Elsevier

Biological Psychiatry

Volume 80, Issue 12, 15 December 2016, Pages 896-904
Biological Psychiatry

Archival Report
Functional Decoding and Meta-analytic Connectivity Modeling in Adult Attention-Deficit/Hyperactivity Disorder

https://doi.org/10.1016/j.biopsych.2016.06.014Get rights and content

Abstract

Background

Task-based functional magnetic resonance imaging (fMRI) studies of adult attention-deficit/hyperactivity disorder (ADHD) have revealed various ADHD-related dysfunctional brain regions, with heterogeneous findings across studies. Here, we used novel meta-analytic data-driven approaches to characterize the function and connectivity profile of ADHD-related dysfunctional regions consistently detected across studies.

Methods

We first conducted an activation likelihood estimation meta-analysis of 24 task-based fMRI studies in adults with ADHD. Each ADHD-related dysfunctional region resulting from the activation likelihood estimation meta-analysis was then analyzed using functional decoding based on ~7500 fMRI experiments in the BrainMap database. This approach allows mapping brain regions to functions not necessarily tested in individual studies, thus suggesting possible novel functions for those regions. Additionally, ADHD-related dysfunctional regions were clustered based on their functional coactivation profiles across all the experiments stored in BrainMap (meta-analytic connectivity modeling).

Results

ADHD-related hypoactivation was found in the left putamen, left inferior frontal gyrus (pars opercularis), left temporal pole, and right caudate. Functional decoding mapped the left putamen to cognitive aspects of music perception/reproduction and the left temporal lobe to language semantics; both these regions clustered together on the basis of their meta-analytic functional connectivity. Left inferior gyrus mapped to executive function tasks; right caudate mapped to both executive function tasks and music-related processes.

Conclusions

Our study provides meta-analytic support to the hypothesis that, in addition to well-known deficits in typical executive functions, impairment in processes related to music perception/reproduction and language semantics may be involved in the pathophysiology of adult ADHD.

Section snippets

Search Strategy

Cortese et al. (6) included 16 studies in adults, published up to June 30, 2011. We updated this meta-analysis (last search on March 15, 2015) using the same search strategy, as detailed in the Supplement.

Study Eligibility Criteria

Studies were retained if 1) they presented data on adults with ADHD; 2) ADHD diagnosis was made according to DSM (III, IV, IV-TR) or ICD (9 or 10); 3) a matched group of healthy subjects was included; 4) data were reported as three-dimensional coordinates in stereotactic space; and 5)

Literature Search

We found 10 pertinent studies (13, 35, 36, 37, 38, 39, 40, 41, 42, 43) published after the search date of our prior meta-analysis (6), increasing the sample size by 40% relative to our previous meta-analysis in adults. Figure 1 shows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) flow chart (44) of the selected studies. Including the 16 previously included datasets (10, 11, 12, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57) from Cortese et al. (6), we

Discussion

This updated meta-analysis of task-based fMRI studies in adults with ADHD is the first to apply meta-analytic connectivity modeling and functional decoding to characterize ADHD-related dysfunctional regions, pointing to possible novel functions of dysfunctional brain regions not necessarily tested in individual studies. These methods leverage a large curated cognitive neuroscience database (BrainMap) to support data-driven interpretation of novel results. This is also the largest ALE

Acknowledgments and Disclosures

This work was supported by Grant Nos. R01MH083246 and R01MH074457, the Helmholtz Portfolio Theme “Supercomputing and Modeling for the Human Brain” and the European Union Seventh Framework Programme (FP7/2007-2013) under Grant No. 604102.

SC has received royalties from Argon Healthcare, Italy (2012–2014). GM was on the advisory boards for Eli Lilly, Shire, and Angelini; has received research grants from Eli Lilly and Shire; and has been a speaker for Eli Lilly, Shire, Lundbeck, and Otsuka. All

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