Atypical coupling between posterior regions of the default mode network in attention-deficit/hyperactivity disorder: a pharmaco-magnetoencephalography study

Atypical coupling between posterior regions of the default mode network in attention-deficit/hyperactivity disorder: a pharmaco-magnetoencephalography study

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J Psychiatry Neurosci 2013; 38(5): 333-340

J.D. Franzen, E. Heinrichs-Graham, M.L. White, M.W. Wetzel, N.L. Knott, T.W. Wilson

Franzen, Wetzel — Department of Psychiatry, University of Nebraska Medical Center, Omaha, Neb.; Franzen — Department of Psychiatry, Creighton University School of Medicine, Omaha, Neb.; Heinrichs-Graham, Knott, Wilson — Center for Magnetoencephalography, University of Nebraska Medical Center, Omaha, Neb.; Heinrichs-Graham — Department of Psychology, University of Nebraska, Omaha, Neb.; White — Department of Radiology, University of Nebraska Medical Center, Omaha, Neb.; Wetzel – Mental Health Unit, Lincoln Correctional Center, Nebraska Department of Correctional Services, Lincoln, Neb.; Wilson — Departments of Pharmacology & Experimental Neuroscience, and Neurological Sciences, University of Nebraska Medical Center, Omaha, Neb., USA

Abstract

Background: Dysfunction in the default mode network (DMN), a group of cortical areas more active during the resting state, has been linked to attentional deficits and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Prior imaging studies have shown decreased functional connectivity between DMN nodes in patients with ADHD, primarily between anterior and posterior regions. Using magnetoencephalography (MEG), we evaluated phase coherence (i.e., functional connectivity) among regions of the DMN in healthy controls and adults with ADHD before and after stimulant therapy.

Methods: We obtained a resting-state MEG recording for all participants. Magnetoencephalography data were transformed into a ~30 node regional source model using inverse spatial filtering, including regions corresponding to the DMN. We computed the zero-lag phase coherence between these regions pairwise for 5 distinct frequency bands, and we assessed group and medication effects.

Results: Twelve adults with and 13 without ADHD participated in our study. Functional connectivity was stronger between particular node pairs and showed frequency-specific effects. Unmedicated patients showed reduced phase locking between posterior cingulate/precuneus regions (PCC) and right inferior parietal cortices (RIPL), and between medial prefrontal regions (MPFC) and the left inferior parietal region (LIPL) and the PCC. Unmedicated patients had increased phase locking between the RIPL and LIPL regions compared with controls. Administration of stimulants improved phase locking abnormalities along the MPFC–PCC and LIPL–RIPL pathways in patients with ADHD.

Limitations: Modest sample size and lack of duration of patient treatment history may limit the generalizability of our findings.

Conclusion: Adults with ADHD exhibit hyper- and hypoconnectivity between regions of the DMN during rest, which were suppressed after stimulant medication administration.


Submitted Mar. 14, 2012; Revised Sept. 20, Nov. 26, 2012; Accepted Feb. 12, 2013.

Acknowledgements: Funding for the Center for Magnetoencephalography has been generously provided by an anonymous private donor. E. Heinrichs-Graham was supported by the Hattie B. Munroe Foundation through a graduate research assistantship.

Competing interests: None declared by J.D. Franzen and N.L. Knott. As above for E. Heinrichs-Graham. M.L. White reported consulting fees from Philips Healthcare, serves on the advisory board for Bayer HealthCare Pharmaceuticals Inc., and has received grant funding from Bracco Diagnostics Inc. M.W. Wetzel has received speaker honoraria from Shire. T.W. Wilson receives grant funding through his institution from the National Institutes of Health. The funders had no role in study design, data collection and analysis, decisions to publish, or preparation of the manuscript.

Contributors: M.W. Wetzel and T.W. Wilson designed the study. E. Heinrichs-Graham and T.W. Wilson acquired the data. J.D. Franzen, E. Heinrichs-Graham, M.L. White and T.W. Wilson analyzed the data. J.D. Franzen, E. Heinrichs-Graham and T.W. Wilson wrote the article. E. Heinrichs-Graham, M.L. White, M.W. Wetzel, N.L. Knott and T.W. Wilson reviewed the article. All authors approved its publication.

DOI: 10.1503/jpn.120054

Correspondence to: T.W. Wilson, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center,
988422 Nebraska Medical Center, Omaha NE 68198, United States; tony.w.wilson@gmail.com