Electrophysiological evidence of the time course of Attentional Bias in Nonpatients Reporting Symptoms of Depression With and Without Co-Occurring Anxiety

Anxiety is characterized by attentional biases to threat, but findings are inconsistent for depression. To address this inconsistency, the present study systematically assessed the role of co-occurring anxiety in attentional bias in depression. In addition, the role of emotional valence, arousal, and gender was explored. Ninety-two non-patients completed the Penn State Worry Questionnaire (Meyer et al., 1990; Molina and Borkovec, 1994) and portions of the Mood and Anxiety Symptom Questionnaire (Watson et al., 1995a,b). Individuals reporting high levels of depression and low levels of anxiety (depression only), high levels of depression and anxiety (combined), or low levels of both (control) completed an emotion-word Stroop task during event-related brain potential recording. Pleasant and unpleasant words were matched on emotional arousal level. An attentional bias was not evident in the depression-only group. Women in the combined group had larger N200 amplitude for pleasant than unpleasant stimuli, and the combined group as a whole had larger right-lateralized P300 amplitude for pleasant than unpleasant stimuli, consistent with an early and later attentional bias that is specific to unpleasant valence in the combined group. Men in the control group had larger N200 amplitude for pleasant than unpleasant stimuli, consistent with an early attentional bias that is specific to pleasant valence. The present study indicates that the nature and time course of attention prompted by emotional valence and not arousal differentiates depression with and without anxiety, with some evidence of gender moderating early effects. Overall, results suggest that co-occurring anxiety is more important than previously acknowledged in demonstrating evidence of attentional biases in depression

Differential Functional Connectivity of Rostral Anterior Cingulate Cortex During Emotional Interference

The rostral-ventral subdivision of the anterior cingulate cortex (rACC) plays a key role in the regulation of emotional processing. Although rACC has strong anatomical connections with anterior insular cortex (AIC), amygdala, prefrontal cortex and striatal brain regions, it is unclear whether the functional connectivity of rACC with these regions changes when regulating emotional processing. Furthermore, it is not known whether this connectivity changes with deficits in emotion regulation seen in different kinds of anxiety and depression. To address these questions regarding rACC functional connectivity, non-patients high in self-reported anxious apprehension (AP), anxious arousal (AR), anhedonic depression (AD) or none (CON) indicated the ink color of pleasant, neutral and unpleasant words during functional magnetic resonance imaging. While ignoring task-irrelevant unpleasant words, AD and CON showed an increase in the functional connectivity of rACC with AIC, putamen, caudate and ventral pallidum. There was a decrease in this connectivity in AP and AR, with AP showing greater reduction than AR. These findings provide support for the role of rACC in integrating interoceptive, emotional and cognitive functions via interactions with insula and striatal regions during effective emotion regulation in healthy individuals and a failure of this integration that may be specific to anxiety, particularly AP

Differential Functional Connectivity of Rostral Anterior Cingulate Cortex During Emotional Interference

The rostral-ventral subdivision of the anterior cingulate cortex (rACC) plays a key role in the regulation of emotional processing. Although rACC has strong anatomical connections with anterior insular cortex (AIC), amygdala, prefrontal cortex and striatal brain regions, it is unclear whether the functional connectivity of rACC with these regions changes when regulating emotional processing. Furthermore, it is not known whether this connectivity changes with deficits in emotion regulation seen in different kinds of anxiety and depression. To address these questions regarding rACC functional connectivity, non-patients high in self-reported anxious apprehension (AP), anxious arousal (AR), anhedonic depression (AD) or none (CON) indicated the ink color of pleasant, neutral and unpleasant words during functional magnetic resonance imaging. While ignoring task-irrelevant unpleasant words, AD and CON showed an increase in the functional connectivity of rACC with AIC, putamen, caudate and ventral pallidum. There was a decrease in this connectivity in AP and AR, with AP showing greater reduction than AR. These findings provide support for the role of rACC in integrating interoceptive, emotional and cognitive functions via interactions with insula and striatal regions during effective emotion regulation in healthy individuals and a failure of this integration that may be specific to anxiety, particularly AP

Time Course of Brain Network Reconfiguration Supporting Inhibitory Control

Hemodynamic research has recently clarified key nodes and links in brain networks implementing inhibitory control. Although fMRI methods are optimized for identifying the structure of brain networks, the relatively slow temporal course of fMRI limits the ability to characterize network operation. The latter is crucial for developing a mechanistic understanding of how brain networks shift dynamically to support inhibitory control. To address this critical gap, we applied spectrally resolved Granger causality (GC) and random forest machine learning tools to human EEG data in two large samples of adults (test sample n = 96, replication sample n = 237, total N = 333, both sexes) who performed a color–word Stroop task. Time–frequency analysis confirmed that recruitment of inhibitory control accompanied by slower behavioral responses was related to changes in theta and alpha/beta power. GC analyses revealed directionally asymmetric exchanges within frontal and between frontal and parietal brain areas: top-down influence of superior frontal gyrus (SFG) over both dorsal ACC (dACC) and inferior frontal gyrus (IFG), dACC control over middle frontal gyrus (MFG), and frontal–parietal exchanges (IFG, precuneus, MFG). Predictive analytics confirmed a combination of behavioral and brain-derived variables as the best set of predictors of inhibitory control demands, with SFG theta bearing higher classification importance than dACC theta and posterior beta tracking the onset of behavioral response. The present results provide mechanistic insight into the biological implementation of a psychological phenomenon: inhibitory control is implemented by dynamic routing processes during which the target response is upregulated via theta-mediated effective connectivity within key PFC nodes and via beta-mediated motor preparation

