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.

Autism-Related Differences in Cortical Activation When Observing, Producing, and Imitating Communicative Gestures: An fNIRS Study.

Children with autism spectrum disorder (ASD) have difficulties in gestural communication during social interactions. However, the neural mechanisms involved in naturalistic gestural communication remain poorly understood. In this study, cortical activation patterns associated with gestural communication were examined in thirty-two children with and without ASD (mean age: 11.0 years, SE: 0.6 years). Functional near-infrared spectroscopy (fNIRS) was used to record cortical activation while children produced, observed, or imitated communicative gestures. Children with ASD demonstrated more spatial and temporal errors when performing and imitating communicative gestures. Although both typically developing (TD) children and children with ASD showed left-lateralized cortical activation during gesture production, children with ASD showed hyperactivation in the middle/inferior frontal gyrus (MIFG) during observation and imitation, and hypoactivation in the middle/superior temporal gyrus (MSTG) during gesture production compared to their TD peers. More importantly, children with ASD exhibited greater MSTG activation during imitation than during gesture production, suggesting that imitation could be an effective intervention strategy to engage cortical regions crucial for processing and producing gestures. Our study provides valuable insights into the neural mechanisms underlying gestural communication difficulties in ASD, while also identifying potential neurobiomarkers that could serve as objective measures for evaluating intervention effectiveness in children with ASD.

fNIRS-Based Differences in Cortical Activation during Tool Use, Pantomimed Actions, and Meaningless Actions between Children with and without Autism Spectrum Disorder (ASD).

Children with autism spectrum disorder (ASD) have difficulties with tool use and pantomime actions. The current study utilized functional near-infrared spectroscopy (fNIRS) to examine the neural mechanisms underlying these gestural difficulties. Thirty-one children with and without ASD (age (mean ± SE) = 11.0 ± 0.6) completed a naturalistic peg-hammering task using an actual hammer (hammer condition), pantomiming hammering actions (pantomime condition), and performing meaningless actions with similar joint motions (meaningless condition). Children with ASD exhibited poor praxis performance (praxis error: TD = 17.9 ± 1.7; ASD = 27.0 ± 2.6, p < 0.01), which was significantly correlated with their cortical activation (R = 0.257 to 0.543). Both groups showed left-lateralized activation, but children with ASD demonstrated more bilateral activation during all gestural conditions. Compared to typically developing children, children with ASD showed hyperactivation of the inferior parietal lobe and hypoactivation of the middle/inferior frontal and middle/superior temporal regions. Our findings indicate intact technical reasoning (typical left-IPL activation) but atypical visuospatial and proprioceptive processing (hyperactivation of the right IPL) during tool use in children with ASD. These results have important implications for clinicians and researchers, who should focus on facilitating/reducing the burden of visuospatial and proprioceptive processing in children with ASD. Additionally, fNIRS-related biomarkers could be used for early identification through early object play/tool use and to examine neural effects following gesture-based interventions.

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.

Cortical activation during cooperative joint actions and competition in children with and without an autism spectrum condition (ASC): an fNIRS study.

Children with an Autism Spectrum Condition (ASC) have social communication and perceptuomotor difficulties that affect their ability to engage in dyadic play. In this study, we compared spatio-temporal errors and fNIRS-related cortical activation between children with and without an ASC during a Lincoln Log dyadic game requiring them to play leader or follower roles, move in synchrony or while taking turns, and move cooperatively or competitively with an adult partner. Children with an ASC had greater motor, planning, and spatial errors and took longer to complete the building tasks compared to typically developing (TD) children. Children with an ASC had lower superior temporal sulcus (STS) activation during Turn-take and Compete, and greater Inferior Parietal Lobe (IPL) activation during Lead and Turn-take compared to TD children. As dyadic play demands increased, TD children showed greater STS activation during Turn-take (vs. Synchrony) and Compete (vs. Cooperate) whereas children with an ASC showed greater IPL activation during Lead and Compete (vs. Cooperate). Our findings suggest that children with an ASC rely on self-generated action plans (i.e., increased IPL activation) more than relying on their partner's action cues (i.e., reduced STS activation) when engaging in dyadic play including joint actions and competition.

Movement kinematics and cortical activation in children with and without autism spectrum disorder during sway synchrony tasks: an fNIRS study.

