Uncoupling of behavioral and autonomic responses after lesions of the primate orbitofrontal cortex

Abstract

Successful adaptation to changes in an animal's emotional and motivational environment depends on behavioral flexibility accompanied by changes in bodily responses, e.g., autonomic and endocrine, which support the change in behavior. Here, we identify the orbitofrontal cortex (OFC) as pivotal in the flexible regulation and coordination of behavioral and autonomic responses during adaptation. Using an appetitive Pavlovian task, we demonstrate that OFC lesions in the marmoset (i) impair an animal's ability to rapidly suppress its appetitive cardiovascular arousal upon termination of a conditioned stimulus and (ii) cause an uncoupling of the behavioral and autonomic components of the adaptive response after reversal of the reward contingencies. These findings highlight the role of the OFC in emotional regulation and are highly relevant to our understanding of disorders such as schizophrenia and autism in which uncoupling of emotional responses may contribute to the experiential distress and disadvantageous behavior associated with these disorders.behavioral inhibition ͉ emotion ͉ reversal learning T he orbitofrontal cortex (OFC) has long been implicated in behavioral f lexibility as measured by tests of discrimination reversal learning and extinction (1, 2). In reversal learning, an animal is first taught to respond to one of two visual stimuli to receive food reward, a response to the other being unrewarded. Lesions of the OFC do not affect initial acquisition of the visual discrimination, but the ability to alter responding when the association between the stimuli and reward is reversed is markedly impaired across a range of species (3-9). Similarly, animals with OFC lesions display prolonged responding during extinction when the response no longer results in the receipt of food reward (1, 10, 11). However, an alteration in behavioral output is just one component of the overall adaptive response of an animal to changes in its environment. It is important to recognize that behavioral adaptation is accompanied by alterations in the bodily state, including autonomic and endocrine activity, appropriate to the motivational and emotional context. Thus, Pavlov showed that dogs stopped salivating to a buzzer when it no longer predicted reward (12), and, had the behavioral response also been measured, it would have presumably shown that they stopped approaching the buzzer too. Indeed, if, despite inhibiting their salivation during extinction, Pavlov's dogs found themselves still approaching the buzzer, or vice versa, such incongruency between the somatic and autonomic feedback might be expected to produce emotional ambiguity, an issue that will be considered in more detail in Discussion.Currently, we have very little understanding of the neural circuitry underlying the coordination of behavioral and bodily responses in adaptive responding. Although the OFC is critical for behavioral adaptation, its role in the overall coordination of the adaptive response is unknown. Indeed, few studies have investigated the role of the O...

A role for primate subgenual cingulate cortex in sustaining autonomic arousal

“…Specifically, OFC lesions render monkeys less able to suppress arousal when the contingency between a CS+ and reward is abolished. By contrast, lesions of this area spare acquisition and expression of conditioned autonomic arousal (24). It therefore seems unlikely that damaging fibers running to or from the OFC could account for the present pattern of results.…”

“…This study sought to identify the previously uncharacterized effects of lesions specifically targeting the subgenual ACC, and is one of only a handful to assess the effects of cortical lesions on autonomic arousal in primates (23)(24)(25)(26). The subgenual ACC is one of the least accessible parts of the frontal cortex.…”

Localization of Dysfunction in Major Depressive Disorder: Prefrontal Cortex and Amygdala

“…In that case, Reekie et al (115) found an effect of PFo lesions on autonomic responses. On a probe test in which the CS stops and the predicted reward fails to appear, marmosets with PFo lesions maintain an abnormally high level of arousal (Fig.…”

Interactions between orbital prefrontal cortex and amygdala: advanced cognition, learned responses and instinctive behaviors

“…Then, on a probe test in which the CS stops and the predicted reward fails to appear, marmosets with PFo lesions maintain an abnormally high level of arousal (Fig. 3b) [16••]. …”

“…On a subsequent probe trial, the tone stopped (CS off) and the predicted food failed to appear (US omission). Points to left show BP during tone presentation; the series of points to the right show BP as a function of time after CS offset on the probe trial [16••]. Error bars: SEM.…”