Default mode network resting-state functional connectivity and attention-deficit/disorder symptoms: perspectives from three different populations

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder characterised by persistent and age-inappropriate levels of inattention, hyperactivity and impulsivity. The condition is debilitating, disrupting academic and social development. In Chapters 1-4 we discuss a paradigm shift in psychopathology that has driven interest in the role of the default mode network (DMN) in ADHD and conduct disorder (CD) – a condition characterised by aggressive and rule-breaking behaviour which frequently co-occurs with ADHD. We conclude that relatively little empirical research has investigated how alterations to the functional integrity of the DMN affect cognition. In Chapter 5, we provide novel evidence that CD may affect the functional architecture of the DMN. Relative to age- and sex-matched healthy controls (n=29),we find adolescents with CD (n=29) show DMN core subsystem hypo-connectivity, although only after adjusting for co-occurring ADHD symptoms. In contrast, ADHD symptoms were independently associated with DMN hyper-connectivity. In Chapter 6, we explore for the first time how DMN resting-state functional connectivity may be affected by a rare deprivation-related variant of ADHD. We studied adoptees who experienced extended, but time-limited, exposure to institutional deprivation in early childhood (n=46) compared with adoptees with <6months exposure (n=21) and non-deprived UK adoptees (n=21) as a control group.Prolonged deprivation was associated with DMN core subsystem hyper-connectivity.There was also a deprivation-by-ADHD interaction, suggesting that deprivation moderates whether ADHD is associated with DMN hyper- or hypo-connectivity. In Chapter 7, we explore how resting-state DMN functional connectivity may contribute to the neuropsychological profile associated with ADHD. In a clinical sample of children with ADHD (n=20) and age- and sex-matched controls (n=22) we find DMN hypo-connectivity was correlated with suboptimal inter-temporal decision making and exaggerated delay aversion, with the latter domain partially mediating the relationship between ADHD and the connectivity patterns observed. This thesis provides robust evidence for effects of ADHD on the functional integrity of the DMN across three different samples, with the direction of connectivity changes (whether ADHD is associated with hypo- or hyper-connectivity) related to the putative causes of ADHD. DMN hypo-connectivity may contribute to suboptimal decision-making in non-deprivation related ADHD.

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Identifiers

ORCID for Graeme Fairchild: orcid.org/0000-0001-7814-9938

ORCID for Samuele Cortese: orcid.org/0000-0001-5877-8075

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