Sustained attention or the ability to maintain an alert, goal-directed focus is critical for many levels of human behavior. Failures of sustained attention occur when there is a transient decrease in endogenous control of behavior leaving one prone to goal-neglect and distraction by irrelevant stimuli. Frequent lapses in sustained attention are a core feature of performance in the elderly, sleep-deprived individuals, and patients with brain injury and mental disorders with attentional components, such as attention-deficit hyperactivity disorder and schizophrenia. Even healthy individuals differ substantially in their ability to sustain attention. Recent studies have linked deficits in sustaining attention to less stable (i.e., more noisy) cortical signals in particular in frontal brain areas. Although recent research has shed light on the neural mechanisms underlying lapses of attention, less is known about how an individual’s ability to sustain attention might be improved. This knowledge is clearly imperative for the development of interventions that can address sustained attention deficits in patients or for individuals who are prone to attentional lapses due to e.g., disturbed sleeping patterns. The aim of this research project is to study the neural and neurochemical mechanisms underlying the ability to maintain an alert, goal-directed focus, and the effects of an alertness training strategy on this ability. We propose to conduct three studies that will test our main hypothesis that increased volitional control of arousal during sustained attention task performance will enhance cortical signal stability, and thereby attentional stability. The third study will examine the effects of the noradrenergic agonist clonidine on the hypothesized interaction between arousal and attention. The proposed research will use a unique multidisciplinary combination of techniques from psychophysiology, neuroscience (EEG and fMRI), psychology, and pharmacology.