Methylphenidate and cognitive flexibility: Dissociated dose effects in hyperactive children

Tannock, Rosemary; Schachar, Russell; Logan, Gordon D.

doi:10.1007/bf01447091

Cited by 205 publications

(140 citation statements)

References 54 publications

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“…However, the behavioral and cognitive mechanisms of control display different dose-response functions. Dose-related improvements in response inhibition are characterized by an inverted U-shape function, whereas effects on response activation reveal linear dose-response curves (e.g., Tannock et al, 1995). Such observations, along with the present findings, challenge the assumption that stimulants have a unitary mechanism of action that results in a uniform facilitation of performance independent of behavioral and cognitive domains (e.g., response inhibition, memory, etc.).…”

Section: Discussionsupporting

confidence: 52%

“…Moreover, the presence of these slopes provides verification that subjects understood the task requirements and followed instructions. In studies of other populations, such as young children, task performance can be affected by inattention and by random response strategies, owing to a lack of motivation or interest on the part of the subject (e.g., Schachar et al, 1995;Tannock et al, 1995). Such response styles are detected by the slope function.…”

Section: Discussionmentioning

confidence: 99%

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Effects of d-amphetamine in human models of information processing and inhibitory control

Fillmore

Kelly

Martin

2005

Drug and Alcohol Dependence

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Although stimulants are generally associated with enhanced information processing, reports of stimulant effects on behavioral functions that rely on inhibitory processes have been inconsistent. The present research tested the joint effects of d-amphetamine on information processing and inhibitory control in healthy adults (N = 22) with no reported history of illicit stimulant use or drug dependence. Information processing was measured by a rapid information processing (RIP) task and inhibitory control was measured using a stop-signal task. Performance was measured in response to 15 mg/70 kg, 7.5 mg/70 kg, and 0 mg/70 mg (placebo) doses of d-amphetamine, administered double-blind in a randomized, within-subjects design. Results showed that damphetamine improved information processing in a dose-dependent manner. By contrast, no enhancement of response inhibition was observed. Stimulant effects were also observed in physiological and subjective effects measures. The findings indicate that a stimulant drug can enhance aspects of cognitive functioning without producing a concomitant improvement in inhibitory control of behavior. The findings highlight the complex nature of stimulant effects on human behavior and the utility of performance tasks as models of complex behavioral and cognitive functions.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Effects of d-amphetamine in human models of information processing and inhibitory control

Fillmore

Kelly

Martin

2005

Drug and Alcohol Dependence

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“…Other studies using the stop-signal reaction time task to measure impulsivity have also found baseline dependent effects of amphetamine and methylphenidate on impulsivity [24,25,28]. Further, in humans, individuals with high baseline levels of impulsivity, such as those with attention deficit/hyperactivity disorder (ADHD), show stimulant-induced decreases in impulsivity [69,84,85], further illustrating the importance of preexisting differences in impulsivity on the subsequent effects of stimulant drugs.…”

Section: Discussionmentioning

confidence: 93%

Impulsive choice and environmental enrichment: Effects of d-amphetamine and methylphenidate

Perry

Stairs

Bardo

2008

Behavioural Brain Research

123

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Individual differences in impulsive choice and rearing in differential environments are factors that predict vulnerability to drug abuse. The present study determined if rearing influences impulsive choice, and if d-amphetamine or methylphenidate alters impulsive choice in differentially-reared rats. Male Sprague-Dawley rats were raised from 21 days of age in either an enriched condition (EC) or an isolated condition (IC) and were tested as young adults on an adjusting delay task. In this task, two levers were available and a response on one lever yielded one 45 mg food pellet immediately, whereas a response on the other yielded three pellets after an adjusting delay. The delay was initially set at 6 sec, and it decreased or increased by 1 sec following responses on the immediate or delayed levers, respectively. A mean adjusted delay (MAD) was calculated upon completion of each daily session, and it served as the quantitative measure of impulsivity. Once MADs stabilized, rats were injected with saline, d-amphetamine (0.5, 1.0, or 2.0 mg/kg, s.c.), or methylphenidate (2.5, 5.0, or 10.0 mg/kg, s.c.) 15 min prior to adjusting delay sessions. EC rats had higher baseline MADs (were less impulsive) than IC rats. Additionally, administration of d-amphetamine, but not methylphenidate, dose-dependently increased impulsive choice (decreased MADs) in EC rats. In IC rats, d-amphetamine and methylphenidate dose-dependently decreased impulsivity (increased MADs). These results indicate that rearing environment influences impulsive choice and moderates the effect of psychostimulants on impulsive choice. Specifically, psychostimulants may decrease environment-dependent impulsive choice in individuals with high levels of impulsivity (e.g., those with ADHD), whereas they may increase impulsive choice in individuals with low levels of impulsivity.

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“…The stop signal task in which the subject is required to stop an ongoing behavior in response to a signal has been shown to be relatively specific to ADHD and to improve with stimulant treatment (Tannock et al, 1995b). The task is considered to activate prefrontal cortex (PFC) and basal ganglia.…”

Section: Comorbidity and Adhdmentioning

confidence: 99%

Synaptic Gating and ADHD: A Biological Theory of Comorbidity of ADHD and Anxiety

Lévy

2004

Neuropsychopharmacol

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To derive a biologically based theory of comorbidity in Attention Deficit Hyperactivity Disorder (ADHD). Theoretical concepts and empirical studies were reviewed to determine whether the behavioral inhibition concept provided an understanding of biological processes involved in comorbidity in ADHD. Empirical studies of ADHD have shown comorbidity of ADHD and anxiety, while studies of behavioral inhibition tend to suggest independent disruptive and anxiety traits. This paradox can be resolved by an understanding of the dynamics of mesolimbic dopamine (DA) systems, where reward and delay of reinforcement are determined by tonic/phasic DA relationships, resulting in impulsive 'fearless' responses when impaired. On the other hand, comorbid anxiety is related to impaired synaptic processes, which selectively gate fear (or aggressive) responses from the amygdala at the accumbens. Monosynaptic convergence between prefrontal, hippocampal, and amygdala projection neurons at the accumbens allows the operation of a synaptic gating mechanism between prefrontal cortex (PFC), hippocampus, and amygdala. Impairment of this mechanism by lowered PFC inhibition allows greater amygdala input, and anxiety-related processes more impact, over the accumbens. In conclusion, a dual theory incorporating long-term tonic/phasic mesolimbic DA relationships and secondly impairment of PFC and hippocampal inputs to synaptic gating of anxiety at the accumbens has implications for comorbidity in ADHD, as well as for possible pharmacological interventions, utilizing either stimulant or axiolytic interventions. The use of DA partial agonists may also be of interest.

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Methylphenidate and cognitive flexibility: Dissociated dose effects in hyperactive children

Abstract: A randomized, double-blind, placebo-controlled trial was conducted to assess the acute effects of placebo and three doses of methylphenidate (MPH) (0.3, 0.6, O. 9

Cited by 205 publications

References 54 publications

Effects of d-amphetamine in human models of information processing and inhibitory control

Effects of d-amphetamine in human models of information processing and inhibitory control

Impulsive choice and environmental enrichment: Effects of d-amphetamine and methylphenidate

Synaptic Gating and ADHD: A Biological Theory of Comorbidity of ADHD and Anxiety

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