TY - JOUR T1 - Altered neural connectivity during response inhibition in adolescents with attention-deficit/hyperactivity disorder and their unaffected siblings. AU - van Rooij,Daan, AU - Hartman,Catharina A, AU - Mennes,Maarten, AU - Oosterlaan,Jaap, AU - Franke,Barbara, AU - Rommelse,Nanda, AU - Heslenfeld,Dirk, AU - Faraone,Stephen V, AU - Buitelaar,Jan K, AU - Hoekstra,Pieter J, Y1 - 2015/01/13/ PY - 2014/12/22/received PY - 2015/01/06/accepted PY - 2015/1/23/entrez PY - 2015/1/23/pubmed PY - 2015/9/25/medline KW - ADHD KW - ADHD, attention deficit/hyperactivity disorder KW - CD, conduct disorder KW - Connectivity KW - DMN, default mode network KW - GEE, generalized estimating equations KW - ICV, intraindividual coefficient of variance KW - ODD, oppositional defiant disorder KW - PPI KW - RD, reading disorder KW - ROI, region of interest KW - Response inhibition KW - SI, supplementary information KW - SSRT, stop-signal reaction time KW - SST, Stop-signal task KW - Siblings KW - WM, white matter SP - 325 EP - 35 JF - NeuroImage. Clinical JO - Neuroimage Clin VL - 7 N2 - INTRODUCTION: Response inhibition is one of the executive functions impaired in attention-deficit/hyperactivity disorder (ADHD). Increasing evidence indicates that altered functional and structural neural connectivity are part of the neurobiological basis of ADHD. Here, we investigated if adolescents with ADHD show altered functional connectivity during response inhibition compared to their unaffected siblings and healthy controls. METHODS: Response inhibition was assessed using the stop signal paradigm. Functional connectivity was assessed using psycho-physiological interaction analyses applied to BOLD time courses from seed regions within inferior- and superior frontal nodes of the response inhibition network. Resulting networks were compared between adolescents with ADHD (N = 185), their unaffected siblings (N = 111), and controls (N = 125). RESULTS: Control subjects showed stronger functional connectivity than the other two groups within the response inhibition network, while subjects with ADHD showed relatively stronger connectivity between default mode network (DMN) nodes. Stronger connectivity within the response inhibition network was correlated with lower ADHD severity, while stronger connectivity with the DMN was correlated with increased ADHD severity. Siblings showed connectivity patterns similar to controls during successful inhibition and to ADHD subjects during failed inhibition. Additionally, siblings showed decreased connectivity with the primary motor areas as compared to both participants with ADHD and controls. DISCUSSION: Subjects with ADHD fail to integrate activation within the response inhibition network and to inhibit connectivity with task-irrelevant regions. Unaffected siblings show similar alterations only during failed stop trials, as well as unique suppression of motor areas, suggesting compensatory strategies. These findings support the role of altered functional connectivity in understanding the neurobiology and familial transmission of ADHD. SN - 2213-1582 UR - https://www.unboundmedicine.com/medline/citation/25610797/Altered_neural_connectivity_during_response_inhibition_in_adolescents_with_attention_deficit/hyperactivity_disorder_and_their_unaffected_siblings_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-1582(15)00005-4 DB - PRIME DP - Unbound Medicine ER -