FMRI Study of Performance During a Probabilistic Reversal Learning Task in Depression
Condition: Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      When depressed subjects perceive they have failed while performing a neuropsychological task
      their performance on subsequent trials becomes impaired. Elliott et al. showed that MDD
      subjects were far more likely to fail on subsequent tasks after failure on one task than
      controls. This effect has been described as an "abnormal response' to negative feedback or a
      'catastrophic response to perceived failure.'

      Murphy et al. investigated this further using a probabilistic reversal learning task in which
      subjects were faced with occasional negative feedback that was actually false. On each trial
      of the task subjects choose one of two stimuli on screen, one considered correct and the
      other incorrect, this is followed by feedback. Instructions prior to starting the task inform
      the subject that sometimes the rule will change and the previously correct stimulus will be
      incorrect, but sometimes the computer will give them incorrect feedback. They are instructed
      to switch responding only when they are sure the rule has actually changed. MDD subjects
      demonstrate intact acquisition and reversal of probabilistic learning but are impaired in
      their ability to maintain a response in the face of misleading negative feedback. This
      profile of impairment may be relatively specific to MDD as, for example, it is not found in
      subjects with other neuropsychiatric conditions. This 'abnormal response' to negative
      feedback may represent a significant link between negative affect and cognitive impairments
      in depression.

      During the proposed study functional magnetic resonance images will be acquired while
      subjects perform a version of the probabilistic reversal learning task. Four groups will take
      part: MDD, bipolar depressed, unmedicated MDD in remission and healthy control subjects.
      These images will be used to investigate differences in neural activation between the four
      groups, to clarify whether this specific profile of behavioral response extends to bipolar
      depressed subjects and to assess the mood state dependences of this effect. This would
      increase understanding of the specific profile of performance on this task and neural basis
      of this abnormal response to negative feedback that contributes to impairment of cognitive
      performance in depression.
    

Keywords: Major Depressive Disorder; Bipolar Disorder; Negative Feedback; Cognitive Performance; Negative Affect; Depression; Major Depression; MDD; Healthy Volunteer; HV