Greg Hajcak Proudfit

The reward positivity: From basic research on reward to a biomarker for depression

Feedback indicating monetary loss elicits an apparent negative deflection in the event-related potential (ERP) that has been referred to as the feedback error-related negativity, medial frontal negativity, feedback-related negativity, and feedback negativity-all conceptualizations that suggest a negative ERP component that is greater for loss than gain. In the current paper, I review a programmatic line of research indicating that this apparent negativity actually reflects a reward-related positivity (RewP) that is absent or suppressed following nonreward. I situate the RewP within a broader nomological network of reward processing and individual differences in sensitivity to rewards. Further, I review work linking reductions in the RewP to increased depressive symptoms and risk for depression. Finally, I discuss future directions for research on the RewP.

Anxiety and error monitoring: the importance of motivation and emotion

Moser et al. (2013) report a novel meta-analysis across 37 studies demonstrating a small-to-medium association between the error-related negativity (ERN) and self-report measures of anxiety (r = −0.25); the meta-analysis further indicates a stronger relationship between the ERN and anxious apprehension (r = −0.35) than anxious arousal (r = −0.09). Based on these results, Moser et al. articulate their compensatory error monitoring hypothesis (CEMH). In brief, the CEMH proposes that the relationship between anxious apprehension and an increased ERN is due to the distracting effects of worry: worrisome thoughts make it more difficult for anxious individuals to maintain task-related goals; as a result, increased effort must be employed. The CEMH suggests that an increased ERN reflects the transient increase in effort to compensate for the distracting effects of worry. Though we agree with many aspects of the CEMH (e.g., the importance of apprehensive anxiety; the potential impact of worry on the ERN), we believe that motivation and emotion are central constructs to understanding both within- and between-subjects variation in the ERN.

Reward dysfunction in major depression: Multimodal neuroimaging evidence for refining the melancholic phenotype

Reward dysfunction is thought to play a core role in the pathophysiology of major depressive disorder (MDD). Event-related potential (ERP) and functional magnetic resonance imaging (fMRI) studies have identified reward processing deficits in MDD, but these methods have yet to be applied together in a single MDD sample. We utilized multimodal neuroimaging evidence to examine reward dysfunction in MDD. Further, we explored how neurobiological reward dysfunction would map onto subtypes of MDD. The feedback negativity (FN), an ERP index of reward evaluation, was recorded in 34 unmedicated depressed individuals and 42 never-depressed controls during a laboratory gambling task. Ventral striatal (VS) activation to reward was recorded in a separate fMRI session, using an identical task, among a subgroup of 24 depressed individuals and a comparison group of 18 non-depressed controls. FN amplitude was blunted in MDD. This effect was driven by a MDD subgroup characterized by impaired mood reactivity to positive events, a core feature of melancholic MDD. A similar pattern was observed for VS activation, which was also blunted among the MDD subgroup with impaired mood reactivity. Neither FN amplitude nor VS activation was related to the full, DSM-defined melancholic or atypical MDD subtypes. Across the MDD sample, FN amplitude and VS activation were correlated, indicating convergence across methods. These results indicate that not all MDD is characterized by reward dysfunction, and that there is meaningful heterogeneity in reward processing within MDD. The current study offers neurobiological evidence that impaired mood reactivity is a key phenotypic distinction for subtyping MDD, and further suggests that the existing melancholic phenotype may require further refinement.

Neural reactivity to rewards and losses in offspring of mothers and fathers with histories of depressive and anxiety disorders.

Depression appears to be characterized by reduced neural reactivity to receipt of reward. Despite evidence of shared etiologies and high rates of comorbidity between depression and anxiety, this abnormality may be relatively specific to depression. However, it is unclear whether children at risk for depression also exhibit abnormal reward responding, and if so, whether risk for anxiety moderates this association. The feedback negativity (FN) is an event-related potential component sensitive to receipt of rewards versus losses that is reduced in depression. Using a large community sample (N = 407) of 9-year-old children who had never experienced a depressive episode, we examined whether histories of depression and anxiety in their parents were associated with the FN following monetary rewards and losses. Results indicated that maternal history of depression was associated with a blunted FN in offspring, but only when there was no maternal history of anxiety. In addition, greater severity of maternal depression was associated with greater blunting of the FN in children. No effects of paternal psychopathology were observed. Results suggest that blunted reactivity to rewards versus losses may be a vulnerability marker that is specific to pure depression, but is not evident when there is also familial risk for anxiety. In addition, these findings suggest that abnormal reward responding is evident as early as middle childhood, several years prior to the sharp increase in the prevalence of depression and rapid changes in neural reward circuitry in adolescence.

Anterior cingulate activity to monetary loss and basal ganglia activity to monetary gain uniquely contribute to the feedback negativity

OBJECTIVE The feedback negativity (FN) is an event-related potential that differentiates unfavorable versus favorable outcomes. Although thought to reflect error-related activity within the anterior cingulate cortex, recent work indicates the FN may also reflect reward-related activity that has been linked to the basal ganglia. To date, it remains unclear how to reconcile these conflicting perspectives. METHODS We decomposed the FN by applying time-frequency analysis to isolate activity unique to monetary losses and gains. The FN was recorded from 84 individuals during a laboratory gambling task. RESULTS Two signals contributed to the FN elicited by unpredictable outcomes: theta activity (4-7Hz) was increased following monetary loss, and delta activity (<3Hz) was increased following monetary gain. Predictable outcomes elicited delta but not theta activity. Source analysis revealed distinct generators, with loss-related theta localized to the anterior cingulate cortex and gain-related delta to a possible source in the striatum. Symptoms of depression, anxiety, and stress reactivity were specifically associated with blunted gain-related delta. CONCLUSIONS The FN may be a composite of loss- and gain-related neural activity, reflecting distinct facets of reward processing. SIGNIFICANCE Gain-related delta activity may provide unique information about reward dysfunction in major depression and other internalizing psychopathology.

