Brady D. Nelson

Amygdala-prefrontal coupling underlies individual differences in emotion regulation

Despite growing evidence on the neural bases of emotion regulation, little is known about the mechanisms underlying individual differences in cognitive regulation of negative emotion, and few studies have used objective measures to quantify regulatory success. Using a trait-like psychophysiological measure of emotion regulation, corrugator electromyography, we obtained an objective index of the ability to cognitively reappraise negative emotion in 56 healthy men (Session 1), who returned 1.3 years later to perform the same regulation task using fMRI (Session 2). Results indicated that the corrugator measure of regulatory skill predicted amygdala-prefrontal functional connectivity. Individuals with greater ability to down-regulate negative emotion as indexed by corrugator at Session 1 showed not only greater amygdala attenuation but also greater inverse connectivity between the amygdala and several sectors of the prefrontal cortex while down-regulating negative emotion at Session 2. Our results demonstrate that individual differences in emotion regulation are stable over time and underscore the important role of amygdala-prefrontal coupling for successful regulation of negative emotion.

Does intolerance of uncertainty predict anticipatory startle responses to uncertain threat

Intolerance of uncertainty (IU) has been proposed to be an important maintaining factor in several anxiety disorders, including generalized anxiety disorder, obsessive-compulsive disorder, and social phobia. While IU has been shown to predict subjective ratings and decision-making during uncertain/ambiguous situations, few studies have examined whether IU also predicts emotional responding to uncertain threat. The present study examined whether IU predicted aversive responding (startle and subjective ratings) during the anticipation of temporally uncertain shocks. Sixty-nine participants completed three experimental conditions during which they received: no shocks, temporally certain/predictable shocks, and temporally uncertain shocks. Results indicated that IU was negatively associated with startle during the uncertain threat condition in that those with higher IU had a smaller startle response. IU was also only related to startle during the uncertain (and not the certain/predictable) threat condition, suggesting that it was not predictive of general aversive responding, but specific to responses to uncertain aversiveness. Perceived control over anxiety-related events mediated the relation between IU and startle to uncertain threat, such that high IU led to lowered perceived control, which in turn led to a smaller startle response. We discuss several potential explanations for these findings, including the inhibitory qualities of IU. Overall, our results suggest that IU is associated with attenuated aversive responding to uncertain threat.

Biomarkers of Threat and Reward Sensitivity Demonstrate Unique Associations With Risk for Psychopathology

Two emotional/motivational constructs that have been posited to underlie anxiety and depressive disorders are heightened sensitivity to threat and reduced sensitivity to reward, respectively. It is unclear, though, whether these constructs are only epiphenomena or also connote risk for these disorders (and relatedly, whether they connote risk for separate disorders). Using family history of psychopathology as an indicator of risk, the present study examined whether biomarkers of sensitivity to threat (startle potentiation) and reward (frontal EEG asymmetry) were associated with similar or different familial liabilities. In addition, the present study examined whether these biomarkers were associated with risk independent of proband DSM-IV diagnosis. One-hundred and seventy-three individuals diagnosed with panic disorder (PD), early onset major depressive disorder (MDD), both (comorbids), or controls completed two laboratory paradigms assessing sensitivity to predictable/unpredictable threat (measured via startle response) and reward (measured via frontal EEG asymmetry during a gambling task). Results indicated that across all participants: (a) startle potentiation to unpredictable threat was associated with family history of PD (but not MDD); and (b) frontal EEG asymmetry while anticipating reward was associated with family history of MDD (but not PD). Additionally, both measures continued to be associated with family history of psychopathology after controlling for proband DSM-IV diagnosis. Results suggest that the proposed biomarkers of sensitivity to unpredictable threat and reward exhibit discriminant validity and may add to the predictive validity of the DSM-IV defined constructs of PD and MDD, respectively.

