Altered molecular signaling pathways in the hippocampus of rhesus monkeys following chronic alcohol use.

Throughout the course of the day, human behavior and cognitive ability are simultaneously influenced by circadian phase and homeostatic sleep pressure. Factors such as time awake and chronotype contribute to an oscillatory pattern of performance in cognitive tasks requiring attention, working memory, and decision making (for review see ref. ). The underlying neurobiological rhythms that accompany these performance trends are adaptive when experienced during typical waking hours. However, prolonged or improperly timed wakefulness can render these rhythms maladaptive, leading to heightened emotional reactivity and impaired decision-making. Under such conditions, circadian-phase-driven changes in brain network connectivity may exacerbate the cognitive deficits of sleep loss, resulting in periods of exaggerated emotional vulnerability and diminished self-regulatory control. Endogenous circadian rhythms orchestrate fluctuations in physiology and behavior over the 24-h day, including subtle but measurable oscillations in brain activity. Neuroimaging studies have shown that resting-state network connectivity exhibits time-of-day–dependent variation. Similar studies show that diurnal changes in functional connectivity vary with chronotype, further indicating that circadian phase affects large-scale network organization of the brain. These findings suggest that the functional architecture of the brain is not static throughout the day but reorganizes in a manner that is influenced by circadian processes. Such dynamic changes in connectivity may contribute to circadian components of cognitive functioning such as learning and memory and psychomotor vigilance. Extending this line of reasoning, it is also plausible that neural network reorganization associated with circadian phase may also influence other cognitive domains, including the processing of emotional stimuli. Emotional regulation, like other cognitive functions, shows signs of diurnal variability with circadian modulation. This relationship is evident in research showing that circadian misalignment is frequently associated with deficits in emotional regulation. While a causal role cannot be inferred from co-morbidity, more direct experimental approaches inducing circadian desynchrony through simulated shift work have been shown to enhance depressive mood. Different chronotypes also show significant differences in emotional state; evening type individuals tend to report higher levels of depressive mood when compared to morning types. This evidence suggests that circadian fluctuations may not only affect arousal, but also have an impact on circadian patterns of positive and negative affect. Extending wakefulness into the biological night may heighten emotional reactivity, in part due to altered functional dynamics driven by circadian phase.