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Séminaire impromptu - Elizabeth MurrayFrom knowledge to action: the role of the primate orbitofrontal cortex

Abstract :

 The orbitofrontal cortex (OFC) has long been thought to play a critical role in behavioral flexibility, including behavioral inhibition and the regulation of emotion.
Neuropsychological studies in humans and macaque monkeys have repeatedly found that damage to OFC leads, for example, to an inability to rapidly alter object-reward associations, as assessed by object reversal learning tasks. In addition, the “snake test” shows that OFC regulates the emotional reactivity of macaques. Recent evidence1 has overturned these ideas by showing that inadvertent damage to fiber pathways account for the reported deficits. The use of a more selective lesion method in macaque monkeys has shown that OFC has a more specific and different function: representing and updating the value of specific expected outcomes, based on current biological states. These updated valuations, in turn, guide choice behavior.

Given that areas outside the traditional OFC have functions previously ascribed to OFC, we have recently attempted to identify the cortical areas that perform these functions. Accordingly, we recently contrasted the contributions of OFC and the neighboring ventrolateral prefrontal cortex (VLPFC) to value updating. Specifically, we trained monkeys with selective, excitotoxic lesions of either OFC or VLPFC on tasks that assess two different kinds of value updating. The devaluation task was used to measure the ability of monkeys to update value based on their current internal state (e.g., satiety). The 3-arm-bandit task was used to measure the ability of monkeys to update value based on the probability of reward2. The former reflects what predicted outcomes (or their sensory features) are worth at any given time (desirability); the latter reflects an estimation of whether a predicted outcome will occur (availability). We found that OFC, but not VLPFC, is necessary for updating valuations based on current biological needs. In contrast, VLPFC, but not OFC, is necessary for updating valuations based on changing reward probabilities. Thus, OFC and VLPFC play complementary roles in value updating and—by extension—decision making. OFC guides choices based on the current desirability of a predicted outcome; VLPFC guides choices based on the likelihood of a desired outcome. The former depends on dynamic internal states; the latter depends on dynamic external contingencies.

Subsequent experiments have revealed that the posterior part of OFC, area 13, is necessary for its value updating function, while the anterior part, area 11, translates this knowledge into adaptive actions3. Given that these two areas emerged during the evolution of primates4, a comparative analysis suggests that these capacities built on OFC functions inherited from early mammals, as reflected in experimental results from rodents and carnivores.

Selected publications

1)    PH Rudebeck et al., Nature Neurosci., 2013

2)    ME Walton et al., Neuron, 2010

3)    EA Murray et al., eLife, 2015

4)    TM Preuss, J Cog Neurosci, 1995

Scientific focus :

 Research Interests

Dr. Murray’s laboratory studies the neural basis of learning, memory, emotion and response selection, with two main areas of focus. The first of these two research programs involves the independent mnemonic contributions of the different medial temporal lobes structures, the extent to which different medial temporal lobe structures must interact in storing information and their interaction with the prefrontal cortex. Her work has demonstrated that, for some types of memory, the entorhinal and perirhinal cortical regions in the ventral medial temporal lobe play a more important role than does the hippocampus. Not only does this area, termed the rhinal cortex, specialize in storing knowledge about objects, but it may serve as the core system for semantic memory.

A second focus of the Murray laboratory is the neural bases of decision making. This work examines the neural circuits critical for affective processing and the way in which affective information, including reward, guides response selection. This work has shown that the amygdala and orbital prefrontal cortex operate as part of a network involved in emotion, reward-based learning and goal-directed behavior. These circuits contribute importantly to behavioral flexibility in the face of changes in reward contingencies or reward value. A key hypothesis is that the orbital prefrontal cortex is part of a larger prefrontal region critical for the valuation of choice outcomes.

Dr. Murray’s laboratory has pioneered the use of MRI-guided stereotaxic surgery, a method that has for the first time allowed examination of the selective mnemonic contributions of various medial temporal lobe structures.