Effects of modafinil and methylphenidate on visual attention capacity: a TVA-based study
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Theory of visual attention (TVA; Bundesen 1990) whole report tasks allow the independent measurement of visual perceptual processing speed and visual short-term memory (vSTM) storage capacity, unconfounded by motor speed. This study investigates how cognitive enhancing effects of psychostimulants depend on baseline performance and individual plasma levels.
Materials and methods
Eighteen healthy volunteers (aged 20–35 years) received single oral doses of either 40 mg methylphenidate, 400 mg modafinil or placebo in a counterbalanced, double-blind crossover design. A whole report of visually presented letter arrays was performed 2.5–3.5 h after drug administration, and blood samples for plasma level analysis were taken.
Methylphenidate and modafinil both enhanced perceptual processing speed in participants with low baseline (placebo) performance. These improvements correlated with subjective alertness. Furthermore, we observed differential plasma level-dependent effects of methylphenidate in lower and higher performing participants: higher plasma levels led to a greater improvement in low-performing participants and to decreasing improvement in high-performing participants. Modafinil enhanced visual short-term memory storage capacity in low-performing participants.
This is the first pharmacological investigation demonstrating the usefulness of a TVA task for high-resolution and repeated cognitive parameter estimation after cognitive-enhancing medication. Our results confirm previous findings of attentional capacity improvements in low performers and extend the baseline dependency model to methylphenidate. Plasma level-dependent effects of psychostimulants can be modelled on an inverted U-shaped dose–response relationship, which is highly relevant to predict cognitive enhancing and detrimental effects of psychostimulants in patients with cognitive deficits (e.g., attention deficit hyperactivity disorder) and healthy volunteers (e.g., self-medicating academics).
KeywordsDopamine ADHD Arousal Attention Behaviour Cognitive Human Perception
We would like to thank Hermann J. Müller, Werner X. Schneider and Trevor W. Robbins for their support of this research. This study was funded by grants of the Medical Research Council (MRC) to TM and of the Deutsche Forschungsgemeinschaft (DFG; project MU 773/6-1). UM was supported by an MRC pathfinder grant.
Disclosure/Conflict of interest
U. Müller has received research grant support from Janssen-Cilag and honoraria or travel expenses from Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Pharmacia-Upjohn, and UCB Pharma. R. Regenthal has received research grant support from Pfizer.
- Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AFT, Kelley AE, Schmeichel B, Hamilton C, Spencer RC (2006) Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognition. Biol Psychiatry 60:1111–1120CrossRefPubMedGoogle Scholar
- Bublak P, Finke K, Krummenacher J, Preger R, Kyllingsbæk S, Müller HJ, Schneider WX (2005) Usability of a theory of visual attention (TVA) for parameter-based measurement of attention II: evidence from two patients with frontal or parietal damage. J Int Neuropsychol Soc 11:843–854CrossRefPubMedGoogle Scholar
- Clatworthy PL, Lewis SJG, Birchard L, Hong YT, Izquierdo D, Clark L, Cools R, Aigbirhio FI, Baron J-C, Fryer TD, Robbins TW (2009) Dopamine release in dissociable striatal subregions predicts the different effects of oral methylphenidate on reversal learning and spatial working memory. J Neurosci 29:4690–4696CrossRefPubMedGoogle Scholar
- Desimone R, Duncan J (1995) Neural mechanisms of selective visual attention. Ann Rev Psychol 18:193–222Google Scholar
- Evans SW, Pelham WE, Smith BH, Bukstein O, Gnagy EM, Greiner AR, Altenderfer L, Baron-Myak C (2001) Dose-response effects of methylphenidate on ecologically valid measures of academic performance and classroom behavior in adolescents with ADHD. Exp Clin Psychopharmacol 9:163–175CrossRefPubMedGoogle Scholar
- Hebb DO (1949) Organization of behavior. Wiley, New YorkGoogle Scholar
- Matthias E, Bublak P, Müller HJ, Schneider WX, Krummenacher J, Finke K (2010) The influence of phasic alertness on spatial and non-spatial components of visual attention. J Exp Psychol: Hum Percept Perform 33:38–56Google Scholar
- Mehta MA, Owen AM, Sahakian BJ, Mavaddat N, Pickard JD, Robbins TW (2000) Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain. J Neurosci: 20: RC65: 1–6Google Scholar
- Milner AD, Goodale MA (1995) The visual brain in action. Oxford University Press, OxfordGoogle Scholar
- National Institute for Health and Clinical Excellence (NICE) (2008) Attention deficit hyperactivity disorder. Diagnosis and management of ADHD in children, young people and adults. NICE clinical guideline 72. London: NICEGoogle Scholar
- Roberts AOH (1980) Regression toward the mean and the regression-effect bias. In: Echternacht G (ed) New directions for testing and measurement, vol 8. Jossey-Bass, San Francisco, pp 59–82Google Scholar
- Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, Hopwood A, Wallace C, Deakin JFW, Sahakian BJ, Robbins TW (1999) Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology 146:482–491CrossRefPubMedGoogle Scholar
- Ross SM (2000) Introduction to probability and statistics for engineers and scientists. Academic Press, San DiegoGoogle Scholar
- Sperling G (1960) The information available in brief visual presentations. Psychological Monogr 74:1–29Google Scholar
- Ungerleider LG, Mishkin M (1982) Two cortical visual systems. In: Ingle DJ, Goodale MA, Mansfield RJW (eds) Analysis of visual behavior. MIT Press, Cambridge, pp 549–586Google Scholar
- Volkow ND, Wang G, Fowler JS, Logan J, Gerasimov M, Maynard L, Ding Y, Gatley SJ, Gifford A, Franceschi D (2001) Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci 21:121Google Scholar
- Volkow ND, Fowler JS, Logan J, Alexoff D, Zhu W, Telang F, Wang G-J, Jayne M, Hooker JM, Wong C, Hubbard B, Carter P, Warner D, King P, Shea C, Xu Y, Muench L, Apelskog-Torres K (2009) Effects of modafinil on dopamine and dopamine transporters in the male human brain. J Am Med Assoc 301:1148–1154CrossRefGoogle Scholar
- Winder-Rhodes SE, Chamberlain SR, Idris MI, Robbins TW, Sahakian BJ, Müller U (2009) Effects of modafinil and prazosin on cognitive and physiological functions in healthy volunteers. J Psychopharmacol [Epub ehead of publication]Google Scholar