Amygdala-Orbitofrontal interplay in cognitive flexibility November 29, 2007Posted by Johan in Learning, Neural Networks, Neuroscience.
This rat doesn’t get sucrose, but is probably happier than Stalnaker et al’s rats
Today’s title may be the least accessible yet, but bear with me; this is an interesting paper. Stalnaker et al (2007) investigated the neural basis of what they call cognitive flexibility – this is a very fancy term for a rat’s ability to handle a conditioning paradigm known as reversal learning. The method that Stalnaker et al used serves as a good example of the paradigm.
Rats were first trained on an odour discrimination task. Poking at one little door that is laced with odour A produces delivery of a tasty sucrose solution. Poking at another little door that is laced with odour B produces delivery of an unpleasant quinine solution (incidentally, quinine is a component in Vermouth, but we’ll assume that these particular rats like their martinis very dry). The actual door that is associated with each odour is varied, so that the rats have to rely on the odour cues alone to learn how to get their treat. Once the rats have achieved a criterion level of accuracy at this task, the contingency reverses, so that odour B now produces a treat while odour A produces quinine. The model finding is that the rats will be slower to learn the reversal than they were to learn the original task.
Stalnaker et al were interested in investigating the role of orbitofrontal cortex (OFC) and the basolateral amygdala (ABL) in bringing about this reversal. There are two basic ideas on how this might work: the OFC might directly encode the preferred stimulus, or the OFC might play an indirect role where it facilitates changes in downstream areas, such as the ABL. So in other words, downstream areas bring about the actual behaviour, while the OFC plays more of a modulatory role in telling the downstream areas when contingencies change.
To test these notions, Stalnaker et al lesioned the OFC in one group of rats, the ABL in another group, and both the OFC and the ABL in a third group. After this, the rats learned the odour discrimination task. The three groups did not differ significantly at this point. In other words, neither area or the combination of them was necessary to learn the task. Next, the rats went through two serial reversals – odour A switched places with odour B, and then back again. The effect of the brain lesions was measured by the number of trials taken to learn the reversals to the same accuracy level as the initial odour task.
Rats with OFC damage were slower to learn the reversals than the other groups. However, rats with ABL lesions and rats with combined OFC and ABL lesions did not significantly. So in other words, although OFC lesions in isolation cause impairments, this effect is abolished when the ABL is sectioned as well.
Stalnaker et al interpret these findings as support for an indirect role for the OFC in reversal learning. The ABL is stubborn, simply put. Without the modulatory influence of the OFC, the ABL persists in responding as though the contingency had not reversed, which produces slower reversal learning. By removing the ABL as well, this persistent influence is gone and reversal learning can occur normally. It is somewhat counter-intuitive that lesioning more of the brain helps, but there you go.
This is a nice study because it answers one question, but asks a number of new questions. If the rats can carry out reversal learning normally without either the OFC or the ABL, why is this circuit even involved in the paradigm, that is, why should OFC lesions have an effect, if the pathway as a whole is not needed? Also, if the ABL produces such deficient behaviour when the OFC is lesioned, why don’t lesions to the ABL affect behaviour? And most importantly, if behaviour is normal after ABL and OFC lesions, which other area must be lesioned to impair behaviour yet again. And what happens if this area is lesioned in isolation?
Enough questions to make your head spin, but the take-home message for those studying humans is that there is an entire range of complex interactions in the brain that fMRI, with its blurry temporal resolution and lack of experimental manipulation, can only hint at. We know much about functional localisation in the human brain, but the issue of how these areas connect and interact is largely uncharted territory.
Stalnaker, T.A., Franz, T.M., Singh, T., and Schoenbaum, G. (2007). Basolateral Amygdala Lesions Abolish Orbitofrontal-Dependent Reversal Impairments. Neuron, 54, 51-58.