Showing papers by "Diego A. Pizzagalli published in 2008"
TL;DR: These findings indicate that MDD is characterized by an impaired tendency to modulate behavior as a function of prior reinforcements, and provides initial clues about which aspects of hedonic processing might be dysfunctional in depression.
643 citations
TL;DR: Unmedicated patients with major depressive disorder showed reduced accuracy and potentiated error-related negativity immediately after committing errors, highlighting dysfunctions in the automatic detection of unfavorable performance outcomes.
Abstract: Cognitive theories of depression have long postulated that automatically activated cognitive schemata and a predisposition to process information in a negative manner are prominent features of depression.1 Consistent with this, depression is characterized by ineffective inhibition of negative information,2 difficulty disengaging attention from negative cues,3 greater interference from negative distractors,4 amplification of the significance of failure,5 and increased likelihood of committing errors immediately after an initial mistake.6–10 Although these negative processing biases have been critically implicated in the etiology and maintenance of depression, little is known about their underlying mechanisms and neural substrates.
Emerging neuroimaging evidence suggests that, in major depressive disorder (MDD), negative processing biases may result from dysfunctions in paralimbic regions implicated in affective responses such as the amygdala and the rostral anterior cingulate cortex (ACC)11–13 and/or dysfunctions in cortical regions involved in cognitive control (ie, the ability to guide action and thought in accordance with internally generated goals), such as the dorsolateral prefrontal cortex (PFC) and dorsal ACC.13–18 Moreover, patients with MDD show reduced connectivity between the dorsolateral PFC and rostral ACC regions after the presentation of personally relevant negative stimuli.13 Collectively, these findings suggest that abnormal responses to errors and negative cues in depression6–10 might be due to exaggerated paralimbic activation, a failure to recruit PFC-based cognitive control after committing an error, or a combination of these 2 factors, possibly resulting from disrupted frontocingulate connectivity. To the best of our knowledge, these hypotheses have yet to be fully investigated.
The goal of this study was to address these important questions. To this end, we capitalized on the high temporal resolution of event-related potentials (ERPs) and on novel approaches to investigate spatiotemporal dynamics of brain mechanisms that underlie error processing in a sample of unmedicated patients with MDD. The ERP analyses focused on error-related negativity (ERN) and error positivity (Pe), 2 components assumed to reflect dissociable aspects of error processing and partially originating from regions within the ACC.19
The ERN, a negative voltage deflection measured over midline frontocentral regions beginning with the occurrence of an incorrect response and peaking approximately 50 to 150 milliseconds later,20,21 is hypothesized to represent a negative reinforcement learning signal conveyed through the mesencephalic dopamine system22,23; accordingly, the ERN is assumed to index the automatic initial detection of unfavorable performance outcomes, which then triggers recruitment of PFC-based cognitive control.24 The Pe, a positive voltage deflection peaking approximately 150 to 500 milliseconds after mistakes, is hypothesized to index conscious error awareness and subjective affective evaluative processes after errors.20 Fitting these conceptualizations, ERN is not contingent on the conscious experience of errors, whereas the Pe is observed when subjects are aware of having committed an error.25–27
Extending reports of abnormal error processing in depression,6–10 recent ERP studies have described enhanced ERN amplitude in clinically depressed patients,28 elderly patients with MDD who remain symptomatic after antidepressant treatment,29 and individuals with increased levels of negative affect30,31 but not in medicated patients with MDD in remission.32 Moreover, increased ERN amplitude has been found to predict poor treatment response in a small sample of patients with geriatric depression.33 Although these ERN findings highlight dysfunctional error processing in depression, at first glance, they appear paradoxical in light of theoretical considerations22 and empirical findings21,34 that link increased ERN with adaptive performance adjustments. To reconcile these data, we hypothesized that, in depression, initial exaggerated error processing (increased ERN) is not followed by successful recruitment of PFC-based cognitive control, leading to posterror impairments. Notably, decreased ERN in error trials after a prior mistake32 has been described in patients with MDD, providing indirect support for this hypothesis.
