Inter-brain synchrony during mother-infant interactive parenting in 3-4-month-old infants with and without an elevated likelihood of autism spectrum disorder.

Maternal bonding for mammalian infants is critical for their survival. Additionally, it is important for human infants' development into social creatures. However, despite the ample neurobiological evidence of attachment for the mother's brain, the interplay of this system in infants is poorly understood. We aimed to identify the neural substrates of synchrony in mothers and infants under three interactive conditions and compare the differences between groups with (n = 16) and without (n = 71) an elevated likelihood of autism spectrum disorder by examining the inter-brain synchrony between mothers and their 3-4-month-old infants. Mother-infant hyperscanning with functional near-infrared spectroscopy was performed during breastfeeding and while each of the mother and experimenter was holding the infants. The results showed almost no group differences, with both groups demonstrating the strongest inter-brain coupling for breastfeeding. The cerebral foci underlying these couplings differed between mothers and infants: the ventral prefrontal cortex, focusing on the right orbitofrontal cortex, in the mother and the left temporoparietal junction in the infant were chiefly involved in connecting the two brains. Furthermore, these synchronizations revealed many significant correlations with behavioral measures, including subsequent language development. The maternal reward-motivational system and the infant's elementary mentalization system seem to underlie mother-infant coupling during breastfeeding.

Special Section Guest Editorial: Thirty Years of Functional Near-Infrared Spectroscopy.

Functional Near-Infrared Spectroscopy (fNIRS) is a non-invasive optical technique that measures cerebral hemodynamics across multiple regions of interest, and thereby characterises brain functional activation. Since its first description in 1993, fNIRS has undergone substantial developments in hardware, analysis techniques, and applications. Thirty years later, this technique is significantly enchancing our understanding in diverse areas of neuroscience research such as neurodevelopment, cognitive neuroscience, psychiatric disorders, neurodegenerative conditions, and brain injury management in intensive care settings. This special issue outlines the latest progress in instrumentation and analysis techniques and showcases some applications within the expanding field of fNIRS over the past decade.

Using functional near-infrared spectroscopy to study the early developing brain: future directions and new challenges.

Significance: Functional near-infrared spectroscopy (fNIRS) is a frequently used neuroimaging tool to explore the developing brain, particularly in infancy, with studies spanning from birth to toddlerhood (0 to 2 years). We provide an overview of the challenges and opportunities that the developmental fNIRS field faces, after almost 25 years of research. Aim: We discuss the most recent advances in fNIRS brain imaging with infants and outlines the trends and perspectives that will likely influence progress in the field in the near future. Approach: We discuss recent progress and future challenges in various areas and applications of developmental fNIRS from methodological and technological innovations to data processing and statistical approaches. Results and Conclusions: The major trends identified include uses of fNIRS "in the wild," such as global health contexts, home and community testing, and hyperscanning; advances in hardware, such as wearable technology; assessment of individual variation and developmental trajectories particularly while embedded in studies examining other environmental, health, and context specific factors and longitudinal designs; statistical advances including resting-state network and connectivity, machine learning and reproducibility, and collaborative studies. Standardization and larger studies have been, and will likely continue to be, a major goal in the field, and new data analysis techniques, statistical methods, and collaborative cross-site projects are emerging.

Two-in-one system and behavior-specific brain synchrony during goal-free cooperative creation: an analytical approach combining automated behavioral classification and the event-related generalized linear model.

Significance: In hyperscanning studies of natural social interactions, behavioral coding is usually necessary to extract brain synchronizations specific to a particular behavior. The more natural the task is, the heavier the coding effort is. We propose an analytical approach to resolve this dilemma, providing insights and avenues for future work in interactive social neuroscience. Aim: The objective is to solve the laborious coding problem for naturalistic hyperscanning by proposing a convenient analytical approach and to uncover brain synchronization mechanisms related to human cooperative behavior when the ultimate goal is highly free and creative. Approach: This functional near-infrared spectroscopy hyperscanning study challenged a cooperative goal-free creative game in which dyads can communicate freely without time constraints and developed an analytical approach that combines automated behavior classification (computer vision) with a generalized linear model (GLM) in an event-related manner. Thirty-nine dyads participated in this study. Results: Conventional wavelet-transformed coherence (WTC) analysis showed that joint play induced robust between-brain synchronization (BBS) among the hub-like superior and middle temporal regions and the frontopolar and dorsomedial/dorsolateral prefrontal cortex (PFC) in the right hemisphere, in contrast to sparse within-brain synchronization (WBS). Contrarily, similar regions within a single brain showed strong WBS with similar connection patterns during independent play. These findings indicate a two-in-one system for performing creative problem-solving tasks. Further, WTC-GLM analysis combined with computer vision successfully extracted BBS, which was specific to the events when one of the participants raised his/her face to the other. This brain-to-brain synchrony between the right dorsolateral PFC and the right temporo-parietal junction suggests joint functioning of these areas when mentalization is necessary under situations with restricted social signals. Conclusions: Our proposed analytical approach combining computer vision and WTC-GLM can be applied to extract inter-brain synchrony associated with social behaviors of interest.

