Sensory Stimulus-mediated Neural Synchrony in the Prefrontal Cortex: An Investigation into the Effects of Caffeine

Abstract

Caffeine, a legal central nervous system stimulant, is commonly consumed by university students in a variety of ways with an implicit belief that it may increase cognitive function. The scientific literature on such benefits has been mixed. In low to moderate doses, caffeine has been shown to reduce fatigue and improve alertness and motor speed while high caffeine consumption is associated with undesirable effects including an inability to focus and increased generalized anxiety. Because the structure of caffeine closely resembles adenosine, it works as an antagonist to increase neuronal excitability. To clarify the effects of caffeine on the brain, this study will examine sensory stimulus-mediated neural synchrony within the prefrontal cortex, a region of the brain associated with executive decision-making as well as in coping with anxiety. When a train of clicks is presented at a particular frequency, neural networks in the brain show oscillatory entrainment at the same frequency. These oscillations represent neighboring neurons firing nearly simultaneously. Such synchronous activation of large networks of neurons is fundamental to the brain’s ability to process and respond to environmental cues and is conveniently measured by the technique of electroencephalography (EEG). EEG as an index of neural network function is well conserved across mammals and used as a translational biomarker to understand the pharmacological effects of drugs within preclinical and human drug development studies. Doses of caffeine mimicking the average range of consumption among college students (100-300 mg/day) are converted into doses suitable for SD rats (10.28 - 30.83 mg/kg) using the FDA’s allometric scaling tool. It is hypothesized that low and medium doses of caffeine may either improve or not affect prefrontal cortical synchrony while high doses may disrupt. The same group of rats will be used for all treatments, including vehicle, in a Latin square crossover design with at least 4 days of gap between dosing. The synchrony response will be evaluated at multiple time points, post-dose. Artifact-free EEG data is averaged to arrive at a synchrony response for each rat and these are further grouped based on treatment and time. Comparisons across treatment and time are done using a 2-factor repeated measures ANOVA, using well-known neural synchrony metrics like evoked power and intertrial phase coherence. These results should inform how caffeine affects the neurophysiological function of the rodent prefrontal cortex, a key region for prioritization, decision-making, and cognitive control. Findings from this study may explain why high doses of caffeine can be disruptive to mental function and performance and lay the groundwork for analogous future studies in humans. On the other hand, if synchrony is unaffected, a chronic regimen of caffeine exposure may be explored to mimic the human consumption pattern of this stimulant