A case of congenital fiber-type disproportion syndrome presenting dilated cardiomyopathy with ACTA1 mutation.

BACKGROUND: Actin, alpha, skeletal muscle 1 (ACTA1) is one of the causative genes of nemaline myopathy (NM) and congenital fiber-type disproportion (CFTD). CFTD is characterized by type 1 fiber atrophy and distinguished from NM in the absence of rods. Eight patients with CFTD, including one patient with dilated cardiomyopathy (DCM), have previously been reported. Herein, we report the case of a 10-year-old boy presenting with CFTD and DCM. METHODS: We performed exome sequencing and analyzed the effect of Met327Lys mutations on cultured C2C12 muscle cells compared with that seen in the wild type (WT, ACTA1) and previously identified Asp294Val mutations associated with a severe phenotype of CFTD without cardiomyopathy. RESULTS: Exome sequencing revealed a de novo mutation, c.980 T > A, p.(Met327Lys), in ACTA1 (NM_001100.4). C2C12 cells transfected with the WT plasmid expressed ACTA1 in the nucleus and cytoplasm. Cells with the Asp294Val mutant showed needle-like structures in the cytoplasm, whereas the expression of the Met327Lys mutant resulted in few aggregations but many apoptotic cells. CONCLUSION: Apoptosis induced in Met327Lys-transfected muscle cells supports the pathogenicity of the mutation and can be implicated as one of the histopathological features associated with CFTD, as in NM.

Recurrent pneumonia in three patients with MECP2 duplication syndrome with aspiration as the possible cause.

INTRODUCTION: Methyl-CpG binding protein 2 gene (MECP2) is located on the X chromosome (Xq28) and is important for nervous and immune system functioning. Patients with MECP2 duplication syndrome (MDS) have recurrent respiratory infections (RRIs). Although RRIs often occur with MDS because some patients with MDS also have hypoimmunoglobulinemia and duplication of the interleukin-1-receptor-associated kinase-1 gene (IRAK1), which is also located on Xq28, the phenotype of IRAK1 duplication in patients with MDS remains unclear. METHODS: The clinical course of three patients with MDS who underwent laryngotracheal separation (LTS) at two institutions was summarized. RESULTS: Three patients with MDS were identified to have recurrent pneumonia characteristic of aspiration pneumonia, sometimes requiring artificial ventilation therapy; they had no other bacterial infections. After LTS, they rarely had pneumonia. In MDS, MECP2 expression increased two-fold naturally, while IRAK-1 expression showed no difference compared with a healthy subject. CONCLUSIONS: Since RRIs in MDS are thought to be caused by aspiration and not susceptibility to infection previously estimated to be major complication, the evaluation of aspiration is recommended for RRIs for better management of MDS.

Computational identification of variables in neonatal vocalizations predictive for postpubertal social behaviors in a mouse model of 16p11.2 deletion.

Autism spectrum disorder (ASD) is often signaled by atypical cries during infancy. Copy number variants (CNVs) provide genetically identifiable cases of ASD, but how early atypical cries predict a later onset of ASD among CNV carriers is not understood in humans. Genetic mouse models of CNVs have provided a reliable tool to experimentally isolate the impact of CNVs and identify early predictors for later abnormalities in behaviors relevant to ASD. However, many technical issues have confounded the phenotypic characterization of such mouse models, including systematically biased genetic backgrounds and weak or absent behavioral phenotypes. To address these issues, we developed a coisogenic mouse model of human proximal 16p11.2 hemizygous deletion and applied computational approaches to identify hidden variables within neonatal vocalizations that have predictive power for postpubertal dimensions relevant to ASD. After variables of neonatal vocalizations were selected by least absolute shrinkage and selection operator (Lasso), random forest, and Markov model, regression models were constructed to predict postpubertal dimensions relevant to ASD. While the average scores of many standard behavioral assays designed to model dimensions did not differentiate a model of 16p11.2 hemizygous deletion and wild-type littermates, specific call types and call sequences of neonatal vocalizations predicted individual variability of postpubertal reciprocal social interaction and olfactory responses to a social cue in a genotype-specific manner. Deep-phenotyping and computational analyses identified hidden variables within neonatal social communication that are predictive of postpubertal behaviors.