Does physical anhedonia play a role in depression? A 20-year longitudinal study

BACKGROUND Anhedonia towards physical or sensory experiences (i.e., physical anhedonia) has most often been examined as a differentia of schizophrenia and not depression, despite the fact that general anhedonia is a core feature of many models of Major Depressive Disorder (MDD). METHODS Forty-nine participants with non-psychotic MDD were recruited from inpatient settings and followed-up six times over 20 years. The three aims of the study was to assess a) the stability of physical anhedonia over time, b) whether physical anhedonia relates to the course of depressive symptoms over time, and c) whether physical anhedonia relates to three domains of functioning - work, social functioning, or re-hospitalizations. RESULTS We found that over time physical anhedonia was relatively stable and related to depressive symptoms (both between and within person). Physical anhedonia was also related to certain aspects of functioning, though less robustly than depressive symptoms. LIMITATIONS Because depressive symptoms, functioning, and physical anhedonia were measured concurrently at each follow-up, the direction of causality among these variables could not be assessed. Additionally, because our sample was recruited from inpatient settings, our findings may not generalize to individuals with less severe depression. CONCLUSIONS A trait tendency to experience decreased pleasure to positive physical stimuli is a clinically meaningful variable for those with MDD and may be a behavioral endophenotype for a more severe form of depression.

Do positive and negative temperament traits interact in predicting risk for depression? A resting EEG study of 329 preschoolers

Researchers have long been interested in whether particular temperamental traits in childhood connote risk for depressive disorders. For example, children characterized as having high negative emotionality (NE; sadness, fear, anger) and low positive emotionality (PE; anhedonia, listlessness, and lack of enthusiasm) are hypothesized to be at risk for depression. Few studies, however, have examined whether (and how) these two temperamental dimensions interact to confer risk. In a sample of 329 preschoolers, the present study addressed this question by examining the relation between PE and NE and asymmetry in resting EEG activity in frontal and posterior regions, which are putative biomarkers for depression. Using a laboratory battery to define temperament, we found an interaction of PE and NE on posterior asymmetry. Specifically, when PE was high, NE was associated with greater relative right activity. When PE was low, NE was not related to posterior asymmetry. These results were driven by differences in EEG activity in right posterior regions, an area associated with emotional processing and arousal, and were specific to girls. We found no relation between temperament and frontal asymmetry. These findings suggest that, at least for girls, PE and NE may have an interactive effect on risk for depression.

Anterior insula responds to temporally unpredictable aversiveness: an fMRI study

A heightened sensitivity to unpredictable aversiveness is a key component of several anxiety disorders. Neuroimaging studies of unpredictable aversiveness have shown that the anterior region of the insula cortex (AIC) plays a central role in the anticipation of unpredictable aversiveness. The present study extended these findings by examining the role of the AIC in temporal unpredictability (i.e. not knowing when the stimulus will occur), a particularly critical aspect of unpredictability as it increases contextual anxiety and vigilance, given that the danger could happen ‘at any time’. Nineteen healthy participants underwent functional MRI while anticipating either temporally unpredictable or predictable aversive (or neutral) images. Participants showed greater right AIC activation while anticipating unpredictable relative to predictable aversive images. In addition, activation in this region was correlated positively with self-reported individual differences in a key facet of intolerance of uncertainty (inhibitory behavior). Taken together, the present study suggests that the AIC plays an important role in the anticipation of temporally unpredictable aversiveness and may mediate key deficits in anxiety disorders.

Event-related potentials to acoustic startle probes during the anticipation of predictable and unpredictable threat

The startle reflex is a robust measure of defense system activation. Startle probes also elicit ERP P300 and N100 responses that capture attentional engagement. The startle probe-elicited P300 and N100 have been primarily examined during affective picture viewing paradigms, and no study has examined these measures in the context of a threat anticipation task or in relation to threat predictability. In the present study, 131 participants completed a no (N), predictable (P), and unpredictable (U) threat-of-shock task, and the startle eye blink reflex, P300, and N100 responses to the startle probe were measured. We also examined several psychometric properties of these psychophysiological measures. Results indicated probe P300 attenuation during the P and U relative to N condition. In contrast, probe N100 enhancement was present only for the U condition. The P300 and N100 decreased (i.e., habituated) at comparable rates across the different threat conditions. The startle reflex also decreased, but only startle during the U (and not P) condition continued to differ from the N condition by the end of the task. Internal consistency of the ERP measures was acceptable and comparable to the startle reflex. Finally, the startle reflex was correlated with the probe N100, but not P300, across threat conditions. This study is one of the first to use startle probe ERPs to demonstrate that a context of potential threat also elicits attentional engagement. Furthermore, this study provides novel evidence that the probe N100 may provide a measure that is uniquely sensitive to unpredictable threat.

Intolerance of uncertainty mediates reduced reward anticipation in major depressive disorder.

