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

Mariko Y. Momoi,Eiju Watanabe,Yuji Gunji,Tsutomu Mizutani,Masako Nagashima,Takanori Yamagata,Ippeita Dan,Daisuke Hirano,Yukifumi Monden,Daisuke Tsuzuki,Takamichi Taniguchi,Yasushi Kyutoku,Haruka Dan,Hideo Shimoizumi

doi:10.1016/j.nicl.2014.09.001

Abstract

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.

Highlights

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent developmental disorders, affecting between 5 and 9% of school-aged children (Dittmann et al, 2009; Willcutt, 2012)
We found no significant differences in accuracy for go and no-go trials or in reaction times (RT) for correct trials between control and pre-medication, post-placebo and post-ATX ADHD subjects (Table 2)
Through assessing cortical activation data of ADHD and healthy control subjects performing a go/no-go task reflecting function of the motor-related inhibitory network, we revealed that the right IFG/MFG is a neural substrate of ATX effects in ADHD children based on the following findings

Summary

Introduction

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent developmental disorders, affecting between 5 and 9% of school-aged children (Dittmann et al, 2009; Willcutt, 2012). ADHD is associated with a primary impairment in executive controls, including response inhibition and working memory (Barkley, 1997; Dias et al, 2013; Dittmann et al, 2009; Willcutt, 2012). Symptoms of ADHD typically develop during early elementary school years, and, in most cases, progress to a chronic state during adulthood (Drechsler et al, 2005). Recommended treatments for ADHD children include both medication and behavioral therapy (Hodgkins et al, 2012). Nagashima et al / NeuroImage: Clinical 6 (2014) 192–201 biased toward the NA system with the K(i) of ATX to NA and DA transporters being 5 and 1451 nM, respectively (Bymaster et al, 2002)

Methods

Results

Discussion

Conclusion