Acute administration of methylphenidate differentially affects cortical processing of emotional facial expressions in attention-deficit hyperactivity disorder children as studied by functional near-infrared spectroscopy.

Significance: It has been reported that children with attention-deficit hyperactivity disorder (ADHD) have impairment in the recognition of angry but not of happy facial expressions, and they show atypical cortical activation patterns in response to facial expressions. However, little is known about neural mechanisms underlying the impaired recognition of facial expressions in school-aged children with ADHD and the effects of acute medication on their processing of facial expressions. Aim: We aimed to investigate the possibility that acute administration of methylphenidate (MPH) affects processing of facial expressions in ADHD children. Approach: We measured the hemodynamic changes in the bilateral temporo-occipital areas of ADHD children observing the happy and angry facial expressions before and 1.5 h after MPH or placebo administration in a randomized, double-blind, placebo-controlled, crossover design study. Results: We found that, regardless of medication, happy expressions induced increased oxyhemoglobin (oxy-Hb) responses in the right inferior occipital region but not in the superior temporal region. For angry expressions, oxy-Hb responses increased after MPH administration, but not after placebo administration, in the left inferior occipital area, whereas there was no significant activation before MPH administration. Conclusions: Our results suggest that (1) ADHD children consistently recruit the right inferior occipital regions to process happy expressions and (2) MPH administration to ADHD children enhances cortical activation in the left inferior occipital regions when they process angry expressions.

Atypical Dynamic-Connectivity Recruitment in Attention-Deficit/Hyperactivity Disorder Children: An Insight Into Task-Based Dynamic Connectivity Through an fNIRS Study.

Connectivity between brain regions has been redefined beyond a stationary state. Even when a person is in a resting state, brain connectivity dynamically shifts. However, shifted brain connectivity under externally evoked stimulus is still little understood. The current study, therefore, focuses on task-based dynamic functional-connectivity (FC) analysis of brain signals measured by functional near-infrared spectroscopy (fNIRS). We hypothesize that a stimulus may influence not only brain connectivity but also the occurrence probabilities of task-related and task-irrelevant connectivity states. fNIRS measurement (of the prefrontal-to-inferior parietal lobes) was conducted on 21 typically developing (TD) and 21 age-matched attention-deficit/hyperactivity disorder (ADHD) children performing an inhibitory control task, namely, the Go/No-Go (GNG) task. It has been reported that ADHD children lack inhibitory control; differences between TD and ADHD children in terms of task-based dynamic FC were also evaluated. Four connectivity states were found to occur during the temporal task course. Two dominant connectivity states (states 1 and 2) are characterized by strong connectivities within the frontoparietal network (occurrence probabilities of 40%-56% and 26%-29%), and presumptively interpreted as task-related states. A connectivity state (state 3) shows strong connectivities in the bilateral medial frontal-to-parietal cortices (occurrence probability of 7-15%). The strong connectivities were found at the overlapped regions related the default mode network (DMN). Another connectivity state (state 4) visualizes strong connectivities in all measured regions (occurrence probability of 10%-16%). A global effect coming from cerebral vascular may highly influence this connectivity state. During the GNG stimulus interval, the ADHD children tended to show decreased occurrence probability of the dominant connectivity state and increased occurrence probability of other connectivity states (states 3 and 4). Bringing a new perspective to explain neuropathophysiology, these findings suggest atypical dynamic network recruitment to accommodate task demands in ADHD children.

Exploring attentive task-based connectivity for screening attention deficit/hyperactivity disorder children: a functional near-infrared spectroscopy study.

