Functional dysconnectivity of corticostriatal circuitry and differential response to methylphenidate in youth with attention-deficit/hyperactivity disorder

Functional dysconnectivity of corticostriatal circuitry and differential response to methylphenidate in youth with attention-deficit/hyperactivity disorder

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J Psychiatry Neurosci 2015;40(1):46-57

Soon-Beom Hong, MD, PhD; Ben J. Harrison, PhD; Alex Fornito, PhD; Chul-Ho Sohn, MD, PhD; In-Chan Song, PhD; Jae-Won Kim, MD, PhD

Abstract

Background: Brain frontostriatal circuits have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, effects of methylphenidate on circuit-level functional connectivity are as yet unclear. The aim of the present study was to comprehensively investigate the functional connectivity of major striatal subregions in children with ADHD, including subanalyses directed at mapping cognitive and treatment response characteristics.

Methods: Using a comprehensive seeding strategy, we examined resting-state functional connectivity of dorsal and ventral subdivisions of the caudate nucleus and putamen in children and adolescents with ADHD and in age- and sex-matched healthy controls.

Results: We enrolled 83 patients with ADHD and 22 controls in our study. Patients showed significantly reduced dorsal caudate functional connectivity with the superior and middle prefrontal cortices as well as reduced dorsal putamen connectivity with the parahippocampal cortex. These connectivity measures were correlated in opposite directions in patients and controls with attentional performance, as assessed using the Continuous Performance Test. Patients showing a good response to methylphenidate had significantly reduced ventral caudate/nucleus accumbens connectivity with the inferior frontal cortices compared with poor responders.

Limitations: Possible confounding effects of age-related functional connectivity change were not excluded owing to the wide age range of participants.

Conclusion: We observed a region-specific effect of methylphenidate on resting-state functional connectivity, suggesting the pretreatment level of ventral frontostriatal functional connectivity as a possible methylphenidate response biomarker of ADHD.


Submitted Dec. 18, 2013; Revised Apr. 23, Mar 20, 2014; Accepted May 26, 2014; Early-released Aug. 19, 2014.

Funding: This work was supported by the Basic Science Program through the National Research Foundation of Korea (2010-0002283 to J.-W. Kim). S.-B. Hong was supported by a National Research Foundation of Korea (NRF) grant (Global Internship Program) funded by the Korean government (MEST). B.J. Harrison is supported by a National Health and Medical Research Council of Australia (NHMRC) Clinical Career Development Fellowship (I.D. 628509). A. Fornito is supported by a Monash University Larkins Fellowship. The funding organizations had no influence on the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. S.- B. Hong had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Affiliations: Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Parkville, Victoria, Australia (Hong, Harrison, Fornito); Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia (Hong); Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea (Hong, Kim); Monash Clinical and Imaging Neuroscience, School of Psychology and Psychiatry & Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia ( Fornito); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (Sohn, Song).

Competing interests: None declared.

Contributors: S.-B. Hong, C.-H. Sohn, I.-C. Song and J.-W. Kim designed the study and acquired the data, which S.-B. Hong, B.J. Harrison, A. Fornito and J.-W. Kim analyzed. S.-B. Hong, B.J. Harrison, A. Fornito and J.-W. Kim wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.130290

Correspondence to: J.-W. Kim, Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, 101 Daehak-No, Chongno-Gu, Seoul, Republic of Korea; kimjw412@snu.ac.kr or I.-C. Song, Department of Radiology, Seoul National University Hospital, 101 Daehak-No, Chongno-Gu, Seoul, Republic of Korea; icsong91@gmail.com