Neural correlates of suspiciousness and interactions with anxiety during emotional and neutral word processing

Suspiciousness is usually classified as a symptom of psychosis, but it also occurs in depression and anxiety disorders. Though how suspiciousness overlaps with depression is not obvious, suspiciousness does seem to overlap with anxious apprehension and anxious arousal (e.g., verbal iterative processes and vigilance about environmental threat). However, suspiciousness also has unique characteristics (e.g., concern about harm from others and vigilance about social threat). Given that both anxiety and suspiciousness have been associated with abnormalities in emotion processing, it is unclear whether it is the unique characteristics of suspiciousness or the overlap with anxiety that drive abnormalities in emotion processing. Event-related brain potentials were obtained during an emotion-word Stroop task. Results indicated that suspiciousness interacts with anxious apprehension to modulate initial stimulus perception processes. Suspiciousness is associated with attention to all stimuli regardless of emotion content. In contrast, anxious arousal is associated with a later response to emotion stimuli only. These results suggest that suspiciousness and anxious apprehension share overlapping processes, but suspiciousness alone is associated with a hyperactive early vigilance response. Depression did not interact with suspiciousness to predict response to emotion stimuli. These findings suggest that it may be informative to assess suspiciousness in conjunction with anxiety in order to better understand how these symptoms interact and contribute to dysfunctional emotion processing

Influence of participant and reviewer characteristics in application scores for a hematology research training program

The American Society of Hematology Clinical Research Training Institute (CRTI) is a clinical research training program with a competitive application process. The objectives were to compare application scores based on applicant and reviewer sex and underrepresented minority (URM) status. We included applications to CRTI from 2003 to 2019. The application scores were transformed into a scale from 0 to 100 (100 was the strongest). The factors considered were applicant and reviewer sex and URM status. We evaluated whether there was an interaction between the characteristics and time related to application scores. In total, 713 applicants and 2106 reviews were included. There was no significant difference in scores according to applicant sex. URM applicants had significantly worse scores than non-URM applicants (mean [standard error] 67.9 [1.56] vs 71.4 [0.63]; P = .0355). There were significant interactions between reviewer sex and time (P = .0030) and reviewer URM status and time (P = .0424); thus, results were stratified by time. For the 2 earlier time periods, male reviewers gave significantly worse scores than did female reviewers; this difference did not persist for the most recent time period. The URM reviewers did not give significantly different scores across time periods. URM applicants received significantly lower scores than non-URM applicants. The impact of reviewer sex and URM status changed over time. Although male reviewers gave lower scores in the early periods, this effect did not persist in the late period. Efforts are required to mitigate the impact of applicant URM status on application scores

Opioids in patients with COPD and refractory dyspnea:literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD)

BACKGROUND: Refractory dyspnea or breathlessness is a common symptom in patients with advanced chronic obstructive pulmonary disease (COPD), with a high negative impact on quality of life (QoL). Low dosed opioids have been investigated for refractory dyspnea in COPD and other life-limiting conditions, and some positive effects were demonstrated. However, upon first assessment of the literature, the quality of evidence in COPD seemed low or inconclusive, and focused mainly on morphine which may have more side effects than other opioids such as fentanyl. For the current publication we performed a systematic literature search. We searched for placebo-controlled randomized clinical trials investigating opioids for refractory dyspnea caused by COPD. We included trials reporting on dyspnea, health status and/or QoL. Three of fifteen trials demonstrated a significant positive effect of opioids on dyspnea. Only one of four trials reporting on QoL or health status, demonstrated a significant positive effect. Two-thirds of included trials investigated morphine. We found no placebo-controlled RCT on transdermal fentanyl. Subsequently, we hypothesized that both fentanyl and morphine provide a greater reduction of dyspnea than placebo, and that fentanyl has less side effects than morphine.METHODS: We describe the design of a robust, multi-center, double blind, double-dummy, cross-over, randomized, placebo-controlled clinical trial with three study arms investigating transdermal fentanyl 12 mcg/h and morphine sustained-release 10 mg b.i.d. The primary endpoint is change in daily mean dyspnea sensation measured on a numeric rating scale. Secondary endpoints are change in daily worst dyspnea, QoL, anxiety, sleep quality, hypercapnia, side effects, patient preference, and continued opioid use. Sixty patients with severe stable COPD and refractory dyspnea (FEV1 &lt; 50%, mMRC ≥ 3, on optimal standard therapy) will be included.DISCUSSION: Evidence for opioids for refractory dyspnea in COPD is not as robust as usually appreciated. We designed a study comparing both the more commonly used opioid morphine, and transdermal fentanyl to placebo. The cross-over design will help to get a better impression of patient preferences. We believe our study design to investigate both sustained-release morphine and transdermal fentanyl for refractory dyspnea will provide valuable information for better treatment of refractory dyspnea in COPD. Trial registration NCT03834363 (ClinicalTrials.gov), registred at 7 Feb 2019, https://clinicaltrials.gov/ct2/show/NCT03834363 .</p