Resting anterior cingulate activity and abnormal responses to errors in subjects with elevated depressive symptoms: a 128-channel EEG study

Abstract

Depression has been associated with dysfunctional executive functions and abnormal activity within the anterior cingulate cortex (ACC), a region critically involved in action regulation. Prior research invites the possibility that executive deficits in depression may arise from abnormal responses to negative feedback or errors, but the underlying neural substrates remain unknown. We hypothesized that abnormal reactions to error would be associated with dysfunctional rostral ACC activity, a region previously implicated in error detection and evaluation of the emotional significance of events. To test this hypothesis, subjects with low and high Beck Depression Inventory (BDI) scores performed an Eriksen Flanker task. To assess whether tonic activity within the rostral ACC predicted post-error adjustments, 128-channel resting EEG data were collected before the task and analyzed with low-resolution electromagnetic tomography (LORETA) using a region-of-interest approach. High BDI subjects were uniquely characterized by significantly lower accuracy after incorrect than correct trials. Mirroring the behavioral findings, high BDI subjects had significantly reduced pretask gamma (36.5-44 Hz) current density within the affective (rostral; BA24, BA25, BA32) but not cognitive (dorsal; BA24', BA32') ACC subdivision. For low, but not high, BDI subjects pretask gamma within the affective ACC subdivision predicted post-error adjustments even after controlling for activity within the cognitive ACC subdivision. Abnormal responses to errors may thus arise due to lower activity within regions subserving affective and/or motivational responses to salient cues. Because rostral ACC regions have been implicated in treatment response in depression, our findings provide initial insight into putative mechanisms fostering treatment response.

Figure 1

A: Summary of neuroimaging studies highlighting functional specialization within the ACC. Green and red circles denote locations of increased activation during increased conflict monitoring and interference effects [Braver et al., 2001; Bush et al., 2003; Carter et al., 1998, 2000; Fassbender et al., 2004; Kerns et al., 2004; Kiehl et al., 2000; Laurens et al., 2003; MacDonald et al., 2000; Menon et al., 2001; Ruff et al., 2001]. The red circles denote activations associated with the compatibility (Eriksen) or conflict‐adaptation (Gratton) effects in studies using the Eriksen task [Botvinick et al., 2001; Bunge et al., 2002; Casey et al., 2000; Hazeltine et al., 2003; van Veen et al., 2001]. Orange triangles denote activations during error commission, predominantly during go/nogo tasks [Braver et al., 2001; Fassbender et al., 2004; Garavan et al., 2003; Kiehl et al., 2000; Laurens et al., 2003; Menon et al., 2001; Rubia et al., 2003; Ullsperger and von Cramon, 2001]. Yellow diamonds denote the locations of rostral ACC regions that have been linked to treatment response in depression [Buchsbaum et al., 1997; Davidson et al., 2003; Mayberg et al., 1997; Pizzagalli et al., 2001; Saxena et al., 2003; Smith et al., 1999; Wu et al., 1999]. Note that this region is pregenual, i.e., slightly more inferior and anterior than the one implicated in error processing. B: Location and extent of various ACC subdivisions as defined by the Structure‐Probability Maps [Lancaster et al., 1997] and displayed on the LORETA template. Coordinates in mm (MNI space); origin at anterior commissure; (X) = left(–) to right(+); (Y) = posterior(–) to anterior(+); (Z) = inferior(–) to superior(+). C: Mean (and SD) gamma current density within five general ACC regions for low (n = 16) and high (n = 17) BDI subjects. D: Mean (and SD) gamma current density within the affective and cognitive ACC subdivisions for low (n = 16) and high (n = 17) BDI subjects. *Group differences (P < 0.05).

Figure 2

A: Mean accuracy (and SE) after incorrect and correct trials for high BDI (n = 17) and low BDI (n = 17) subjects. B: Individual scores for the post‐error adjustment (Laming) effect [Accuracy_{After incorrect trial} – Accuracy_{After correct trials}] for low (gray triangles) and high (dark circles) BDI subjects. To eliminate potential overlap between the post‐error adjustment and conflict adaptation effects, values were derived from trials subsequent to incompatible trials.

Figure 3

Scatterplot and Pearson's correlation between (A) the post‐error adjustment (Laming) effect and the MASQ Anhedonic Depression scores; (B) the post‐error adjustment (Laming) effect and the MASQ General Depression scores; (C) the mean accuracy after incorrect trials and the Anhedonic Depression scores; and (D) the mean accuracy after incorrect trials and the General Depression scores. High BDI subjects only (n = 17).

Figure 4

Scatterplot and regression slope between the post‐error adjustment (Laming) effect and (standardized) residuals of the gamma current density in the affective ACC subdivision (BA24) after removing variance associated with the cognitive ACC subdivision (BA24′ and BA32′). The Pearson's correlation between the post‐error adjustment effect and BA24 gamma residuals is r = 0.81, P < 0.005. Low BDI subjects only (n = 16).