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Abstract
IntroductionResponse 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.MethodsResponse 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).ResultsControl 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.DiscussionSubjects 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.
Highlights
Response inhibition is one of the executive functions impaired in attention-deficit/hyperactivity disorder (ADHD)
Probands with ADHD had to have six or more hyperactive/impulsive and/or inattentive symptoms according to DSM-IV criteria (American Psychiatric Association, 2000); unaffected siblings and unrelated controls had to have less than two symptoms overall, based on a structured psychiatric interview (K-SADS) and Conners questionnaires
Stop Signal Reaction Time (SSRT) was slower in subjects with ADHD as compared to both unaffected siblings and healthy controls, but did not differ between the latter two groups
Summary
Response inhibition is one of the executive functions impaired in attention-deficit/hyperactivity disorder (ADHD). (Katya Rubia et al, 2005), and adults with ADHD (Cubillo et al, 2011; Mulligan et al, 2011), including a study by our group (Van Rooij et al, 2014) These studies demonstrated that alterations within the neural networks responsible for cognitive control, inhibition, and attention can be found in the absence of behavioral response inhibition deficits. These alterations have been found even in unaffected siblings of subjects with ADHD (Van Rooij et al, 2014), adolescents with subthreshold ADHD (Whelan et al, 2012), and adults with ADHD (Cubillo et al, 2010). The pre-supplementary motor area and subcortical regions on the other hand are thought to be involved in the execution of the stop processes (A.R. Aron et al, 2007a; Cai et al, 2012; Chao et al, 2009; de Wit et al, 2012; N.C. Swann et al, 2012; Tabu et al, 2011), whereas the parietal areas are thought to reflect attentional redirection and task-set maintenance during response inhibition (C. Fassbender et al, 2006; Chambers et al, 2009)
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