Caffeine and Cognition in Functional Magnetic Resonance Imaging

Abstract

Abstract. Caffeine has been consumed since ancient times due to its beneficial effects on attention, psychomotor function, and memory. Caffeine exerts its action mainly through an antagonism of cerebral adenosine receptors, although there are important secondary effects on other neurotransmitter systems. Recently, functional MRI (fMRI) entered the field of neuropharmacology to explore the intracerebral sites and mechanisms of action of pharmacological agents. However, as caffeine possesses vasoconstrictive properties it may interfere with the mechanisms underlying the functional contrast in fMRI. Yet, only a limited number of studies dealt with the effect of caffeine on measures in fMRI. Even fewer neuroimaging studies examined the effects that caffeine exerts on cognition: Portas and colleagues used fMRI in an attentional task under different levels of arousal (sleep deprivation or caffeine administration), concluding that the thalamus is involved in mediating the interaction of attention and arousal. Bendlin and colleagues found caffeine to stabilize the extent of neuronal activation in repetitive word stem completion, counteracting the general task practice effect. Recently, Koppelstaetter and colleagues assessed the effect of caffeine on verbal working memory demonstrating a modulatory effect of caffeine on brain regions (medial frontopolar and anterior cingulate cortex) that have been associated with attentional and executive functions. This review surveys and discusses neuroimaging findings on 1) how caffeine affects the contrast underlying fMRI techniques, particularly the blood oxygen level dependent contrast (BOLD fMRI), and 2) how caffeine operates on neuronal activity underlying cognition, to understand the effect of caffeine on behavior and its neurobiological underpinnings.

Acute caffeine administration impact on working memory-related brain activation and functional connectivity in the elderly: A BOLD and perfusion MRI study

“…Early studies postulated that caffeine's effects on brain activation depend on a complex and potentially regionally variable interaction of neuronal and vascular responses (Laurienti et al, 2003;Koppelstaetter et al, 2010). At the neuronal level, caffeine causes most of its biological effects via the antagonism of all types of adenosine receptors A1, A2A, A3, and A2B mainly in the striatal neurons projecting to the basal ganglia (for reviews see Fisone et al (2004) and Costenla et al (2010)).…”

“…Caffeine is the most widely consumed psychoactive drug with beneficial neurocognitive effects including enhanced attention and memory (Koppelstaetter et al, 2010). Early studies postulated that caffeine's effects on brain activation depend on a complex and potentially regionally variable interaction of neuronal and vascular responses (Laurienti et al, 2003;Koppelstaetter et al, 2010).…”

The effect of caffeine on working memory load-related brain activation in middle-aged males

“…When investigating the effect of caffeine on the blood oxygen level--dependent (BOLD) response utilised by fMRI as an indirect measure of neural activity, it is important to recognise that changes in the BOLD response can arise from both neural and cerebrovascular mechanisms (for a review see Koppelstaetter et al, 2010;Laurienti et al, 2003). Caffeine, a non--selective adenosine receptor antagonist (Pelligrino et al, 2010), elicits: 1) neurostimulant effects, primarily via A1 receptors and the dopamine system (Ferre, 2008;Pelligrino et al, 2010); 2) cerebrovascular effects, primarily via A2A and A2B receptors located on blood vessels (Pelligrino et al, 2010); and 3) arousal enhancing effects, via A2A receptors and the histaminergic arousal system (Ferre, 2008); with tolerance thought to arise as the brain regulates its population of adenosine receptors to reach a new state of equilibrium in response to levels of caffeine chronically present in the body (Jacobson et al, 1996;Ralevic and Burnstock, 1998;Sousa et al, 2011).…”

Concluding Remarks

“…Evidence from some but not all epidemiological studies (reviewed in [3,4]) may suggest a beneficial effect for moderate doses of caffeine but a possible deleterious effect for larger doses. It should also be kept in mind that the finding of consistent objective effects for the acute administration of low doses of caffeine in humans (100-200 mg, equivalent to about 1-2 cups of coffee), namely on central electrophysiological measures [24], as well as functional neuroimaging studies [25], does not necessarily mean that these are the relevant doses for the neuroprotective effects of chronically-administered caffeine. Clearly, basic research is required to provide a rationale for the choice of the adequate dose of caffeine to be tested.…”