Neurofunctional Effects of Methylphenidate and Atomoxetine in Boys with Attention-Deficit/Hyperactivity Disorder During Time Discrimination

Smith, Anna; Cubillo, Ana; Barrett, Nadia; Giampietro, Vincent; Simmons, Andrew; Brammer, Mick; Rubia, Katya

doi:10.1016/j.biopsych.2013.03.030

Cited by 45 publications

(50 citation statements)

References 57 publications

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“…However, this interpretation must be treated with caution, as our study was limited by a small sample size and we might therefore have failed to detect significant MPH effects. Indeed, two recently conducted studies found MPH to reduce time discrimination deficits in children and adolescents with ADHD (Smith et al, 2013; Rubia et al, 2014). As a number of further studies also failed to detect drug effects, probably due to limited statistical power on the basis of small sample sizes (Barkley et al, 1997; Rubia et al, 2003, 2009), our knowledge about MPH effects on perceptual timing task performance in children with ADHD is still limited, and it is almost exclusively restricted on the time discrimination paradigm.…”

Section: Discussionmentioning

confidence: 99%

“…In the domain of timing, two studies found MPH to reduce time discrimination deficits in children and adolescents with ADHD (Smith et al, 2013; Rubia et al, 2014), whereas two studies did not (Rubia et al, 2003, 2009). Furthermore, one study did not find MPH to reduce time reproduction deficits in children and adolescents with ADHD (Barkley et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Living in the Fast Lane: Evidence for a Global Perceptual Timing Deficit in Childhood ADHD Caused by Distinct but Partially Overlapping Task-Dependent Cognitive Mechanisms

Marx¹,

Weirich²,

Berger³

et al. 2017

Front. Hum. Neurosci.

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Dysfunctions in perceptual timing have been reported in children with ADHD, but so far only from studies that have not used the whole set of timing paradigms available from the literature, with the diversity of findings complicating the development of a unified model of timing dysfunctions and its determinants in ADHD. Therefore, we employed a comprehensive set of paradigms (time discrimination, time estimation, time production, and time reproduction) in order to explore the perceptual timing deficit profile in our ADHD sample. Moreover, we aimed to detect predictors responsible for timing task performance deficits in children with ADHD and how the timing deficits might be positively affected by methylphenidate. Male children with ADHD and healthy control children, all aged between 8 and 13 years, participated in this longitudinal study with three experimental sessions, where children with ADHD were medicated with methylphenidate at the second session but discontinued their medication at the remaining sessions. The results of our study reveal that children with ADHD were impaired in all timing tasks, arguing for a general perceptual timing deficit in ADHD. In doing so, our predictor analyses support the notion that distinct but partially overlapping cognitive mechanisms might exist for discriminating, estimating/producing, and reproducing time intervals. In this sense, working memory deficits in terms of an abnormally fast internal counting process might be common to dysfunctions in the time estimation/time production tasks and in the time reproduction task, with attention deficits (e.g., in terms of disruptions of the counting process) additionally contributing to time estimation/time production deficits and motivational alterations additionally contributing to time reproduction deficits. Methylphenidate did not significantly alter performance of the ADHD sample, presumably due to limited statistical power of our study. The findings of our study demonstrate a pivotal role of disturbed working memory processes in perceptual timing task performance in childhood ADHD, at the same time broadening the view for additional attentional and motivational determinants of impaired task performance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Living in the Fast Lane: Evidence for a Global Perceptual Timing Deficit in Childhood ADHD Caused by Distinct but Partially Overlapping Task-Dependent Cognitive Mechanisms

Marx¹,

Weirich²,

Berger³

et al. 2017

Front. Hum. Neurosci.

