Negative Emotional Bias Research Articles

Disrupted limbic-prefrontal effective connectivity in response to fearful faces in lifetime depression

BackgroundMultiple brain imaging studies of negative emotional bias in major depressive disorder (MDD) have used images of fearful facial expressions and focused on the amygdala and the prefrontal cortex. The results have, however, been inconsistent, potentially due to small sample sizes (typically N<50). It remains unclear if any alterations are a characteristic of current depression or of past experience of depression, and whether there are MDD-related changes in effective connectivity between the two brain regions. MethodsActivations and effective connectivity between the amygdala and dorsolateral prefrontal cortex (DLPFC) in response to fearful face stimuli were studied in a large population-based sample from Generation Scotland. Participants either had no history of MDD (N=664 in activation analyses, N=474 in connectivity analyses) or had a diagnosis of MDD during their lifetime (LMDD, N=290 in activation analyses, N=214 in connectivity analyses). The within-scanner task involved implicit facial emotion processing of neutral and fearful faces. ResultsCompared to controls, LMDD was associated with increased activations in left amygdala (PFWE=0.031,kE=4) and left DLPFC (PFWE=0.002,kE=33), increased mean bilateral amygdala activation (β=0.0715,P=0.0314), and increased inhibition from left amygdala to left DLPFC, all in response to fearful faces contrasted to baseline. Results did not appear to be attributable to depressive illness severity or antidepressant medication status at scan time. LimitationsMost studied participants had past rather than current depression, average severity of ongoing depression symptoms was low, and a substantial proportion of participants were receiving medication. The study was not longitudinal and the participants were only assessed a single time. ConclusionsLMDD is associated with hyperactivity of the amygdala and DLPFC, and with stronger amygdala to DLPFC inhibitory connectivity, all in response to fearful faces, unrelated to depression severity at scan time. These results help reduce inconsistency in past literature and suggest disruption of ‘bottom-up’ limbic-prefrontal effective connectivity in depression.

The enhanced emotional negativity bias in parents of atypically developing children: Evidence from an event-related potentials study.

Parents of atypically developing children such as parents of children with ASD, attention deficit hyperactivity disorder, and intellectual disability experience higher levels of parenting stress than parents of typically developing children. However, whether they possess enhanced emotional negativity bias was unclear. In the present study, 28 parents of typically developing children and 29 parents of atypically developing children were recruited. The emotional Stroop task and event-related potentials were adopted to measure their emotional negativity bias, in which participants were required to respond to the borders' color of face pictures. Behaviorally, the impact of parenting stress on emotional negativity bias was not found. At the electrophysiological level, the P2 differential amplitude (negative minus positive) was greater in parents of atypically developing children than in parents of typically developing children, reflecting an enhanced early attentional bias toward negative faces. N2 amplitude for the emotionally negative face was smaller than the positive face in parents of atypically developing children, indicating a too weak attentional control to inhibit distractors. Furthermore, sustained attention to negative faces was observed in parents of atypically developing children, that is, the emotionally negative face elicited greater frontal P3 (300 ~ 500 ms) than the positive faces. These findings revealed that compared to parents of typically developing children, parents of atypically developing children owned an enhanced emotional negativity bias at the early and late stages of information processing.

The Effect of Negative Emotions on Sleep Procrastination Behaviours: Chain Mediation of Self-control and Time Management Tendencies

This study aims to research the effects of negative emotions on bedtime procrastination behaviors, with self-control and time management as chain mediating variables. Using relevant scales, a questionnaire survey was conducted among 300 participants. The results showed significant negative correlations between bedtime procrastination and negative emotional bias, self-control, and time management tendency. Mediation analysis indicated that, Controlling for gender and age., negative emotions significantly positively predict bedtime procrastination. The significant mediating role of time management tendency, and Interlocking mediating effects of self-control and time management tendencies is significant. In essence, individuals with high levels of negative emotions are more likely to engage in bedtime procrastination behaviors and negative emotions can lead to bedtime procrastination behaviors by affecting self-control and time management tendencies.

60 Recognition of Emotional Words: Relationship Between Rumination, Depression, Objective and Subjective Cognitive Impairment

