fMRI of intrasubject variability in ADHD: Anomalous premotor activity with prefrontal compensation

Kennedy Krieger Institute.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 6.35). 09/2008; 47(10):1141-50. DOI: 10.1097/CHI.0b013e3181825b1f
Source: PubMed

ABSTRACT Children with attention-deficit/hyperactivity disorder (ADHD) consistently display increased intrasubject variability (ISV) in response time across varying tasks, signifying inefficiency of response preparation compared to typically developing (TD) children. Children with ADHD also demonstrate impaired response inhibition; inhibitory deficits correlate with ISV, suggesting that similar brain circuits may underlie both processes. To better understand the neural mechanisms underlying increased ISV and inhibitory deficits in children with ADHD, functional magnetic resonance imaging was used to examine the neural correlates of ISV during Go/No-go task performance.
Event-related functional magnetic resonance imaging was used to study 25 children with ADHD and 25 TD children ages 8 to 13 years performing a simplified Go/No-go task. Brain-behavior correlations were examined between functional magnetic resonance imaging activation and ISV within and between groups.
For TD children, increased rostral supplementary motor area (pre-supplementary motor area) activation during No-go events was associated with less ISV, whereas the reverse was true for children with ADHD for whom increased pre-supplementary motor area activation was associated with more ISV. In contrast, children with ADHD with less ISV showed greater prefrontal activation, whereas TD children with more prefrontal activation demonstrated more ISV.
These findings add to evidence that dysfunction of premotor systems may contribute to increased variability and impaired response inhibition in children with ADHD and that compensatory strategies eliciting increased cognitive control may improve function. However, recruitment of prefrontal resources as a compensatory mechanism for motor task performance may preclude the use of those prefrontal resources for higher order, more novel executive functions with which children with ADHD often struggle.

    • "Recently, investigations have examined whether EF can be trained in young children using a play-based approach (Diamond and Lee 2011). It is hypothesized that such EF training interventions promote neural and social development and recent neuroimaging (Rueda et al. 2005; Schulz et al. 2005; Shaw et al. 2006; Suskauer et al. 2008), and neuropsychological (Halperin et al. 2008; Healey et al. 2011) data demonstrate that directed-play EF interventions improve neural functioning. Directed play involves the use of games and activities that are specifically selected and designed to target skills such as inhibitory control, working memory, and motor coordination which are known to be "
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    ABSTRACT: Executive functions (EF) are impaired in children with attention-deficit/hyperactivity disorder (ADHD). It may be especially critical for interventions to target EF in early childhood given the developmental progression of EF deficits that may contribute to later functional impairments. This proof-of-concept study examined the initial efficacy of an intervention program on EF and ADHD. We also examined child performance on three neurocognitive tasks assessing cognitive flexibility, auditory/visual attention, and sustained/selective attention. Children with ADHD (ages 3-7) and their parents were randomized to receive an intervention targeting metacognitive EF deficits (n = 13) or to a waitlist control condition (n = 12). Linear model analysis of covariance compared groups on parent EF ratings, blinded clinician ratings of ADHD symptoms and improvement, and child performance on neurocognitive measures. Children who received the intervention significantly improved on parent ratings of attention shifting and emotion regulation in addition to clinician ratings of inattention. Moderate effect sizes showed additional intervention effects on parent ratings of inhibition, memory, and planning, and clinician ratings of hyperactivity/impulsivity and overall improvement. Small effect sizes were observed for improvement on child neurocognitive measures. Although replication with a larger sample and an active control group is needed, EF training with a metacognitive focus is a potentially promising intervention for young children with ADHD.
    ADHD Attention Deficit and Hyperactivity Disorders 01/2015; DOI:10.1007/s12402-014-0162-x
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    • "The current results suggest that a large area of the medial frontal cortex exhibits dysfunctional connectivity and atypical support of attentional control in children with ADHD. Previous studies have likewise identified the dMFC as a region with atypical function using both task fMRI (Bush et al., 1999; Christakou et al., 2013; Rubia et al., 2014; Suskauer et al., 2008) and resting state connectivity (Castellanos et al., 2008; Sun et al., 2012; Tian et al., 2006). In addition, structural imaging studies have found that this region is atypical in ADHD (Shaw et al., 2013). "
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    ABSTRACT: Intra-subject variability (ISV) is the most consistent behavioral deficit in Attention Deficit Hyperactivity Disorder (ADHD). ISV may be associated with networks involved in sustaining task control (cingulo-opercular network: CON) and self-reflective lapses of attention (default mode network: DMN). The current study examined whether connectivity supporting attentional control is atypical in children with ADHD. Group differences in full-brain connection strength and brain-behavior associations with attentional control measures were examined for the late-developing CON and DMN in 50 children with ADHD and 50 typically-developing (TD) controls (ages 8-12 years).
    11/2014; 7. DOI:10.1016/j.nicl.2014.11.011
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    • "If slow drift rate, effects on τ, and/or differences in non-decision times account for RT variability in ADHD (or in comorbid ASD+ADHD), what mechanisms might this implicate either cognitively or neurobiologically? Numerous cognitive and neural hypotheses have been suggested to account for RT variability, including attention lapses (e.g., Leth-Steensen, et al., 2000), poor behavioural inhibition (e.g., Barkley, 1997), deficient neuroenergetic supply (Killeen, Russell, & Sergeant, 2013), temporal information processing deficits (e.g., Sonuga-Barke, Bitsakou, & Thompson, 2010), deficits in motor preparatory and output processes (e.g., Suskauer et al., 2008), abnormalities in default-mode network functioning (e.g., Castellanos, et al., 2005), and working memory deficits (e.g., Rapport et al., 2008), to name but some of the many proposed (see Kofler et al., 2013 "
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    ABSTRACT: Background Intraindividual variability in reaction time (RT) has received extensive discussion as an indicator of cognitive performance, a putative intermediate phenotype of many clinical disorders, and a possible trans-diagnostic phenotype that may elucidate shared risk factors for mechanisms of psychiatric illnesses. Scope and MethodologyUsing the examples of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), we discuss RT variability. We first present a new meta-analysis of RT variability in ASD with and without comorbid ADHD. We then discuss potential mechanisms that may account for RT variability and statistical models that disentangle the cognitive processes affecting RTs. We then report a second meta-analysis comparing ADHD and non-ADHD children on diffusion model parameters. We consider how findings inform the search for neural correlates of RT variability. FindingsResults suggest that RT variability is increased in ASD only when children with comorbid ADHD are included in the sample. Furthermore, RT variability in ADHD is explained by moderate to large increases (d = 0.63–0.99) in the ex-Gaussian parameter τ and the diffusion parameter drift rate, as well as by smaller differences (d = 0.32) in the diffusion parameter of nondecision time. The former may suggest problems in state regulation or arousal and difficulty detecting signal from noise, whereas the latter may reflect contributions from deficits in motor organization or output. The neuroimaging literature converges with this multicomponent interpretation and also highlights the role of top-down control circuits. Conclusion We underscore the importance of considering the interactions between top-down control, state regulation (e.g. arousal), and motor preparation when interpreting RT variability and conclude that decomposition of the RT signal provides superior interpretive power and suggests mechanisms convergent with those implicated using other cognitive paradigms. We conclude with specific recommendations for the field for next steps in the study of RT variability in neurodevelopmental disorders.
    Journal of Child Psychology and Psychiatry 03/2014; 55(6). DOI:10.1111/jcpp.12217 · 5.67 Impact Factor
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