Arousal state has an “inverted-U” dose response effect on PFC functioning. PFC synapses require stimulation from the arousal systems (acetylcholine, norepinephrine, dopamine, serotonin) in order to function properly, and inadequate levels e.g. during fatigue, weaken PFC function. Conversely, excessive norepinephrine and dopamine release during uncontrollable stress also weakens PFC function, by rapidly weakening PFC synaptic connections. It is noteworthy that caffeine increases the release of acetylcholine in the PFC, which may explain why it can be helpful to cognitive function in rested individuals.