Prefrontal mechanisms of behavioral flexibility, emotion regulation and value updating

Abstract

Two ideas have dominated neuropsychology concerning the orbitofrontal cortex (OFC). One holds that OFC regulates emotion and enhances behavioral flexibility through inhibitory control. The other ascribes to OFC a role in updating valuations on the basis of current motivational states. Neuroimaging, neurophysiological and clinical observations are consistent with either or both hypotheses. Although these hypotheses are compatible in principle, we present results supporting the latter view of OFC function and arguing against the former. We found that excitotoxic, fiber-sparing lesions confined to OFC in monkeys did not alter either behavioral flexibility, as measured by object reversal learning, or emotion regulation, as assessed by fear of snakes. A follow-up experiment indicated that a previously reported loss of inhibitory control resulted from damage to nearby fiber tracts and not from OFC dysfunction. Thus, OFC has a more specialized role in reward-guided behavior and emotion than has been thought, a function that includes value updating.

Figure 1

Excitotoxic lesions of OFC. The first column shows the extent of the intended lesion (shaded region) on a ventral view and on standard coronal sections through the frontal lobe of a macaque brain. The lesions correspond approximately to Walker’s areas 11, 13 and 14. The second and third columns show coronal images at corresponding levels taken from T₂-weighted MRI scans obtained within one week of surgery from OFC_EXC cases 3 and 6. White hypersignal – set off by arrowheads – is associated with edema that follows injections of excitotoxins and indicates the extent of the lesion. Left and right sides of the MR images are from different scans and have been placed together for ease in viewing. Numerals indicate the distance in mm from the interaural plane.

Figure 2

Excitotoxic lesions of OFC fail to disrupt object reversal learning. The plot shows the number of errors to criterion scored by monkeys during acquisition (ACQ) and the nine subsequent serial reversals (1–9) in the object reversal learning task. In contrast to monkeys with aspiration lesions of OFC, monkeys with excitotoxic lesions of OFC scored in the same range as unoperated controls. Error bars show SEM. CON_ASP and CON_EXC, unoperated control monkeys; OFC_ASP, monkeys with bilateral aspiration lesions of the orbital prefrontal cortex; OFC_EXC, monkeys with bilateral excitotoxic lesions of the orbital prefrontal cortex. Data for groups OFC_ASP and CON_ASP are from an earlier study .

Figure 3

Excitotoxic lesions of OFC fail to alter emotional responses but disrupt monkeys’ ability to link objects with food value. a) Like unoperated controls, monkeys with excitotoxic lesions of OFC showed increasingly greater fear when in the presence of increasingly anxiogenic objects, arranged from left to right (neutral objects – moving snake), as indexed by their greater food-retrieval latencies across conditions. Symbols represent the scores of individual monkeys. Error bars show SEM. A trial limit of 30 sec was imposed. b) When required to link objects with food value, unoperated controls chose objects overlying the higher-value food on a high proportion of trials; higher Difference scores indicate greater sensitivity to changes in reward value. Monkeys with either excitotoxic or aspiration lesions of OFC, unlike controls, were unable to link objects with current food value. Symbols represent the scores of individual monkeys. Error bars show SEM.

Figure 4

Strip lesions situated in posterior OFC. The left side of the figure shows the extent of the intended lesion (shaded region) on a ventral view and on standard coronal sections through the frontal lobe of a macaque brain. The right side shows coronal images at corresponding levels taken from a T₁-weighted MRI scan obtained from OFC_STRIP case 1. Arrowheads mark the boundaries of the lesion at +28. Numerals indicate the distance in mm from the interaural plane.

Figure 5

Monkeys with aspiration lesions of a narrow strip of posterior OFC, like monkeys with complete aspiration lesions of OFC, were impaired on object reversal learning and showed reduced emotional responsiveness. a) When retested on object reversal learning, monkeys with a strip lesion of the posterior OFC (OFC_STRIP) performed significantly worse than unoperated controls (CON_STRIP). Plot shows number of errors to criterion scored by monkeys during acquisition (ACQ) and the nine subsequent serial reversals (1–9) in the object reversal learning task. Error bars show SEM. b) When retested on responses to neutral and fear-inducing objects, monkeys with a strip lesion of the posterior OFC showed reduced emotional responses relative to controls. This pattern matches that seen for monkeys with complete aspiration lesions of OFC. Symbols represent the scores of individual monkeys. Error bars show SEM.