Methylphenidate affects task-switching and neural signaling in non-human primates

Rajala, Abigail Z.; Populin, Luis C.; Jenison, Rick L.

doi:10.1007/s00213-020-05478-z

Cited by 10 publications

(14 citation statements)

References 51 publications

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“…There is some evidence from studies of rhesus monkeys given therapeutic doses of methylphenidate that the drug can impair task-switching performance. This indicates that the improved ability to focus attention may come at the expense of hindering flexibility 110 . Taken together, these findings suggest that serotonergic and dopaminergic signalling are critically involved in flexible cognition and behaviour.…”

Section: Drugs and Training Of Flexibilitymentioning

confidence: 99%

Cognitive and behavioural flexibility: neural mechanisms and clinical considerations

2021

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Cognitive and behavioural flexibility permit the appropriate adjustment of thoughts and behaviours in response to changing environmental demands. Brain mechanisms enabling flexibility have been examined using non-invasive neuroimaging and behavioural approaches in humans alongside pharmacological and lesion studies in animals. This work has identified large-scale functional brain networks encompassing lateral and orbital frontoparietal, midcingulo-insular and frontostriatal regions that support flexibility across the lifespan. Flexibility can be compromised in early-life neurodevelopmental disorders, clinical conditions that emerge during adolescence and late-life dementias. We critically evaluate evidence for the enhancement of flexibility through cognitive training, physical activity and bilingual experience.

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Section: Drugs and Training Of Flexibilitymentioning

confidence: 99%

Cognitive and behavioural flexibility: neural mechanisms and clinical considerations

2021

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“…We used between 2-6 mg/kg (see Methods; Kodama et al, 2017;Oemisch et al, 2016;Rajala et al, 2012;2020), and the data from all dosages were included together in the analyses to avoid best dose analyses (Soto et al, 2013; while our goal was to use the systemic administration of methylphenidate as a causal test of our hypotheses, not to test for dosedependent effects, we have included analyses per dosage in the Supplementary Figures).…”

Section: Resultsmentioning

confidence: 99%

“…People use stimulants both with and without prescription with the goal of enhancing selective cognitive processes such as the ability to focus on one task or one aspect of the environment while ignoring distractions (Bagot & Kaminer, 2014;Maher, 2008;Swanson et al, 2011;Wickens et al, 2011). Yet, while we have progressed our understanding of the neuronal mechanisms underlying the effects of these drugs on memory, learning, cognitive flexibility, motivation, and impulsivity (Berridge & Arnsten, 2015;Clatworthy et al, 2009;Devilbiss & Berridge, 2008;Dinse et al, 2003;Dodds et al, 2008;Gamo et al, 2010;Garrett et al, 2015;Kodama et al, 2017;Mehta et al, 2000;Rajala et al, 2012;2020), we have only begun to understand the neuronal effects of these stimulants on selective attention in the context of a controlled laboratory setting (Bain et al, 2003;Prendergast et al, 1998;Tomasi et al, 2011;Tremblay et al, 2019). The neural mechanisms underlying stimulant-related changes in selective cognition have remained a mystery: our study is to our knowledge the first electrophysiological report of how changes in neuronal population responses correspond to increased selective attention with ADHD drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Fig. 1b; though see Rajala et al, 2012;2020). pairs of days, t(6) = -4.1, p = 6.1 x 10 -3 ; Monkey 2: n = 5 pairs of days, t(4) = -6.6, p = 2.7 x 10 -3 ).…”

Section: Improved Motivationmentioning

confidence: 95%

“…). It should be noted that it was not our goal to test for dose-dependent effects, and that prior studies have found that the same stimulant can have different effects on different cognitive processes depending on the dosage administered (Pietrzak et al, 2006;Rajala et al, 2012;2020;Swanson et al, 2011;Wickens et al, 2011). Maunsell, 2018;Sridharan et al, 2017).…”

Section: Supplementary Figuresmentioning

confidence: 99%

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Methylphenidate as a causal test of translational and basic neural coding hypotheses

Bowes

Ruff

et al. 2021

Preprint

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Most systems neuroscience studies fall into one of two categories: basic science work aimed at understanding the relationship between neurons and behavior, or translational work aimed at developing treatments for neuropsychiatric disorders. Here we use these two approaches to inform and enhance each other. Our study both tests hypotheses about basic science neural coding principles and elucidates the neuronal mechanisms underlying new, clinically relevant behavioral effects of systemically administered methylphenidate (Ritalin). We discovered that orally administered methylphenidate, used clinically to treat Attention Deficit Hyperactivity Disorder (ADHD) and generally to enhance cognition (Lakhan & Kirchgessner, 2012; Maher, 2008), increases spatially selective visual attention, enhancing visual performance at only the attended location. And as predicted by our previous work (Ni et al., 2018), we found that this causal manipulation enhances vision in rhesus macaques specifically when it decreases the mean correlated variability of neurons in visual area V4. Our findings demonstrate that the visual system is a platform for understanding the neural underpinnings of both complex cognitive processes (basic science) and neuropsychiatric disorders (translation). Addressing basic science hypotheses, our results are consistent with a scenario in which methylphenidate has cognitively specific effects by working through naturally selective cognitive mechanisms. Clinically, our findings suggest that the often staggeringly specific symptoms of neuropsychiatric disorders may be caused and treated by leveraging general mechanisms.

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The effect of methylphenidate and mixed amphetamine salts on cognitive reflection: a field study

Yechiam

Zeif

2021

Psychopharmacology

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Methylphenidate affects task-switching and neural signaling in non-human primates

Cited by 10 publications

References 51 publications

Cognitive and behavioural flexibility: neural mechanisms and clinical considerations

Cognitive and behavioural flexibility: neural mechanisms and clinical considerations

Methylphenidate as a causal test of translational and basic neural coding hypotheses

The effect of methylphenidate and mixed amphetamine salts on cognitive reflection: a field study

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