Therefore, on the basis of prior findings,11,13,28,29 we hypothesized that unmedicated patients with MDD would show (1) decreased performance in trials immediately after errors, (2) increased scalp ERN and rostral ACC activation after committing errors, and/or (3) disrupted connectivity between the rostral ACC and dorsolateral PFC regions, which might explain deficits in the recruitment of cognitive control and the lack of adaptive performance after error commission. With respect to Pe, we hypothesized that patients with MDD would display higher amplitudes, reflecting increased subjective affective evaluation of errors. Because of inconsistent Pe findings in depression,28,29 we considered this latter hypothesis tentative.
270 citations
TL;DR: These findings show that a single low dose of pramipexole impaired the acquisition of reward-related behavior in healthy participants, and they are consistent with prior evidence suggesting that phasic DA signaling is required to reinforce actions leading to reward.
Abstract: Rationale
The dopaminergic system, particularly D2-like dopamine receptors, has been strongly implicated in reward processing. Animal studies have emphasized the role of phasic dopamine (DA) signaling in reward-related learning, but these processes remain largely unexplored in humans.
218 citations
TL;DR: Preliminary evidence is provided indicating that BPD, even during euthymic states, is characterized by dysfunctional reward learning in situations requiring integration of reinforcement information over time and thus offers initial insights about the potential source of dysfunctional reward processing in this disorder.
160 citations
TL;DR: The 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.
135 citations
TL;DR: It is suggested that a single dose of nicotine enhances response to non-drug-related rewards in the environment, with lasting effects, which may contribute to reinforcement of early smoking behavior and development of nicotine dependence.
127 citations
TL;DR: Findings raise the possibility that learners in the probabilistic reinforcement task were characterized by stronger dACC and BG responses to rewarding outcomes, and highlight the importance of the dACC to Probabilistic reward learning in humans.
121 citations
TL;DR: It is confirmed that distinct regional dynamics characterize neural responses to affective valence and affective response-inhibition, and implications for understanding psychiatric pathologies characterized by a detrimental susceptibility to emotional cues are discussed, with an emphasis on major depressive disorder.
108 citations
TL;DR: 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.
Abstract: 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.
108 citations
TL;DR: It is suggested that the earliest modulation of spatial attention by face stimuli is manifested in the P1 component, and insights about mechanisms underlying attentional orienting toward cues of threat and social disapproval are provided.
107 citations
TL;DR: Electromyographic measures confirmed that individuals increased and decreased negative affect according to ER condition and theories of emotional incongruity (N400) and resource allocation (P300) were discussed in the context of the developing ER literature.
Abstract: 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).
TL;DR: 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 by examining automatic associations between the self and mood state and between the future and moodState.
TL;DR: Anhedonia may be characterized by disruptions of mPFC-mediated neuroendocrine regulation, which could constitute a vulnerability to the development of stress-related disorders.
Abstract: The medial prefrontal cortex (mPFC), hippocampus, and amygdala are implicated in the regulation of affect and physiological processes, including hypothalamic-pituitary-adrenal (HPA) axis function. Anhedonia is likely associated with dysregulation of these processes. Dense-array resting electroencephalographic and cortisol were obtained from healthy and anhedonic groups. Low-resolution electromagnetic tomography was used to compute intracerebral current density. For the control group, voxelwise analyses found a relationship between current density in beta and gamma bands and steeper cortisol slope (indicative of more adaptive HPA axis functioning) in regions of the hippocampus, parahippocampal gyrus, and mPFC. For the anhedonic group, the mPFC finding was absent. Anhedonia may be characterized by disruptions of mPFC-mediated neuroendocrine regulation, which could constitute a vulnerability to the development of stress-related disorders.
Journal Article•
TL;DR: The purpose of this study was to validate anhedonia as a potential endophenotype in major depressive disorder and to test the hypothesis that depressed patients with high anhedonic symptoms show reduced responsiveness to reward compared to patients with low or noAnhedonia.