Oscillator decomposition of infant fNIRS data.

The functional near-infrared spectroscopy (fNIRS) can detect hemodynamic responses in the brain and the data consist of bivariate time series of oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) on each channel. In this study, we investigate oscillatory changes in infant fNIRS signals by using the oscillator decompisition method (OSC-DECOMP), which is a statistical method for extracting oscillators from time series data based on Gaussian linear state space models. OSC-DECOMP provides a natural decomposition of fNIRS data into oscillation components in a data-driven manner and does not require the arbitrary selection of band-pass filters. We analyzed 18-ch fNIRS data (3 minutes) acquired from 21 sleeping 3-month-old infants. Five to seven oscillators were extracted on most channels, and their frequency distribution had three peaks in the vicinity of 0.01-0.1 Hz, 1.6-2.4 Hz and 3.6-4.4 Hz. The first peak was considered to reflect hemodynamic changes in response to the brain activity, and the phase difference between oxy-Hb and deoxy-Hb for the associated oscillators was at approximately 230 degrees. The second peak was attributed to cardiac pulse waves and mirroring noise. Although these oscillators have close frequencies, OSC-DECOMP can separate them through estimating their different projection patterns on oxy-Hb and deoxy-Hb. The third peak was regarded as the harmonic of the second peak. By comparing the Akaike Information Criterion (AIC) of two state space models, we determined that the time series of oxy-Hb and deoxy-Hb on each channel originate from common oscillatory activity. We also utilized the result of OSC-DECOMP to investigate the frequency-specific functional connectivity. Whereas the brain oscillator exhibited functional connectivity, the pulse waves and mirroring noise oscillators showed spatially homogeneous and independent changes. OSC-DECOMP is a promising tool for data-driven extraction of oscillation components from biological time series data.

Neurovascular, Metabolic, and Glymphatic Dynamics of the Brain Measured with fNIRS.

We developed a multidistance and multiwavelength continuous wave NIRS instrument to detect dynamic changes in oxygenated and deoxygenated hemoglobin (oxy- and deoxy-Hb), oxidized cytochrome-c-oxidase (oxCCO) and water of the brain and muscle. We performed measurements of the forehead during resting state and paced breathing and of the forearm during ischemic challenge in human adults. Time series analysis focusing on rhythmic signals over different time scales and different depths of the tissue revealed specific patterns of phase relationships among the signals in each of the measurement. This method can be a promising tool to understand the dynamic interaction among the neurovascular, metabolic and glymphatic system in a wide variety of subject fields.

Anticipatory regulation of cardiovascular system on the emergence of auditory-motor interaction in young infants.

Humans develop auditory-motor interaction to produce a variety of rhythmic sounds using body movements, which are often produced and amplified with tools, such as drumming. The extended production of sounds allows us to express a wide range of emotions, accompanied by physiological changes. According to previous studies, even young infants enhance movements in response to auditory feedback. However, their exhibition of physiological adaptation on the emergence of auditory-motor interaction is unclear. We investigated the movement and cardiac changes associated with auditory feedback to spontaneous limb movements in 3-month-old infants. The results showed that infants increased the frequency of limb movements inducing auditory feedback, while they exhibited a more regular rhythm of the limb movements. Furthermore, heart rate increase associated with the limb movement was first inhibited immediately after the timing of the auditory feedback, which may reflect sustained attention to the auditory stimuli. Then, through auditory-motor experience, the heart rate increase was inhibited even prior to the auditory feedback, leading to suppression of the peak intensity of the heart rate increase. These findings suggest that young infants regulate the cardiovascular system as well as limb movements in anticipation of the auditory feedback. The anticipatory regulation associated with movement and attentional changes may contribute to reduced cardiovascular stress in auditory-motor interaction, and provide a developmental basis for more sophisticated goal-directed behavior of producing rhythmic sounds.

Multiple patterns of infant rolling in limb coordination and ground contact pressure.

