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Abstract Background A variety of neuroimaging software packages have been released from various laboratories worldwide, and many researchers use these packages in combination. Though most of these software packages are freely available, some people find them difficult to install and configure because they are mostly based on UNIX-like operating systems. We developed a live USB-bootable Linux package named "Lin4Neuro." This system includes popular neuroimaging analysis tools. The user interface is customized so that even Windows users can use it intuitively. Results The boot time of this system was only around 40 seconds. We performed a benchmark test of inhomogeneity correction on 10 subjects of three-dimensional T1-weighted MRI scans. The processing speed of USB-booted Lin4Neuro was as fast as that of the package installed on the hard disk drive. We also installed Lin4Neuro on a virtualization software package that emulates the Linux environment on a Windows-based operation system. Although the processing speed was slower than that under other conditions, it remained comparable. Conclusions With Lin4Neuro in one's hand, one can access neuroimaging software packages easily, and immediately focus on analyzing data. Lin4Neuro can be a good primer for beginners of neuroimaging analysis or students who are interested in neuroimaging analysis. It also provides a practical means of sharing analysis environments across sites.

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., (© The Author(s) 2023. Published by Oxford University Press.)

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.

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., Competing Interests: The authors declare no conflict of interest.

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2022. The Author(s).)

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., (© 2021. The Author(s).)

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.

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 (I 2 : 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., (© 2020 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

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., Competing Interests: No authors have any competing interests.

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., Competing Interests: Declaration of Competing Interest TN is a consultant to Daiichi Sankyo and Kitasato Daiichi Sankyo Vaccines and received a research grant from Daiichi Sankyo and Kitasato Daiichi Sankyo Vaccines; EV is an employee of Sanofi Pasteur, DT, SN, TS, YI, and HM are employees of Sanofi; HT is an employee of Daiichi Sankyo., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2020 Su, Culotta, Hoffman, Trost, Pelphrey, Tsuzuki and Bhat.)

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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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 (HbO 2 ) 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.

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.

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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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., (© 2015 Wiley Periodicals, Inc.)

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.

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.

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.

The current study aimed to explore the neural substrate for atomoxetine effects on attentional control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS), which can be applied to young children with ADHD more easily than conventional neuroimaging modalities. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 15 ADHD children (6 to 14 years old) performing an oddball task before and 1.5 h after atomoxetine or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Fifteen age-, gender-, and intelligence quotient-matched normal controls without atomoxetine administration were also monitored. In the control subjects, the oddball task recruited the right prefrontal and inferior parietal cortices. The right prefrontal and parietal activation was normalized after atomoxetine administration in ADHD children. This was in contrast to our previous study using a similar protocol showing methylphenidate-induced normalization of only the right prefrontal function. fNIRS allows the detection of differential neuropharmacological profiles of both substances in the attentional network: the neuropharmacological effects of atomoxetine to upregulate the noradrenergic system reflected in the right prefrontal and inferior parietal activations and those of methylphenidate to upregulate the dopamine system reflected in the prefrontal cortex activation.

The object of the current study is to explore the neural substrate for effects of atomoxetine (ATX) on inhibitory control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS). We monitored the oxy-hemoglobin signal changes of sixteen ADHD children (6-14 years old) performing a go/no-go task before and 1.5 h after ATX or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Sixteen age- and gender-matched normal controls without ATX administration were also monitored. In the control subjects, the go/no-go task recruited the right inferior and middle prefrontal gyri (IFG/MFG), and this activation was absent in pre-medicated ADHD children. The reduction of right IFG/MFG activation was acutely normalized after ATX administration but not placebo administration in ADHD children. These results are reminiscent of the neuropharmacological effects of methylphenidate to up-regulate reduced right IFG/MFG function in ADHD children during inhibitory tasks. As with methylphenidate, activation in the IFG/MFG could serve as an objective neuro-functional biomarker to indicate the effects of ATX on inhibitory control in ADHD children. This promising technique will enhance early clinical diagnosis and treatment of ADHD in children, especially in those with a hyperactivity/impulsivity phenotype.

