Christen M. Deveney

Enhanced Negative Feedback Responses in Remitted Depression

Major depressive disorder (MDD) is characterized by hypersensitivity to negative feedback that might involve frontocingulate dysfunction. MDD patients exhibit enhanced electrophysiological responses to negative internal (errors) and external (feedback) cues. Whether this dysfunction extends to remitted depressed (RD) individuals with a history of MDD is currently unknown. To address this issue, we examined the feedback-related negativity in RD and control participants using a probabilistic punishment learning task. Despite equivalent behavioral performance, RD participants showed larger feedback-related negativities to negative feedback relative to controls; group differences remained after accounting for residual anxiety and depressive symptoms. The present findings suggest that abnormal responses to negative feedback extend to samples at increased risk for depressive episodes in the absence of current symptoms.

Reduced sustained brain activity during processing of positive emotional stimuli in major depression.

BACKGROUND This study examines the directionality and temporal specificity of brain activity during sustained processing of emotional stimuli in individuals with current major depressive disorder (MDD) and nondepressed control participants. METHODS Slow wave (SW) components of the event-related brain potential (ERP) were recorded from 16 control participants and 15 participants with MDD during a working memory task. During the task, individuals were shown a positive, neutral, or negative word and were asked to maintain it in memory for 5 sec. Participants then saw a letter and had to decide whether it was a part of the previously presented word. The ERP components were measured from nine scalp sites (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4) during the encoding of emotional words. RESULTS Compared with control individuals, MDD participants exhibited decreased brain responses to positive relative to negative or neutral stimuli. This decrease in brain activity during processing of positive information was evident across all sites and SW components. CONCLUSIONS Our findings suggest that cognitive deficits in MDD may stem from diminished brain responses during processing of positive information and may not be associated with an augmented response to negative stimuli.

A preliminary investigation of cognitive flexibility for emotional information in major depressive disorder and non-psychiatric controls.

Clinical research suggests that individuals with major depressive disorder (MDD) are cognitively inflexible, exhibiting ruminative, rigid, and automatic thoughts within a negative schema. However, existing neuropsychological research on cognitive flexibility in this population has not employed emotional stimuli. Because research suggests that the performance of individuals with MDD is modulated when emotional stimuli are used, this study investigates the impact of emotional stimuli on cognitive flexibility performance through a novel emotional modification of the Wisconsin Card Sorting Test. Controls were less flexible when stimuli were positive and individuals with MDD were less flexible when stimuli were negative relative to the controls. These divergent styles of responding to emotional information may contribute to the relative risk or protection from depressed mood.

Prediction of “Fear” Acquisition in Healthy Control Participants in a De Novo Fear-Conditioning Paradigm:

Studies using fear-conditioning paradigms have found that anxiety patients are more conditionable than individuals without these disorders, but these effects have been demonstrated inconsistently. It is unclear whether these findings have etiological significance or whether enhanced conditionability is linked only to certain anxiety characteristics. To further examine these issues, the authors assessed the predictive significance of relevant subsyndromal characteristics in 72 healthy adults, including measures of worry, avoidance, anxious mood, depressed mood, and fears of anxiety symptoms (anxiety sensitivity), as well as the dimensions of Neuroticism and Extraversion. Of these variables, the authors found that the combination of higher levels of subsyndromal worry and lower levels of behavioral avoidance predicted heightened conditionability, raising questions about the etiological significance of these variables in the acquisition or maintenance of anxiety disorders. In contrast, the authors found that anxiety sensitivity was more linked to individual differences in orienting response than differences in conditioning per se.

Memory of Faces: A Slow Wave ERP Study of Major Depression

This study examined slow wave (SW) event-related brain potential (ERP) amplitudes in response to happy, neutral, and sad faces during a working memory task to further identify the associated component processes and physiological changes of mood-congruent memory biases in individuals with and without major depression. The results suggest that individuals with and without a diagnosis of major depressive disorder (MDD) differentially maintain valenced facial information in their working memory. Specifically, the nondepressed individuals displayed a marked reduction in SW amplitude to the negative faces. Individuals with MDD exhibited equivalent SW amplitudes for positive and negative facial stimuli. Results are discussed in terms of avoidance coping, previous ERP studies of working memory, and facial recognition deficits in individuals with MDD.

A slow wave investigation of working memory biases in mood disorders.

Mood-congruent working memory biases were examined in a delayed matching to sample paradigm using the slow wave (SW) event-related brain potential (ERP) component. Mood-congruent working memory biases, indexed by SW amplitudes, were demonstrated among individuals experiencing a major depressive episode (MDE) and nondepressed controls but not individuals with dysthymia. However, analyses of symptom severity demonstrated that those with dysthymia exhibited significantly less negative SW amplitudes with increasing depressive mood severity, whereas individuals with major depression demonstrated more negative SW amplitudes with increasing depressive mood severity. These results are discussed in the context of diagnostic specificity for cognitive biases associated with working memory of mood-disordered individuals.