Infants acquire the ability to roll over from the supine to the prone position, which requires body coordination of multiple degrees of freedom under dynamic interactions with the ground. Although previous studies on infant rolling observed kinematic characteristics, little is known about the kinetic characteristics of body segments in contact with the surface. We measured the ground contact pressure under the arms, legs, head, and proximal body segments using a pressure mat and their displacements using a three-dimensional motion capture system. The data obtained from 17 infants aged 9-10 months indicated that most of them showed 2-4 of 6 highly observed movement patterns, including 1 axial rolling, 2 spinal flexion, and 3 shoulder girdle leading patterns. The arms and legs had small contributions to the ground contact pressure in the axial rolling and spinal flexion patterns. The ipsilateral leg in relation to the rolling direction was involved in supporting the body weight in only 1 shoulder girdle leading pattern. The contralateral leg showed large peak pressure to push on the floor before rolling in 3 shoulder girdle leading patterns. The results indicate that infants can produce multiple rolling-over patterns with different strategies to coordinate their body segments and interact with the floor. The results of the analysis of the movement patterns further suggest that few patterns correspond to those reported in adults. This implies that infants generate unique motor patterns by taking into account their own biomechanical constraints.

Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS.

A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants.

Developmental changes in cortical sensory processing during wakefulness and sleep.

Infants are exposed to auditory and visual information during sleep as well as wakefulness. Little is known, however, about the differences in cortical processing of sensory input between these different behavioral states. In the present study, cortical hemodynamic responses to auditory and visual stimuli during wakefulness and sleep were measured in infants aged 2-10 months using functional near-infrared spectroscopy (fNIRS). While asynchronously presented auditory and visual stimuli during wakefulness induced focal responses in the corresponding sensory regions of the occipital and temporal cortices, the responses to the same stimuli during sleep were dramatically different. Auditory stimuli during sleep induced global responses over the frontal, temporal, and occipital regions, and the response pattern did not change between 2 and 10 months of age. In contrast, visual stimuli during sleep induced responses in the occipital cortex, and the response pattern exhibited developmental changes from a pattern of activation to one of deactivation around a half year of age. The functional connectivity among the cortical regions was generally higher during sleep than during wakefulness. The hemoglobin phase of oxygenation and deoxygenation (hPod) and the phase locking index of hPod (hPodL) showed general developmental changes and behavioral state dependent differences but no significant differences were seen between the stimulus types. The results suggest that the behavioral states have a fundamental impact on cortical sensory processing; (1) sensory processing during wakefulness is performed in more localized regions, (2) auditory processing is active during both wakefulness and sleep, (3) visual processing undergoes development of inhibitory mechanisms during sleep, and (4) these phenomena primarily reflect neural development rather than vascular and metabolic development.

Early motor signs of autism spectrum disorder in spontaneous position and movement of the head.

We examined the characteristics of spontaneous movements at 9-20 weeks postterm age in very low birth-weight infants who later developed autism spectrum disorder (ASD). We analyzed video recordings of spontaneous movements of 39 children who had no clinical issues [typically developing (TD) group], 21 children who showed developmental delay, and 14 children who were diagnosed with ASD (ASD group) at 6 years of age. Head position in each video frame was classified by visual inspection. The percentage of midline head position (PMHP) and number of changes in head position were calculated. Spontaneous limb movements were quantified using six indices. The values of PMHP were significantly lower in the ASD group than in the TD group. The lower PMHP during early infancy is associated with later development of ASD. Poorer performance in maintaining midline position of the head at this period may distinguish infants who later develop ASD from those who show TD.

Movement patterns of limb coordination in infant rolling.

Infants must perform dynamic whole-body movements to initiate rolling, a key motor skill. However, little is known regarding limb coordination and postural control in infant rolling. To address this lack of knowledge, we examined movement patterns and limb coordination during rolling in younger infants (aged 5-7 months) that had just begun to roll and in older infants (aged 8-10 months) with greater rolling experience. Due to anticipated difficulty in obtaining measurements over the second half of the rolling sequence, we limited our analysis to the first half. Ipsilateral and contralateral limbs were identified on the basis of rolling direction and were classified as either a stationary limb used for postural stability or a moving limb used for controlled movement. We classified the observed movement patterns by identifying the number of stationary limbs and the serial order of combinational limb movement patterns. Notably, older infants performed more movement patterns that involved a lower number of stationary limbs than younger infants. Despite the wide range of possible movement patterns, a small group of basic patterns dominated in both age groups. Our results suggest that the fundamental structure of limb coordination during rolling in the early acquisition stages remains unchanged until at least 8-10 months of age. However, compared to younger infants, older infants exhibited a greater ability to select an effective rotational movement by positioning themselves with fewer stationary limbs and performing faster limb movements.

