Plasma level-dependent effects of methylphenidate on task-related functional magnetic resonance imaging signal changes

Müller, Ulrich; Suckling, John; Zelaya, Fernando; Honey, Garry D.; Faessel, Hélène M.; Williams, Steven; Routledge, Carol; Brown, John R.; Robbins, Trevor W.; Bullmore, Edward T.

doi:10.1007/s00213-005-2264-9

Cited by 43 publications

(32 citation statements)

References 53 publications

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“…Other pharmacological fMRI studies using oral MPH generally show enhanced cortical and subcortical blood oxygen level-dependent (BOLD) responses in healthy controls or individuals with ADHD (reviewed in ref. 42), which are most consistently shown in the PFC (including the ACC and OFC) and dorsal striatum (43). Nevertheless, disparity in direction of results may also be attributed to other factors [e.g., type of task (it would be important to use a sensorimotor task as an active control task) and severity of impairment (baseline capacity needs to be tested in studies with larger sample sizes)] and remains to be tested.…”

Section: Discussionmentioning

confidence: 99%

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

Goldstein

Woicik

Maloney

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

107

106

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Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.D rug addiction is a chronically relapsing disorder associated with dysregulated dopaminergic neurotransmission as well as functional impairments in the brain regions innervated by dopamine [e.g., the prefrontal cortex (PFC)] (1, 2). Psychostimulants such as cocaine have high abuse and dependence potential because of their ability to increase dopamine in limbic brain regions. Similarly to cocaine, methylphenidate (MPH; e.g., Ritalin) blocks the dopamine transporter increasing extracellular dopamine. However, although speed of uptake of both drugs is similar, rate of clearance of MPH from the brain is substantially slower than that for cocaine (90-vs. 20-min half-life), and these slower pharmacokinetic properties may contribute to the lower abuse potential for MPH (1). Both these neuropharmacological mechanisms, interference with the binding of the drug to its target and different (i.e., slower) pharmacokinetics, proved valuable in the management of heroin (e.g., with methadone and buprenorphine) and nicotine addiction (e.g., with nicotine patch and nicotine gum) (3). In contrast, adapting a similar pharmacological strategy (use of stimulant medications such as MPH) in individuals with cocaine-use disorders (CUD) did not decrease cocaine use or prevent relapse (1).Nevertheless, oral MPH decreases abnormal risk taking in patients with frontotemporal dementia (4) and children with attention deficit hyperactivity disorder (ADHD) (5). Furthermore, when on stimulant medication (including MPH), youth with ADHD showed a trend to improved inhibitor...

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Section: Discussionmentioning

confidence: 99%

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

Goldstein

Woicik

Maloney

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

107

106

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“…We used a single-dose 40 mg of methylphenidate, which was comparable or below those in more recent studies showing cognitive effects (Clatworthy et al 2009;Elliott et al 1997;Mehta et al 2000;Turner et al 2003b;Rogers et al 1999), whereas we used a relatively high 400 mg dose of modafinil which was above those in most other studies (Randall et al 2003(Randall et al , 2004(Randall et al , 2005aTurner et al 2003a;Müller et al 2005;Winder-Rhodes et al 2009;). Thus, an alternative explanation for the differences in the effects on working memory storage capacity would be a dose difference, i.e., a relatively low and inefficient dose of methylphenidate as compared to a sufficiently high dose of modafinil.…”

Section: Drug Effects On Visual Perceptual Processing Speedmentioning

confidence: 94%

“…Cognitive testing was carried out between 150 min and 210 min after drug intake, i.e., around expected maximum plasma concentrations (c max ) of modafinil (McClellan and Spencer 1998;Wong et al 1999) and methylphenidate, where c max is reached ca. 60 min earlier (from 90 to 150 min in different studies) and has a higher inter-subject variability (e.g., Gualtieri et al 1982;Midha et al 2001;Müller et al 2005;Wong et al 1998). Nevertheless, in both drug conditions, it can be assumed that participants were tested near c max and, thus, at biologically effective plasma levels.…”

Section: Experimental Drugsmentioning

confidence: 97%

Effects of modafinil and methylphenidate on visual attention capacity: a TVA-based study

et al. 2010

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This is the first pharmacological investigation demonstrating the usefulness of a TVA task for high-resolution and repeated cognitive parameter estimation after cognitive-enhancing medication. Our results confirm previous findings of attentional capacity improvements in low performers and extend the baseline dependency model to methylphenidate. Plasma level-dependent effects of psychostimulants can be modelled on an inverted U-shaped dose-response relationship, which is highly relevant to predict cognitive enhancing and detrimental effects of psychostimulants in patients with cognitive deficits (e.g., attention deficit hyperactivity disorder) and healthy volunteers (e.g., self-medicating academics).

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“…plasma levels for each of the study drugs (12)(13)(14) and doses were selected based upon 84 clinical relevance (15)(16)(17) and demonstrated cognitive effects (18)(19)(20). Figure 1).…”

Section: Processes 35 36mentioning

confidence: 99%

The Effects of Methylphenidate on the Neural Signatures of Sustained Attention

Dockree

Barnes

Matthews

et al. 2017

Biological Psychiatry

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Plasma level-dependent effects of methylphenidate on task-related functional magnetic resonance imaging signal changes

Cited by 43 publications

References 53 publications

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

Effects of modafinil and methylphenidate on visual attention capacity: a TVA-based study

The Effects of Methylphenidate on the Neural Signatures of Sustained Attention

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