Children with Autism Spectrum Disorder (ASD) have difficulties with socially embedded movements such as imitation and interpersonal synchrony (IPS); however, related movement characteristics and underlying neural mechanisms are not well understood. This study compared the movement characteristics and cortical activation patterns of children with and without ASD during a whole-body, sway synchrony task when different levels of social information were provided. Thirty children with and without ASD (mean age: 12.6 years, SE: 0.6 years) participated. Movement kinematics and fNIRS-based cortical activation were recorded when the child observed an adult tester sway side to side, when they swayed solo, or when they swayed face to face with the tester with or without fingertips touching (i.e., IPS). Children with ASD showed reduced synchrony and smaller sway amplitude compared to typically developing children without ASD. They showed reduced cortical activation over the inferior frontal gyrus and superior temporal sulcus during IPS and did not show significant increase in cortical activation when more social information was provided. The cortical activation findings were significantly associated with IPS behaviors and social communication performance. The ASD-related neurobiomarkers identified in our study could be used as objective measures to evaluate intervention effects in children with ASD.

Epidemiology and burden of illness of seasonal influenza among the elderly in Japan: A systematic literature review and vaccine effectiveness meta-analysis.

BACKGROUND: Elderly populations are particularly vulnerable to influenza and often require extensive clinical support. In Japan, nationwide passive surveillance monitors seasonal influenza but does not capture the full disease burden. We synthesized existing evidence on the epidemiology, vaccine effectiveness (VE), and economic burden of seasonal influenza in the elderly population. METHODS: PubMed, EMBASE, and ICHUSHI were searched for articles on seasonal influenza in Japan, published between 1997 and 2018, in English or Japanese. Grey literature was also assessed. A random-effects meta-analysis characterized VE of influenza vaccines among studies reporting this information. RESULTS: Of 1,147 identified articles, 143 met inclusion criteria. Reported incidence rates varied considerably depending on study design, season, study setting and, most importantly, case definition. In nursing homes, the maximum reported attack rate was 55.2% and in the 16 articles reporting mortality rates, case fatality rates varied from 0.009% to 14.3%. Most hospitalizations were in people aged >60; healthcare costs were partially mitigated by vaccine administration. Meta-analysis estimated overall VE of 19.1% (95% CI: 2.3% - 33.0%) with a high proportion of heterogeneity (I2 : 89.1%). There was a trend of lower VE in older people (40.1% [-57.3-77.2] in the <65 group; 12.9% [-8.0-29.8] in those 65; P = .21). CONCLUSIONS: Despite differences between studies that make comparisons challenging, the influenza burden in elderly Japanese is significant. While vaccines are effective, current vaccination programs offer suboptimal protection. Health economic data and cost-effectiveness analyses were limited and represent areas for policy-relevant future research.

Immunogenicity and Safety of a Two-Dose Series of a Meningococcal (Groups A, C, W, and Y) Polysaccharide Diphtheria Toxoid Conjugate Vaccine (Men-ACWY-D) in Healthy Japanese Adults.

The quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (Men-ACWY-D) has been licensed for use in Japan since 2014. An earlier registration study demonstrated the immunogenicity of a single dose in Japanese adults, wherein the immunogenicity against serogroup C was the lowest. The determination of the potential to increase the serogroup C response with a second dose was, therefore, of interest. This study (NCT02591290) evaluated the safety and immunogenicity of two doses administered 8 weeks apart to 60 healthy Japanese adults aged 20-55 years. Blood samples were collected at 28-35 days after vaccination. Immunogenicity endpoints included seroprotection and seroconversion rates. Safety assessments included systemic adverse events (AEs), non-serious AEs, and serious AEs. Fifty-eight participants (96.7%) completed the study. The seroprotection rates for serogroups A, C, W, and Y before vaccination were 76.8%, 26.8%, 26.8%, and 50.0%, respectively, increasing to 100%, 83.9%, 91.1%, and 96.4% and 100%, 92.9%, 94.6%, and 94.6%, respectively, after two doses. The seroconversion rates for the four serogroups were 100%, 93.8%, 97.1%, and 94.1%, respectively, after the first dose, and 100%, 96.9%, 100%, and 100%, respectively, after the second. The increase between the doses was insignificant, and there were no safety concerns. The two-dose series was well tolerated; however, the clinical benefits of a second dose within 8 weeks seemed to be low.

Differences in cortical activation patterns during action observation, action execution, and interpersonal synchrony between children with or without autism spectrum disorder (ASD): An fNIRS pilot study.