Developmental changes in intralimb coordination during spontaneous movements of human infants from 2 to 3 months of age.

Human infants show a variety of spontaneous movements in the first few months of life. Although the pattern of spontaneous movements changes at approximately 2 months of age, the precise mechanism that governs the developmental changes in intralimb coordination remains unclear. In the present study, we focused on knee-ankle coordination during spontaneous movements of human infants from 2 to 3 months of age. Multiple attitude sensors were used to measure three-dimensional angular motion of knee and ankle joint motions. We acquired a one-dimensional time series of the knee joint angle around the putative hinge joint and a two-dimensional time series of ankle motions on the putative sagittal and frontal plane. First, we found that 3-month-old infants show a significant predominance to extend their knee joints, remarkably so on the left side. To quantify dissociated motions of the knee and ankle, we calculated the temporal correlation and the regression slope between them. We observed that 3-month-old infants moved their ankle joints more independently of knee motions than 2-month-old infants. Finally, we found that dissociated motions of the knee and ankle simultaneously develop with knee extension predominance. The developmental change from synchronization to dissociation of intralimb joint movements during spontaneous movements suggests that the development of the cortical and/or subcortical mechanism may mediate selective activation and inhibition of joint motions at approximately 2 months of age.

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) Down's 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.

Decomposition of spontaneous movements of infants as combinations of limb synergies.

We hypothesized that a variety of limb movements in infants, including spontaneous movements and movements during interactions with the environment, can be represented as combinations of limb synergies, which are building blocks for generating coordinated movements of multiple limbs. A decomposition algorithm based on a nonnegative matrix factorization was applied to the discrete data segments taken from continuous data of limb movements in 298 infants (age, 3-4 months). The data were linearly decomposed into bases, which were referred to as synergies. The results showed that approximately 70% of the variance in the velocity profiles of the data segments of the four limbs can be explained by a set of five simple synergies that represent single-limb movements and the synchronous movement of all limbs. The present method showed that the complex properties of limb movements can be represented as combinations of synergies. Furthermore, comparisons of movement patterns across different age groups showed that in older infants, the contribution ratios of each synergy were different between spontaneous movements and movements during playing with a toy, whereas in younger infants, there were no differences in the contribution ratios between the different movement conditions. These results demonstrate that decomposition into limb synergies is useful for determining the spatiotemporal properties of interlimb coordination during spontaneous movements and task-constrained movements in infants.

Effect of auditory input on activations in infant diverse cortical regions during audiovisual processing.

A fundamental question with regard to perceptual development is how multisensory information is processed in the brain during the early stages of development. Although a growing body of evidence has shown the early emergence of modality-specific functional differentiation of the cortical regions, the interplay between sensory inputs from different modalities in the developing brain is not well understood. To study the effects of auditory input during audio-visual processing in 3-month-old infants, we evaluated the spatiotemporal cortical hemodynamic responses of 50 infants while they perceived visual objects with or without accompanying sounds. The responses were measured using 94-channel near-infrared spectroscopy over the occipital, temporal, and frontal cortices. The effects of sound manipulation were pervasive throughout the diverse cortical regions and were specific to each cortical region. Visual stimuli co-occurring with sound induced the early-onset activation of the early auditory region, followed by activation of the other regions. Removal of the sound stimulus resulted in focal deactivation in the auditory regions and reduced activation in the early visual region, the association region of the temporal and parietal cortices, and the anterior prefrontal regions, suggesting multisensory interplay. In contrast, equivalent activations were observed in the lateral occipital and lateral prefrontal regions, regardless of sound manipulation. Our findings indicate that auditory input did not generally enhance overall activation in relation to visual perception, but rather induced specific changes in each cortical region. The present study implies that 3-month-old infants may perceive audio-visual multisensory inputs by using the global network of functionally differentiated cortical regions.

Specific characteristics of spontaneous movements in preterm infants at term age are associated with developmental delays at age 3 years.

