regions and whole brain fMRI signals. Therefore, it remains unclear whether NIRS signals obtained at diverse regions correlate with regional fMRI signals close to the NIRS measurement channels, especially in relation to the RSNs. In this study, we tested whether the signals measured by these different modalities during the resting state have the consistent characteristics of the RSNs. Specifically, NIRS signals during the resting state were acquired over the frontal, temporal, and occipital cortices while whole brain fMRI data was simultaneously recorded. First, by projecting the NIRS channel positions over the cerebral cortical surface, we identified the most likely anatomical locations of all NIRS channels used in the study. Next, to investigate the regional signal relationship between NIRS and fMRI, we calculated the cross-correlation between NIRS signals and fMRI signals in the brain regions adjacent to each NIRS channel. For each NIRS channel, we observed the local maxima of correlation coefficients between NIRS and fMRI signals within a radius of 2 voxels from the projection point. Furthermore, we also found that highly correlated voxels with the NIRS signal were mainly localized within brain tissues for all NIRS channels, with the exception of 2 frontal channels. Finally, by calculating the correlation between NIRS signals at a channel and whole brain fMRI signals, we observed that NIRS signals correlate with fMRI signals not only within brain regions adjacent to NIRS channels but also within distant brain regions constituting RSNs, such as the dorsal attention, fronto-parietal control, and default mode networks. These results support the idea that NIRS signals obtained at several cortical regions during the resting state mainly reflect regional spontaneous hemodynamic fluctuations that originate from spontaneous cortical activity, and include information that characterizes the RSNs. Because NIRS is relatively easy to use and a less physically demanding neuroimaging technique, our findings should facilitate a broad application of this technique to examine RSNs, especially for clinical populations and conditions unsuitable for fMRI.

Functional activation in diverse regions of the developing brain of human infants.

To understand the functional organization of the human cortex during the early postnatal period, we performed neuroimaging studies for visual perception in awake 3-month-old infants. Cortical hemodynamic responses to 2 different video images, moving mobile objects and black-and-white checkerboard pattern reversals, were observed using multichannel near-infrared spectroscopy (NIRS). Although a focal region of the occipital cortex was equally activated by both stimuli, the occipitotemporal region was activated only by the mobile objects. A possible explanation of the result is that the former and the latter regions are involved in the primary processing of visual stimuli and perception of objects with complex visual features, respectively. Furthermore, the prefrontal region was distinctly activated by the mobile objects. These results suggest that the early sensory region and the higher sensory/association and prefrontal regions are functionally differentiated by 3 months of age and that diverse regions of the cortex including the prefrontal region function during perception of visual events.

Effects of source-detector distance of near infrared spectroscopy on the measurement of the cortical hemodynamic response in infants

One of the practical problems in neuroimaging using near infrared spectroscopy (NIRS) is to choose an appropriate source-detector distance to maximize the sensitivity to cerebral blood oxygenation and to improve the spatial resolution for mapping cortical activation. While NIRS has attracted increasing attention in neuroimaging in infants, there has been no report of comparative data regarding source-detector distance for the infant brain. In the present study, 9 quietly sleeping 3-month-old infants were exposed to 3-s speech sounds, and hemodynamic responses over the bilateral temporal cortices were assessed by using multiple pairs of source and detector of NIR light with varying distances (1, 2, 3 and 4 cm) and varying intensities (0.6 and 1.2 mW). The statistical analyses of the group-averaged hemodynamic responses and the frequency analyses of the signal-to-noise ratios revealed that a 2-cm source-detector distance with 0.6-mW NIR light provided the highest sensitivity to cortical responses. This indicates that NIRS can be used to detect the activation of the cortical regions, in the infant brain, by using the source-detector distance scaled to the smaller head size of infants and a relatively low intensity of NIR light compared to the ones that have been routinely used in adult studies.