The current study aimed to explore the neural substrate for methylphenidate effects on attentional control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS), which can be applied to young children with ADHD more easily than conventional neuroimaging modalities. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 22 ADHD children (6 to 14 years old) performing an oddball task before and 1.5 h after methylphenidate or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Twenty-two age- and gender-matched normal controls without methylphenidate administration were also monitored. In the control subjects, the oddball task recruited the right prefrontal and inferior parietal cortices, and this activation was absent in premedicated ADHD children. The reduced right prefrontal activation was normalized after methylphenidate but not placebo administration in ADHD children. These results are consistent with the neuropharmacological effects of methylphenidate to upregulate the dopamine system in the prefrontal cortex innervating from the ventral tegmentum (mesocortical pathway), but not the noradrenergic system from the parietal cortex to the locus coeruleus. Thus, right prefrontal activation would serve as an objective neurofunctional biomarker to indicate the effectiveness of methylphenidate on ADHD children in attentional control. fNIRS monitoring enhances early clinical diagnosis and the treatment of ADHD children, especially those with an inattention phenotype.

Functional near infrared spectroscopy (fNIRS), which is compact, portable, and tolerant of body movement, is suitable for monitoring infant brain functions. Nevertheless, fNIRS also poses a technical problem in that it cannot provide structural information. Supplementation with structural magnetic resonance images (MRI) is not always feasible for infants who undergo fNIRS measurement. Probabilistic registration methods using an MRI database instead of subjects' own MRIs are optimized for adult studies and offer only limited resources for infant studies. To overcome this, we used high-quality infant MRI data for a 12-month-old infant and manually delineated segmented gyri from among the highly visible macroanatomies on the lateral cortical surface. These macroanatomical regions are primarily linked to the spherical coordinate system based on external cranial landmarks, and further to traditional 10-20-based head-surface positioning systems. While macroanatomical structures were generally comparable between adult and infant atlases, differences were found in the parietal lobe, which was positioned posteriorly at the vertex in the infant brain. The present study provides a referential framework for macroanatomical analyses in infant fNIRS studies. With this resource, multichannel fNIRS functional data could be analyzed in reference to macroanatomical structures through virtual and probabilistic registrations without acquiring subject-specific MRIs., (Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Functional near-infrared spectroscopy (fNIRS) has now become widely accepted as a common functional imaging modality. In order for fNIRS to achieve genuine neuroimaging citizenship, it would ideally be equipped with functional and structural image analyses. However, fNIRS measures cortical activities from the head surface without anatomical information of the object being measured. In this review article, we will present a methodological overview of spatial registration of fNIRS data to overcome this technical drawback of fNIRS. We first introduce and explore the use of standard stereotaxic space and anatomical labeling. Second, we explain different ways of describing scalp landmarks using 10-20 based systems. Third, we describe the simplest case of fNIRS data co-registration to a subject's own MRI. Fourth, we extend the concept to fNIRS data registration of group data. Fifth, we describe probabilistic registration methods, which use a reference-MRI database instead of a subject's own MRIs, and thus enable MRI-free registration for standalone fNIRS data. Sixth, we further extend the concept of probabilistic registration to three-dimensional image reconstruction in diffuse optical tomography. Seventh, we describe a 3D-digitizer-free method for the virtual registration of fNIRS data. Eighth, we provide practical guidance on how these techniques are implemented in software. Finally, we provide information on current resources and limitations for spatial registration of child and infant data. Through these technical descriptions, we stress the importance of presenting fNIRS data on a common platform to facilitate both intra- and inter-modal data sharing among the neuroimaging community., (© 2013 Elsevier Inc. All rights reserved.)

