Lower white matter microstructure in the superior longitudinal fasciculus is associated with increased response time variability in adults with attention-deficit/ hyperactivity disorder

Lower white matter microstructure in the superior longitudinal fasciculus is associated with increased response time variability in adults with attention-deficit/ hyperactivity disorder

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J Psychiatry Neurosci 2015;40(5):344-351

Thomas Wolfers, MSc*; A. Marten H. Onnink, MSc*; Marcel P. Zwiers, PhD; Alejandro Arias-Vasquez, PhD; Martine Hoogman, PhD; Jeanette C. Mostert, MSc; Cornelis C. Kan, MD, PhD; Dorine Slaats-Willemse, PhD; Jan K. Buitelaar, MD, PhD; Barbara Franke, PhD

Abstract

Background: Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV.

Methods: We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and τ, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging–derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest.

Results: We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed.

Limitations: Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks.

Conclusion: This study suggests that reduced microstructural integrity of the right SLF is associated with elevated τ in patients with ADHD.


*These authors contributed equally to this work.

Submitted June 11, 2014; Revised Oct. 7, 2014; Accepted Oct. 29, 2014; Early-released June 16, 2015.

Acknowledgements: The authors thank Paul Gaalman for technical assistance with MRI scanning and Janneke Dammers for assistance with recruitment and testing. The authors also thank all of the participants of this study. This study was funded in part by grants awarded to B. Franke from the Brain & Cognition Excellence Program of the Netherlands Organization for Scientific Research (NWO, grant 433-09- 229), the Netherlands Brain Foundation (Nederlandse Hersenstichting, grant 15F07[2]27), and by a Vici grant from NWO (grant 016.130.669). The research leading to these results has also received funding from the European Community‘s Seventh Framework Programme (FP7/2007–2013) under grant 60245 (IMAGEMEND). The funders had no further role in study design; in the collection, analysis and interpretation of data; in writing the report; or in the decision to submit the paper for publication. The sample used in this study is part of the international multicentre persistent ADHD collaboration (IMpACT). IMpACT unites major research centers working on the biology of ADHD persistence across the lifespan and has participants in the Netherlands, Germany, Spain, Norway, the United Kingdom, Sweden, the United States and Brazil. Principal investigators of IMpACT are Barbara Franke (chair), Andreas Reif (vice-chair), Stephen V. Faraone, Jan Haavik, Bru Cormand, Antoni Ramos Quiroga, Philip Asherson, Klaus-Peter Lesch, Jonna Kuntsi, Claiton Bau, Jan Buitelaar, Stefan Johansson, Henrik Larsson, Alysa Doyle, and Eugenio Grevet.

Affiliations: From the Department of Human Genetics, Radboud University Medical Center (Wolfers, Arias-Vasquez, Mostert, Franke); the Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center ( Onnink, Arias-Vasquez, Hoogman, Kan, Franke); the Donders Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University (Wolfers, Zwiers, Mostert); the Department of Cognitive Neurosciences, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center (Arias-Vasquez, Buitelaar); and the Karakter Child and Adolescent Psychiatry University Centre (Slaats-Willemse, Buitelaar), Nijmegen, the Netherlands.

Competing interests: C. Kan was a paid member of the European Adult ADHD Advisory Board of Eli Lilly in 2011 and 2012 and was a paid lecturer at the Adult ADHD Academy. J. Buitelaar has served as a consultant, advisory board member and speaker for Bristol-Myers Squibb, Janssen Cilag BV, Eli Lilly, Novartis, Schering- Plough, Shire, Servier, Lundbeck and UCB. He is not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, and royalties. No other competing interests declared.

Contributors: M. Onnink, M. Zwiers, M. Hoogman, D. Slaats-Willemse, J. Buitelaar and B. Franke designed the study. T. Wolfers, M. Onnink, M. Hoogman, J. Mostert, C. Kan and B. Franke acquired the data, which T. Wolfers, M. Onnink, M. Zwiers, A. Arias-Vasquez, M. Hoogman, C. Kan, J. Buitelaar and B. Franke analyzed. T. Wolfers, M. Onnink, M. Hoogman, C. Kan and B. Franke wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140154

Correspondence to: B. Franke, Department of Human Genetics, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, the Netherlands; barbara.franke@radboudumc.nl