Engaging in socially embedded actions such as imitation and interpersonal synchrony facilitates relationships with peers and caregivers. Imitation and interpersonal synchrony impairments of children with Autism Spectrum Disorder (ASD) might contribute to their difficulties in connecting and learning from others. Previous fMRI studies investigated cortical activation in children with ASD during finger/hand movement imitation; however, we do not know whether these findings generalize to naturalistic face-to-face imitation/interpersonal synchrony tasks. Using functional near infrared spectroscopy (fNIRS), the current study assessed the cortical activation of children with and without ASD during a face-to-face interpersonal synchrony task. Fourteen children with ASD and 17 typically developing (TD) children completed three conditions: a) Watch-observed an adult clean up blocks; b) Do-cleaned up the blocks on their own; and c) Together-synchronized their block clean up actions to that of an adult. Children with ASD showed lower spatial and temporal synchrony accuracies but intact motor accuracy during the Together/interpersonal synchrony condition. In terms of cortical activation, children with ASD had hypoactivation in the middle and inferior frontal gyri (MIFG) as well as middle and superior temporal gyri (MSTG) while showing hyperactivation in the inferior parietal cortices/lobule (IPL) compared to the TD children. During the Together condition, the TD children showed bilaterally symmetrical activation whereas children with ASD showed more left-lateralized activation over MIFG and right-lateralized activation over MSTG. Additionally, using ADOS scores, in children with ASD greater social affect impairment was associated with lower activation in the left MIFG and more repetitive behavior impairment was associated with greater activation over bilateral MSTG. In children with ASD better communication performance on the VABS was associated with greater MIFG and/or MSTG activation. We identified objective neural biomarkers that could be utilized as outcome predictors or treatment response indicators in future intervention studies.

Immunogenicity and safety of a DTaP-IPV/Hib pentavalent vaccine given as primary and booster vaccinations in healthy infants and toddlers in Japan.

BACKGROUND: Globally, the use of single DTaP-IPV/Hib vaccines that combine DTaP-IPV and Hib is widespread, but in Japan vaccination is usually concomitant at separate sites. The immunogenicity and safety of a primary vaccination series and booster of a combined pentavalent DTaP-IPV/Hib vaccine were evaluated and compared to separate administration of DTaP-IPV and Hib in Japanese infants. METHODS: Healthy Japanese infants were administered DTaP-IPV/Hib (Group A: N = 207) or DTaP-IPV + Hib (Group B: N = 207) by the subcutaneous (SC) or DTaP-IPV/Hib by the intramuscular (IM) route (Group C: N = 10). All subjects received a 3-dose primary vaccination series and a booster. Non-inferiority (Group A versus Group B) was tested post-primary series and subsequent post hoc analyses were performed for anti-Hib. Safety was assessed by parental reports. RESULTS: Non-inferiority for SC administration of Group A versus Group B for the primary series was demonstrated for antibody responses to all antigens except Hib using the threshold of 1.0 µg/mL. Post hoc analyses for anti-Hib demonstrated non-inferiority for the primary series response using 0.15 µg/mL, and for pre-booster antibody persistence and the booster response using 0.15 µg/mL and 1.0 µg/mL. The immune response was similar for each antigen following SC or IM administration. There were no safety concerns in any group, and a lower incidence of injection sites for the IM route was observed as expected. CONCLUSIONS: These data show the good immunogenicity and safety profile of the DTaP-IPV/Hib vaccine as a 3-dose infant primary series followed by a booster in the second year of life in Japan.

Developmental Differences in Cortical Activation During Action Observation, Action Execution and Interpersonal Synchrony: An fNIRS Study.

Interpersonal synchrony (IPS) is an important everyday behavior influencing social cognitive development; however, few studies have investigated the developmental differences and underlying neural mechanisms of IPS. functional near-infrared spectroscopy (fNIRS) is a novel neuroimaging tool that allows the study of cortical activation in the presence of natural movements. Using fNIRS, we compared cortical activation patterns between children and adults during action observation, execution, and IPS. Seventeen school-age children and 15 adults completed a reach to cleanup task while we obtained cortical activation data from bilateral inferior frontal gyrus (IFG), superior temporal sulcus (STS), and inferior parietal lobes (IPL). Children showed lower spatial and temporal accuracy during IPS compared to adults (i.e., spatial synchrony scores (Mean ± SE) in children: 2.67 ± 0.08 and adults: 2.85 ± 0.06; temporal synchrony scores (Mean ± SE) in children: 2.74 ± 0.06 and adults: 2.88 ± 0.05). For both groups, the STS regions were more activated during action observation, while the IFG and STS were more activated during action execution and IPS. The IPS condition involved more right-sided activation compared to action execution suggesting that IPS is a higher-order process involving more bilateral cortical activation. In addition, adults showed more left lateralization compared to the children during movement conditions (execution and IPS); which indicated greater inhibition of ipsilateral cortices in the adults compared to children. These findings provide a neuroimaging framework to study imitation and IPS impairments in special populations such as children with Autism Spectrum Disorder.