In Japan, verbal fluency tasks are commonly utilized as a standard paradigm for neuropsychological testing of cognitive and linguistic abilities. The Japanese "letter fluency task" is a mora/letter fluency task based on the phonological and orthographical characteristics of the Japanese language. Whether there are similar activation patterns across languages or a Japanese-specific mora/letter fluency pattern is not certain. We investigated the neural correlates of overt mora/letter and category fluency tasks in healthy Japanese. The category fluency task activated the bilateral fronto-temporal language-related regions with left-superior lateralization, while the mora/letter fluency task led to wider activation including the inferior parietal regions (left and right supramarginal gyrus). Specific bilateral supramarginal activation during the mora/letter fluency task in Japanese was distinct from that of similar letter fluency tasks in syllable-alphabet-based languages: this might be due to the requirement of additional phonological processing and working memory, or due to increased cognitive load in general., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: When people are asked to adjust the color of familiar objects such as fruits until they appear achromatic, the subjective gray points of the objects are shifted away from the physical gray points in a direction opposite to the memory color (memory color effect). It is still unclear whether the discrepancy between memorized and actual colors of objects is dependent on the familiarity of the objects. Here, we conducted two experiments in order to examine the relationship between the degree of a subject's familiarity with objects and the degree of the memory color effect by using logographs of food and beverage companies., Methods and Findings: In Experiment 1, we measured the memory color effects of logos which varied in terms of their familiarity (high, middle, or low). Results demonstrate that the memory color effect occurs only in the high-familiarity condition, but not in the middle- and low-familiarity conditions. Furthermore, there is a positive correlation between the memory color effect and the actual number of domestic stores of the brand. In Experiment 2, we assessed the semantic association between logos and food/beverage names by using a semantic priming task to elucidate whether the memory color effect of logos relates to consumer brand cognition, and found that the semantic associations between logos and food/beverage names in the high-familiarity brands were stronger than those in the low-familiarity brands only when the logos were colored correctly, but not when they were appropriately or inappropriately colored, or achromatic., Conclusion: The current results provide behavioral evidence of the relationship between the familiarity of objects and the memory color effect and suggest that the memory color effect increases with the familiarity of objects, albeit not constantly.

A fundamental question with regard to perceptual development is how multisensory information is processed in the brain during the early stages of development. Although a growing body of evidence has shown the early emergence of modality-specific functional differentiation of the cortical regions, the interplay between sensory inputs from different modalities in the developing brain is not well understood. To study the effects of auditory input during audio-visual processing in 3-month-old infants, we evaluated the spatiotemporal cortical hemodynamic responses of 50 infants while they perceived visual objects with or without accompanying sounds. The responses were measured using 94-channel near-infrared spectroscopy over the occipital, temporal, and frontal cortices. The effects of sound manipulation were pervasive throughout the diverse cortical regions and were specific to each cortical region. Visual stimuli co-occurring with sound induced the early-onset activation of the early auditory region, followed by activation of the other regions. Removal of the sound stimulus resulted in focal deactivation in the auditory regions and reduced activation in the early visual region, the association region of the temporal and parietal cortices, and the anterior prefrontal regions, suggesting multisensory interplay. In contrast, equivalent activations were observed in the lateral occipital and lateral prefrontal regions, regardless of sound manipulation. Our findings indicate that auditory input did not generally enhance overall activation in relation to visual perception, but rather induced specific changes in each cortical region. The present study implies that 3-month-old infants may perceive audio-visual multisensory inputs by using the global network of functionally differentiated cortical regions., (Copyright © 2011 Wiley Periodicals, Inc.)

There is an increasing need for a pig model for use in functional brain studies, but a system for determining precise stereotactic coordinates has yet to be developed. Thus, we devised a frameless navigation system for stereotactic positioning, and measured coordinates for the rostral region and the primary somatosensory cortex in the pig brain. Raw coordinates for somatic evoked potential recordings were obtained by passive optical tracking. The location was registered to a computed tomographic image in reference to four stable skull landmarks: the upper margin of each auditory meatus, the external occipital protuberance, and the point where the interfrontal suture crosses a line drawn between the two supraorbital foramina ("IF" point). The cortical position with the greatest response in evoked potential was mapped -51.0 ± 4.67 mm rostro-caudally, 9.1 ± 1.19 mm medio-laterally, and -8.8 ± 0.48 mm dorso-ventrally (means ± SD; n=3) to the IF point. These results show that frameless registration is useful for coordinate-based evoked-potential mapping of the rostral region of the Mexican hairless pig., (Copyright © 2012 Elsevier B.V. All rights reserved.)

