ADHD- and medication-related brain activation effects in concordantly affected parent–child dyads with ADHD

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Journal of Child Psychology and Psychiatry (Impact Factor: 6.46). 10/2007; 48(9):899-913. DOI: 10.1111/j.1469-7610.2007.01761.x
Source: PubMed


Several studies have documented fronto-striatal dysfunction in children and adolescents with attention deficit/hyperactivity disorder (ADHD) using response inhibition tasks. Our objective was to examine functional brain abnormalities among youths and adults with ADHD and to examine the relations between these neurobiological abnormalities and response to stimulant medication.
A group of concordantly diagnosed ADHD parent-child dyads was compared to a matched sample of normal parent-child dyads. In addition, ADHD dyads were administered double-blind methylphenidate and placebo in a counterbalanced fashion over two consecutive days of testing. Frontostriatal function was measured using functional magnetic resonance imaging (fMRI) during performance of a go/no-go task.
Youths and adults with ADHD showed attenuated activity in fronto-striatal regions. In addition, adults with ADHD appeared to activate non-fronto-striatal regions more than normals. A stimulant medication trial showed that among youths, stimulant medication increased activation in fronto-striatal and cerebellar regions. In adults with ADHD, increases in activation were observed in the striatum and cerebellum, but not in prefrontal regions.
This study extends findings of fronto-striatal dysfunction to adults with ADHD and highlights the importance of frontostriatal and frontocerebellar circuitry in this disorder, providing evidence of an endophenotype for examining the genetics of ADHD.

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    • "Additionally, those with worse inattentive symptomatology or the inattentive subtype have a greater likelihood of being diagnosed with ADHD/+RD (Levy, Young, Bennett, Martin, & Hay, 2013; Mayes & Calhoun, 2007). Some neuroimaging studies have implicated right hemispheric frontostriatal and frontoparietal attention networks in ADHD (Banich et al., 2009; Durston et al., 2003; Epstein et al., 2007). However, in our previous study (Mohl et al., 2013), we reported no activation differences along attention-related areas in ADHD/+RD compared to TDC in response to the fMRI task of sustained attention with digits as stimuli (i.e., a non-linguistic Continuous Performance Task). "
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    ABSTRACT: Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous, neurodevelopmental disorder which co-occurs often with Reading Disability (RD). ADHD with and without RD consistently have higher inattentive ratings compared with typically developing controls, with co-occurring ADHD and RD also demonstrating impaired phonological processing. Accordingly, inattention has been associated with greater phonological impairment, though the neural correlates of the association are poorly understood from a functional neuroimaging perspective. It was postulated that only the co-occurring subgroup would demonstrate hypoactivation of posterior, left hemispheric, reading-related areas and, to a lesser extent, alterations in right hemispheric, attention areas compared with controls. A novel word rhyming Continuous Performance Task assesses functional activation differences in phonology- and attention-related areas between three groups: ten boys with ADHD and RD, fourteen boys with ADHD without RD, and fourteen typically developing controls. Subjects respond to words that rhyme with a target word as mono- and disyllabic, English words are visually presented over 90s blocks. Behavioral performance was not different between groups. Some hypoactivation of left hemispheric, reading-related areas was apparent in ADHD and RD, but not ADHD without RD, compared with controls. Right hemispheric, attention areas showed alterations in both ADHD subgroups relative to controls; however, the differences for each subgroup were dissimilar. The dorsal decoding subnetwork may not be grossly compromised in ADHD with Reading Disability. The role of cognitive impairments, including the level of inattention, on phonology requires clarification from a neuroimaging perspective. Copyright © 2015 Elsevier Inc. All rights reserved.
    Brain and Cognition 07/2015; 99:1-7. DOI:10.1016/j.bandc.2015.04.009 · 2.48 Impact Factor
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    • "observed group differences. Some previous studies on executive function have shown that posterior areas of the brain, including the cerebellum, occipital and parietal lobe, and especially the precuneus may show hyperactivation accompanying adequate or impaired performance in ADHD [Dillo et al., 2010; Epstein et al., 2007]. This is especially characteristic of adults and has been interpreted as evidence for compensatory activity [Dibbets et al., 2009]. "
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    ABSTRACT: Adult ADHD has been linked to impaired motor response inhibition and reduced associated activation in the right inferior frontal cortex (IFC). However, it is unclear whether abnormal inferior frontal activation in adult ADHD is specifically related to a response inhibition deficit or reflects a more general deficit in attentional processing. Using functional magnetic resonance imaging, we tested a group of 19 ADHD patients with no comorbidities and a group of 19 healthy control volunteers on a modified go/no-go task that has been shown previously to distinguish between cortical responses related to response inhibition and attentional shifting. Relative to the healthy controls, ADHD patients showed increased commission errors and reduced activation in inferior frontal cortex during response inhibition. Crucially, this reduced activation was observed when controlling for attentional processing, suggesting that hypoactivation in right IFC in ADHD is specifically related to impaired response inhibition. The results are consistent with the notion of a selective neurocognitive deficit in response inhibition in adult ADHD associated with abnormal functional activation in the prefrontal cortex, whilst ruling out likely group differences in attentional orienting, arousal and motivation. Hum Brain Mapp, 2014. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
    Human Brain Mapping 10/2014; 35(10). DOI:10.1002/hbm.22539 · 5.97 Impact Factor
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    • "Maxima of clusters of prefrontal dysfunctions during five components of impulse control (stimulus interference, response interference, behavioral inhibition, risky decision making, and delay discounting) are displayed as reported by Banich et al. (2009), Burgess and Braver (2010), Bush et al. (1999), Cubillo et al. (2010, 2011), Epstein et al. (2007), Hart et al. (2013), Holtmann et al. (2013), Jacob et al. (2013), Rubia et al. (2009b), Sebastian et al. (2012), Silbersweig et al. (2007), Wilbertz et al. (2012), Wingenfeld et al. (2009), and Völlm et al. (2007). Blue, prefrontal dysfunctions associated with impulse control in ADHD; red, prefrontal dysfunctions associated with impulse control in BPD; pink, overlap of ADHD and BPD. "
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    ABSTRACT: Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference reso-lution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control.The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these con-cepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along differ-ent impulse control components in direct comparison of these disorders.Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control com-ponents to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.
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