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

Epstein, Jeffery N.; Casey, B. J.; Tonev, Simon T.; Davidson, Matthew C.; Reiss, Allan L.; Garrett, Amy; Hinshaw, Stephen P.; Greenhill, Laurence L.; Glover, Gary H.; Shafritz, Keith M.; Vitolo, Alan; Kotler, Lisa A.; Jarrett, Matthew A.; Spicer, Julie

doi:10.1111/j.1469-7610.2007.01761.x

Cited by 148 publications

(161 citation statements)

References 62 publications

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“…The findings echo previous findings of fronto-temporo-striatal upregulation/normalization in ADHD children with MPH during WM (PrehnKristensen et al 2011) and other cognitive control tasks (Vaidya et al 1998;Epstein et al 2007;Rubia et al 2011a,b) and extend for the first time previous evidence of enhanced IFC/STG activation after a singledose ATX challenge in healthy adults (Chamberlain et al 2009) to a paediatric ADHD group.…”

Section: Discussionsupporting

confidence: 79%

Drug-specific laterality effects on frontal lobe activation of atomoxetine and methylphenidate in attention deficit hyperactivity disorder boys during working memory

et al. 2013

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Background The catecholamine reuptake inhibitors methylphenidate (MPH) and atomoxetine (ATX) are the most common treatments for attention deficit hyperactivity disorder (ADHD). This study compares the neurofunctional modulation and normalization effects of acute doses of MPH and ATX within medication-naive ADHD boys during working memory (WM). Method A total of 20 medicationnaive ADHD boys underwent functional magnetic resonance imaging during a parametric WM n-back task three times, under a single clinical dose of either MPH, ATX or placebo in a randomized, doubleblind, placebo-controlled, cross-over design. To test for normalization effects, brain activations in ADHD under each drug condition were compared with that of 20 age-matched healthy control boys. Results Relative to healthy boys, ADHD boys under placebo showed impaired performance only under high WM load together with significant underactivation in the bilateral dorsolateral prefrontal cortex (DLPFC). Both drugs normalized the performance deficits relative to controls. ATX significantly enhanced right DLPFC activation relative to MPH within patients, and significantly normalized its underactivation relative to controls. MPH, by contrast, both relative to placebo and ATX, as well as relative to controls, upregulated the left inferior frontal cortex (IFC), but only during 2-back. Both drugs enhanced frontotemporo-striatal activation in ADHD relative to control boys and deactivated the default-mode network, which were negatively associated with the reduced DLPFC activation and performance deficits, suggesting compensation effects. Conclusions The study shows both shared and drug-specific effects. ATX upregulated and normalized right DLPFC underactivation, while MPH upregulated left IFC activation, suggesting drug-specific laterality effects on prefrontal regions mediating WM. Background. The catecholamine reuptake inhibitors methylphenidate (MPH) and atomoxetine (ATX) are the most common treatments for attention deficit hyperactivity disorder (ADHD). This study compares the neurofunctional modulation and normalization effects of acute doses of MPH and ATX within medication-naive ADHD boys during working memory (WM).

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Section: Discussionsupporting

confidence: 79%

Drug-specific laterality effects on frontal lobe activation of atomoxetine and methylphenidate in attention deficit hyperactivity disorder boys during working memory

et al. 2013

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“…Caudate functional abnormalities were found in the above meta-analysis, just as they have been fairly consistently found with individual fMRI studies, especially when using response inhibition tasks, such as go/no-go or stop-signal tasks (Durston et al, 2003b;Epstein et al, 2007;Rubia et al, 1999;Vaidya et al, 1998). Vance et al (2007) also recently reported lower right caudate in ADHD during a mental rotation task.…”

Section: Functional Studies: Pet and Fmrimentioning

confidence: 94%

“…An acute MPH medication fMRI study showed MPH consistently (i.e., in both children and adults) produced increased activation of the caudate and cerebellum, along with inconsistent changes in other brain regions (Epstein et al, 2007). Pliszka et al (2007) using ERPs found that stimulant treatment increases ACC activity in ADHD.…”