Evaluation of a Telehealth Parent-Training Program in Japan: Collaboration with Parents to Teach Novel Mand Skills to Children Diagnosed with Autism Spectrum Disorder.

This study developed a telehealth parent-training program to teach parents of children with autism spectrum disorder the process of mand-training implementation in Japan, and to further the international dissemination of evidence-based training strategies. Parent-training sessions were based on a behavioral skills training (BST) model, combined with weekly graphic and video feedback. The sessions were conducted by a board-certified behavior analyst-doctoral residing in Japan. Four parents with children with autism spectrum disorder participated in this study. The results preliminarily support the effectiveness and social validity of the program. This study extends previous parent-training research conducted in Japan by comprising all of the following features: (1) online program design; (2) mand training; (3) BST model; (4) session-by-session data on children's behavioral changes and procedural integrity; (5) within-subject experimental design; and (6) social validity evaluation.

Infants' Prefrontal Hemodynamic Responses and Functional Connectivity During Joint Attention in an Interactive-Live Setting.

The present study examined cerebral hemodynamic responses and functional connectivity during joint attention either initiated by infants (Initiating Joint Attention, IJA condition) or by their partner (Responding to Joint Attention, RJA condition). To capture responses to natural social cues in infants aged 7-12 months using functional near-infrared spectroscopy (fNIRS), we employed an interactive-live paradigm for IJA and RJA. During the measurement, an adult sat facing an infant, and objects, such as small stuffed animals, paired with sound toys were presented to the right or left side of the screen. In the RJA condition, the adult gazed at the infants' eyes and then to the objects to encourage the infants to follow the adult's gaze. On the other hand, in the IJA condition, the adult followed the infant's gaze as it shifted to the presented object. Our results indicate that the concentration of oxy-Hb in the bilateral ventral prefrontal region had significantly decreased, then followed by an increase in the right dorsal prefrontal region in the RJA. In addition, a selective activation in the bilateral dorsal prefrontal region was seen in the IJA condition. Moreover, the infants exhibited increased functional connectivity especially within the right ventral prefrontal region during RJA condition when compared with IJA conditions. These findings suggest that RJA and IJA recruit specific brain networks localized in the prefrontal cortex of infants.

Effects of Hemodynamic Differences on the Assessment of Inter-Brain Synchrony Between Adults and Infants.

The simultaneous recording of brain activity in two or more people, termed hyperscanning, is an emerging field of research investigating the neural basis of social interaction. Hyperscanning studies of adult-infant dyads (e.g., parent and infant) have great potential to provide insights into how social functions develop. In particular, taking advantage of functional near-infrared spectroscopy (fNIRS) for its spatial resolution and invulnerability to motion artifacts, adult-infant fNIRS may play a major role in this field. However, there remains a problem in analyzing hyperscanning data between adult and young populations. Namely, there are intrinsic differences in hemodynamic time latencies depending on age, and the peak latency of the hemodynamic response function (HRF) is longer in younger populations. Despite this fact, the effects of such differences on quantified synchrony have not yet been examined. Consequently, the present study investigated the influence of intrinsic hemodynamic differences on wavelet coherence for assessing brain synchrony, and further examined the statistical removal of these effects through simulation experiments. First, we assumed a social signal model, where one counterpart of the dyad (e.g., infant) sends a social signal to the other (e.g., parent), which eventually results in simultaneous brain activation. Based on this model, simulated fNIRS activation sequences were synthesized by convolving boxcar event sequences with HRFs. We set two conditions for the event: synchronized and asynchronized event conditions. We also modeled the HRFs of adults and infants by referring to previous studies. After preprocessing with additional statistical processing, we calculated the wavelet coherence for each synthesized fNIRS activation sequence pair. The simulation results showed that the wavelet coherence in the synchronized event condition was attenuated for the combination of different HRFs. We also confirmed that prewhitening via an autoregressive filter could recover the attenuation of wavelet coherence in the 0.03-0.1 Hz frequency band, which was regarded as being associated with synchronous neural activity. Our results showed that variability in hemodynamics affected the analysis of inter-brain synchrony, and that the application of prewhitening is critical for such evaluations between adult and young populations.

