Clinical studies We are exploring the role of damage to specific brain areas, including the reward pathways, in the genesis of fatigue, amotivation, and other common, unexplained complaints of military personnel returning from deployment. This study combines intensive neuroimaging with standard and experimental behavioral measures focusing on effort generation. Another study in collaboration with the Naval Medical Research Center and the Walter Reed Army Institute of Research is looking for evidence of behavioral and brain changes in military personnel with occupational exposure to blast. Neurophysiological probe studies We have successfully shown changes in the motor cortex response to transcranial magnetic stimulation (TMS) that are linked to the expectation of reward. Studies are underway using physiological responses to see how expected effort acts to discount anticipated reward. We are using theta-burst transcranial magnetic stimulation of the motor and premotor cortex to produce a temporary impairment on learning tasks, as a model for traumatic brain injury. We then see whether adding various forms of reward to the same tasks can overcome this temporary blockade. This study has shown that theta-burst inhibition of the motor cortex has no significant effect on the acquisition of a motor sequence but impairs its retention 45 minutes later. Adding reward and punishment feedback during the acquisition phase, effectively reverses this deficit and produces its own beneficial effects on acquisition and recall in subjects receiving sham theta-burst stimulation. An experiment to examine these effects with functional MRI has been completed and is being analyzed. We are also doing a similar study with theta-burst inhibition of the dorsolateral prefrontal cortex. Acute exercise as an intervention to enhance memory consolidation We are starting a study of brief and intense exercise as a way of enhancing the retention of verbal, visual, and rule-based information in healthy subjects and people with chronic moderate traumatic brain injury and memory deficits. The primary outcome measure is recall 7 days after exposure. The study also contains a fMRI experiment looking at how exercise alters brain activity during recall of visual information.