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.

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.

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.

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.

Wearable strain sensor suit for infants to measure limb movements under interaction with caregiver.

Development of motion capture technology has enabled the measurement of body movements over long periods of time in daily life. Although accelerometers have been used as primary sensors, problems arise when they are used to measure the movements of infants. Because infants and caregivers interact frequently, accelerometer data from infants may be significantly distorted by a caregiver's movement. To overcome this problem, a strain sensor suit was developed for infants to measure flexion and extension movements of the limbs. A case study was performed to analyze the strain sensor data of an infant in relation to the accelerometer data of the infant's and a caregiver's body under various types of infant-caregiver interaction. The results demonstrated that the strain sensor data had low correlation with the accelerometer data of the infant and caregiver while the accelerometer data between infant and caregiver had higher correlation. This suggests that the strain sensor is suitable to detect limbs' angular displacements mostly independent from the translational body movements exerted by a caregiver.

Evaluation of Fidgety Movements of Infants Based on Gestalt Perception Reflects Differences in Limb Movement Trajectory Curvature.

BACKGROUND: Infants aged 2 to 5 months show spontaneous general movements (GMs) of the whole body, which are referred to as fidgety movements (FMs). Although previous studies have shown that evaluation of GMs by the General Movement Assessment (GMA) has predictive value about later neurological impairments, it remains unknown whether raters consistently perceive and rate such complex kinematic information. OBJECTIVE: The purpose of this study was to construct a method to reveal which movement features are associated with each rater's evaluation of FMs based on the GMA. DESIGN: GMA scores of 163 healthy infants aged 11 to 16 weeks postterm were matched with data obtained from a 3-dimensional motion analysis system. METHODS: Three physical therapists performed the GMA and classified GMs into 9 types, from which we focused on 3 subtypes differing in the temporal organization of FMs (continual, intermittent, and sporadic FMs). We also calculated 6 movement indices (average velocity of limb movements, number of movement units, kurtosis of acceleration, jerk index, average curvature, and correlation between limb velocities) for arms and legs for each infant and analyzed which movement indices were associated with the ratings of the 3 FM subtypes by each rater. RESULTS: Only the average curvature differed significantly among the ratings of the 3 FM subtypes for all 3 raters. Each rater showed significant differences in the average curvature in either arms or legs. LIMITATIONS: It is difficult to generalize the present results to raters with various levels of expertise and experience in using the GMA. This issue calls for further research. CONCLUSIONS: The method used revealed commonality and individuality about the perceived movement features that can be associated with the rating of FMs.

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.

Spatial variation in the hemoglobin phase of oxygenation and deoxygenation in the developing cortex of infants.

Spontaneous low-frequency oscillatory changes in oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) are observed using functional near-infrared spectroscopy (fNIRS). A previous study showed that the time-averaged phase difference between oxy-Hb and deoxy-Hb changes, referred to as hemoglobin phase of oxygenation and deoxygenation (hPod), is sensitive to the development of the cortex. We examined phase-locking index of hPod, referred to as [Formula: see text], in addition to hPod, in neonates and 3- and 6-month-old infants using the 94-channel fNIRS data, which covered large lateral regions of the cortex. The results showed that (1) developmental changes in hPod exhibited spatial dependency; (2) [Formula: see text] increased between the neonate group and 3-month-old infant group over the posterior, but not anterior, regions of the cortex; and (3) the cortical regions of each age group were clustered in several domains with specific characteristics of hPod and [Formula: see text]. This study indicates that the neonatal cortex is composed of regions with specific characteristics of hPod and [Formula: see text], and drastic changes occur between the neonatal period and 3 months of age. This study suggests that hPod and [Formula: see text] are sensitive to the cortical region-specific development of the circulatory, blood flow, metabolic, and neurovascular functions in young infants.

Macroanatomical Landmarks Featuring Junctions of Major Sulci and Fissures and Scalp Landmarks Based on the International 10-10 System for Analyzing Lateral Cortical Development of Infants.

The topographic relationships between the macroanatomical structure of the lateral cortex, including sulci and fissures, and anatomical landmarks on the external surface of the head are known to be consistent. This allows the coregistration of EEG electrodes or functional near-infrared spectroscopy over the scalp with underlying cortical regions. However, limited information is available as to whether the topographic relationships are maintained in rapidly developing infants, whose brains and heads exhibit drastic growth. We used MRIs of infants ranging in age from 3 to 22 months old, and identified 20 macroanatomical landmarks, featuring the junctions of major sulci and fissures, as well as cranial landmarks and virtually determined positions of the international 10-20 and 10-10 systems. A Procrustes analysis revealed developmental trends in changes of shape in both the cortex and head. An analysis of Euclidian distances between selected pairs of cortical landmarks at standard stereotactic coordinates showed anterior shifts of the relative positions of the premotor and parietal cortices with age. Finally, cortical landmark positions and their spatial variability were compared with 10-10 landmark positions. The results indicate that variability in the distribution of each macroanatomical landmark was much smaller than the pitch of the 10-10 landmarks. This study demonstrates that the scalp-based 10-10 system serves as a good frame of reference in infants not only for assessing the development of the macroanatomy of the lateral cortical structure, but also for functional studies of cortical development using transcranial modalities such as EEG and fNIRS.