Spatial complexity method for tracking brain development and degeneration using functional near-infrared spectroscopy.

Brain complexity analysis using functional near-infrared spectroscopy (fNIRS) has attracted attention as a biomarker for evaluating brain development and degeneration processes. However, most methods have focused on the temporal scale without capturing the spatial complexity. In this study, we propose a spatial time-delay entropy (STDE) method as the spatial complexity measure based on the time-delay measure between two oxy-hemoglobin (Δ[HbO]) or two deoxy-hemoglobin (Δ[Hb]) oscillations within the 0.01-0.1 Hz frequency band. To do this, we analyze fNIRS signals recorded from infants in their sleeping state, children, adults, and healthy seniors in their resting states. We also evaluate the effects of various noise to STDE calculations and STDE's performance in distinguishing various developmental age groups. Lastly, we compare the results with the normalized global spatial complexity (NGSC) and sample entropy (SampEn) measures. Among these measures, STDEHbO (STDE based on Δ[HbO] oscillations) performs best. The STDE value increases with age throughout childhood (p < 0.001), and then decreases in adults and healthy seniors in the 0.01-0.1 Hz frequency band. This trajectory correlates with cerebrovascular development and degeneration. These findings demonstrate that STDE can be used as a new tool for tracking cerebrovascular development and degeneration across a lifespan based on the fNIRS resting-state measurements.

Differential age-dependent development of inter-area brain connectivity in term and preterm neonates.

BACKGROUND: Among preterm infants, higher morbidities of neurological disturbances and developmental delays are critical issues. Resting-state networks (RSNs) in the brain are suitable measures for assessing higher-level neurocognition. Since investigating task-related brain activity is difficult in neonates, assessment of RSNs provides invaluable insight into their neurocognitive development. METHODS: The participants, 32 term and 71 preterm neonates, were divided into three groups based on gestational age (GA) at birth. Cerebral hemodynamic activity of RSNs was measured using functional near-infrared spectroscopy in the temporal, frontal, and parietal regions. RESULTS: High-GA preterm infants (GA ≥ 30 weeks) had a significantly stronger RSN than low-GA preterm infants and term infants. Regression analyses of RSNs as a function of postnatal age (PNA) revealed a steeper regression line in the high-GA preterm and term infants than in the low-GA infants, particularly for inter-area brain connectivity between the frontal and left temporal areas. CONCLUSIONS: Slower PNA-dependent development of the frontal-temporal network found only in the low-GA group suggests that significant brain growth optimal in the intrauterine environment takes place before 30 weeks of gestation. The present study suggests a likely reason for the high incidence of neurodevelopmental impairment in early preterm infants. IMPACT: Resting-state fNIRS measurements in three neonate groups differing in gestational age (GA) showed stronger networks in the high-GA preterm infants than in the term and low-GA infants, which was partly explained by postnatal age (PNA). Regression analyses revealed a similar PNA-dependence in the development of the inter-area networks in the frontal and temporal lobes in the high-GA and term infants, and significantly slower development in the low-GA infants. These results suggest that optimal intrauterine brain growth takes place before 30 weeks of gestation. This explains one of the reasons for the high incidence of neurodevelopmental impairment in early preterm infants.

The effect of haptic stimulation simulating heartbeats on the regulation of physiological responses and prosocial behavior under stress: The influence of interoceptive accuracy.

Research has discovered the modulatory effect of peripheral stimulation simulating altered bodily signals on emotion. Whether such an effect varies depending on one's interoceptive accuracy (IAc) remains unclear. Therefore, we provided haptic stimulation simulating participants' slowed-down heartbeats or no stimulation while they engaged in socially stressful tasks to examine whether participants reacted differently depending on their IAc. Results showed that haptic stimulation exhibited the opposite effect on participants with different levels of IAc for both heart rate and heart rate variability (HRV). When receiving the stimulation, participants with higher IAc showed less increased heart rate and more elevated HF than participants with lower IAc. In contrast, in the absence of stimulation, an opposite pattern of response depending on participants' IAc was observed. The modulatory effect of stimuli and IAc on prosocial behavior was not significant. Individual differences in IAc were shown to affect how one perceives/responds to altered bodily signals.

