Bipolar disorder is a chronic mental illness affecting up to 3% of the population. It is one of the top ten causes of disability worldwide, yet the neurophysiologic basis of the disorder remains unknown. The use of functional neuroimaging techniques (e.g. fMRI, PET) in combination with neuropsychological (activation) paradigms has served to deepen our understanding of regional brain dysfunction in psychiatric disorders, but the application of such types of functional studies to patients with bipolar disorder has been minimal. This application proposes to combine a neuropsychological paradigm with fMRI data to map functional data to structural MRI data. This has not, to our knowledge, been attempted in the bipolar population. We will use novel computational anatomy techniques to develop average anatomic representations for coregistration with fMRI images in bipolar subjects and compare this to normal controls. This approach will be used to assess the relationship between brain functional deficits seen on fMRI in patients with bipolar disorder and the structural integrity/volume of brain gray and white matter. Using such methods, we hope to clarify whether gray and/or white matter structural deficits are associated with the reduction in neural activity seen in fMRI. This exploration may clarify the neural/biologic underpinnings of bipolar disorder. The discovery of specific anatomic abnormalities that are associated with clear functional consequences may direct the pursuit of targeted neuropharmacologic development and lead to better treatments for bipolar patients. [unreadable] [unreadable] [unreadable]