Previous research has demonstrated that depression is associated with difficulties inhibiting the processing of emotional material (Joormann, 2004
; Goeleven et al., 2006
). Importantly, these studies have proposed that these inhibitory deficits play a significant role in the maintenance of depressive episodes (Joormann et al., 2007
). The present study was designed to examine neural correlates of these deficits in the inhibition of emotional material and, more specifically, to investigate whether these deficits are related to abnormalities in rACC activation. Currently depressed and never-depressed participants completed the NAP task, which assesses the ability to inhibit the processing of emotional words, while their BOLD response was recorded.
Consistent with our hypothesis, inhibition of negative stimuli was associated with increased activation in the rACC in the depressed, but not in the nondepressed, participants. This finding suggests that depressed individuals' difficulty disengaging attention from negative stimuli is related to anomalous functioning in rACC. This result is consistent with data reported recently by Mitterschiffthaler et al. (2008)
, who found that depressed individuals exhibited greater rACC activation than did nondepressed individuals when responding to negative words in an emotional Stroop task. The present results extend Mitterschiffthaler et al.'s findings by demonstrating increased rACC activation in depression is specific to inhibition of negative words; MDD participants did not exhibit greater rACC activation during inhibition of positive stimuli.
Taken together, these results underscore the links among depression, inhibition of negative material, and abnormalities in rACC functioning. The rACC is involved in tasks that require selective attention and conflict monitoring (Bush et al., 2000
, Shafritz et al., 2006
), and is a critical component in neural models of depression, particularly with respect to assessing the emotional salience of stimuli (Mayberg, 1997
). In this context, the increased activation of this area in response to negative irrelevant material in depression could reflect both the increased salience of this material for the depressed participants, leading to increased conflict when negative material has to be ignored, and the difficulties experienced by these participants when they attempt to override automatic responding to these salient stimuli. Indeed, previous work has implicated the engagement of rACC in conflict monitoring and overriding responses (Botvinick et al., 1999
), and has documented the role of rACC in solving interference from irrelevant emotional material (Etkin et al., 2006
Importantly, in the current study rACC activation was associated with inhibition of positive stimuli in HC but not in MDD participants. Although not predicted, this double dissociation is important in suggesting that depression is associated with abnormal processing not only of negative, but also of positive, stimuli. This formulation is supported by correlational analyses showing that more severe depressive symptoms are associated with lower activity in the rACC during inhibition of positive words. Indeed, some authors have suggested that depressed individuals not only preferentially process negative stimuli, but also lack a bias for the preferential processing of positive stimuli (see Leppänen, 2006
). Our findings suggest that while depressed participants recruit rACC when inhibiting negative stimuli, healthy individuals recruit this brain area when inhibiting positive stimuli. These findings may reflect depression-associated differences in the relative difficulty of disengaging from negative and positive material and, thus, support our interpretation of increased rACC activation as reflecting greater difficulty in disengaging from a stimulus.
It is noteworthy that investigators have found that greater activation in the rACC during a depressive episode predicts better response to treatment (e.g., Ebert et al., 1991
; Wu et al., 1992
; Mayberg et al., 1997
; Wu et al., 1999
; Pizzagalli et al., 2001
; Davidson et al., 2003
). Because these studies focused on resting-state metabolism or on rACC activation during passive viewing of emotional stimuli, while the present study focused on rACC activation during the effortful inhibition of negative stimuli, it is not clear whether the current findings are related to clinical outcome in depression. It remains for future research, therefore, to examine more explicitly whether the magnitude of rACC activation during the inhibition of negative stimuli predicts treatment response in MDD.
The whole-brain analyses revealed that inhibition of negative words was also associated with increased activation in the putamen in depressed participants. Although some investigators have found depressed participants to be characterized by reduced putamen activity during selective attention tasks (e.g., Halari et al., 2009
), it is important to note that these findings were obtained with tasks using emotionally neutral material. Interestingly, our findings are consistent with those reported by Surguladze et al. (2005)
, who found putamen activation in depressed individuals to be associated with passive viewing of negative stimuli. Thus, even though participants were instructed to ignore the negative distracters, we obtained activation in the present study in a neural structure that has been found to be activated by passive viewing of negative material in MDD. This result provides further support for our hypothesis that MDD participants had difficulty disengaging from the processing of negative material and suggests that depression is associated with increased activation in neural regions, such as the putamen, that are posited to be involved in the response to emotional stimuli, even when participants are instructed to ignore the stimuli (e.g., Phillips et al., 2003
We should note two limitations of the present study. First, we did not find significant behavioral differences between depressed and nondepressed participants. Because this task was used successfully in previous behavioral studies (e.g., Joormann, 2004
), it is likely that we did not obtain significant group differences in RT because of the scanning environment. Interestingly, it is frequently the case that group differences observed in behavioral studies are not replicated in fMRI studies using similar designs (e.g., Wagner et al., 2006
). Second, because we did not include a psychiatric control group in this study, we cannot address the issue of the specificity of our findings to depression. Indeed, it is likely that combined rACC and inhibitory dysfunctions are also involved in other disorders, such as posttraumatic stress disorder (Shin et al., 2001
; Bremner et al., 2004
) and schizophrenia (Carter et al., 2001
; Rubia et al., 2001
). Future research should address this issue by examining how neural correlates of inhibition differ in participants diagnosed with other psychiatric disorders.
In closing, we have demonstrated in this study that inhibitory difficulties that prevent diagnosed depressed individuals from disengaging their attention from negative information in their environment are associated with increased rACC response. By demonstrating a potential link between neural functioning and inhibitory processing in MDD, this study represents an important step in developing a more comprehensive understanding of depression through the integration of neural and cognitive models of this disorder.