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.

Explicit Performance in Girls and Implicit Processing in Boys: A Simultaneous fNIRS-ERP Study on Second Language Syntactic Learning in Young Adolescents.

Learning a second language (L2) proceeds with individual approaches to proficiency in the language. Individual differences including sex, as well as working memory (WM) function appear to have strong effects on behavioral performance and cortical responses in L2 processing. Thus, by considering sex and WM capacity, we examined neural responses during L2 sentence processing as a function of L2 proficiency in young adolescents. In behavioral tests, girls significantly outperformed boys in L2 tests assessing proficiency and grammatical knowledge, and in a reading span test (RST) assessing WM capacity. Girls, but not boys, showed significant correlations between L2 tests and RST scores. Using functional near-infrared spectroscopy (fNIRS) and event-related potential (ERP) simultaneously, we measured cortical responses while participants listened to syntactically correct and incorrect sentences. ERP data revealed a grammaticality effect only in boys in the early time window (100-300 ms), implicated in phrase structure processing. In fNIRS data, while boys had significantly increased activation in the left prefrontal region implicated in syntactic processing, girls had increased activation in the posterior language-related region involved in phonology, semantics, and sentence processing with proficiency. Presumably, boys implicitly focused on rule-based syntactic processing, whereas girls made full use of linguistic knowledge and WM function. The present results provide important fundamental data for learning and teaching in L2 education.

Cortical Activation during Action Observation, Action Execution, and Interpersonal Synchrony in Adults: A functional Near-Infrared Spectroscopy (fNIRS) Study.

Introduction: Humans engage in Interpersonal Synchrony (IPS) as they synchronize their own actions with that of a social partner over time. When humans engage in imitation/IPS behaviors, multiple regions in the frontal, temporal, and parietal cortices are activated including the putative Mirror Neuron Systems (Iacoboni, 2005; Buxbaum et al., 2014). In the present study, we compared fNIRS-based cortical activation patterns across three conditions of action observation ("Watch" partner), action execution ("Do" on your own), and IPS (move "Together"). Methods: Fifteen typically developing adults completed a reach and cleanup task with the right arm while cortical activation was examined using a 24-channel, Hitachi fNIRS system. Each adult completed 8 trials across three conditions (Watch, Do, and Together). For each fNIRS channel, we obtained oxy hemoglobin (HbO2) and deoxy hemoglobin (HHb) profiles. Spatial registration methods were applied to localize the cortical regions underneath each channel and to define six regions of interest (ROIs), right and left supero-anterior (SA or pre/post-central gyri), infero-posterior (IP or angular/supramarginal gyri), and infero-anterior (IA or superior/middle temporal gyri) regions. Results: In terms of task-related differences, the majority of the ROIs were more active during Do and Together compared to Watch. Only the right/ipsilateral fronto-parietal and inferior parietal cortices had greater activation during Together compared to Do. Conclusions: The similarities in cortical activation between action execution and IPS suggest that neural control of IPS is more similar to its execution than observational aspects. To be clear, the more complex the actions performed, the more difficult the IPS behaviors. Secondly, IPS behaviors required slightly more right-sided activation (vs. execution/observation) suggesting that IPS is a higher-order process involving more bilateral activation compared to its sub-components. These findings provide a neuroimaging framework to study imitation and IPS impairments in special populations such as infants at risk for and children with ASD.

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.

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.

Individual classification of ADHD children by right prefrontal hemodynamic responses during a go/no-go task as assessed by fNIRS.

While a growing body of neurocognitive research has explored the neural substrates associated with attention deficit hyperactive disorder (ADHD), an objective biomarker for diagnosis has not been established. The advent of functional near-infrared spectroscopy (fNIRS), which is a noninvasive and unrestrictive method of functional neuroimaging, raised the possibility of introducing functional neuroimaging diagnosis in young ADHD children. Previously, our fNIRS-based measurements successfully visualized the hypoactivation pattern in the right prefrontal cortex during a go/no-go task in ADHD children compared with typically developing control children at a group level. The current study aimed to explore a method of individual differentiation between ADHD and typically developing control children using multichannel fNIRS, emphasizing how spatial distribution and amplitude of hemodynamic response are associated with inhibition-related right prefrontal dysfunction. Thirty ADHD and thirty typically developing control children underwent a go/no-go task, and their cortical hemodynamics were assessed using fNIRS. We explored specific regions of interest (ROIs) and cut-off amplitudes for cortical activation to distinguish ADHD children from control children. The ROI located on the border of inferior and middle frontal gyri yielded the most accurate discrimination. Furthermore, we adapted well-formed formulae for the constituent channels of the optimized ROI, leading to improved classification accuracy with an area under the curve value of 85% and with 90% sensitivity. Thus, the right prefrontal hypoactivation assessed by fNIRS would serve as a potentially effective biomarker for classifying ADHD children at the individual level.

