Neural Evidence for Enhanced Error Detection in Major Depressive Disorder

Computational Psychiatry Unit, Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 04/2007; 164(4):608-16. DOI: 10.1176/appi.ajp.164.4.608
Source: PubMed


Anomalies in error processing have been implicated in the etiology and maintenance of major depressive disorder. In particular, depressed individuals exhibit heightened sensitivity to error-related information and negative environmental cues, along with reduced responsivity to positive reinforcers. The authors examined the neural activation associated with error processing in individuals diagnosed with and without major depression and the sensitivity of these processes to modulation by monetary task contingencies.
The error-related negativity and error-related positivity components of the event-related potential were used to characterize error monitoring in individuals with major depressive disorder and the degree to which these processes are sensitive to modulation by monetary reinforcement. Nondepressed comparison subjects (N=17) and depressed individuals (N=18) performed a flanker task under two external motivation conditions (i.e., monetary reward for correct responses and monetary loss for incorrect responses) and a nonmonetary condition. After each response, accuracy feedback was provided. The error-related negativity component assessed the degree of anomaly in initial error detection, and the error positivity component indexed recognition of errors.
Across all conditions, the depressed participants exhibited greater amplitude of the error-related negativity component, relative to the comparison subjects, and equivalent error positivity amplitude. In addition, the two groups showed differential modulation by task incentives in both components.
These data implicate exaggerated early error-detection processes in the etiology and maintenance of major depressive disorder. Such processes may then recruit excessive neural and cognitive resources that manifest as symptoms of depression.

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Available from: Patricia J Deldin, Dec 17, 2013
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    • "Error processing refers to monitoring performance, detecting errors, and modifying behaviour adaptively in the absence of overt reinforcement (Holroyd and Coles, 2002). Error processing dysfunction has been demonstrated in several psychiatric conditions, including schizophrenia (Becerril et al., 2011; Mathalon et al., 2009; Morris et al., 2008), depression (Chiu and Deldin, 2007; Steele et al., 2004; Tucker et al., 2003) and a range of drug dependencies (Connolly et al., 2012; Easdon et al., 2005; Forman et al., 2004; Li et al., 2010). In all these conditions, the dysfunction is characterised by hypoactivity in the error-related network, most consistently in the dorsal anterior cingulate gyrus (dACC). "
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    ABSTRACT: The chronic use of cannabis has been associated with error processing dysfunction, in particular, hypoactivity in the dorsal anterior cingulate cortex (dACC) during the processing of cognitive errors. Given the role of such activity in influencing post-error adaptive behaviour, we hypothesised that chronic cannabis users would have significantly poorer learning from errors. Fifteen chronic cannabis users (four females, mean age=22.40 years, SD=4.29) and 15 control participants (two females, mean age=23.27 years, SD=3.67) were administered a paired associate learning task that enabled participants to learn from their errors, during fMRI data collection. Compared with controls, chronic cannabis users showed (i) a lower recall error-correction rate and (ii) hypoactivity in the dACC and left hippocampus during the processing of error-related feedback and re-encoding of the correct response. The difference in error-related dACC activation between cannabis users and healthy controls varied as a function of error type, with the control group showing a significantly greater difference between corrected and repeated errors than the cannabis group. The present results suggest that chronic cannabis users have poorer learning from errors, with the failure to adapt performance associated with hypoactivity in error-related dACC and hippocampal regions. The findings highlight a consequence of performance monitoring dysfunction in drug abuse and the potential consequence this cognitive impairment has for the symptom of failing to learn from negative feedback seen in cannabis and other forms of dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Drug and alcohol dependence 07/2015; 155. DOI:10.1016/j.drugalcdep.2015.07.671 · 3.42 Impact Factor
    • "Error commission is aversive (Hajcak and Foti, 2008) and it has been reported that depressed patients have an abnormal response to feedback of poor behavioural performance (Elliott et al., 1997; Murphy et al., 2003; Roiser et al., 2012). Electrophysiological studies of behavioural errors in MDD have reported an abnormally increased error-related negativity (Chiu and Deldin, 2007; Holmes and Pizzagalli, 2010; Georgiadi et al., 2011) and an abnormally increased feedback-related error signal which may be associated with enhanced avoidance learning (Cavanagh et al., 2011). While abnormal responses to rewarding events imply abnormal (Nestler and Carlezon, 2006) and blunted dopaminergic reward learning activity (Kumar et al., 2008; Gradin et al., 2011; although see Huys et al., 2013), the role of putative serotonergic abnormalities in MDD remains unclear (Boureau and Dayan, 2011; Faulkner and Deakin, 2014). "
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    ABSTRACT: Major depressive disorder is characterized by anhedonia, cognitive biases, ruminations, hopelessness and increased anxiety. Blunted responses to rewards have been reported in a number of recent neuroimaging and behavioural studies of major depressive disorder. In contrast, neural responses to aversive events remain an under-studied area. While selective serotonergic reuptake inhibitors are often effective in treating major depressive disorder, their mechanism of action remains unclear. Following a series of animal model investigations of depressive illness and serotonergic function, Deakin and Graeff predicted that brain activity in patients with major depressive disorder is associated with an overactive dorsal raphe nucleus with overactive projections to the amygdala, periaqueductal grey and striatum, and an underactive median raphe nucleus with underactive projections to the hippocampus. Here we describe an instrumental loss-avoidance and win-gain reinforcement learning functional magnetic resonance imaging study with 40 patients with highly treatment-resistant major depressive disorder and never-depressed controls. The dorsal raphe nucleus/ periaqueductal grey region of the midbrain and hippocampus were found to be overactive in major depressive disorder during unsuccessful loss-avoidance although the median raphe nucleus was not found to be underactive. Hippocampal overactivity was due to a failure to deactivate during loss events in comparison to controls, and hippocampal over-activity correlated with depression severity, self-report 'hopelessness' and anxiety. Deakin and Graeff argued that the median raphe nucleus normally acts to inhibit consolidation of aversive memories via the hippocampus and this system is underactive in major depressive disorder, facilitating the development of ruminations, while the dorsal raphe nucleus system is engaged by distal cues predictive of threats and is overactive in major depressive disorder. During win events the striatum was underactive in major depressive disorder. We tested individual patient consistency of these findings using within-study replication. Abnormal hippocampal activity correctly predicted individual patient diagnostic status in 97% (sensitivity 95%, specificity 100%) of subjects, and abnormal striatal activity predicted diagnostic status in 84% (sensitivity 79%, specificity 89%) of subjects. We conclude that the neuroimaging findings were largely consistent with Deaken and Graeff's predictions, abnormally increased hippocampal activity during loss events was an especially consistent abnormality, and brainstem serotonergic nuclei merit further study in depressive illness. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:
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    • "Participants in the EMBARC study complete an extensive clinical evaluation battery, including clinicianand participant-rated instruments probing various domains, including lifetime diagnosis, personality traits, and social functioning. Because flanker performance is sensitive to anhedonia (Dubal et al. 2000; Dubal & Jouvent, 2004) and may be influenced by depressive severity (Chiu & Deldin, 2007), we concentrate on data from the QIDS-SR 16 and the Snaith Hamilton Pleasure Scale (SHAPS; Snaith et al. 1995). The QIDS-SR 16 is a self-report instrument that assesses core DSM-IV diagnostic criteria for MDD. "
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    ABSTRACT: Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study. One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials). Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = -0.28, p = 0.007). Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.
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