Section: Functional Studies: Pet and Fmrimentioning

confidence: 99%

Attention-Deficit/Hyperactivity Disorder and Attention Networks

Bush

2009

Neuropsychopharmacol

285

244

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Research attempting to elucidate the neuropathophysiology of attention-deficit/hyperactivity disorder (ADHD) has not only shed light on the disorder itself, it has simultaneously provided new insights into the mechanisms of normal cognition and attention. This review will highlight and integrate this bidirectional flow of information. Following a brief overview of ADHD clinical phenomenology, ADHD studies will be placed into a wider historical perspective by providing illustrative examples of how major models of attention have influenced the development of neurocircuitry models of ADHD. The review will then identify major components of neural systems potentially relevant to ADHD, including attention networks, reward/feedbackbased processing systems, as well as a 'default mode' resting state network. Further, it will suggest ways in which these systems may interact and be influenced by neuromodulatory factors. Recent ADHD imaging data will be selectively provided to both illustrate the field's current level of knowledge and to show how such data can inform our understanding of normal brain functions. The review will conclude by suggesting possible avenues for future research.

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“…In particular, a growing literature reports normalization of function in task-related networks (e.g., fronto-striato-parieto-cerebellar circuits) and the default network (a network of medial wall-based brain regions typically deactivated during goal-directed tasks) (Schweren et al 2013;Spencer et al 2013;Rubia et al 2014). Although fewer in number, fMRI studies of ADHD in adults have also highlighted normalization of function (Epstein et al 2007;Bush et al 2008). Still, stimulant effects may differ between children and adults.…”

Section: Introductionmentioning

confidence: 99%

“…Still, stimulant effects may differ between children and adults. For example, in a single study, MPH increased frontostriatal and cerebellar activation in children with ADHD, whereas it increased striatal activation but decreased frontoparietal activation in adults with ADHD (Epstein et al 2007). Thus, it is critical to independently study the neural systems underlying stimulant effects to better guide the treatment of adult patients.…”

Section: Introductionmentioning

confidence: 99%

Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults with Attention-Deficit/Hyperactivity Disorder

Yang

Kelly

Castellanos

et al. 2016

Journal of Child and Adolescent Psychopharmacology

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Objective: The purposes of this study were to examine the impact of 3 weeks of amphetamine administration on intrinsic connectome-wide connectivity patterns in adults with attention-deficit/hyperactivity disorder (ADHD) and explore the association between stimulant-induced symptom improvement and functional connectivity alteration. Methods: Participants included 19 adults (age 20-55 years) diagnosed with ADHD using the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria per the Adult Clinician Diagnostic Scale taking part in amphetamine trials. For each patient, two 6-minute resting-state functional magnetic resonance imaging (R-fMRI) scans were acquired at baseline and after treatment. A fully data-driven multivariate analytic approach (i.e., multivariate distance matrix regression [MDMR]) was applied to R-fMRI data to characterize the distributed pharmacological effects in the entire functional connectome. Clinical efficacy was assessed using ADHD rating scale with adult prompts and the Adult Self-Report Scale v1.1 Symptom Checklist. We linked stimulant-induced functional connectivity changes to symptom amelioration using Spearman's correlation. Results: Three weeks of administration of a stimulant significantly reduced ADHD symptoms. MDMR-based analyses on RfMRI data highlighted the left dorsolateral prefrontal cortex (DLPFC, a key cognitive control region) and the medial prefrontal cortex (MPFC, the anterior core of default network) whose distributed patterns of functional connectivity across the entire brain were altered by psychostimulants. Follow-up intrinsic functional connectivity revealed that stimulants specifically decreased the positive functional connectivity between DLPFC-insula, DLPFC-anterior cingulate cortex, and MPFC-insula. Importantly, these functional connectivity changes are associated with symptom improvement. Conclusion: These results suggested that ADHD is associated with increased functional integration or decreased functional segregation between core regions of cognitive control, default, and salience networks. The apparent normalization of intrinsic functional interaction in these circuits (i.e., increased functional segregation) may underlie the clinical benefits produced by 3 weeks of amphetamine treatment.

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

Abstract: 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.

Cited by 148 publications

References 62 publications

Drug-specific laterality effects on frontal lobe activation of atomoxetine and methylphenidate in attention deficit hyperactivity disorder boys during working memory

Drug-specific laterality effects on frontal lobe activation of atomoxetine and methylphenidate in attention deficit hyperactivity disorder boys during working memory

Attention-Deficit/Hyperactivity Disorder and Attention Networks

Neural Correlates of Symptom Improvement Following Stimulant Treatment in Adults with Attention-Deficit/Hyperactivity Disorder

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