FMRI Study of Performance During a Probabilistic Reversal Learning Task in Depression

This study will examine how the brains of depressed people function during learning and respond to feedback. Participants perform a "probabilistic reversal learning task" to determine whether depressed people perform worse on a task than non-depressed people when they sometimes receive misleading negative feedback.

Right-handed healthy volunteers, people with major depression who are currently depressed or have previously been depressed and people with bipolar depression between 18 and 50 years of age may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, electrocardiogram, blood and urine tests. They are also interviewed to evaluate mood, sleep, energy, work and school performance, and social relationships, and asked to answer questions to investigate whether any history of paranoia, panic attacks, obsession, compulsions, suicidal thoughts, eating disturbances, and alcohol or drug abuse is present. They complete rating scales for depression, anxiety, and negative thinking; history of alcohol and tobacco use; physical movement; socioeconomic status; overall level of functioning; and depression type. Finally, they undergo a battery of neuropsychological tests to assess general intelligence, handedness, and specific cognitive abilities, including memory and concentration.

Participants perform the probabilistic reversal learning task either in a testing room seated in front of a computer or lying down while undergoing functional magnetic resonance imaging (FMRI). FMRI is a diagnostic test that uses a strong magnet and radio waves to obtain pictures of brain structure and function. For the scan, the subject lies on a narrow bed with a plastic-encased metal coil close to the head. The bed slides into the scanner - a small tunnel about 6 feet long. All subjects, whether in the testing room or in the MRI scanner, undergo the learning task as follows:

Two patterns are presented on a computer screen. One pattern is designated "correct" and the other "incorrect." Subjects are asked to choose the correct pattern on each try and are provided feedback as to whether the response was right or wrong. Sometimes the rule changes, and the pattern that was correct is now wrong, and vice versa, so that the new correct pattern must be chosen. In addition, misleading feedback is sometimes given intentionally, indicating the subject chose the wrong pattern when in fact the response was correct. Subjects should change their response only when they are sure that the rule has changed, and not because they were incorrectly told that they were wrong. For patients undergoing MRI, blood flow in the different areas of the brain is measured during the test.

After the test, outside the scanner, participants undergo additional tests of attention, memory, and concentration like those that were administered during the screening procedures.