An objective biomarker is a compelling need for the early diagnosis of attention deficit hyperactivity disorder (ADHD), as well as for the monitoring of pharmacological treatment effectiveness. The advent of fNIRS, which is relatively robust to the body movements of ADHD children, raised the possibility of introducing functional neuroimaging diagnosis in younger ADHD children. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 16 ADHD children (6 to 13 years old) performing a go/no-go task before and 1.5 h after MPH or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. 16 age- and gender-matched normal controls without MPH administration were also monitored. Relative to control subjects, unmedicated ADHD children exhibited reduced activation in the right inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during go/no-go tasks. The reduced right IFG/MFG activation was acutely normalized after MPH administration, but not after placebo administration. The MPH-induced right IFG/MFG activation was significantly larger than the placebo-induced activation. Post-scan exclusion rate was 0% among 16 right-handed ADHD children with IQ > 70. We revealed that the right IFG/MFG activation could serve as a neuro-functional biomarker for monitoring the acute effects of methylphenidate in ADHD children. fNIRS-based examinations were applicable to ADHD children as young as 6 years old, and thus would contribute to early clinical diagnosis and treatment of ADHD children.

We describe the validation of an anatomical brain atlas approach to the analysis of diffuse optical tomography (DOT). Using MRI data from 32 subjects, we compare the diffuse optical images of simulated cortical activation reconstructed using a registered atlas with those obtained using a subject's true anatomy. The error in localization of the simulated cortical activations when using a registered atlas is due to a combination of imperfect registration, anatomical differences between atlas and subject anatomies and the localization error associated with diffuse optical image reconstruction. When using a subject-specific MRI, any localization error is due to diffuse optical image reconstruction only. In this study we determine that using a registered anatomical brain atlas results in an average localization error of approximately 18 mm in Euclidean space. The corresponding error when the subject's own MRI is employed is 9.1 mm. In general, the cost of using atlas-guided DOT in place of subject-specific MRI-guided DOT is a doubling of the localization error. Our results show that despite this increase in error, reasonable anatomical localization is achievable even in cases where the subject-specific anatomy is unavailable., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Confrontation naming tasks assess cognitive processes involved in the main stage of word production. However, in fMRI, the occurrence of movement artifacts necessitates the use of covert paradigms, which has limited clinical applications. Thus, we explored the feasibility of adopting multichannel functional near-infrared spectroscopy (fNIRS) to assess language function during covert and overt naming tasks. Thirty right-handed, healthy adult volunteers underwent both naming tasks and cortical hemodynamics measurement using fNIRS. The overt naming task recruited the classical left-hemisphere language areas (left inferior frontal, superior and middle temporal, precentral, and postcentral gyri) exemplified by an increase in the oxy-Hb signal. Activations were bilateral in the middle and superior temporal gyri. However, the covert naming task recruited activation only in the left-middle temporal gyrus. The activation patterns reflected a major part of the functional network for overt word production, suggesting the clinical importance of fNIRS in the diagnosis of aphasic patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

For functional neuroimaging with near-infrared spectroscopy (NIRS), we recently introduced a probabilistic registration method that uses a reference magnetic resonance image (MRI) database instead of the subject's own MRI, and probabilistically registers the NIRS optode or channel positions onto a canonical brain template in the standard stereotactic brain coordinate systems. As an alternative method, we devised an anchor-based registration method utilizing roughly obtained anchor positions on the scalp instead of strictly defined landmarks such as 10/20 landmarks. This method uses a spherical coordinate system to seek a position in the reference MRI database that corresponds to the anchor position, and eventually presents NIRS optode and channel positions in the standard stereotactic brain coordinate system. For comparison against conventional probabilistic registration, we simulated NIRS optode holder placement on 100 synthesized virtual heads, and found holistic tendencies for probe position estimations were similar between the two methods. Comparison among anchor-based probabilistic registration, conventional probabilistic registration, and SPM-based registration via co-registration to a subject's own MRI revealed that intra-method variability was comparable to a small inter-method variability. Thus, anchor-based registration is a practical alternative, especially to avoid burdening a subject and to reduce experimental time., (Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