Acquisition of vowel articulation in childhood investigated by acoustic-to-articulatory inversion.

While the acoustical features of speech sounds in children have been extensively studied, limited information is available as to their articulation during speech production. Instead of directly measuring articulatory movements, this study used an acoustic-to-articulatory inversion model with scalable vocal tract size to estimate developmental changes in articulatory state during vowel production. Using a pseudo-inverse Jacobian matrix of a model mapping seven articulatory parameters to acoustic ones, the formant frequencies of each vowel produced by three Japanese children over time at ages between 6 and 60 months were transformed into articulatory parameters. We conducted the discriminant analysis to reveal differences in articulatory states for production of each vowel. The analysis suggested that development of vowel production went through gradual functionalization of articulatory parameters. At 6-9 months, the coordination of position of tongue body and lip aperture forms three vowels: front, back, and central. At 10-17 months, recruitments of jaw and tongue apex enable differentiation of these three vowels into five. At 18 months and older, recruitment of tongue shape produces more distinct vowels specific to Japanese. These results suggest that the jaw and tongue apex contributed to speech production by young children regardless of kinds of vowel. Moreover, initial articulatory states for each vowel could be distinguished by the manner of coordination between lip and tongue, and these initial states are differentiated and refined into articulations adjusted to the native language over the course of development.

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.

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.

MinR 10/20 system: Quantitative and reproducible cranial landmark setting method for MRI based on minimum initial reference points.

BACKGROUND: The international 10/20 system is not only a fundamental method for describing positioning for electroencephalography (EEG), but also provides intermediate cranial landmarks for the probabilistic spatial registration methods that use a reference-MRI database. However, the presence of the inion, one of the four initial reference landmarks of the international 10/20 system, is inconspicuous and can be difficult to locate on MRIs. NEW METHOD: The MinR 10/20 system utilizes only three initial reference points, the nasion (Nz) and the right and left preauricular points (AR and AL), but does not employ the inion (Iz). With the MinR 10/20 system, first the most posterior point on the occipital protuberance, IIz (Imitated Iz), is identified as an exploratory alternative to the Iz point. Next, the other landmarks are calculated according to the conventional international 10/20 system referring to these four reference points (Nz, AL, AR and IIz). RESULTS: Holistic tendencies for landmark position estimations on the heads and cortices in MNI space did not vary greatly between MinR and international 10/20 systems. COMPARISON WITH EXISTING METHODS: A comparison of MinR and international 10/20 systems applied to seventeen adult head MRIs revealed little variance in holistic tendencies for landmark position estimations on head and cortex surfaces in the MNI coordinate system. Furthermore, variability was smaller with the MinR 10/20 system than with the conventional international 10/20 system. CONCLUSIONS: The MinR 10/20 system proved to be a practical alternative to the conventional international 10/20 system in modern computational spatial analysis for scalp-based brain mapping methods.

Jerky spontaneous movements at term age in preterm infants who later developed cerebral palsy.

BACKGROUND: Assessment of spontaneous movements in infants has been a powerful predictor of cerebral palsy (CP). Recent advancements on computer-based video analysis can provide detailed information about the properties of spontaneous movements. AIMS: The aim of this study was to investigate the relationship between spontaneous movements of the 4 limbs at term age and the development of CP at 3 years of age by using a computer-based video analysis system. STUDY DESIGN AND SUBJECTS: We analyzed video recordings of spontaneous movements at 36-44 weeks postmenstrual age (PMA) for 145 preterm infants who were born preterm (22-36 weeks PMA with birthweights of 460-1498g). Sixteen of the infants developed CP by 3 years of age, while 129 developed normally. We compared 6 movement indices calculated from 2-dimensional trajectories of all limbs between the 2 groups. RESULTS: We found that the indices of jerkiness were higher in the CP group than in the normal group (p<0.1 for arms and p<0.01 for legs). No decline was observed in the average velocity and number of movement units in the CP group compared with to the normal group. CONCLUSIONS: Jerkiness of spontaneous movements at term age provides additional information for predicting CP in infants born preterm.

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.

Precursors of dancing and singing to music in three- to four-months-old infants.

Dancing and singing to music involve auditory-motor coordination and have been essential to our human culture since ancient times. Although scholars have been trying to understand the evolutionary and developmental origin of music, early human developmental manifestations of auditory-motor interactions in music have not been fully investigated. Here we report limb movements and vocalizations in three- to four-months-old infants while they listened to music and were in silence. In the group analysis, we found no significant increase in the amount of movement or in the relative power spectrum density around the musical tempo in the music condition compared to the silent condition. Intriguingly, however, there were two infants who demonstrated striking increases in the rhythmic movements via kicking or arm-waving around the musical tempo during listening to music. Monte-Carlo statistics with phase-randomized surrogate data revealed that the limb movements of these individuals were significantly synchronized to the musical beat. Moreover, we found a clear increase in the formant variability of vocalizations in the group during music perception. These results suggest that infants at this age are already primed with their bodies to interact with music via limb movements and vocalizations.