AIM: The aim of this study was to investigate the relationship between the characteristics of spontaneous movements in preterm infants at term age and developmental delay at 3 years of age. METHOD: We analysed video recordings of the spontaneous movements in the supine position of 124 preterm infants (44 males, 80 females) at 36 to 44 weeks postmenstrual age (PMA). The infants were born preterm (22-36wks PMA; birthweight 489-1696g) and had not received a diagnosis of a neurological or developmental disorder by the age of 3 years. The recorded spontaneous movements were quantified using six movement indices, which were calculated from two-dimensional trajectories of all limbs. The infants were divided into three developmental groups, normal, borderline, or delayed, based on their developmental quotient as calculated using the Kyoto Scale of Psychological Development 2001 (Kyoto Scale) at 3 years of age. Group differences in the movement indices were analysed. RESULTS: In the delayed group, average velocity of arms and legs were significantly lower (p<0.05 and p<0.01 respectively), the numbers of movement units of arms and legs were significantly lower (p<0.05 and p<0.01 respectively), kurtosis of acceleration of arms and legs was significantly higher (p<0.05 in each case), and correlation between limb velocities was higher (p<0.05) than in the normal group. INTERPRETATION: In children who exhibited developmental delay at 3 years of age, the spontaneous movements at term age can be described as less active with intermittent occurrences of abrupt and synchronized movements of the limbs. Recognition of these characteristics of spontaneous movements at term age may be used as a predictor for subsequent cognitive and behavioural development in preterm infants.

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 development in the infant brain for auditory pitch processing.

Understanding how the developing brain processes auditory information is a critical step toward the clarification of infants' perception of speech and music. We have reported that the infant brain perceives pitch information in speech sounds. Here, we used multichannel near-infrared spectroscopy to examine whether the infant brain is sensitive to information of pitch changes in auditory sequences. Three types of auditory sequences with distinct temporal structures of pitch changes were presented to 3- and 6-month-old infants: a long condition of 12 successive tones constructing a chromatic scale (600 ms), a short condition of four successive tones constructing a chromatic scale (200 ms), and a random condition of random tone sequences (50 ms per tone). The difference among the conditions was only in the sequential order of the tones, which causes pitch changes between the successive tones. We found that the bilateral temporal regions of both ages of infants showed significant activation under the three conditions. The stimulus-dependent activation was observed in the right temporoparietal region of the both infant groups; the 3- and 6-month-old infants showed the most prominent activation under the random and short conditions, respectively. Our findings indicate that the infant brain, which shows functional differentiation and lateralization in auditory-related areas, is capable of responding to more than single tones of pitch information. These results suggest that the right temporoparietal region of the infants increases sensitivity to auditory sequences, which have temporal structures similar to those of syllables in speech sounds, in the course of development.

Increasing selectivity of interlimb coordination during spontaneous movements in 2- to 4-month-old infants.

In the field of motor development, a question exists whether spontaneous activity in early infancy serves as a precursor to later-emerging goal-directed behaviors. To answer this question, it is necessary to investigate in detail the properties of spontaneous movements in individual infants. In the current study, we longitudinally examined the spontaneous movements of the end points of the limbs in 6 infants aged 2-4 months. Examinations were carried out every week by using a motion analysis system, and the number of recordings performed for each infant varied from 6 to 9 times. Our major finding was that there was an age-related increase in the velocity and position correlation between arms and between legs, whereas there was no significant change in the velocity, duration, and amplitude of movements of individual limbs. That is, the pattern of spontaneous movements changes from a general activity involving all the limbs to an activity involving more selective interlimb coordination from 2 to 4 months of age. These findings suggest that the dissociated movements of a selective combination of arms or legs during spontaneous movements may be a precursor to functionally dissociated movements during goal-directed behaviors.

Activation and deactivation in response to visual stimulation in the occipital cortex of 6-month-old human infants.

