The interaction between the orbitofrontal cortex (OFC) and the amygdala is critical for learning and subsequently changing associations between stimuli and reinforcement. However, the precise role of the OFC in this kind of reward processing and the contribution of the amygdala, if any, remained unclear until our work during this reporting period. We studied reward processing in subjects with either OFC or amygdala lesions in a task of flexible reward processing: object reversal learning. We found that subjects with OFC lesions were, compared with control subjects and subjects with amygdala lesions, poor at using correctly performed trials to guide subsequent choices. Subjects with amygdala lesions, by contrast, benefited more than controls from correctly performed trials that followed an error. These findings show that the OFC and the amygdala make different contributions to reward processing, one of the kinds of information processing disrupted in patients with major depressive disorder. These findings support the idea that OFC, in particular, represents value in a common currency. A common value system allows the comparison of different kinds of rewards so that the most advantageous choices can be made. The next stage of the present project is to test the idea that the OFC represents the values used for decision making. This valuation must be independent of any sensory modality and it must come into operation whenever there are multiple competing outcomes, as opposed to when only one type of outcome is possible. In the upcoming year we will begin a more in-depth, mechanistic examination of OFC and MFC in order to examine their relationship to predicted outcome for different types of stimulus-outcome mappings, as well as the role of the amygdala in this function. These experiments follow up the work described above, as well as neuropsychological and neurophysiological findings suggesting that value is encoded in the OFC based on inputs from the amygdala, and that, in the absence of the amygdala, the associative encoding linking stimuli with outcomes becomes disrupted. We will study OFC and MFC neurons before and after selective excitotoxic amygdala lesions. If associative value encoding requires the amygdala, then before amygdala lesions the neural activity in OFC and MFC should reflect the value of objects in a common currency, but after amygdala lesions this activity should be disrupted or disappear. We will also compare OFC and MFC associative valuations for both familiar objects and novel ones, presented as subjects learn the value of an initially neutral object, as well as the contribution of the amygdala to both kinds of valuations.
| Rudebeck, Peter H; Murray, Elisabeth A (2008) Amygdala and orbitofrontal cortex lesions differentially influence choices during object reversal learning. J Neurosci 28:8338-43 |
| Murray, Elisabeth A; O'Doherty, John P; Schoenbaum, Geoffrey (2007) What we know and do not know about the functions of the orbitofrontal cortex after 20 years of cross-species studies. J Neurosci 27:8166-9 |
