Response Conflict and Frontocingulate Dysfunction in Unmedicated Participants with Major Depression

Individuals with major depressive disorder (MDD) often exhibit impaired executive function, particularly in experimental tasks that involve response conflict and require adaptive behavioral adjustments. Prior research suggests that these deficits might be due to dysfunction within frontocingulate pathways implicated in response conflict monitoring and the recruitment of cognitive control. However, the temporal unfolding of conflict monitoring impairments in MDD remains poorly understood. To address this issue, we recorded 128-channel event-related potentials while 20 unmedicated participants with MDD and 20 demographically matched, healthy controls performed a Stroop task. Compared to healthy controls, MDD subjects showed larger Stroop interference effects and reduced N2 and N450 amplitudes. Source localization analyses at the time of maximal N450 activity revealed that MDD subjects had significantly reduced dorsal anterior cingulate cortex (dACC; Brodmann area 24/32) and left dorsolateral prefrontal cortex (Brodmann area 10/46) activation to incongruent relative to congruent trials. Consistent with the heterogeneous nature of depression, follow-up analyses revealed that depressed participants with the lowest level of conflict-related dACC activation 620 ms post-stimulus were characterized by the largest Stroop interference effects (relatively increased slowing and reduced accuracy for incongruent trials). Conversely, MDD participants with relatively stronger dACC recruitment did not differ from controls in terms of interference effects. These findings suggest that for some, but not all individuals, MDD is associated with impaired performance in trials involving competition among different response options, and reduced recruitment of frontocingulate pathways implicated in conflict monitoring and cognitive control.Psycholog

Task Feedback Effects on Conflict Monitoring and Executive Control: Relationship to Subclinical Measures of Depression

Emerging evidence suggests that depression is associated with executive dysfunction, particularly after committing errors or receiving negative performance feedback. To test this hypothesis, 57 participants performed two executive tasks known to elicit errors (the Simon and Stroop Tasks) during positive or negative performance feedback. Participants with elevated depressive symptoms (Beck Depression Inventory scores >= 13) were characterized by impaired posterror and postconflict performance adjustments, especially during emotionally negative task-related feedback. Additionally, for both tasks, depressive symptoms were inversely related to postconflict reaction time adjustments following negative, but not positive, feedback. These findings suggest that subclinical depression is associated with impairments in behavioral adjustments after internal (perceived failure) and external feedback about deficient task performance.Psycholog

Dissociable Recruitment of Rostral Anterior Cingulate and Inferior Frontal Cortex in Emotional Response Inhibition

The integrity of decision-making under emotionally evocative circumstances is critical to navigating complex environments, and dysfunctions in these processes may play an important role in the emergence and maintenance of various psychopathologies. The goal of the present study was to examine the spatial and temporal dynamics of neural responses to emotional stimuli and emotion-modulated response inhibition. High-density event-related brain potentials (ERPs) were measured as participants (N=25) performed an emotional Go/NoGo task that required button presses to words of a "target" emotional valence (i.e., positive, negative, neutral) and response inhibition to words of a different "distractor" valence. Using scalp ERP analyses in conjunction with source-localization techniques, we identified distinct neural responses associated with affective salience and affect- modulated response inhibition, respectively. Both earlier (similar to 300 ms) and later (similar to 700 ms) ERP components were enhanced with successful response inhibition to emotional distractors. Only ERPs to target stimuli differentiated affective from neutral cues. Moreover, Source localization analyses revealed right ventral lateral prefrontal cortex (VLPFC) activation in affective response inhibition regardless of emotional valence, whereas rostral anterior cingulate activation (rACC) was potentiated by emotional valence but was not modulated by response inhibition. This dissociation was supported by a significant Region x Trial Type x Emotion interaction, confirming that distinct regional dynamics characterize neural responses to affective valence and affective response-inhibition. The results are discussed in the context of an emerging affective neuroscience literature and implications for understanding psychiatric pathologies characterized by a detrimental susceptibility to emotional cues, with an emphasis on major depressive disorder.Psycholog

Anxiety Shapes Amygdala-Prefrontal Dynamics During Movie Watching

Background: A well-characterized amygdala–dorsomedial prefrontal circuit is thought to be crucial for threat vigilance during anxiety. However, engagement of this circuitry within relatively naturalistic paradigms remains unresolved. // Methods: Using an open functional magnetic resonance imaging dataset (Cambridge Centre for Ageing Neuroscience; n = 630), we sought to investigate whether anxiety correlates with dynamic connectivity between the amygdala and dorsomedial prefrontal cortex during movie watching. // Results: Using an intersubject representational similarity approach, we saw no effect of anxiety when comparing pairwise similarities of dynamic connectivity across the entire movie. However, preregistered analyses demonstrated a relationship between anxiety, amygdala-prefrontal dynamics, and anxiogenic features of the movie (canonical suspense ratings). Our results indicated that amygdala-prefrontal circuitry was modulated by suspense in low-anxiety individuals but was less sensitive to suspense in high-anxiety individuals. We suggest that this could also be related to slowed habituation or amplified anticipation. Moreover, a measure of threat-relevant attentional bias (accuracy/reaction time to fearful faces) demonstrated an association with connectivity and suspense. // Conclusions: Overall, this study demonstrated the presence of anxiety-relevant differences in connectivity during movie watching, varying with anxiogenic features of the movie. Mechanistically, exactly how and when these differences arise remains an opportunity for future research

