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

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.

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

“…We could conclude that, when taken together, the current fNIRS results illustrate the specific neuropharmacological mechanism of ATX underlying the functional normalization of the attention network components. Furthermore, these results extend the conclusions of our previous fNIRS studies revealing ATX-and MPH-induced normalization in the right MFG/ IFG: 25,26,28 fNIRS-based measurement can distinguish between neural substrates of the DA and NA systems differentially involved in inhibitory and attentional controls.…”

“…On the other hand, in post-MPH and ATX administration ADHD groups, functional normalization was observed, using fNIRS, in the right MFG/IFG during go/no-go tasks. 25,26,28 These activation patterns were consistent with the results of previous fMRI studies. 33,34 In essence, the right prefrontal dysfunction in ADHD children was normalized by MPH for both inhibitory and attentional controls, and by ATX for inhibitory control.…”

“…fNIRS, which is convenient and robust, is suitable for the functional monitoring of children with ADHD who have difficulty performing active cognitive tasks in the enclosed environments of other imaging modalities. In fact, the cumulative postscan exclusion rate of our previous fNIRS studies (all studies) [25][26][27][28] was <5% of a total of 66 right-handed ADHD children and 54 control subjects including six year olds. [25][26][27][28] This is far lower than the rejection rate of functional magnetic resonance imaging (fMRI) studies, which is typically 50% for ADHD subjects six years old and older and 30% for the corresponding normal controls.…”

“…30 In order to clarify the differences in the neuronal substrate for both substances, our previous studies have aimed to assess the pharmacological neuromodulation of inhibitory control (using go/no-go tasks) by MPH 25,26 and ATX, 28 and of attention control (using oddball tasks) by MPH, 27 using a randomized, doubleblind, placebo-controlled, crossover design, with fNIRS measurement. In summary, we first detected brain activation in the right middle frontal gyrus/inferior frontal gyrus (MFG/IFG) during go/no-go tasks [25][26][27][28] and in the right MFG/IFG and inferior parietal lobe (IPL) during oddball tasks 27 in healthy control subjects. These activation patterns were consistent with the results of previous fMRI studies and were considered especially important for inhibitory control 18 and attention control.…”

fNIRS Studies on Hemispheric Asymmetry in Atypical Neural Function in Developmental Disorders

“…These studies have revealed hypoactivation in the right frontal lobe including the prefrontal cortex (PFC; Xiao et al, 2012; Yasumura et al, 2014), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) (Monden et al, 2012, 2015; Nagashima et al, 2014a,b,c), presumably because NIRS probes can easily be applied to the frontal region (see Table 1). These studies also found hypoactivation in the temporal (Ichikawa et al, 2014; Köchel et al, 2015) and parietal cortices (Nagashima et al, 2014b) as well.…”