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Abstract
Methylphenidate (MPH), a stimulant drug with dopamine and noradrenaline reuptake inhibition
properties, is mainly prescribed in attention deficit hyperactivity disorder, is increasingly
used by the general population, intending to enhance their cognitive function. In
this literature review, we aim to answer whether this is effective. We present a novel
way to determine the extent to which MPH enhances cognitive performance in a certain
domain. Namely, we quantify this by a percentage that reflects the number of studies
showing performance enhancing effects of MPH. To evaluate whether the dose-response
relationship follows an inverted-U-shaped curve, MPH effects on cognition are also
quantified for low, medium and high doses, respectively. The studies reviewed here
show that single doses of MPH improve cognitive performance in the healthy population
in the domains of working memory (65% of included studies) and speed of processing
(48%), and to a lesser extent may also improve verbal learning and memory (31%), attention
and vigilance (29%) and reasoning and problem solving (18%), but does not have an
effect on visual learning and memory. MPH effects are dose-dependent and the dose-response
relationship differs between cognitive domains. MPH use is associated with side effects
and other adverse consequences, such as potential abuse. Future studies should focus
on MPH specifically to adequately asses its benefits in relation to the risks specific
to this drug.
Dopamine (DA) acts as a key neurotransmitter in the brain. Numerous studies have shown its regulatory role for motor and limbic functions. However, in the early stages of Parkinson's disease (PD), alterations of executive functions also suggest a role for DA in regulating cognitive functions. Some other diseases, which can also involve DA dysfunction, such as schizophrenia or attention deficit hyperactivity disorder (ADHD) in children, as shown from the ameliorative action of dopaminergic antagonists and agonists, respectively, also show alteration of cognitive functions. Experimental studies showed that selective lesions of the dopaminergic neurons in rats or primates can actually provide cognitive deficits, especially when the mesocorticolimbic component of the dopaminergic systems is altered. Data from the experiments also showed significant alteration in attentional processes, thus raising the question of direct involvement of DA in regulating attention. Since the dopaminergic influence is mainly exerted over the frontal lobe and basal ganglia, it has been suggested that cognitive deficits express alteration in these subcortical brain structures closely linked to cortical areas, more than simple deficit in dopaminergic transmission. This point is still a matter of debate but, undoubtedly, DA acts as a powerful regulator of different aspects of cognitive brain functions. In this respect, normalizing DA transmission will contribute to improve the cognitive deficits not only related to neurologic or psychiatric diseases, but also in normal aging. Ontogenic and phylogenetic analysis of dopaminergic systems can provide evidences for a role of DA in the development of cognitive general capacities. DA can have a trophic action during maturation, which may influence the later cortical specification, particularly of pre-frontal cortical areas. Moreover, the characteristic extension of the dopaminergic cortical innervation in the rostro-caudal direction during the last stages of evolution in mammals can also be related to the appearance of progressively more developed cognitive capacities. Such an extension of cortical DA innervation could be related to increased processing of cortical information through basal ganglia, either during the course of evolution or development. DA has thus to be considered as a key neuroregulator which contributes to behavioral adaptation and to anticipatory processes necessary for preparing voluntary action consequent upon intention. All together, it can be suggested that a correlation exists between DA innervation and expression of cognitive capacities. Altering the dopaminergic transmission could, therefore, contribute to cognitive impairment. Copyright 2002 Elsevier Science Ltd.
The term neuroenhancement refers to improvement in the cognitive, emotional and motivational functions of healthy individuals through, inter alia, the use of drugs. Of known interventions, psychopharmacology provides readily available options, such as methylphenidate and modafinil. Both drugs are presumed to be in widespread use as cognitive enhancers for non-medical reasons. Based on a systematic review and meta-analysis we show that expectations regarding the effectiveness of these drugs exceed their actual effects, as has been demonstrated in single- or double-blind randomised controlled trials. Only studies with sufficient extractable data were included in the statistical analyses. For methylphenidate an improvement of memory was found, but no consistent evidence for other enhancing effects was uncovered. Modafinil on the other hand, was found to improve attention for well-rested individuals, while maintaining wakefulness, memory and executive functions to a significantly higher degree in sleep deprived individuals than did a placebo. However, repeated doses of modafinil were unable to prevent deterioration of cognitive performance over a longer period of sleep deprivation though maintaining wakefulness and possibly even inducing overconfidence in a person's own cognitive performance. Copyright 2010 Elsevier Ltd. All rights reserved.
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