Connectivity impairment has frequently been associated with the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). Although the connectivity of the resting state has mainly been studied, we expect the transition between baseline and task may also be impaired in ADHD children. Twenty-three typically developing (i.e., control) and 36 disordered (ADHD and autism-comorbid ADHD) children were subjected to connectivity analysis. Specifically, they performed an attention task, visual oddball, while their brains were measured by functional near-infrared spectroscopy. The results of the measurements revealed three key findings. First, the control group maintained attentive connectivity, even in the baseline interval. Meanwhile, the disordered group showed enhanced bilateral intra- and interhemispheric connectivities while performing the task. However, right intrahemispheric connectivity was found to be weaker than those for the control group. Second, connectivity and activation characteristics might not be positively correlated with each other. In our previous results, disordered children lacked activation in the right middle frontal gyrus. However, within region connectivity of the right middle frontal gyrus was relatively strong in the baseline interval and significantly increased in the task interval. Third, the connectivity-based biomarker performed better than the activation-based biomarker in terms of screening. Activation and connectivity features were independently optimized and cross validated to obtain the best performing threshold-based classifier. The effectiveness of connectivity features, which brought significantly higher training accuracy than the optimum activation features, was confirmed (88% versus 76%). The optimum screening features were characterized by two trends: (1) strong connectivities of right frontal, left frontal, and left parietal lobes and (2) weak connectivities of left frontal, left parietal, and right parietal lobes in the control group. We conclude that the attentive task-based connectivity effectively shows the difference between control and disordered children and may represent pathological characteristics to be feasibly implemented as a supporting tool for clinical screening.

Rapid progression of a walking disability in a 5-year-old boy with a CLN6 mutation.

INTRODUCTION: Neuronal ceroid lipofuscinoses (NCLs; CLN) are mainly autosomal recessive neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigments in neuronal and other cells. Symptoms include visual disabilities, motor decline, and epilepsy. Causative genes are CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN8, CLN10, CLN11, CLN12, CLN13, and CLN14. We present the fourth Japanese case with a CLN6 mutation. CASE PRESENTATION: At 3 years of age, our patient became clumsy and fell down easily. He developed focal seizures with impaired consciousness and was started on carbamazepine. He showed ataxic walking and dysarthria with increased deep tendon reflexes. Interictal electroencephalogram revealed slow waves in the left temporal and occipital areas. Brain magnetic resonance imaging showed cerebellar atrophy and ventriculomegaly. In optical coherence tomography (OCT), the inner layer of the retina was thick and highly reflective. Exome sequencing revealed a known homozygous mutation, C.794_976del, p. (Ser265del) in CLN6. DISCUSSION: A total of 130 cases of NCL with CLN6 mutations have been reported globally, of which only four were from Japan including the current patient. The deletion of serine at position 265 has been reported in six cases. Ser265 is located in a region of short repeated sequences that is susceptible to mutation. Clinical trials of gene therapy using adeno-associated virus serotype 9 have started for NCL6, making early diagnosis crucial. OCT examination might be helpful in achieving a diagnosis.

Distinct Methylphenidate-Evoked Response Measured Using Functional Near-Infrared Spectroscopy During Go/No-Go Task as a Supporting Differential Diagnostic Tool Between Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Comorbid Children.

Attention deficit/hyperactivity disorder (ADHD) has been frequently reported as co-occurring with autism spectrum disorder (ASD). However, ASD-comorbid ADHD is difficult to diagnose since clinically significant symptoms are similar in both disorders. Therefore, we propose a classification method of differentially recognizing the ASD-comorbid condition in ADHD children. The classification method was investigated based on functional brain imaging measured by near-infrared spectroscopy (NIRS) during a go/no-go task. Optimization and cross-validation of the classification method was carried out in medicated-naïve and methylphenidate (MPH) administered ADHD and ASD-comorbid ADHD children (randomized, double-blind, placebo-controlled, and crossover design) to select robust parameters and cut-off thresholds. The parameters could be defined as either single or averaged multi-channel task-evoked activations under an administration condition (i.e., pre-medication, post-MPH, and post-placebo). The ADHD children were distinguished by significantly high MPH-evoked activation in the right hemisphere near the midline vertex. The ASD-comorbid ADHD children tended to have low activation responses in all regions. High specificity (86 ± 4.1%; mean ± SD), sensitivity (93 ± 7.3%), and accuracy (82 ± 1.6%) were obtained using the activation of oxygenated-hemoglobin concentration change in right middle frontal, angular, and precentral gyri under MPH medication. Therefore, the significantly differing MPH-evoked responses are potentially effective features and as supporting differential diagnostic tools.