Neural Mechanisms of Frustration in Chronically Irritable Children

OBJECTIVE Irritability is common in children and adolescents and is the cardinal symptom of disruptive mood dysregulation disorder, a new DSM-5 disorder, yet its neural correlates remain largely unexplored. The authors conducted a functional MRI study to examine neural responses to frustration in children with severe mood dysregulation. METHOD The authors compared emotional responses, behavior, and neural activity between 19 severely irritable children (operationalized using criteria for severe mood dysregulation) and 23 healthy comparison children during a cued-attention task completed under nonfrustrating and frustrating conditions. RESULTS Children in both the severe mood dysregulation and the healthy comparison groups reported increased frustration and exhibited decreased ability to shift spatial attention during the frustration condition relative to the nonfrustration condition. However, these effects of frustration were more marked in the severe mood dysregulation group than in the comparison group. During the frustration condition, participants in the severe mood dysregulation group exhibited deactivation of the left amygdala, the left and right striatum, the parietal cortex, and the posterior cingulate on negative feedback trials, relative to the comparison group (i.e., between-group effect) and to the severe mood dysregulation groups responses on positive feedback trials (i.e., within-group effect). In contrast, neural response to positive feedback during the frustration condition did not differ between groups. CONCLUSIONS In response to negative feedback received in the context of frustration, children with severe, chronic irritability showed abnormally reduced activation in regions implicated in emotion, attention, and reward processing. Frustration appears to reduce attention flexibility, particularly in severely irritable children, which may contribute to emotion regulation deficits in this population. Further research is needed to relate these findings to irritability specifically, rather than to other clinical features of severe mood dysregulation.

Amygdala Hyperactivation During Face Emotion Processing in Unaffected Youth at Risk for Bipolar Disorder

OBJECTIVE Youth at familial risk for bipolar disorder (BD) show deficits in face emotion processing, but the neural correlates of these deficits have not been examined. This preliminary study tests the hypothesis that, relative to healthy comparison (HC) subjects, both BD subjects and youth at risk for BD (i.e., those with a first-degree BD relative) will demonstrate amygdala hyperactivation when viewing fearful and happy faces. The at-risk youth were unaffected, in that they had no history of mood disorder. METHOD Amygdala activity was examined in 101 unrelated participants, 8 to 18 years old. Age, gender, and IQ-matched groups included BD (N = 32), unaffected at-risk (N = 13), and HC (N = 56). During functional magnetic resonance imaging, participants attended to emotional and nonemotional aspects of fearful and happy faces. RESULTS While rating their fear of fearful faces, both BD and unaffected at-risk subjects exhibited amygdala hyperactivity versus HC. There were no between-group differences in amygdala activity in response to happy faces. Post-hoc comparisons revealed that, in at-risk youth, familial risk status (offspring versus sibling), presence of Axis I diagnosis (n = 1 attention-deficit/hyperactivity disorder [ADHD], n = 1 social phobia), and history of medication exposure (n = 1) did not influence imaging findings. CONCLUSIONS We found amygdala hyperactivation in both unaffected at-risk and BD youth while rating their fear of fearful faces. These pilot data suggest that both face emotion labeling deficits and amygdala hyperactivity during face processing should receive further study as potential BD endophenotypes. Longitudinal studies should test whether amygdala hyperactivity to fearful faces predicts conversion to BD in at-risk youth.

The Cognitive Consequences of Emotion Regulation: An ERP Investigation

Increasing evidence suggests that emotion regulation (ER) strategies modulate encoding of information presented during regulation; however, no studies have assessed the impact of cognitive reappraisal ER strategies on the processing of stimuli presented after the ER period. Participants in the present study regulated emotions to unpleasant pictures and then judged whether a word was negative or neutral. Electromyographic measures (corrugator supercilli) confirmed that individuals increased and decreased negative affect according to ER condition. Event-related potential analyses revealed smallest N400 amplitudes to negative and neutral words presented after decreasing unpleasant emotions and smallest P300 amplitudes to words presented after increasing unpleasant emotions whereas reaction time data failed to show ER modulations. Results are discussed in the context of the developing ER literature, as well as theories of emotional incongruity (N400) and resource allocation (P300).

Parametric Modulation of Neural Activity by Emotion in Youth With Bipolar Disorder, Youth With Severe Mood Dysregulation, and Healthy Volunteers

CONTEXT Youth with bipolar disorder (BD) and those with severe, nonepisodic irritability (severe mood dysregulation [SMD]) exhibit amygdala dysfunction during facial emotion processing. However, studies have not compared such patients with each other and with comparison individuals in neural responsiveness to subtle changes in facial emotion; the ability to process such changes is important for social cognition. To evaluate this, we used a novel, parametrically designed faces paradigm. OBJECTIVE To compare activation in the amygdala and across the brain in BD patients, SMD patients, and healthy volunteers (HVs). DESIGN Case-control study. SETTING Government research institute. PARTICIPANTS Fifty-seven youths (19 BD, 15 SMD, and 23 HVs). MAIN OUTCOME MEASURE Blood oxygenation level-dependent data. Neutral faces were morphed with angry and happy faces in 25% intervals; static facial stimuli appeared for 3000 milliseconds. Participants performed hostility or nonemotional facial feature (ie, nose width) ratings. The slope of blood oxygenation level-dependent activity was calculated across neutral-to-angry and neutral-to-happy facial stimuli. RESULTS In HVs, but not BD or SMD participants, there was a positive association between left amygdala activity and anger on the face. In the neutral-to-happy whole-brain analysis, BD and SMD participants modulated parietal, temporal, and medial-frontal areas differently from each other and from that in HVs; with increasing facial happiness, SMD patients demonstrated increased, and BD patients decreased, activity in the parietal, temporal, and frontal regions. CONCLUSIONS Youth with BD or SMD differ from HVs in modulation of amygdala activity in response to small changes in facial anger displays. In contrast, individuals with BD or SMD show distinct perturbations in regions mediating attention and face processing in association with changes in the emotional intensity of facial happiness displays. These findings demonstrate similarities and differences in the neural correlates of facial emotion processing in BD and SMD, suggesting that these distinct clinical presentations may reflect differing dysfunctions along a mood disorders spectrum.