Large-Scale Brain Networks Underlying Language Acquisition in Early Infancy

A critical issue in human development is that of whether the language-related areas in the left frontal and temporal regions work as a functional network in preverbal infants. Here, we used 94-channel near-infrared spectroscopy to reveal the functional networks in the brains of sleeping 3-month-old infants with and without presenting speech sounds. During the first 3 min, we measured spontaneous brain activation (period 1). After period 1, we provided stimuli by playing Japanese sentences for 3 min (period 2). Finally, we measured brain activation for 3 min without providing the stimulus (period 3), as in period 1. We found that not only the bilateral temporal and temporoparietal regions but also the prefrontal and occipital regions showed oxygenated hemoglobin signal increases and deoxygenated hemoglobin signal decreases when speech sounds were presented to infants. By calculating time-lagged cross-correlations and coherences of oxy-Hb signals between channels, we tested the functional connectivity for the three periods. The oxy-Hb signals in neighboring channels, as well as their homologous channels in the contralateral hemisphere, showed high correlation coefficients in period 1. Similar correlations were observed in period 2; however, the number of channels showing high correlations was higher in the ipsilateral hemisphere, especially in the anterior–posterior direction. The functional connectivity in period 3 showed a close relationship between the frontal and temporal regions, which was less prominent in period 1, indicating that these regions form the functional networks and work as a hysteresis system that has memory of the previous inputs. We propose a hypothesis that the spatiotemporally large-scale brain networks, including the frontal and temporal regions, underlie speech processing in infants and they might play important roles in language acquisition during infancy.

Spatiotemporal properties of cortical haemodynamic response to auditory stimuli in sleeping infants revealed by multi-channel near-infrared spectroscopy

Multi-channel near-infrared spectroscopy (NIRS) has been used as a neuroimaging tool to study functional activation of the developing brain in infants. In this paper, we focus on spatiotemporal dynamics of cortical oxygenation changes during sensory processing in young infants. We use a 94-channel NIRS system to assess the activity of wide regions of the cortex in quietly sleeping three-month-old infants. Auditory stimuli composed of a random sequence of pure tones induced haemodynamic changes not only in the temporal auditory regions, but also in the occipital and frontal regions. Analyses of phase synchronization showed that mutual synchronizations of signal changes among the cortical regions were much stronger than the stimulus-induced synchronizations of signal changes. Furthermore, analyses of phase differences among cortical regions revealed phase advancement of the bilateral temporal auditory regions, and phase gradient in a posterior direction from the temporal auditory regions to the occipital regions and in an anterior direction within the frontal regions. We argue that multi-channel NIRS is capable of detecting the precise timing of cortical activation and its flow in the global network of the developing brain.

Functional connectivity of the cortex of term and preterm infants and infants with Down's syndrome

Near-infrared spectroscopy (NIRS) imaging studies have revealed the functional development of the human brain in early infancy. By measuring spontaneous fluctuations in cerebral blood oxygenation with NIRS, we can examine the developmental status of the functional connectivity of networks in the cortex. However, it has not been clarified whether premature delivery and/or chromosomal abnormalities affect the development of the functional connectivity of the cortex. In the current study, we investigated the spontaneous brain activity of sleeping infants who were admitted to a neonatal intensive care unit at term age. We classified them into the 3 following infant groups: (i) term-or-late-preterm, (ii) early-preterm, and (iii) Downs syndrome (DS). We used multichannel NIRS to measure the spontaneous changes in oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) at 10 measurement channels, which covered the frontal, temporal, and occipital regions. In order to reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of the time-course signals among all of the pairs of measurement channels. The functional connectivity was classified into the 4 following types: (i) short-range, (ii) contralateral-transverse, (iii) ipsilateral-longitudinal, and (iv) control. In order to examine whether the local properties of hemodynamics reflected any pathological conditions, we calculated the phase differences between the oxy- and deoxy-Hb time-course signals in the 3 groups. The statistical analyses of the functional connectivity data showed main effects of group and the types of connectivity. For the group effect, the mean functional connectivity of the infants in the term-or-late-preterm group did not differ from that in the early-preterm group, and the mean functional connectivity of the infants in the DS group was lower than that in the other 2 groups. For the effect of types of connectivity, short-range connectivity was highest compared to any of the other types of connectivity, and the second highest connectivity was the contralateral-transverse one. The phase differences between the oxy- and deoxy-Hb changes showed that there were significant differences between the DS group and the other 2 groups. Our findings suggested that the development of the functional connectivity of cortical networks did not differ between term-or-late-preterm infants and early-preterm infants around term-equivalent ages, while DS infants had alterations in their functional connectivity development and local hemodynamics at term age. The highest short-range connectivity and the second highest contralateral-transverse connectivity suggested that the precursors for the basic cortical networks of functional connectivity were present at term age.