Threat vigilance and intrinsic amygdala connectivity

A well-documented amygdala-dorsomedial prefrontal circuit is theorized to promote attention to threat (“threat vigilance”). Prior research has implicated a relationship between individual differences in trait anxiety/vigilance, engagement of this circuitry, and anxiogenic features of the environment (e.g., through threat-of-shock and movie-watching). In the present study, we predicted that—for those scoring high in self-reported anxiety and a behavioral measure of threat vigilance—this circuitry is chronically engaged, even in the absence of anxiogenic stimuli. Our analyses of resting-state fMRI data (N = 639) did not, however, provide evidence for such a relationship. Nevertheless, in our planned exploratory analyses, we saw a relationship between threat vigilance behavior (but not self-reported anxiety) and intrinsic amygdala-periaqueductal gray connectivity. Here, we suggest this subcortical circuitry may be chronically engaged in hypervigilant individuals, but that amygdala-prefrontal circuitry may only be engaged in response to anxiogenic stimuli

Implicit Depression and Hopelessness in Remitted Depressed Individuals

Cognitive theories of depression posit that automatically activated cognitive schemas, including negative thoughts about the self and the future, predispose individuals to develop depressive disorders. However, prior research has largely examined these constructs using explicit tests in currently depressed individuals. Using the Implicit Association Test (IAT), the present study examined automatic associations between the self and mood state ("depression IAT") and between the future and mood state ("hopelessness IAT") before and after a negative mood induction in 19 remitted depressed individuals and 23 healthy controls. In the depression IAT, remitted depressed participants exhibited an overall lower tendency to associate themselves with happiness relative to the healthy controls before the mood induction. Control, but not remitted depressed, participants' automatic associations between the self and happiness diminished following the mood induction. Contrary to our hypotheses, no significant findings emerged when considering the hopelessness IAT. Consistent with prior studies, no significant correlations emerged between implicit and explicit biases, suggesting that these measures probe different processes. Results extend prior IAT research by documenting the presence of a reduced tendency to associate the self with happiness in a sample at increased risk for depression.Psycholog

Dissociation of Neural Regions Associated with Anticipatory Versus Consummatory Phases of Incentive Processing

Incentive delay tasks implicate the striatum and medial frontal cortex in reward processing. However, prior studies delivered more rewards than penalties, possibly leading to unwanted differences in signal-to-noise ratio. Also, whether particular brain regions are specifically involved in anticipation or consumption is unclear. We used a task featuring balanced incentive delivery and an analytic strategy designed to identify activity specific to anticipation or consumption. Reaction time data in two independent samples (n = 13 and n = 8) confirmed motivated responding. Functional magnetic resonance imaging revealed regions activated by anticipation (anterior cingulate) versus consumption (orbital and medial frontal cortex). Ventral striatum was active during reward anticipation but not significantly more so than during consumption. Although the study features several methodological improvements and helps clarify the neural basis of incentive processing, replications in larger samples are needed.Psycholog

Childhood Adversity is Associated with Left Basal Ganglia Dysfunction During Reward Anticipation in Adulthood

Background: Childhood adversity increases the risk of psychopathology, but the neurobiological mechanisms underlying this vulnerability are not well-understood. In animal models, early adversity is associated with dysfunction in basal ganglia regions involved in reward processing, but this relationship has not been established in humans. Methods: Functional magnetic resonance imaging was used to examine basal ganglia responses to (a) cues signaling possible monetary rewards and losses, and (b) delivery of monetary gains and penalties, in 13 young adults who experienced maltreatment before age 14 and 31 non-maltreated controls. Results: Relative to controls, individuals exposed to childhood adversity reported elevated symptoms of anhedonia and depression, rated reward cues less positively, and displayed a weaker response to reward cues in the left globus pallidus. There were no group differences in right hemisphere basal ganglia response to reward cues, or in basal ganglia response to loss cues, no-incentive cues, gains, or penalties. Conclusions: Results indicate that childhood adversity in humans is associated with blunted subjective responses to reward-predicting cues as well as dysfunction in left basal ganglia regions implicated in reward-related learning and motivation. This dysfunction may serve as a diathesis that contributes to the multiple negative outcomes and psychopathologies associated with childhood adversity. The findings suggest that interventions that target motivation and goal-directed action may be useful for reducing the negative consequences of childhood adversity.Psycholog

Individual Differences in Reinforcement Learning: Behavioral, Electrophysiological, and Neuroimaging Correlates

During reinforcement learning, phasic modulations of activity in midbrain dopamine neurons are conveyed to the dorsal anterior cingulate Cortex (dACC) and basal ganglia (BG) and serve to guide adaptive responding. While the animal literature supports a role for the dACC in integrating reward history over time, most human electrophysiological Studies of dACC function have focused on responses to single positive and negative outcomes. The present electrophysiological study investigated the role of the dACC in probabilistic reward learning in healthy subjects using a task that required integration of reinforcement history over time. We recorded the feedback-related negativity (FRN) to reward feedback in subjects who developed a response bias toward a more frequently rewarded ("rich") stimulus ("learners") versus subjects who did not ("non-learners"). Compared to non-learners, learners showed more positive (i.e., smaller) FRNs and greater dACC activation upon receiving reward for correct identification of the rich stimulus. In addition, dACC activation and a bias to select the rich Stimulus were positively correlated. The same participants also completed a monetary incentive delay (MID) task administered during functional magnetic resonance imaging. Compared to non-learners, learners displayed stronger BG responses to reward in the MID task. These findings raise the possibility that learners in the probabilistic reinforcement task were characterized by stronger dACC and BG responses to rewarding outcomes. Furthermore, these results highlight the importance of the dACC to probabilistic reward learning in humans.Psycholog

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.Psycholog