We are proposing to undertake a series of studies with 60 neurological patients with focal lesions (and 40 matched normal controls), and fMRI studies with 40 normal healthy controls to test the hypothesis that normal rational thought requires reciprocal activation between lateral/dorsolateral prefrontal cortex (DLPFC) and ventral medial prefrontal cortex(VMPFC). Our basic strategy is to manipulate the reasoning process by the introduction of emotions. Emotions will be introduced into the reason ing process in the content/substance of the reasoning task and manipulation of the preexisting mood of subjects. We expect to (i) quantify the impact of affective processing deficits (particularly as a consequence of VMPFC lesions) on reasoning processes; (ii) clarify the respective roles of (and relationship between) VMPFC and DLPFC in emotional and neutral reasoning; (iii) determine whether our pilot results are a function of the introduction of emotions or negative emotions into the reasoning process; and (iv) determine whether the different ways of introducing emotions into the reasoning process (content and mood induction) have the same neural basis. Real world human reasoning always occurs against a backdrop of beliefs embedded in an emotional context. Being angry, sad, upset, fearful, etc. affects our reasoning processes, often detrimentally. The goal of this research project to understand the brain functions underlying emotion-reason interactions. We will study the impact of emotions on reasoning processes of normal, healthy adult volunteers using brain imaging techniques and also examine how the system breaks down in certain patients wit h frontal lobe damage. The project will increase our knowledge of the brain basis of emotion- reason interactions and inform the treatment of certain patients in which this interaction is disrupted.