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

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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

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We assessed the effects of atomoxetine administration to ADHD children using fNIRS.
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Normal healthy control subjects recruited the right IFG/MFG during go/no-go tasks.
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Pre-medicated ADHD children exhibited reduced right IFG/MFG activation.
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The activation was acutely normalized by atomoxetine, but not by placebo.
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The right IFG/MFG activation may serve as an objective neuro-functional biomarker.

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Most cited references 92

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Stereotaxic display of brain lesions.

Chris Rorden, Matthew Brett (2000)

Traditionally lesion location has been reported using standard templates, text based descriptions or representative raw slices from the patient's CT or MRI scan. Each of these methods has drawbacks for the display of neuroanatomical data. One solution is to display MRI scans in the same stereotaxic space popular with researchers working in functional neuroimaging. Presenting brains in this format is useful as the slices correspond to the standard anatomical atlases used by neuroimagers. In addition, lesion position and volume are directly comparable across patients. This article describes freely available software for presenting stereotaxically aligned patient scans. This article focuses on MRI scans, but many of these tools are also applicable to other modalities (e.g. CT, PET and SPECT). We suggest that this technique of presenting lesions in terms of images normalized to standard stereotaxic space should become the standard for neuropsychological studies.

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Construction of a 3D probabilistic atlas of human cortical structures.

David W. Shattuck, Mubeena Mirza, Vitria Adisetiyo … (2008)

We describe the construction of a digital brain atlas composed of data from manually delineated MRI data. A total of 56 structures were labeled in MRI of 40 healthy, normal volunteers. This labeling was performed according to a set of protocols developed for this project. Pairs of raters were assigned to each structure and trained on the protocol for that structure. Each rater pair was tested for concordance on 6 of the 40 brains; once they had achieved reliability standards, they divided the task of delineating the remaining 34 brains. The data were then spatially normalized to well-known templates using 3 popular algorithms: AIR5.2.5's nonlinear warp (Woods et al., 1998) paired with the ICBM452 Warp 5 atlas (Rex et al., 2003), FSL's FLIRT (Smith et al., 2004) was paired with its own template, a skull-stripped version of the ICBM152 T1 average; and SPM5's unified segmentation method (Ashburner and Friston, 2005) was paired with its canonical brain, the whole head ICBM152 T1 average. We thus produced 3 variants of our atlas, where each was constructed from 40 representative samples of a data processing stream that one might use for analysis. For each normalization algorithm, the individual structure delineations were then resampled according to the computed transformations. We next computed averages at each voxel location to estimate the probability of that voxel belonging to each of the 56 structures. Each version of the atlas contains, for every voxel, probability densities for each region, thus providing a resource for automated probabilistic labeling of external data types registered into standard spaces; we also computed average intensity images and tissue density maps based on the three methods and target spaces. These atlases will serve as a resource for diverse applications including meta-analysis of functional and structural imaging data and other bioinformatics applications where display of arbitrary labels in probabilistically defined anatomic space will facilitate both knowledge-based development and visualization of findings from multiple disciplines.

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Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10-20 system oriented for transcranial functional brain mapping.

Masako Okamoto, Haruka Dan, Kuniko Sakamoto … (2004)

The recent advent of multichannel near-infrared spectroscopy (NIRS) has expanded its technical potential for human brain mapping. However, NIRS measurement has a technical drawback in that it measures cortical activities from the head surface without anatomical information of the object to be measured. This problem is also found in transcranial magnetic stimulation (TMS) that transcranially activates or inactivates the cortical surface. To overcome this drawback, we examined cranio-cerebral correlation using magnetic resonance imaging (MRI) via the guidance of the international 10-20 system for electrode placement, which had originally been developed for electroencephalography. We projected the 10-20 standard cranial positions over the cerebral cortical surface. After examining the cranio-cerebral correspondence for 17 healthy adults, we normalized the 10-20 cortical projection points of the subjects to the standard Montreal Neurological Institute (MNI) and Talairach stereotactic coordinates and obtained their probabilistic distributions. We also expressed the anatomical structures for the 10-20 cortical projection points probabilistically. Next, we examined the distance between the cortical surface and the head surface along the scalp and created a cortical surface depth map. We found that the locations of 10-20 cortical projection points in the standard MNI or Talairach space could be estimated with an average standard deviation of 8 mm. This study provided an initial step toward establishing a three-dimensional probabilistic anatomical platform that enables intra- and intermodal comparisons of NIRS and TMS brain imaging data.

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Author and article information

Contributors

Yukifumi Monden

Journal

Journal ID (nlm-ta): Neuroimage Clin

Journal ID (iso-abbrev): Neuroimage Clin

Title: NeuroImage : Clinical

Publisher: Elsevier

ISSN (Electronic): 2213-1582

Publication date PMC-release: 10 September 2014

Publication date (Electronic): 10 September 2014

Publication date Collection: 2014

Volume: 6

Pages: 192-201

Affiliations

[a ]Department of Pediatrics, Shimotsuke, Japan

[b ]Department of Neurosurgery, Shimotsuke, Japan

[c ]Functional Brain Science Laboratory, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan

[d ]Applied Cognitive Neuroscience Laboratory, Chuo University, 1-13-27 Kasuga, Bunkyo, Tokyo 112-8551, Japan

[e ]Department of Pediatrics, International University of Health and Welfare, 537-3 Iguchi, Nasushiobara, Tochigi 329-2763, Japan

[f ]International University of Health and Welfare, 2600-1 Kitakanemaru, Otawara, Tochigi, Japan

[g ]Rehabilitation Center, International University of Health and Welfare, 2600-1 Kitakanemaru, Otawara, Tochigi 324-8501, Japan

Author notes

[* ]Corresponding author. mon4441977319@ 123456jichi.ac.jp

Article

Publisher ID: S2213-1582(14)00137-5

DOI: 10.1016/j.nicl.2014.09.001

PMC ID: 4215398

PubMed ID: 25379431

SO-VID: ef01cc0c-a345-4cfb-9de7-9ccd8bf9abb3

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

History

Date received : 8 May 2014

Date revision received : 2 September 2014

Date accepted : 3 September 2014

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

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Most cited references 92

Stereotaxic display of brain lesions.

Construction of a 3D probabilistic atlas of human cortical structures.

Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10-20 system oriented for transcranial functional brain mapping.

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Contributors

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Cited by 26

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