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Research ArticleNew Research, Cognition and Behavior

The Effects of Methylphenidate (Ritalin) on the Neurophysiology of the Monkey Caudal Prefrontal Cortex

Sébastien Tremblay, Florian Pieper, Adam Sachs, Ridha Joober and Julio Martinez-Trujillo
eNeuro 25 February 2019, 6 (1) ENEURO.0371-18.2018; DOI: https://doi.org/10.1523/ENEURO.0371-18.2018
Sébastien Tremblay
Montreal Neurological Institute, McGill University, Montreal, Québec, H3A 2B4, Canada
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  • ORCID record for Sébastien Tremblay
Florian Pieper
Institute for Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf 20251, Hamburg, Germany
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Adam Sachs
Department of Surgery, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, K1H 8L6, Canada
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Ridha Joober
Douglas Mental Health University Institute, McGill University, Montreal, Québec, H4H 1R3, Canada
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Julio Martinez-Trujillo
Robarts Research Institute, Departments of Psychiatry, Physiology and Pharmacology Schulich School of Medicine and Dentistry, Brain and Mind Institute, University of Western Ontario, London, Ontario, N6A 5C1, Canada
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Abstract

Methylphenidate (MPH), commonly known as Ritalin, is the most widely prescribed drug worldwide to treat patients with attention deficit disorders. Although MPH is thought to modulate catecholamine neurotransmission in the brain, it remains unclear how these neurochemical effects influence neuronal activity and lead to attentional enhancements. Studies in rodents overwhelmingly point to the lateral prefrontal cortex (LPFC) as a main site of action of MPH. To understand the mechanism of action of MPH in a primate brain, we recorded the responses of neuronal populations using chronic multielectrode arrays implanted in the caudal LPFC of two macaque monkeys while the animals performed an attention task (N = 2811 neuronal recordings). Over different recording sessions (N = 55), we orally administered either various doses of MPH or a placebo to the animals. Behavioral analyses revealed positive effects of MPH on task performance at specific doses. However, analyses of individual neurons activity, noise correlations, and neuronal ensemble activity using machine learning algorithms revealed no effects of MPH. Our results suggest that the positive behavioral effects of MPH observed in primates (including humans) may not be mediated by changes in the activity of caudal LPFC neurons. MPH may enhance cognitive performance by modulating neuronal activity in other regions of the attentional network in the primate brain.

  • attention
  • methylphenidate
  • multielectrode array
  • prefrontal cortex
  • primates
  • Ritalin

Footnotes

  • The authors declare no competing financial interests.

  • This work was supported by the Gouvernement du Canada | Canadian Institutes of Health Research Grant 501100000024, the NSERC (The Natural Sciences and Engineering Research Council of Canada), and the EJLB Foundation (J.M.-T.) and by the NSERC Alexander Graham Bell Canada Graduate Scholarship (S.T.).

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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eneuro: 6 (1)
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January/February 2019
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The Effects of Methylphenidate (Ritalin) on the Neurophysiology of the Monkey Caudal Prefrontal Cortex
Sébastien Tremblay, Florian Pieper, Adam Sachs, Ridha Joober, Julio Martinez-Trujillo
eNeuro 25 February 2019, 6 (1) ENEURO.0371-18.2018; DOI: 10.1523/ENEURO.0371-18.2018

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The Effects of Methylphenidate (Ritalin) on the Neurophysiology of the Monkey Caudal Prefrontal Cortex
Sébastien Tremblay, Florian Pieper, Adam Sachs, Ridha Joober, Julio Martinez-Trujillo
eNeuro 25 February 2019, 6 (1) ENEURO.0371-18.2018; DOI: 10.1523/ENEURO.0371-18.2018
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Keywords

  • attention
  • methylphenidate
  • multielectrode array
  • prefrontal cortex
  • primates
  • Ritalin

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