Effects of sex and proficiency in second language processing as revealed by a large-scale fNIRS study of school-aged children.

Previous neuroimaging studies in adults have revealed that first and second languages (L1/L2) share similar neural substrates, and that proficiency is a major determinant of the neural organization of L2 in the lexical-semantic and syntactic domains. However, little is known about neural substrates of children in the phonological domain, or about sex differences. Here, we conducted a large-scale study (n = 484) of school-aged children using functional near-infrared spectroscopy and a word repetition task, which requires a great extent of phonological processing. We investigated cortical activation during word processing, emphasizing sex differences, to clarify similarities and differences between L1 and L2, and proficiency-related differences during early L2 learning. L1 and L2 shared similar neural substrates with decreased activation in L2 compared to L1 in the posterior superior/middle temporal and angular/supramarginal gyri for both sexes. Significant sex differences were found in cortical activation within language areas during high-frequency word but not during low-frequency word processing. During high-frequency word processing, widely distributed areas including the angular/supramarginal gyri were activated in boys, while more restricted areas, excluding the angular/supramarginal gyri were activated in girls. Significant sex differences were also found in L2 proficiency-related activation: activation significantly increased with proficiency in boys, whereas no proficiency-related differences were found in girls. Importantly, cortical sex differences emerged with proficiency. Based on previous research, the present results indicate that sex differences are acquired or enlarged during language development through different cognitive strategies between sexes, possibly reflecting their different memory functions.

Anatomical guidance for functional near-infrared spectroscopy: AtlasViewer tutorial.

Functional near-infrared spectroscopy (fNIRS) is an optical imaging method that is used to noninvasively measure cerebral hemoglobin concentration changes induced by brain activation. Using structural guidance in fNIRS research enhances interpretation of results and facilitates making comparisons between studies. AtlasViewer is an open-source software package we have developed that incorporates multiple spatial registration tools to enable structural guidance in the interpretation of fNIRS studies. We introduce the reader to the layout of the AtlasViewer graphical user interface, the folder structure, and user files required in the creation of fNIRS probes containing sources and detectors registered to desired locations on the head, evaluating probe fabrication error and intersubject probe placement variability, and different procedures for estimating measurement sensitivity to different brain regions as well as image reconstruction performance. Further, we detail how AtlasViewer provides a generic head atlas for guiding interpretation of fNIRS results, but also permits users to provide subject-specific head anatomies to interpret their results. We anticipate that AtlasViewer will be a valuable tool in improving the anatomical interpretation of fNIRS studies.

Determination of epileptic focus side in mesial temporal lobe epilepsy using long-term noninvasive fNIRS/EEG monitoring for presurgical evaluation.

Noninvasive localization of an epileptogenic zone is a fundamental step for presurgical evaluation of epileptic patients. Here, we applied long-term simultaneous functional near-infrared spectroscopy (fNIRS)/electroencephalogram (EEG) monitoring for focus diagnosis in patients with mesial temporal lobe epilepsy (MTLE). Six MTLE patients underwent long-term (8-16 h per day for 4 days) fNIRS/EEG monitoring for the occurrence of spontaneous seizures. Four spontaneous seizures were successfully recorded out of the six patients. To determine oxy-Hb amplitude, the period-average values of oxy-Hb across 20 s from the EEG- or clinically defined epileptic onset were calculated for both hemispheres from the simultaneously recorded fNIRS data. The average oxy-Hb values for the temporal lobe at the earlier EEG- or clinically defined epileptic onsets were greater for the epileptic side than for the contralateral side after EEG activity suppression, spike train, and clinical seizure in all four cases. The true laterality was determined based on the relief of seizures by selective amygdalo-hippocampectomy. Thus, oxy-Hb amplitude could be a reliable measure for determining the epileptic focus side. Long-term simultaneous fNIRS/EEG measurement serves as an effective tool for recording spontaneous seizures. Cerebral hemodynamic measurement by fNIRS would serve as a valuable supplementary noninvasive measurement method for presurgical evaluation of MTLE.