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.

Geodesic theory of long association fibers arrangement in the human fetal cortex.

Association fibers connect different areas of the cerebral cortex over long distances and integrate information to achieve higher brain functions, particularly in humans. Prototyped association fibers are developed to the respective tangential direction throughout the cerebral hemispheres along the deepest border of the subplate during the fetal period. However, how guidance to remote areas is achieved is not known. Because the subplate is located below the cortical surface, the tangential direction of the fibers may be biased by the curved surface geometry due to Sylvian fissure and cortical poles. The fiber length can be minimized if the tracts follow the shortest paths (geodesics) of the curved surface. Here, we propose and examine a theory that geodesics guide the tangential direction of long association fibers by analyzing how geodesics are spatially distributed on the fetal human brains. We found that the geodesics were dense on the saddle-shaped surface of the perisylvian region and sparse on the dome-shaped cortical poles. The geodesics corresponded with the arrangement of five typical association fibers, supporting the theory. Thus, the geodesic theory provides directional guidance information for wiring remote areas and suggests that long association fibers emerge from minimizing their tangential length in fetal brains.

Dynamical systems model of development of the action differentiation in early infancy: a requisite of physical agency.

Young infants are sensitive to whether their body movements cause subsequent events or not during the interaction with the environment. This ability has been revealed by empirical studies on the reinforcement of limb movements when a string is attached between an infant limb and a mobile toy suspended overhead. A previous study reproduced the experimental observation by modeling both the infant's limb and a mobile toy as a system of coupled oscillators. The authors then argued that emergence of agency could be explained by a phase transition in the dynamical system: from a weakly coupled state to a state where the both movements of the limb and the toy are highly coordinated. However, what remains unexplained is the following experimental observation: When the limb is connected to the mobile toy by a string, the infant increases the average velocity of the arm's movement. On the other hand, when the toy is controlled externally, the average arm's velocity is greatly reduced. Since young infants produce exuberant spontaneous movements even with no external stimuli, the inhibition of motor action to suppress the formation of spurious action-perception coupling should be also a crucial sign for the emergence of agency. Thus, we present a dynamical system model for the development of action differentiation, to move or not to move, in the mobile task. In addition to the pair of limb and mobile oscillators for providing positive feedback for reinforcement in the previous model, bifurcation dynamics are incorporated to enhance or inhibit self-movements in response to detecting contingencies between the limb and mobile movements. The results from computer simulations reproduce experimental observations on the developmental emergence of action differentiation between 2 and 3 months of age in the form of a bifurcation diagram. We infer that the emergence of physical agency entails young infants' ability not only to enhance a specific action-perception coupling, but also to decouple it and create a new mode of action-perception coupling based on the internal state dynamics with contingency detection between self-generated actions and environmental events.

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.

Global entrainment in the brain-body-environment: retrospective and prospective views.

We celebrate the 60th anniversary of Biological Cybernetics. It has also been 30 years since "Self-organized control of bipedal locomotion by neural oscillators in unpredictable environment" was published in Biological Cybernetics (Taga et al. in Biol Cybern 65(3):147-159, 1991). I would like to look back on the creation of this paper and discuss its subsequent development and future perspectives.

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.

Frequency-specific task modulation of human brain functional networks: A fast fMRI study.

How coherent neural oscillations are involved in task execution is a fundamental question in neuroscience. Although several electrophysiological studies have tackled this issue, the brain-wide task modulation of neural coherence remains uncharacterized. Here, with a fast fMRI technique, we studied shifts of brain-wide neural coherence across different task states in the ultraslow frequency range (0.01-0.7 Hz). First, we examined whether the shifts of the brain-wide neural coherence occur in a frequency-dependent manner. We quantified the shift of a region's average neural coherence by the inter-state variance of the mean coherence between the region and the rest of the brain. A clustering analysis based on the variance's spatial correlation between frequency components revealed four frequency bands (0.01-0.15 Hz, 0.15-0.37 Hz, 0.37-0.53 Hz, and 0.53-0.7 Hz) showing band-specific shifts of the brain-wide neural coherence. Next, we investigated the similarity of the inter-state variance's spectra between all pairs of regions. We found that regions showing similar spectra correspond to those forming functional modules of the brain network. Then, we investigated the relationship between identified frequency bands and modules' inter-state variances. We found that modules showing the highest variance are those made up of parieto-occipital regions at 0.01-0.15 Hz, while it is replaced with another consisting of frontal regions above 0.15 Hz. Furthermore, these modules showed specific shifting patterns of the mean coherence across states at 0.01-0.15 Hz and above 0.15 Hz, suggesting that identified frequency bands differentially contribute to neural interactions during task execution. Our results highlight that usage of the fast fMRI enables brain-wide investigation of neural coherence up to 0.7 Hz, which opens a promising track for assessment of the large-scale neural interactions in the ultraslow frequency range.

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.

Looking back at fNIRS 2018.

We offer a retrospective report on fNIRS 2018, along with news of the next meeting.

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.