Publication
Altered hierarchical auditory predictive processing after lesions to the orbitofrontal cortex
Publisher:
Cold Spring Harbor Laboratory
Date:
04-01-2023
DOI:
10.1101/2023.01.04.521570
Abstract: Orbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the causal involvement of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a Local-Global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e., between tones within sequences) and at a global (i.e., between sequences ) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) to local prediction violation, as well as a diminished and delayed MMN/P3a complex to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate fundamental impairments in detecting violation of auditory regularity at two hierarchical levels of stimuli abstraction. Orbitofrontal lesions reduce auditory MMN (i.e., prediction error) to unpredicted stimuli at the local level. Orbitofrontal lesions reduce local and global level auditory deviance (i.e., prediction error) response, as manifested by diminished and delayed MMN and P3a.