Correlating functional near-infrared spectroscopy with underlying cortical regions of 0-, 1-, and 2-year-olds using theoretical light propagation analysis.

Significance: The establishment of a light propagation analysis-based scalp-cortex correlation (SCC) between the scalp location of the source-detector (SD) pair and brain regions is essential for measuring functional brain development in the first 2 years of life using functional near-infrared spectroscopy (fNIRS). Aim: We aimed to reveal the optics-based SCC of 0-, 1-, and 2-year-olds (yo) and the suitable SD distance for this age period. Approach: Light propagation analyses using age-appropriate head models were conducted on SD pairs at 10-10 fiducial points on the scalp to obtain optics-based SCC and its metrics: the number of corresponding brain regions ( N C B R ), selectivity and sensitivity of the most likely corresponding brain region (MLCBR), and consistency of the MLCBR across developmental ages. Moreover, we assessed the suitable SD distances for 0-, 1-, and 2-yo by simultaneously considering the selectivity and sensitivity of the MLCBR. Results: Age-related changes in the SCC metrics were observed. For instance, the N C B R of 0-yo was larger than that of 1- and 2-yo. Conversely, the selectivity of 0-yo was lower than that of 1- and 2-yo. The sensitivity of 1-yo was higher than that of 0-yo at 15- to 30-mm SD distances and higher than that of 2-yo at 10-mm SD distance. Notably, the MLCBR of the fiducial points around the longitudinal fissure was inconsistent across age groups. An SD distance between 15 and 25 mm was found to be appropriate for satisfying both sensitivity and selectivity requirements. In addition, this work provides reference tables of optics-based SCC for 0-, 1-, and 2-yo. Conclusions: Optics-based SCC will be informative in designing and explaining child developmental studies using fNIRS. The suitable SD distances were between 15 and 25 mm for the first 2 years of life.

Tracking Brain Development From Neonates to the Elderly by Hemoglobin Phase Measurement Using Functional Near-Infrared Spectroscopy.

The biological and neurological processes during the lifespan are dynamic with significant alterations associated with different stages of life. The phase and coupling of oxy-hemoglobin (Δ[HbO]) and deoxy-hemoglobin concentration changes (Δ[Hb]) measured by functional near-infrared spectroscopy (fNIRS) are shown to characterize the neurovascular and metabolic development of infants. However, the changes in phase and coupling across the human lifespan remain mostly unknown. Here, fNIRS measurements of Δ[HbO] and Δ[Hb] conducted at two sites on different age populations (from newborns to elderly) were combined. Firstly, we assessed the influence of random noise on the calculation of the phase difference and phase-locking index (PLI) in fNIRS measurement. The results showed that the phase difference is close to π as the noise intensity approaches -8 dB, and the coupling strength (i.e., PLI) presents a u-shape curve as the noise increase. Secondly, phase difference and PLI in the frequency range 0.01-0.10 Hz were calculated after denoising. It showed that the phase difference increases from newborns to 3-4-month-olds babies. This phase difference persists throughout adulthood until finally being disrupted in the old age. The children's PLI is the highest, followed by that of adults. These two groups' PLI are significantly higher than those of infants and the elderly (p < 0.001). Lastly, a hemodynamic model was used to explain the observations and found close associations with cerebral autoregulation and speed of blood flow. These results demonstrate that the phase-related parameters measured by fNIRS can be used to study the brain and assess brain health throughout the lifespan.

The effect of different information sources on prosodic boundary perception.

This study aims to quantify the effect of several information sources: acoustic, higher-level linguistic, and knowledge of the prosodic system of the language, on the perception of prosodic boundaries. An experiment with native and non-native participants investigating the identification of prosodic boundaries in Japanese was conducted. It revealed that non-native speakers as well as native speakers with access only to acoustic information can recognize boundaries better than chance level. However, knowledge of both the prosodic system and of higher-level information are required for a good boundary identification, each one having similar or higher importance than that of acoustic information.

Prefrontal Responses to Odors in Individuals With Autism Spectrum Disorders: Functional NIRS Measurement Combined With a Fragrance Pulse Ejection System.

