Cognitive Enhancement: Effects of Methylphenidate, Modafinil, and Caffeine on Latent Memory and Resting State Functional Connectivity in Healthy Adults

Overview

Journal Hum Brain Mapp

Publisher Wiley

Specialty Neurology

Date 2022 Jun 7

PMID 35670369

Authors

Maxi Becker

Dimitris Repantis

Martin Dresler

Simone Kuhn

Affiliations

Soon will be listed here.

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.

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References

Dang L, ONeil J, Jagust W . Dopamine supports coupling of attention-related networks. J Neurosci. 2012; 32(28):9582-7. PMC: 3410707. DOI: 10.1523/JNEUROSCI.0909-12.2012. View

Cabeza R, Ciaramelli E, Olson I, Moscovitch M . The parietal cortex and episodic memory: an attentional account. Nat Rev Neurosci. 2008; 9(8):613-25. PMC: 2692883. DOI: 10.1038/nrn2459. View

James J . Caffeine and cognitive performance: persistent methodological challenges in caffeine research. Pharmacol Biochem Behav. 2014; 124:117-22. DOI: 10.1016/j.pbb.2014.05.019. View

Leshikar E, Duarte A, Hertzog C . Task-selective memory effects for successfully implemented encoding strategies. PLoS One. 2012; 7(5):e38160. PMC: 3364974. DOI: 10.1371/journal.pone.0038160. View

Sheehan D, Lecrubier Y, Sheehan K, Amorim P, Janavs J, Weiller E . The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1999; 59 Suppl 20:22-33;quiz 34-57. View

Jafri M, Pearlson G, Stevens M, Calhoun V . A method for functional network connectivity among spatially independent resting-state components in schizophrenia. Neuroimage. 2007; 39(4):1666-81. PMC: 3164840. DOI: 10.1016/j.neuroimage.2007.11.001. View

Compton W, Han B, Blanco C, Johnson K, Jones C . Prevalence and Correlates of Prescription Stimulant Use, Misuse, Use Disorders, and Motivations for Misuse Among Adults in the United States. Am J Psychiatry. 2018; 175(8):741-755. PMC: 6070393. DOI: 10.1176/appi.ajp.2018.17091048. View

Ferre S . An update on the mechanisms of the psychostimulant effects of caffeine. J Neurochem. 2007; 105(4):1067-79. DOI: 10.1111/j.1471-4159.2007.05196.x. View

Buysse D, Reynolds 3rd C, Monk T, BERMAN S, Kupfer D . The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989; 28(2):193-213. DOI: 10.1016/0165-1781(89)90047-4. View

10.

Sripada C, Kessler D, Angstadt M . Lag in maturation of the brain's intrinsic functional architecture in attention-deficit/hyperactivity disorder. Proc Natl Acad Sci U S A. 2014; 111(39):14259-64. PMC: 4191792. DOI: 10.1073/pnas.1407787111. View

11.

Fredholm B, BATTIG K, Holmen J, Nehlig A, Zvartau E . Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999; 51(1):83-133. View

12.

Pigeau , Naitoh , Buguet , McCann , BARANSKI , Taylor . Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature. J Sleep Res. 1995; 4(4):212-228. DOI: 10.1111/j.1365-2869.1995.tb00172.x. View

13.

Gardner W, Mulvey E, SHAW E . Regression analyses of counts and rates: Poisson, overdispersed Poisson, and negative binomial models. Psychol Bull. 1995; 118(3):392-404. DOI: 10.1037/0033-2909.118.3.392. View

14.

Ilieva I, Hook C, Farah M . Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis. J Cogn Neurosci. 2015; 27(6):1069-89. DOI: 10.1162/jocn_a_00776. View

15.

Berridge C, Devilbiss D, Andrzejewski M, Arnsten A, Kelley A, Schmeichel B . Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry. 2006; 60(10):1111-20. DOI: 10.1016/j.biopsych.2006.04.022. View

16.

Wood S, Sage J, Shuman T, Anagnostaras S . Psychostimulants and cognition: a continuum of behavioral and cognitive activation. Pharmacol Rev. 2013; 66(1):193-221. PMC: 3880463. DOI: 10.1124/pr.112.007054. View

17.

Badre D, DEsposito M . Functional magnetic resonance imaging evidence for a hierarchical organization of the prefrontal cortex. J Cogn Neurosci. 2007; 19(12):2082-99. DOI: 10.1162/jocn.2007.19.12.2082. View

18.

Schermelleh-Engel K, Kerwer M, Klein A . Evaluation of model fit in nonlinear multilevel structural equation modeling. Front Psychol. 2014; 5:181. PMC: 3941193. DOI: 10.3389/fpsyg.2014.00181. View

19.

Arnsten A . Stimulants: Therapeutic actions in ADHD. Neuropsychopharmacology. 2006; 31(11):2376-83. DOI: 10.1038/sj.npp.1301164. View

20.

Nathan Spreng R, Stevens W, Chamberlain J, Gilmore A, Schacter D . Default network activity, coupled with the frontoparietal control network, supports goal-directed cognition. Neuroimage. 2010; 53(1):303-17. PMC: 2914129. DOI: 10.1016/j.neuroimage.2010.06.016. View