BACKGROUND Reduced reward sensitivity has long been considered a fundamental deficit of major depressive disorder (MDD). One way this deficit has been measured is by an asymmetry in electroencephalogram (EEG) activity between left and right frontal brain regions. MDD has been associated with a reduced frontal EEG asymmetry (i.e., decreased left relative to right) while anticipating reward. However, the mechanism (or mediator) of this association is unclear. The present study examined whether intolerance of uncertainty (IU) mediated the association between depression and reduced reward anticipation. METHODS Data were obtained from a prior study reporting reduced frontal EEG asymmetry while anticipating reward in early-onset MDD. Participants included 156 individuals with early-onset MDD-only, panic disorder-only, both (comorbids), or controls. Frontal EEG asymmetry was recorded during an uncertain reward anticipation task. Participants completed a self-report measure of IU. RESULTS All three psychopathology groups reported greater IU relative to controls. Across all participants, greater IU was associated with a reduced frontal EEG asymmetry. Furthermore, IU mediated the relationship between MDD and frontal EEG asymmetry and results remained significant after controlling for neuroticism, suggesting effects were not due to broad negative affectivity. LIMITATIONS MDD participants were limited to those with early-onset depression. Measures were collected cross-sectionally, precluding causal relationships. CONCLUSIONS IU mediated the relationship between MDD and reduced reward anticipation, independent of neuroticism. Explanations are provided regarding how IU may contribute to reduced reward anticipation in depression. Overall, IU appears to be an important mechanism for the association between depression and reduced reward anticipation.

The impact of an unpredictable context and intolerance of uncertainty on the electrocortical response to monetary gains and losses

There is growing evidence that unpredictability and uncertainty can alter reward system functioning. The present study examined the impact of (1) a task-irrelevant unpredictable relative to predictable context and (2) individual differences in intolerance of uncertainty (IU) on the reward-related positivity (RewP), an event-related potential (ERP) response to monetary gains relative to losses. Specifically, 64 participants listened to predictable and unpredictable tone sequences while electroencephalography was recorded during a monetary gambling task. Participants also completed the Intolerance of Uncertainty Scale, which measures both cognitive distress (prospective IU) and behavioral inhibition (inhibitory IU) elicited by uncertainty, in addition to the Depression Anxiety Stress Scale-21 and Penn State Worry Questionnaire. Results indicated that the RewP was reduced during the unpredictable relative to the predictable context. Greater self-reported anxiety elicited by the unpredictable context was associated with a decreased RewP, and a decreased RewP was associated with poorer lose-shift behavioral adjustment. Furthermore, the RewP mediated the relationship between self-reported anxiety elicited by the unpredictable context and lose-shift behavioral adjustment. The IU subscales demonstrated the opposite relationship with the RewP across both contexts—inhibitory IU was associated with an attenuated RewP and prospective IU was associated with an enhanced RewP. In contrast, anxiety, depression, stress, and worry symptomatology were not associated with the RewP. This is the first study to demonstrate that an unpredictable context and individual differences in the degree to which people cannot tolerate uncertainty impact an ERP measure of reward system functioning.

Depression risk and electrocortical reactivity during self-referential emotional processing in 8 to 14 year-old girls.

Cognitive vulnerabilities, such as a negative self-referential processing bias, have been theorized to play a causal role in the development of depression. Indeed, depression is associated with the endorsement and recall of more negative and fewer positive emotional words (i.e., recall biases) in the self-referential encoding task (SRET). In addition, currently depressed adults and adolescents, compared to healthy controls, show an enhanced late positive potential (LPP), an event-related potential (ERP) component that reflects sustained attentional engagement, during the processing of negative relative to positive words in the SRET. However, it is unclear whether these behavioral and neural measures in the SRET are indicators of risk for depression, or are concomitants of the disorder. The present study included 121 8 to 14 year-old girls with no lifetime history of depression, and examined the association between maternal history of depression (i.e., risk) and both behavioral and ERP measures while viewing positive and negative adjectives during the SRET. Lifetime history of major depressive disorder and/or dysthymia in the biological mother was assessed via a semistructured diagnostic interview. Results indicated that participants with maternal history of depression, compared with those with no maternal history of depression, demonstrated an enhanced LPP to negative words. There were no group differences in the LPP to positive words. Maternal history of depression was also related to faster response time when rejecting negative words. Participants current depression symptoms were associated with increased negative recall bias and decreased positive recall bias. The present study provides novel evidence that abnormal electrocortical reactivity to negative self-referential words indexes vulnerability for depression in 8 to 14 year-old girls. (PsycINFO Database Record