Caffeine can compromise working memory function and lead to changes in brain activity patterns

For many of us, caffeine is a daily necessity, providing that morning jolt to kickstart our day or the mid-afternoon pick-me-up during a long workday. We often associate caffeine with improved focus and alertness, but what if this cherished stimulant isn’t quite the brain-boosting elixir we believe it to be? Recent research published in Scientific Reports has shed new light on the relationship between caffeine and cognitive performance. Contrary to common expectations, the study suggests that daily caffeine intake might hinder rather than enhance our working memory. Previous research has indeed suggested that caffeine can have beneficial effects on cognition, such as improving attention and alertness. However, these studies often focused on acute caffeine intake, failing to consider the long-term consequences of daily consumption. This new study aimed to address this gap in our understanding by investigating the effects of sustained caffeine use on cognitive performance. “Caffeine is the most commonly used psychoactive substance to combat drowsiness and improve vigilance. We were curious whether this beneficial effect could be extended to the performance of working memory, which was a cognitive function crucially underpinning various kinds of daily tasks,” said study author Yu-Shiuan Lin, a postdoctoral researcher affiliated with both Harvard Medical School and the University of Basel. “Moreover, despite a large majority of daily caffeine users, a substantial amount of scientific studies had rather focused on the acute effects of caffeine, namely the pharmacological effects derived from a period of caffeine-free state. Therefore, we would like to focus on the effects of daily caffeine intake and an acute discontinuation from daily caffeine on the working memory function and its neural correlates.” The researchers conducted a double-blind, randomized, placebo-controlled crossover study at the Centre for Chronobiology at University Psychiatric Clinics Basel in Switzerland to investigate the effects of daily caffeine intake on working memory-related brain activity and behavioral performance. The study included twenty healthy male volunteers. The choice of a male-only population was made to minimize variability in caffeine metabolism due to hormonal fluctuations in females. Each participant completed three conditions: placebo, caffeine, and caffeine withdrawal, with the order of conditions randomized. In the placebo condition, they received no caffeine, while during the caffeine conditions, they received a daily moderate dose of caffeine over ten days. During the withdrawal condition, they received caffeine for nine days but then underwent a 36-hour caffeine withdrawal period. Cognitive performance was assessed using two main tasks: the 0-back task and the 3-back task. The 0-back task primarily evaluated basic attentional and psychomotor performance, while the 3-back task assessed working memory function. Both error rates and reaction times were measured to gauge participants’ performance. Brain activity was analyzed using functional MRI scans. The researchers examined the differences in brain activity between the 0-back and 3-back tasks to understand how caffeine intake and withdrawal influenced neural responses during memory-related activities. Error rates during basic attention tasks (0-back) did not show a significant effect of condition. Participants made a similar number of errors across the three conditions. Interestingly, caffeine withdrawal had a noticeable impact on participants’ attention processes. Those in the withdrawal condition experienced longer reaction times during 0-back tasks, highlighting the withdrawal’s effect on focus and alertness. “Interestingly, those cognitive elements typically benefited acutely by caffeine, such as the information processing time in a basic attention task, were not enhanced after daily intake of caffeine,” Lin told PsyPost. “This observation echoed the tolerance to chronic caffeine intake that has been frequently reported in both animals and humans. Discontinuing daily caffeine intake, however, led to a slower information processing in this attention task.” The researchers also found evidence that daily moderate-dose caffeine intake might actually compromise working memory. Participants in the caffeine and withdrawal conditions displayed higher error rates and longer reaction times during the 3-back task, indicating that daily caffeine consumption didn’t enhance this aspect of memory. Functional MRI analysis unveiled intriguing patterns of brain activity. During the 3-back task, which required working memory, there was increased activity in brain regions associated with attention and motor control. However, no significant differences in brain activity were observed among the three conditions, indicating that the changes in cognitive performance did not align with corresponding changes in neural activity. The brain imaging results are in line with previous research, which had found “that acute caffeine intake increased brain activity without improving the behavioral performance of working memory,” Lin explained. “Our data added that taking caffeine daily did not significantly change the brain activity yet compromised the behavioral performance of working memory instead. This compromising effect was surprisingly attenuated in the condition when participants discontinued their daily caffeine intake.” Daily caffeine intake was associated with reduced activity in the right hippocampus, a brain region crucial for memory processes. “As an unexpected finding, we observed a reduced blood oxygen-dependent activity in the right hippocampus throughout the working memory task,” Lin told PsyPost. “In our previous report from the same study, we actually observed a reduced grey matter structure in this very region after daily caffeine intake (see here and here). What led to a reduced activity and structure remained unclear.” The study provides valuable insights into the effects of caffeine on memory and brain function. But the study, like all research, includes some limitations. The sample size was relatively small, and the study focused on a male-only population to reduce variability in caffeine metabolism. Future research could explore the effects of caffeine in larger and more diverse groups. The study also used pure caffeine rather than caffeinated beverages, so the findings may not fully represent the effects of coffee or tea consumption. “In general, we believe that more studies with a larger sample size are needed in order to confirm and explain better what we have found so far,” Lin said. Additional research is also needed to understand the molecular mechanisms underlying caffeine’s effects on different cognitive functions. “It has been known that caffeine leads to neurovascular decoupling, namely disproportionate vascular responses to the neural activity,” Lin explained. “As fMRI measurement is highly dependent on neurovascular coupling, our data further raised the question: are the caffeine effects on cognitive performance linked to the neurovascular effect of caffeine? If not, what are the underlying mechanism of the cognitive effect of caffeine?” The study, “Brain activity during a working memory task after daily caffeine intake and caffeine withdrawal: a randomized double-blind placebo-controlled trial“, was authored by Yu-Shiuan Lin, Janine Weibel, Hans-Peter Landolt, Francesco Santini, Helen Slawik, Stefan Borgwardt, Christian Cajochen, and Carolin Franziska Reichert. research psychoactive

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