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Cognitive enhancement: Effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults.

ABSTRACT: Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain-functional mechanisms underlying such cognitive enhancing effects of stimulants are still poorly characterized. Here, we utilized behavioral and resting-state fMRI data from a double-blind randomized placebocontrolled study of methylphenidate, modafinil, and caffeine in 48 healthy male adults. The results show that performance in different memory tasks is enhanced, and functional connectivity (FC) specifically between the frontoparietal network (FPN) and default mode network (DMN) is modulated by the stimulants in comparison to placebo. Decreased negative connectivity between right prefrontal and medial parietal but also between medial temporal lobe and visual brain regions predicted stimulant-induced latent memory enhancement. We discuss dopamine's role in attention and memory as well as its ability to modulate FC between large-scale neural networks (e.g., FPN and DMN) as a potential cognitive enhancement mechanism.

SUBMITTER: Becker M

PROVIDER: S-EPMC9435011 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Cognitive enhancement: Effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults.

Becker Maxi M Repantis Dimitris D Dresler Martin M Kühn Simone S

Human brain mapping 20220607 14

Stimulants like methylphenidate, modafinil, and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain-functional mechanisms underlying such cognitive enhancing effects of stimulants are still poorly characterized. Here, we utilized behavioral and resting-state fMRI data from a double-blind randomized placebocontrolled study of methylphenidate, modafinil, and caffeine in 48 healthy male adults. The results show that performance in different mem ...[more]

PMID: 35670369

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Project description:ImportanceCocaine addiction is associated with altered resting-state functional connectivity among regions of the mesocorticolimbic dopamine pathways. Methylphenidate hydrochloride, an indirect dopamine agonist, normalizes task-related regional brain activity and associated behavior in cocaine users; however, the neural systems-level effects of methylphenidate in this population have not yet been described.ObjectiveTo use resting-state functional magnetic resonance imaging to examine changes in mesocorticolimbic connectivity with methylphenidate and how connectivity of affected pathways relates to severity of cocaine addiction.DesignRandomized, placebo-controlled, before-after, crossover study.SettingClinical research center.ParticipantsEighteen nonabstaining individuals with cocaine use disorders.InterventionsSingle doses of oral methylphenidate (20 mg) or placebo were administered at each of 2 study sessions. At each session, resting scans were acquired twice: immediately after drug administration (before the onset of effects [baseline]) and 120 minutes later (within the window of peak effects).Main outcomes and measuresFunctional connectivity strength was evaluated using a seed voxel correlation approach. Changes in this measure were examined to characterize the neural systems-level effects of methylphenidate; severity of cocaine addiction was assessed by interview and questionnaire.ResultsShort-term methylphenidate administration reduced an abnormally strong connectivity of the ventral striatum with the dorsal striatum (putamen/globus pallidus), and lower connectivity between these regions during placebo administration uniquely correlated with less severe addiction. In contrast, methylphenidate strengthened several corticolimbic and corticocortical connections.Conclusions and relevanceThese findings help elucidate the neural systems-level effects of methylphenidate and suggest that short-term methylphenidate can, at least transiently, remodel abnormal circuitry relevant to the pathophysiologic characteristics of cocaine addiction. In particular, the effects of methylphenidate within striatal and cortical pathways constitute a potentially viable mechanism by which methylphenidate could facilitate control of behavior in cocaine addiction.

Project description:ObjectivesIn healthy aging, the way people cope differently with cognitive and neural decline is influenced by exposure to cognitively enriching life-experiences. Education is one of them, so that in general, the higher the education, the better the expected cognitive performance in aging. At the neural level, it is not clear yet how education can differentiate resting state functional connectivity profiles and their cognitive underpinnings. Thus, with this study, we aimed to investigate whether the variable education allowed for a finer description of age-related differences in cognition and resting state FC.MethodsWe analyzed in 197 healthy individuals (137 young adults aged 20-35 and 60 older adults aged 55-80 from the publicly available LEMON database), a pool of cognitive and neural variables, derived from magnetic resonance imaging, in relation to education. Firstly, we assessed age-related differences, by comparing young and older adults. Then, we investigated the possible role of education in outlining such differences, by splitting the group of older adults based on their education.ResultsIn terms of cognitive performance, older adults with higher education and young adults were comparable in language and executive functions. Interestingly, they had a wider vocabulary compared to young adults and older adults with lower education. Concerning functional connectivity, the results showed significant age- and education-related differences within three networks: the Visual-Medial, the Dorsal Attentional, and the Default Mode network (DMN). For the DMN, we also found a relationship with memory performance, which strengthen the evidence that this network has a specific role in linking cognitive maintenance and FC at rest in healthy aging.DiscussionOur study revealed that education contributes to differentiating cognitive and neural profiles in healthy older adults. Also, the DMN could be a key network in this context, as it may reflect some compensatory mechanisms relative to memory capacities in older adults with higher education.

Project description:BackgroundPsychostimulants such as methylphenidate and modafinil are increasingly used by healthy people for cognitive enhancement purposes, whereas the acute effect of 3,4-methylenedioxymethamphetamine (ecstasy) on cognitive functioning in healthy subjects remains unclear. This study directly compared the acute effects of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine on the neural mechanisms underlying response inhibition in healthy subjects.MethodsUsing a double-blind, within-subject, placebo-controlled, cross-over design, methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine were administrated to 21 healthy subjects while performing a go/no-go event-related functional magnetic resonance imaging task to assess brain activation during motor response inhibition.ResultsRelative to placebo, methylphenidate and modafinil but not 3,4-methylenedioxymethamphetamine improved inhibitory performance. Methylphenidate significantly increased activation in the right middle frontal gyrus, middle/superior temporal gyrus, inferior parietal lobule, presupplementary motor area, and anterior cingulate cortex compared with placebo. Methylphenidate also induced significantly higher activation in the anterior cingulate cortex and presupplementary motor area and relative to modafinil. Relative to placebo, modafinil significantly increased activation in the right middle frontal gyrus and superior/inferior parietal lobule, while 3,4-methylenedioxymethamphetamine significantly increased activation in the right middle/inferior frontal gyrus and superior parietal lobule.ConclusionsDirect comparison of methylphenidate, modafinil, and 3,4-methylenedioxymethamphetamine revealed broad recruitment of fronto-parietal regions but specific effects of methylphenidate on middle/superior temporal gyrus, anterior cingulate cortex, and presupplementary motor area activation, suggesting dissociable modulations of response inhibition networks and potentially the superiority of methylphenidate in the enhancement of cognitive performance in healthy subjects.

Dataset Information

Cognitive enhancement: Effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults.

Publications

Cognitive enhancement: Effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults.

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