A large-scale study of 484 elementary school children (6-10 years) performing word repetition tasks in their native language (L1-Japanese) and a second language (L2-English) was conducted using functional near-infrared spectroscopy. Three factors presumably associated with cortical activation, language (L1/L2), word frequency (high/low), and hemisphere (left/right), were investigated. L1 words elicited significantly greater brain activation than L2 words, regardless of semantic knowledge, particularly in the superior/middle temporal and inferior parietal regions (angular/supramarginal gyri). The greater L1-elicited activation in these regions suggests that they are phonological loci, reflecting processes tuned to the phonology of the native language, while phonologically unfamiliar L2 words were processed like nonword auditory stimuli. The activation was bilateral in the auditory and superior/middle temporal regions. Hemispheric asymmetry was observed in the inferior frontal region (right dominant), and in the inferior parietal region with interactions: low-frequency words elicited more right-hemispheric activation (particularly in the supramarginal gyrus), while high-frequency words elicited more left-hemispheric activation (particularly in the angular gyrus). The present results reveal the strong involvement of a bilateral language network in children's brains depending more on right-hemispheric processing while acquiring unfamiliar/low-frequency words. A right-to-left shift in laterality should occur in the inferior parietal region, as lexical knowledge increases irrespective of language.

We aimed to explore the interactive effects of the accessibility of information and the degree of carbon footprint score on consumers' value judgments of food products. Participants (n=151, undergraduate students in Japan) rated their maximum willingness to pay (WTP) for four food products varying in information accessibility (active-search or read-only conditions) and in carbon footprint values (low, middle, high, or non-display) provided. We also assessed further effects of information accessibly and carbon footprint value on other product attributes utilizing the subjective estimation of taste, quality, healthiness, and environmental friendliness. Results of the experiment demonstrated an interactive effect of information accessibility and the degree of carbon emission on consumer valuation of carbon footprint-labeled food. The carbon footprint value had a stronger impact on participants' WTP in the active-search condition than in the read-only condition. Similar to WTP, the results of the subjective ratings for product qualities also exhibited an interactive effect of the two factors on the rating of environmental friendliness for products. These results imply that the perceived environmental friendliness inferable from a carbon footprint label contributes to creating value for a food product.

A growing number of human studies have reported the beneficial influences of acute as well as chronic exercise on cognitive functions. However, neuroimaging investigations into the neural substrates of the effects of acute exercise have yet to be performed. Using multichannel functional near-infrared spectroscopy (fNIRS), we sought cortical activation related to changes in the Stroop interference test, elicited by an acute bout of moderate exercise, in healthy volunteers (N=20). The compactness and portability of fNIRS allowed on-site cortical examination in a laboratory with a cycle ergometer, enabling strict control of the exercise intensity of each subject by assessing their peak oxygen intake (VO2peak). We defined moderate exercise intensity as 50% of a subject's peak oxygen uptake (50%VO2peak). An acute bout of moderate exercise caused significant improvement of cognitive performance reflecting Stroop interference as measured by reaction time. Consistent with previous functional neuroimaging studies, we detected brain activation due to Stroop interference (incongruent minus neutral) in the lateral prefrontal cortices in both hemispheres. This Stroop-interference-related activation was significantly enhanced in the left dorsolateral prefrontal cortex due to the acute bout of moderate exercise. The enhanced activation significantly coincided with the improved cognitive performance. This suggests that the left dorsolateral prefrontal cortex is likely the neural substrate for the improved Stroop performance elicited by an acute bout of moderate exercise. fNIRS, which allows physiological monitoring and functional neuroimaging to be combined, proved to be an effective tool for examining the cognitive effects of exercise., (2009 Elsevier Inc. All rights reserved.)

We investigated the effect that the parameters of luminance distribution in fresh food have on our visual perception of its freshness. We took pictures of the degradation over 32 h in freshness of a cabbage. We used original images, which were patches of the pictures taken at different sampling hours, and artificially generated pictures, called "matched images," created by fitting the luminance histogram shape of the original image (taken at the 1st hour) to those at various freshness stages using a luminance histogram-matching algorithm. Nine participants rated the perceived freshness of the original and the matched images on a scale of degradation. As a result, we found that the participants could quantitatively estimate the degradation in freshness of the cabbage simply by looking at the presented images. Some parameters of the luminance histograms monotonically change with decreasing freshness, indicating that the freshness of cabbage can be estimated using these parameters. However, the freshness ratings for the matched images after the 8th hour of degradation had lower modification than those for the respective original images. These results suggest that the luminance distribution in the vegetable texture partly contributes to visual freshness perception but other variables, such as spatial patterns, might also be important for estimating visual freshness., (Copyright 2010 Elsevier Ltd. All rights reserved.)