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

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.