Samuele Cortese1, F Xavier Castellanos2, Claudia R Eickhoff3, Giulia D'Acunto4, Gabriele Masi4, Peter T Fox5, Angela R Laird6, Simon B Eickhoff7. 1. Academic Unit of Psychology, Developmental Brain-Behaviour Laboratory, Southampton, United Kingdom; Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, United Kingdom; The Child Study Center, Hassenfeld Children's Hospital of New York, NYU Langone Medical Center, New York; IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Italy. Electronic address: samuele.cortese@gmail.com. 2. The Child Study Center, Hassenfeld Children's Hospital of New York, NYU Langone Medical Center, New York; Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York. 3. Institute of Neuroscience and Medicine (INM-1), Research Center Jülich GmbH, Jülich; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen. 4. IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Italy. 5. Research Imaging Institute, University of Texas Health Science Center, San Antonio, Texas; Department of Radiology, University of Texas Health Science Center, San Antonio, Texas; South Texas Veterans Health Care System, San Antonio, Texas. 6. Department of Physics, Florida International University, Miami, Florida. 7. Institute of Neuroscience and Medicine (INM-1), Research Center Jülich GmbH, Jülich; Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
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.
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.
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