Locus coeruleus neuromelanin predicts ease of attaining and maintaining neural states of arousal

Abstract

The locus coeruleus (LC), a small subcortical structure in the brainstem, is the brains principal source of norepinephrine. It plays a primary role in regulating stress, the sleep-wake cycle, and attention, and its degradation is associated with aging and neurodegenerative diseases associated with cognitive deficits (e.g., Parkinsons, Alzheimers). Yet precisely how norepinephrine drives brain networks to support healthy cognitive function remains poorly understood - partly because LCs small size makes it difficult to study noninvasively in humans. Here, we characterized LCs influence on brain dynamics using a hidden Markov model fitted to functional neuroimaging data from healthy young adults across four attention-related brain networks and LC. We modulated LC activity using a behavioral paradigm and measured individual differences in LC magnetization transfer contrast. The model revealed five hidden states, including a stable state dominated by salience-network activity that occurred when subjects actively engaged with the task. LC magnetization transfer contrast correlated with this states stability across experimental manipulations and with subjects propensity to enter into and remain in this state. These results provide new insight into LCs role in driving spatiotemporal neural patterns associated with attention, and demonstrate that variation in LC integrity can explain individual differences in these patterns even in healthy young adults.