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Adolescent impulsivity phenotypes characterized by distinct brain networks

Abstract

The impulsive behavior that is often characteristic of adolescence may reflect underlying neurodevelopmental processes. Moreover, impulsivity is a multi-dimensional construct, and it is plausible that distinct brain networks contribute to its different cognitive, clinical and behavioral aspects. As these networks have not yet been described, we identified distinct cortical and subcortical networks underlying successful inhibitions and inhibition failures in a large sample (n = 1,896) of 14-year-old adolescents. Different networks were associated with drug use (n = 1,593) and attention-deficit hyperactivity disorder symptoms (n = 342). Hypofunctioning of a specific orbitofrontal cortical network was associated with likelihood of initiating drug use in early adolescence. Right inferior frontal activity was related to the speed of the inhibition process (n = 826) and use of illegal substances and associated with genetic variation in a norepinephrine transporter gene (n = 819). Our results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior.

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Figure 1: A graphical representation of the stop success networks (that is, areas active during trials on which subjects successfully inhibited an already initiated motor response).
Figure 2: A graphical representation of the stop fail networks (that is, areas active during those trials on which subjects failed to inhibit an already initiated motor response).
Figure 3: A graphical representation of the SSRT results showing the anatomical locations of the relevant factors and the mean reaction time.
Figure 4: A graphical representation of substance misuse results.

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Acknowledgements

The IMAGEN study receives research funding from the European Community's Sixth Framework Programme (LSHM-CT-2007-037286). Further support was provided by the FP7 projects ADAMS (genomic variations underlying common neuropsychiatric diseases and disease-related cognitive traits in different human populations; 242257) and the Innovative Medicine Initiative Project EU-AIMS (115300-2), as well as the UK National Institute for Health Research Biomedical Research Centre Mental Health and the Medical Research Council Programme Grant 'Developmental pathways into adolescent substance abuse' (93558).

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H.G., T.W.R. and G.S. conceived the study. P.J.C., H.G., T.W.R. and R.W. designed the study. M.F.-B., H.G. and T.W.R. carried out the functional neuroimaging. G.J.B., C.B., P.J.C., H.F., J.G., H.G., A.H., B.I., E.L., K.M., J.-L.M, F.N., M.N.S., T.P., M.R., R.S., D.S., T.W.R., M.S. and A.S. acquired the data. J.-B.P., B.T. and R.W. carried out neuroimaging data processing and analysis. M.B., M.F.-B., E.C.L., M.S. and S.V.-K. analyzed behavioral data. M.A.B., T.D.R.C., M.L., A.L. and G.S. carried out genotyping and genetic analysis. R.W. and H.G. prepared the manuscript. M.A.B., P.J.C., T.B., T.P., T.W.R. and G.S. edited the manuscript.

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Correspondence to Robert Whelan or Hugh Garavan.

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Competing interests

G.J.B. received honoraria for teaching from General Electric during the course of this study. T.W.R. consults for Cambridge Cognition, E Lilly, GlaxoSmithKline, Merck and Lundbeck and has received recent research grants from Lilly, GSK and Lundbeck. T.B. served in an advisory or consultancy role for Bristol Myers-Sqibb, Develco Pharma, Lilly, Medice, Novartis, Shire and Viforpharma and received conference attendance support and conference support or received speaker's fee from Lilly, Janssen McNeil, Medice, Novartis and Shire. He is/has been involved in clinical trials conducted by Lilly and Shire. The present work is unrelated to the T.B.'s grants and relationships.

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Institute of Psychiatry, King's College London, London, UK.

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Whelan, R., Conrod, P., Poline, JB. et al. Adolescent impulsivity phenotypes characterized by distinct brain networks. Nat Neurosci 15, 920–925 (2012). https://doi.org/10.1038/nn.3092

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