Beyond reversal: a critical role for human orbitofrontal cortex in flexible learning from probabilistic feedback

Abstract

Damage to the orbitofrontal cortex (OFC) has been linked to impaired reinforcement processing and maladaptive behavior in changing environments across species. Flexible stimulus-outcome learning, canonically captured by reversal learning tasks, has been shown to rely critically on OFC in rats, monkeys, and humans. However, the precise role of OFC in this learning remains unclear. Furthermore, whether other frontal regions also contribute has not been definitively established, particularly in humans. In the present study, a reversal learning task with probabilistic feedback was administered to 39 patients with focal lesions affecting various sectors of the frontal lobes and to 51 healthy, demographically matched control subjects. Standard groupwise comparisons were supplemented with voxel-based lesion-symptom mapping to identify regions within the frontal lobes critical for task performance. Learning in this dynamic stimulus-reinforcement environment was considered both in terms of overall performance and at the trial-by-trial level. In this challenging, probabilistic context, OFC damage disrupted both initial and reversal learning. Trial-by-trial performance patterns suggest that OFC plays a critical role in interpreting feedback from a particular trial within the broader context of the outcome history across trials rather than in simply suppressing preexisting stimulus-outcome associations. The findings show that OFC, and not other prefrontal regions, plays a necessary role in flexible stimulus-reinforcement learning in humans.

Figure 1.

Map showing the voxels (blue) where there is sufficient statistical power to detect an effect in this group of patients, overlaid on the MNI brain and shown in three-dimensional views and in axial slices, with numbers indicating the z-coordinates (MNI) of each slice. L, Left; R, right.

Figure 2.

Representative axial slices and midsagittal views of the MNI brain, showing the degree of lesion overlap for subjects with damage affecting OFC (OFC group, n = 11; top row) and those without damage to this region, divided into those with lesions involving lateral prefrontal cortex (LF group, n = 12; second row) or the medial surface of the prefrontal cortex (MF group, n = 13; bottom row). Colors indicate the degree of overlap across subjects, as shown in the legend. L, Left; R, right.

Figure 3.

Total probabilistic reversal learning task scores for each group. Error bars indicate SEM. *p < 0.05, significant differences for pairwise comparisons (Tukey–Kramer test).

Figure 4.

VLSM statistical map computed for total score shown on three-dimensional views of the MNI brain (top), with representative axial slices (bottom). The color scale indicates BM test Z-score, thresholded at p < 0.05, uncorrected.

Figure 5.

A, The number of errors during initial and reversal learning phase in each group. B, The number of consecutive responses to punished choices before switching to the other option in the initial learning phase of the task and after reversals. Error bars indicate SEM. *p < 0.05, significant differences for pairwise comparisons (Tukey–Kramer test).

Figure 6.

Trialwise performance analyses. A, The frequency of win–shift behavior in each group. B, The frequency of lose–shift behavior after congruent or incongruent negative feedback (for details, see Results). Error bars indicate SEM. *p < 0.05, significant differences for pairwise comparisons (Tukey–Kramer test).