Erratum: Adaptive algorithm utilizing acceptance rate for eliminating noisy epochs in block-design functional near-infrared spectroscopy data: application to study in attention deficit/hyperactivity disorder children.

[This corrects the article DOI: 10.1117/1.NPh.5.4.045001.].

Adaptive algorithm utilizing acceptance rate for eliminating noisy epochs in block-design functional near-infrared spectroscopy data: application to study in attention deficit/hyperactivity disorder children.

Functional near-infrared spectroscopy (fNIRS) signals are prone to problems caused by motion artifacts and physiological noises. These noises unfortunately reduce the fNIRS sensitivity in detecting the evoked brain activation while increasing the risk of statistical error. In fNIRS measurements, the repetitive resting-stimulus cycle (so-called block-design analysis) is commonly adapted to increase the sample number. However, these blocks are often affected by noises. Therefore, we developed an adaptive algorithm to identify, reject, and select the noise-free and/or least noisy blocks in accordance with the preset acceptance rate. The main features of this algorithm are personalized evaluation for individual data and controlled rejection to maintain the sample number. Three typical noise criteria (sudden amplitude change, shifted baseline, and minimum intertrial correlation) were adopted. Depending on the quality of the dataset used, the algorithm may require some or all noise criteria with distinct parameters. Aiming for real applications in a pediatric study, we applied this algorithm to fNIRS datasets obtained from attention deficit/hyperactivity disorder (ADHD) children as had been studied previously. These datasets were divided for training and validation purposes. A validation process was done to examine the feasibility of the algorithm regardless of the types of datasets, including those obtained under sample population (ADHD or typical developing children), intervention (nonmedication and drug/placebo administration), and measurement (task paradigm) conditions. The algorithm was optimized so as to enhance reproducibility of previous inferences. The optimum algorithm design involved all criteria ordered sequentially (0.047 mM mm of amplitude change, 0.029 mM mm / s of baseline slope, and 0.6 × interquartile range of outlier threshold for each criterion, respectively) and presented complete reproducibility in both training and validation datasets. Compared to the visual-based rejection as done in the previous studies, the algorithm achieved 71.8% rejection accuracy. This suggests that the algorithm has robustness and potential to substitute for visual artifact-detection.

Atypical neural modulation in the right prefrontal cortex during an inhibitory task with eye gaze in autism spectrum disorder as revealed by functional near-infrared spectroscopy.

Autism spectrum disorder (ASD) is characterized by impairment in social communication and the presence of restricted and repetitive behaviors and interests. Executive function impairment is reportedly partially responsible for these symptoms. Executive function includes planning, flexibility, and inhibitory control. Although planning and flexibility in ASD have been consistently reported as atypical, the atypicality of inhibitory control remains controversial. As most previous studies have used nonsocial stimuli to investigate inhibitory control in ASD, the effects of socially relevant information on the inhibitory control system in individuals with ASD remain unclear. Therefore, we developed a go/no-go task with gaze stimuli and measured hemodynamic responses in the right prefrontal cortex (PFC), involved in inhibitory processing in both typically developing (TD) children and children with ASD, using functional near-infrared spectroscopy. Direct gaze induced commission errors to similar extents in both groups. Contrary to the behavioral responses, neural activation in the right PFC was modulated by gaze direction only in the TD group. These findings suggest that the gaze-processing mechanisms in the prefrontal region may be affected by atypical gaze processing in other brain regions during an inhibitory control task with socially relevant information in ASD.

Rituximab was effective for acute disseminated encephalomyelitis followed by recurrent optic neuritis with anti-myelin oligodendrocyte glycoprotein antibodies.