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“…A number of imaging studies indicate that cognition-enhancing doses of psychostimulants normalize ADHD-related hypoactivity within frontostriatal circuitry (12,68–70). However, additional evidence indicates that clinically-relevant doses of psychostimulants exert a more complex pattern of actions on frontostriatal activity that are task, region, and hemisphere-dependent (13,71–74).…”

Section: Clinically-relevant Doses Of Psychostimulants Strengthen Neumentioning

confidence: 99%

The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex

Spencer

Devilbiss

Berridge

2015

Biological Psychiatry

141

111

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Psychostimulants are highly effective in the treatment of attention deficit hyperactivity disorder (ADHD). The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2- and dopamine D1 receptors. In contrast, while the striatum is a critical participant in ‘PFC-dependent’ cognition, where examined, psychostimulant action within the striatum is not sufficient to enhance cognition. At doses that moderately exceed the clinical range, psychostimulants appear to improve PFC-dependent attentional processes at the expense of other PFC-dependent processes (e.g. working memory, response inhibition). This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 vs. α1 receptors. Collectively, this evidence indicates that at low, clinically-relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). This information has potentially important clinical implications as well as relevance for public health policy regarding the widespread clinical use of psychostimulants and for the development of novel pharmacological treatments for ADHD and other conditions associated with PFC dysregulation.

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“…Distinct underlying pharmacological mechanisms may cause these practical differences. There are few neuroimaging studies that examined these differences [12, 13]. Cubillo et al showed that ATX upregulated and normalized right dorsolateral prefrontal cortex under activation measured by functional magnetic resonance imaging (fMRI), while MPH upregulated left inferior frontal cortex activation [13].…”

Section: Introductionmentioning

confidence: 99%

Differential therapeutic effects of atomoxetine and methylphenidate in childhood attention deficit/hyperactivity disorder as measured by near-infrared spectroscopy

Nakanishi

Ota

Iida

et al. 2017

Child Adolesc Psychiatry Ment Health

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BackgroundThe stimulant methylphenidate (MPH) and the nonstimulant atomoxetine (ATX) are the most commonly-prescribed pharmacological treatments for attention deficit/hyperactivity disorder (ADHD). However, the drug-specific mechanism of action on brain function in ADHD patients is not well known. This study examined differences in prefrontal hemodynamic activity between MPH and ATX in children with ADHD as measured by near-infrared spectroscopy (NIRS) using the Stroop color-word task.MethodsThirty children with ADHD participated in the present study. We used 24-channel NIRS (ETG-4000) to measure the relative concentrations of oxyhemoglobin in the frontal lobes of participants in the drug-naïve condition and those who had received MPH (n = 16) or ATX (n = 14) for 12 weeks. Measurements were conducted every 0.1 s during the Stroop color-word task. We used the ADHD RS-IV-J (Home Version) to evaluate ADHD symptoms.ResultsTreatment with either MPH or ATX significantly reduced ADHD symptoms, as measured by the ADHD RS-IV-J, and improved performance on the Stroop color-word task in terms of number of correct words. We found significantly higher levels of oxyhemoglobin changes in the prefrontal cortex of participants in the ATX condition compared with the values seen at baseline (pre-ATX). In contrast, we found no oxyhemoglobin changes between pre- and post-treatment with MPH.ConclusionsThe present study suggests that MPH and ATX have differential effects on prefrontal hemodynamic activity in children with ADHD.

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Neurofunctional Effects of Methylphenidate and Atomoxetine in Boys with Attention-Deficit/Hyperactivity Disorder During Time Discrimination

Cited by 45 publications

References 57 publications

Living in the Fast Lane: Evidence for a Global Perceptual Timing Deficit in Childhood ADHD Caused by Distinct but Partially Overlapping Task-Dependent Cognitive Mechanisms

Living in the Fast Lane: Evidence for a Global Perceptual Timing Deficit in Childhood ADHD Caused by Distinct but Partially Overlapping Task-Dependent Cognitive Mechanisms

The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex

Differential therapeutic effects of atomoxetine and methylphenidate in childhood attention deficit/hyperactivity disorder as measured by near-infrared spectroscopy

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