Neurochemical enhancement of conscious error awareness

Abstract

How the brain monitors ongoing behavior for performance errors is a central question of cognitive neuroscience. Diminished awareness of performance errors limits the extent to which humans engage in corrective behavior and has been linked to loss of insight in a number of psychiatric syndromes (e.g., attention deficit hyperactivity disorder, drug addiction). These conditions share alterations in monoamine signaling that may influence the neural mechanisms underlying error processing, but our understanding of the neurochemical drivers of these processes is limited. We conducted a randomized, double-blind, placebo-controlled, cross-over design of the influence of methylphenidate, atomoxetine, and citalopram on error awareness in 27 healthy participants. The error awareness task, a go/no-go response inhibition paradigm, was administered to assess the influence of monoaminergic agents on performance errors during fMRI data acquisition. A single dose of methylphenidate, but not atomoxetine or citalopram, significantly improved the ability of healthy volunteers to consciously detect performance errors. Furthermore, this behavioral effect was associated with a strengthening of activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe during the methylphenidate condition for errors made with versus without awareness. Our results have implications for the understanding of the neurochemical underpinnings of performance monitoring and for the pharmacological treatment of a range of disparate clinical conditions that are marked by poor awareness of errors.

Figure 1.

The EAT. The EAT presents a serial stream of single color words in incongruent fonts, with the word presented for 800 ms followed by a 700 ms interstimulus interval. Participants were trained to respond to each of the words with a single go trial (left) button press and to withhold this response when either of two different circumstances arose. The first was if the same word was presented on two consecutive trials (repeat no-go), and the second was if the word and font of the word matched (color no-go). To indicate error awareness, participants were trained to forego the regular go-trial button response (left; L) and instead to respond with the alternative (right; R) button after any commission error. Past studies have demonstrated that error-related BOLD signal is uninfluenced by the awareness response itself (Hester et al., 2005). Although levels of awareness undoubtedly vary on a continuum, we made a qualitative distinction between aware and unaware errors to facilitate our event-related fMRI analysis.

Figure 2.

Behavioral performance on the EAT. A, The proportion of errors for which participants (n = 27) indicated awareness of errors as a function of the four drug conditions: MPH, ATM, CIT, and PLAC. A significant main effect of drug condition was present (F_(3,78) = 10.28, p < 0.001). Participants were aware of a significantly higher proportion of errors in the MPH condition than in the PLAC, ATM, or CIT conditions (*p < 0.008 for all comparisons, Bonferroni's adjusted). B, The percentage of successful response inhibitions on EAT no-go trials during each of the four drug conditions. There was a trend toward a main effect of drug condition on the percentage of response inhibition errors (F_(3,78) = 2.32, p = 0.08).

Figure 3.

Activity within the dACC differentiates errors made with and without awareness. Bar graphs represent the mean BOLD percentage signal change for aware and unaware errors during the PLAC condition. A significant main effect of awareness on error-related ACC activity was observed during the PLAC condition, along with the three other drug conditions. The MNI coordinates for the dACC cluster region are listed in the title, and the sagittal 3D-rendered view of the activity cluster is taken from the MNI center-of-mass x-coordinate (x = −1).

Figure 4.

BOLD activity clusters for aware versus unaware errors demonstrating anatomically dissociable effects of MPH and ATM. The dACC activity cluster (A) (MNI coordinates: x = −1, y = 15, z = 39) and left IPL cluster (B) (MNI coordinates: x = −44, y = −39, z = 51) demonstrating a significant interaction effect between error awareness (aware, unaware) and drug condition (MPH, PLAC). The left IFG (C) (MNI coordinates: x = −54, y = 3, z = 13) and right ITG (D) (MNI coordinates: x = 56, y = −54, z = −6) represent the regions showing a significant interaction between ATM and error awareness. Bar graphs represent the mean BOLD percentage signal change (relative to baseline) for aware and unaware errors, for the MPH, ATM, or PLAC conditions. Error bars represent the SEM. L, Left; R, right.

Figure 5.

BOLD activity clusters from the PLAC condition map showing significant error awareness × drug condition interaction effects. The dACC activity cluster (A) (MNI coordinates: x = −1, y = 9, z = 41) and left IPL cluster (B) (MNI coordinates: x = −45, y = −36, z = 47) and right IPL (C) (MNI coordinates: x = 48, y = −52, z = 36) demonstrating a significant interaction effect between error awareness (aware, unaware) and drug condition (MPH, ATM, PLAC). Bar graphs represent the mean BOLD percentage signal change (relative to baseline) for aware and unaware errors, for the MPH, ATM, or PLAC conditions. Error bars represent the SEM. L, Left; R, right.