BACKGROUND: The effect of rituximab on acute disseminated encephalomyelitis (ADEM) followed by recurrent optic neuritis (ON) is not yet known. PATIENT: We are reporting the case of a 4-year-old Japanese girl who was diagnosed with anti-myelin oligodendrocyte glycoprotein (MOG) antibody positive ADEM followed by recurrent ON. She developed altered mental status, left facial paralysis, left paresis, and experienced three episodes of ON. She was treated with rituximab and azathioprine (AZA) as prevention for recurrent ON. She relapsed under treatment with AZA when CD19 cells reappeared 6 months after the first rituximab infusion. However, she has not relapsed since her CD19 count was reduced and kept low with rituximab infusion. CONCLUSIONS: It is conceivable that anti-MOG antibodies are involved in the pathology of "ADEM followed by recurrent ON," and that the early introduction of rituximab, which is involved in the suppression of antibody production and has effects on CD20 T lymphocytes, may be a feasible treatment for ON. Due to the small number of patients, additional reports on prospectively followed patients are needed.

Leigh syndrome with spinal cord involvement due to a hemizygous NDUFA1 mutation.

Leigh syndrome, which is a common phenotype of pediatric mitochondrial disease, is a progressive neurodegenerative disease. The typical neuroimaging findings of Leigh syndrome include bilateral symmetric lesions in the basal ganglia and/or the brainstem. However, there are a few reports on spinal cord involvement in patients with Leigh syndrome. In the present case, magnetic resonance imaging (MRI) obtained during infancy revealed symmetric lesions in the substantia nigra of a patient with Leigh syndrome with an NDUFA1 mutation; lesions of the bilateral putamen and brainstem were subsequently observed. Additionally, our patient presented large and extended spinal cord lesions. Therefore, this case is suggesting that we should consider the occurrence of spinal cord lesions as an atypical finding in Leigh syndrome.

A case of severe movement disorder with GNAO1 mutation responsive to topiramate.

We report the case of a 19-year-old female patient who had progressive chorea associated with a GNAO1 mutation. Chorea was refractory to multiple anticonvulsants, and the patient suffered from tiapride-induced neuroleptic malignant syndrome. After identification of a GNAO1 missense mutation at the age of 18years, topiramate treatment was initiated and the frequency of chorea decreased dramatically. The efficacy of topiramate may have been related to the inhibitory modulation of voltage-activated Ca2+ channels. Given the side effects and complications associated with neuroleptics and deep brain stimulation, respectively, topiramate is recommended for the first-line management of severe chorea associated with a GNAO1 mutation.

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.

Acute neuropharmacological effects of atomoxetine on inhibitory control in ADHD children: a fNIRS study.

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.

MAOA/B deletion syndrome in male siblings with severe developmental delay and sudden loss of muscle tonus.

Deletion of the monoamine oxidase (MAO)-A and MAO-B was detected in two male siblings and in their mother. The approximately 800-kb deletion, extending from about 43.0MB to 43.8MB, was detected by array comparative genomic hybridization analysis. The MAOA and MAOB genes were included in the deletion, but the adjacent Norrie disease gene, NDP, was not deleted. The boys had short stature, hypotonia, severe developmental delays, episodes of sudden loss of muscle tone, exiting behavior, lip-smacking and autistic features. The serotonin levels in their cerebrospinal fluid were extremely elevated. Another set of siblings with this deletion was reported previously. We propose recognition of MAOA/B deletion syndrome as a distinct disorder.

Neuropharmacological effect of methylphenidate on attention network in children with attention deficit hyperactivity disorder during oddball paradigms as assessed using functional near-infrared spectroscopy.

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.

Neuropharmacological effect of atomoxetine on attention network in children with attention deficit hyperactivity disorder during oddball paradigms as assessed using functional near-infrared spectroscopy.

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.

Right prefrontal activation as a neuro-functional biomarker for monitoring acute effects of methylphenidate in ADHD children: An fNIRS study.

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.