In an infant's developing cortex, the explanation for the mechanisms underlying the activations and deactivations in response to visual stimuli remains controversial. While previous near-infrared spectroscopy (NIRS) studies in awake infants have demonstrated cortical activations in response to meaningful/attractive visual stimuli, functional magnetic resonance imaging (fMRI) studies performed on sleeping infants showed negative blood oxygenation level-dependent (BOLD) responses to high-luminance unpatterned stimulations, such as a photic stimulation. To examine the effect of the characteristics of visual stimuli on cortical processing in awake infants, we measured cortical hemodynamic responses in 6-month-old infants during the presentation of a high-luminance unpatterned stimulus by using a NIRS system with 94 measurement channels. Results from 35 infants showed dissociated cortical responses between the occipital region and the other parts of the cortex, including the temporal and prefrontal regions. Although the visual stimulus produced sustained increases in oxygenated hemoglobin (oxy-Hb) signals in the temporal and prefrontal regions, it produced a transient increase in oxy-Hb signals followed by a salient decrease in oxy-Hb signals during a trial in a focal region of the occipital visual region. This suggests that the deactivation of the occipital visual region in response to visual stimulation is not a phenomenon that occurs only in the sleeping state, but that a high-luminance unpatterned stimulus can induce deactivation even in the awake infants.

Individual variability in the nonlinear development of the corpus callosum during infancy and toddlerhood: a longitudinal MRI analysis.

The human brain spends several years bootstrapping itself through intrinsic and extrinsic modulation, thus gradually developing both spatial organization and functions. Based on previous studies on developmental patterns and inter-individual variability of the corpus callosum (CC), we hypothesized that inherent variations of CC shape among infants emerge, depending on the position within the CC, along the developmental timeline. Here we used longitudinal magnetic resonance imaging data from infancy to toddlerhood and investigated the area, thickness, and shape of the midsagittal plane of the CC by applying multilevel modeling. The shape characteristics were extracted using the Procrustes method. We found nonlinearity, region-dependency, and inter-individual variability, as well as intra-individual consistencies, in CC development. Overall, the growth rate is faster in the first year than in the second year, and the trajectory differs between infants; the direction of CC formation in individual infants was determined within six months and maintained to two years. The anterior and posterior subregions increase in area and thickness faster than other subregions. Moreover, we clarified that the growth rate of the middle part of the CC is faster in the second year than in the first year in some individuals. Since the division of regions exhibiting different tendencies coincides with previously reported divisions based on the diameter of axons that make up the region, our results suggest that subregion-dependent individual variability occurs due to the increase in the diameter of the axon caliber, myelination partly due to experience and axon elimination during the early developmental period.

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.

Frequency-specific functional connectivity in the brain during resting state revealed by NIRS.

Analyses of spontaneous hemodynamic fluctuations observed on functional magnetic resonance imaging (fMRI) have revealed the existence of temporal correlations in signal changes between widely separated brain regions during the resting state, termed "resting state functional connectivity." Recent studies have demonstrated that these correlations are also present in the hemodynamic signals measured by near infrared spectroscopy (NIRS). However, it is still uncertain whether frequency-specific characteristics exist in these signals. In the present study, we used multichannel NIRS to investigate the frequency dependency of functional connectivity between diverse regions in the cerebral cortex by decomposing fluctuations of oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) signals into various frequency bands. First, within a wide frequency range (0.009-0.1Hz), we observed that both oxy-Hb and deoxy-Hb signals showed functional connectivity within local regions and between contralateral hemispheric regions of the cortex. Next, by decomposing measured fluctuations into narrower frequency components, we determined that only oxy-Hb signals showed frequency-specific functional connectivity between the frontal and occipital regions, emerging in a narrow frequency range (0.04-0.1Hz). To clarify the coherency of functional connectivity, we calculated the average coherence values between selected channel pairs. This approach demonstrated that functional connectivity based on the oxy-Hb signals between homologous cortical regions of the contralateral hemisphere (homologous connectivity) showed high coherence over a wide frequency range (0.009-0.1Hz), whereas connectivity between the prefrontal and occipital regions (fronto-posterior connectivity) showed high coherence only within a specific narrow frequency range (0.04-0.1Hz). Our findings suggest that homologous connectivity may reflect synchronization of neural activation over a wide frequency range through direct neuroanatomical connections, whereas fronto-posterior connectivity as revealed by high coherence only within a specific narrow frequency range corresponding to the time scale of typical hemodynamic response to a single event may reflect synchronization of transient neural activation among distant cortical regions. The present study demonstrated that NIRS provides a powerful tool to elucidate network properties of the cortex during resting state.