Individuals with autism spectrum disorders (ASD) are impaired not only in social competencies but also in sensory perception, particularly olfaction. The olfactory ability of individuals with ASD has been examined in several psychophysical studies, but the results have been highly variable, which might be primarily due to methodological difficulties in the control of odor stimuli (e.g., the problem of lingering scents). In addition, the neural correlates of olfactory specificities in individuals with ASD remain largely unknown. To date, only one study has investigated this issue using functional magnetic resonance imaging (fMRI). The present study utilized a sophisticated method-a pulse ejection system-to present well-controlled odor stimuli to participants with ASD using an ASD-friendly application. With this advantageous system, we examined their odor detection, identification, and evaluation abilities and measured their brain activity evoked by odors using functional near-infrared spectroscopy (fNIRS). As the odor detection threshold (DT) of participants with ASD was highly variable, these participants were divided into two groups according to their DT: an ASD-Low DT group and an ASD-High DT group. Behavioral results showed that the ASD-High DT group had a significantly higher DT than the typically developing (control) group and the ASD-Low DT group, indicating their insensitivity to the tested odors. In addition, while there was no significant difference in the odor identification ability between groups, there was some discrepancy between the groups' evaluations of odor pleasantness. The brain data identified, for the first time, that neural activity in the right dorsolateral prefrontal cortex (DLPFC) was significantly weaker in the ASD-High DT group than in the control group. Moreover, the strength of activity in the right DLPFC was negatively correlated with the DT. These findings suggest that participants with ASD have impairments in the higher-order function of olfactory processing, such as olfactory working memory and/or attention.

Capturing Human Perceptual and Cognitive Activities via Event-Related Potentials Measured with Candle-Like Dry Microneedle Electrodes.

We demonstrate capture of event-related potentials (ERPs) using candle-like dry microneedle electrodes (CMEs). CMEs can record an electroencephalogram (EEG) even from hairy areas without any skin preparation, unlike conventional wet electrodes. In our previous research, we experimentally verified that CMEs can measure the spontaneous potential of EEG from the hairy occipital region without preparation with a signal-to-noise ratio as good as that of the conventional wet electrodes which require skin preparation. However, these results were based on frequency-based signals, which are relatively robust compared to noise contamination, and whether CMEs are sufficiently sensitive to capture finer signals remained unclear. Here, we first experimentally verified that CMEs can extract ERPs as good as conventional wet electrodes without preparation. In the auditory oddball tasks using pure tones, P300, which represent ERPs, was extracted with a signal-to-noise ratio as good as that of conventional wet electrodes. CMEs successfully captured perceptual activities. Then, we attempted to investigate cerebral cognitive activity using ERPs. In processing the vowel and prosody in auditory stimuli such as /itta/, /itte/, and /itta?/, laterality was observed that originated from the locations responsible for the process in near-infrared spectroscopy (NIRS) and magnetoencephalography experiments. We simultaneously measured ERPs with CMEs and NIRS in the oddball tasks using the three words. Laterality appeared in NIRS for six of 10 participants, although laterality was not clearly shown in the results, suggesting that EEGs have a limitation of poor spatial resolution. On the other hand, successful capturing of MMN and P300 using CMEs that do not require skin preparation may be readily applicable for real-time applications of human perceptual activities.

Interactive live fNIRS reveals engagement of the temporoparietal junction in response to social contingency in infants.

Live social interaction is the dominant form of human social activity, but it remains unclear if brain processing of live interactive social stimuli differs substantially from processing of non-interactive social stimuli, mainly because of technical difficulties measuring brain activity during natural social interactions. This distinction is particularly important during infancy considering the importance of real-life interactions for various forms of learning. To assess the impact of live social interaction accompanied by ostensive social signals on infant cortical processing, the present study measured the cortical activities of 6-8-month-old and 10-12-month-old infants using functional near-infrared spectroscopy under contingent and non-contingent conditions (appropriately timed versus delayed responsiveness). We found greater activation over the right temporoparietal junction region in response to contingent interactions relative to non-contingent interactions in 6-8-month-old and 10-12-month-old infants. Our study indicates a critical role of contingent responsiveness for differential processing of live interactive social stimuli.

Maternal speech shapes the cerebral frontotemporal network in neonates: A hemodynamic functional connectivity study.

