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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.

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.

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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.

Abstract. 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. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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.

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.