Neural Indicators of Error Processing in Generalized Anxiety Disorder, Obsessive-Compulsive Disorder, and Major Depressive Disorder

The ability to detect and respond to errors is critical to successful adaptation to a changing environment, and variation in error-related brain activity has been linked to psychopathology. The error-related negativity (ERN), an event-related potential component, represents a unique neural response to errors and is generated in the anterior cingulate cortex (ACC). In the present study, we measured the ERN in a sample of individuals with Generalized Anxiety Disorder (GAD), Obsessive Compulsive Disorder (OCD), Major Depressive Disorder (MDD), or some combination of the 3. Also included were 56 healthy control participants. Consistent with previous research, a diagnosis of GAD, only in the absence of a comorbid diagnosis of depression, was characterized by a larger ERN than controls. No such enhancement was evident in the depressed group, or the comorbid group, suggesting comorbid depression may eliminate the relationship between the ERN and GAD. Across all groups, symptoms of checking were associated with a larger ERN, whereas symptoms of psychomotor retardation were associated with a smaller ERN. The results of the present study indicate that interactions among transdiagnostic dimensions will likely need to be considered in the creation of neurobiologically informed classification schemes.

Two-year stability of the late positive potential across middle childhood and adolescence.

The late positive potential (LPP) may be a useful measure of individual differences in emotional processing across development, but little is known about the stability of the LPP across time. We assessed the LPP and behavioral measures of emotional interference following pleasant, unpleasant, and neutral images in 8- to 13-year-old youth. Approximately two years later, the same participants completed the task again (N=34). Results indicated that the LPP is moderately-to-highly reliable across development. Stability was lower and more inconsistent for behavioral measures. In addition, consistent with previous cross-sectional analyses, a decrease in occipital activity was observed at the second assessment. Results indicate that the LPP appears to be a stable measure of emotional processing, even across a fairly large period of development.

Impaired Neural Response to Negative Prediction Errors in Cocaine Addiction

Learning can be guided by unexpected success or failure, signaled via dopaminergic positive reward prediction error (+RPE) and negative reward-prediction error (−RPE) signals, respectively. Despite conflicting empirical evidence, RPE signaling is thought to be impaired in drug addiction. To resolve this outstanding question, we studied as a measure of RPE the feedback negativity (FN) that is sensitive to both reward and the violation of expectation. We examined FN in 25 healthy controls; 25 individuals with cocaine-use disorder (CUD) who tested positive for cocaine on the study day (CUD+), indicating cocaine use within the past 72 h; and in 25 individuals with CUD who tested negative for cocaine (CUD−). EEG was acquired while the participants performed a gambling task predicting whether they would win or lose money on each trial given three known win probabilities (25, 50, or 75%). FN was scored for the period in each trial when the actual outcome (win or loss) was revealed. A significant interaction between prediction, outcome, and group revealed that controls showed increased FN to unpredicted compared with predicted wins (i.e., intact +RPE) and decreased FN to unpredicted compared with predicted losses (i.e., intact −RPE). However, neither CUD subgroup showed FN modulation to loss (i.e., impaired −RPE), and unlike CUD+ individuals, CUD− individuals also did not show FN modulation to win (i.e., impaired +RPE). Thus, using FN, the current study directly documents −RPE deficits in CUD individuals. The mechanisms underlying −RPE signaling impairments in addiction may contribute to the disadvantageous nature of excessive drug use, which can persist despite repeated unfavorable life experiences (e.g., frequent incarcerations).

Psychometric properties of the error-related negativity in children and adolescents

Error processing is frequently examined using the error-related negativity (ERN), a negative-going event-related potential occurring after the commission of an error at frontal-central sites, and has been suggested as a neural biomarker that may be useful in characterizing trajectories of risk for anxiety. While the ERN has been shown to have excellent psychometric properties in adults, few studies have examined psychometric properties of the ERN in children and adolescents. The current study examined the 2-year test-retest reliability of the ERN in a sample of children and adolescents, and the convergent validity of the ERN using a flanker and go/no-go task. Results suggest that the ERN is both reliable and stable across 2 years and across tasks. However, results also indicate that the internal consistency obtained using the flanker task is greater than the internal consistency obtained using the go/no-go task.

Show me the Money: The impact of actual rewards and losses on the feedback negativity

The feedback negativity (FN) is an event-related potential component which is typically conceptualized as a negativity in response to losses that is absent in response to gains. However, there is also evidence that variation in the FN reflects the neural response to gains. The present study sought to explore these possibilities by manipulating the context in which loss and gain feedback was presented in a straightforward gambling task. In half the blocks, participants could win or lose money (Value condition), and in half the blocks, participants could not win or lose any money (No Value condition). The degree to which losses and gains were differentiated from one another (i.e., the ΔFN) was greater in the Value condition than in the No Value condition. Furthermore, though the responses to loss feedback and gain feedback were each enhanced in the Value condition relative to the No-Value condition, the effect of the monetary manipulation was substantially larger for the positivity to gains than the negativity to losses. This is consistent with the notion that the FN might reflect two independent processes, but that variation in the FN depends more upon the response to rewards than losses.