Language development and the capacity for communication in infants are predominantly supported by their mothers, beginning when infants are still in utero. Although a mother's speech should thus have a significant impact on her neonate's brain, neurocognitive evidence for this hypothesis remains elusive. The present study examined 37 neonates using near-infrared spectroscopy and observed the interactions between multiple cortical regions while neonates heard speech spoken by their mothers or by strangers. We analyzed the functional connectivity between regions whose response-activation patterns differed between the two types of speakers. We found that when hearing their mothers' speech, functional connectivity was enhanced in both the neonatal left and right frontotemporal networks. On the left it was enhanced between the inferior/middle frontal gyrus and the temporal cortex, while on the right it was enhanced between the frontal pole and temporal cortex. In particular, the frontal pole was more strongly connected to the left supramarginal area when hearing speech from mothers. These enhanced frontotemporal networks connect areas that are associated with language (left) and voice processing (right) at later stages of development. We suggest that these roles are initially fostered by maternal speech.

Recommendations for motion correction of infant fNIRS data applicable to multiple data sets and acquisition systems.

Despite motion artifacts are a major source of noise in fNIRS infant data, how to approach motion correction in this population has only recently started to be investigated. Homer2 offers a wide range of motion correction methods and previous work on simulated and adult data suggested the use of Spline interpolation and Wavelet filtering as optimal methods for the recovery of trials affected by motion. However, motion artifacts in infant data differ from those in adults' both in amplitude and frequency of occurrence. Therefore, artifact correction recommendations derived from adult data might not be optimal for infant data. We hypothesized that the combined use of Spline and Wavelet would outperform their individual use on data with complex profiles of motion artifacts. To demonstrate this, we first compared, on infant semi-simulated data, the performance of several motion correction techniques on their own and of the novel combined approach; then, we investigated the performance of Spline and Wavelet alone and in combination on real cognitive data from three datasets collected with infants of different ages (5, 7 and 10 months), with different tasks (auditory, visual and tactile) and with different NIRS systems. To quantitatively estimate and compare the efficacy of these techniques, we adopted four metrics: hemodynamic response recovery error, within-subject standard deviation, between-subjects standard deviation and number of trials that survived each correction method. Our results demonstrated that (i) it is always better correcting for motion artifacts than rejecting the corrupted trials; (ii) Wavelet filtering on its own and in combination with Spline interpolation seems to be the most effective approach in reducing the between- and the within-subject standard deviations. Importantly, the combination of Spline and Wavelet was the approach providing the best performance in semi-simulation both at low and high levels of noise, also recovering most of the trials affected by motion artifacts across all datasets, a crucial result when working with infant data.

Symbolic time series analysis of fNIRS signals in brain development assessment.

OBJECTIVE: Assessing an infant's brain development remains a challenge for neuroscientists and pediatricians despite great technological advances. As a non-invasive neuroimaging tool, functional near-infrared spectroscopy (fNIRS) has great advantages in monitoring an infant's brain activity. To explore the dynamic features of hemodynamic changes in infants, in-pattern exponent (IPE), anti-pattern exponent (APE), as well as permutation cross-mutual information (PCMI) based on symbolic dynamics are proposed to measure the phase differences and coupling strength in oxyhemoglobin (HbO) and deoxyhemoglobin (Hb) signals from fNIRS. APPROACH: First, simulated sinusoidal oscillation signals and four coupled nonlinear systems were employed for performance assessments. Hilbert transform based measurements of hemoglobin phase oxygenation and deoxygenation (hPod) and phase-locking index of hPod (hPodL) were calculated for comparison. Then, the IPE, APE and PCMI indices from resting state fNIRS data of preterm, term infants and adults were calculated to estimate the phase difference and coupling of HbO and Hb. All indices' performance was assessed by the degree of monotonicity (DoM). The box plots and coefficients of variation (CV) were employed to assess the measurements and robustness in the results. MAIN RESULTS: In the simulation analysis, IPE and APE can distinguish the phase difference of two sinusoidal oscillation signals. Both hPodL and PCMI can track the strength of two coupled nonlinear systems. Compared to hPodL, the PCMI had higher DoM indices in measuring the coupling of two nonlinear systems. In the fNIRS data analysis, similar to hPod, the IPE and APE can distinguish preterm, term infants, and adults in 0.01-0.05 Hz, 0.05-0.1 Hz, and 0.01-0.1 Hz frequency bands, respectively. PCMI more effectively distinguished the term and preterm infants than hPodL in the 0.05-0.1 Hz frequency band. As symbolic time series measures, the IPE and APE were able to detect the brain developmental changes in subjects of different ages. PCMI can assess the resting-state HbO and Hb coupling changes across different developmental ages, which may reflect the metabolic and neurovascular development. SIGNIFICANCE: The symbolic-based methodologies are promising measures for fNIRS in estimating the brain development, especially in assessing newborns' brain developmental status.