Objective:Cognitive impairment in depression could present as subjective and objective, but the intensity of subjective impairment is higher and is not correlated with the deficits measured by neuropsychological tests. Subjective cognitive impairment lowers quality of life and is associated with the severity of depression. Among depressive patients, negative emotional bias is present. It is better memory for negative or positive information than for neutral information. We hypothesized that rumination is associated with subjective cognitive impairment.Participants and Methods:The study was performed through the online PsyToolkit platform. The study sample consisted of 168 healthy controls and 93 patients with depression were enrolled in the study. Participants completed questionnaires and performed a memory task that contained emotional words. The forty words were chosen from the Nencki Affective Word List. The list for memory test consists of 5 words from each Category: Happiness, Anger, Fear, Sad, Disgusting, and Neutral, and 10 words from category ‘Unclassified’ to balance the valence and arousal of the set. After 15 minutes, they recognized old words from the list of 80 words. Half of them were the same as in the first part, and other words were new, chosen with the same criteria. Depression symptoms were measured using the Beck Depression Inventory-II, subjective cognitive impairment with the Perceived Deficits Questionnaire-20, and intensity of rumination with the Polish Questionnaire of Rumination.Results:Subjective cognitive impairment and rumination were higher in patients with depression. They also had a higher error rate than healthy controls U = 6462.5; p = .021, especially in words from the neutral (U = 6292; p = .008) and happiness category (U = 6585; p = .031). However, there was no association between subjective cognitive impairment and performance in memory tasks. The regression analysis showed that depressive symptoms and intensity of rumination are better predictors of subjective cognitive deficits than objective performance on a memory task. The results of PDQ-20 were correlated with the error rate of words from categories: Happiness (r = -.162**), Sad (r = -.116*) and Neutral (r = -.145**). Words from categories Happiness, Disgust and Neutral were significantly better recognized than Unclassified, Fear or Sad group of words χ 2 F (6) = 132.685; p &lt; .001. In MDD group recognition of Disgust words were statistically highest than Anger and Fear words χ 2 F (6) = 36.795; p &lt; .001. The recognition of Happiness and Neutral word were not significantly different to other words.Conclusions:Cognitive problems are common in depression and affect quality of life. Subjective cognitive impairment is more closely related to rumination than objective cognitive impairment among healthy participants and patients with major depressive disorder. Emotional bias among depressive patients has been partially confirmed. Emotional impact is important for memory of words and subjective perception of cognition.

The neural correlation of emotion recognition ability and depressive symptoms-evidence from the HCP database.

Negative bias of emotional face is the core feature of depression, but its underlying neurobiological mechanism is still unclear. The neuroimaging findings of negative emotional recognition and depressive symptoms are inconsistent. The neural association between depressive symptoms and negative emotional bias were analyzed by measuring the associations between resting state functional connectivity (FC), brain structures, negative emotional bias, and depressive problems. Then, we performed a mediation analysis to assess the potential overlapping neuroimaging mechanisms. We found a negative correlation between depressive symptoms and emotional recognition. Secondly, the structure and function of the inferior and lateral orbitofrontal gyrus are related to depressive symptoms and emotional recognition. Thirdly, the thickness of the inferior orbitofrontal cortex and the FC between the inferior orbitofrontal gyrus and fusiform gyrus, precuneate and cingulate gyrus mediated and even predicted the interaction between emotion recognition and depressive symptoms. Finally, in response to a negative stimulus, the activation of the frontal pole and precuneus lobe associated with the inferior orbitofrontal gyrus was higher in participants with depressive symptoms. The core brain regions centered on the inferior orbitofrontal cortex such as middle temporal gyrus, precuneus lobe, frontal pole, insula and cingulate gyrus are the potential neuroimaging basis for the interaction between depressive symptoms and emotional recognition.

Binge drinking indirectly predicts a negative emotional memory bias through coping motivations and depressive symptoms: The role of sex/gender.

In this three-part study, we investigate whether the associations between binge and problematic drinking patterns with a negative emotional memory bias (NMB) are indirectly related through coping motivations and depressive symptoms. We also address potential sex differences in these relations. Participants (N = 293) completed the Timeline Followback to assess binge drinking, the Alcohol Use Disorder Identification Test (AUDIT) to assess problematic alcohol use, the Drinking Motives Questionnaire-Revised to assess coping motivations, and the Depression, Anxiety, and Stress Scales-21 to assess depression. Participants were asked to identify whether 30 emotional sentences were self-referent or not in an incidental encoding task; 24 h later they were asked to recall as many sentences as possible and a negative memory bias score was calculated. Across all three studies, we found significant bivariate relations between AUDIT scores, coping, depression, and an NMB, particularly for sentences participants deemed self-referent. In two undergraduate samples, there were significant indirect effects through coping motivations and depressive symptoms between binge drinking and an NMB in females as well as between AUDIT scores and an NMB in females only. In the community sample, there was only an indirect effect through coping motives, but this was observed in both females and males. These findings support a relation between binge drinking as well as problematic alcohol use and a self-referent NMB in the context of coping motivations for alcohol use and depressive symptoms. Moreover, the pattern of findings suggests this model primarily holds for females, yet may also apply to males at higher levels of problematic alcohol use.

Decoding of Processing Preferences from Language Paradigms by Means of EEG-ERP Methodology: Risk Markers of Cognitive Vulnerability for Depression and Protective Indicators of Well-Being? Cerebral Correlates and Mechanisms

Depression is a frequent mental affective disorder. Cognitive vulnerability models propose two major cognitive risk factors that favor the onset and severity of depressive symptoms. These include a pronounced self-focus, as well as a negative emotional processing bias. According to two-process models of cognitive vulnerability, these two risk factors are not independent from each other, but affect information processing already at an early perceptual processing level. Simultaneously, a processing advantage for self-related positive information including better memory for positive than negative information has been associated with mental health and well-being. This perspective paper introduces a research framework that discusses how EEG-ERP methodology can serve as a standardized tool for the decoding of negative and positive processing biases and their potential use as risk markers of cognitive vulnerability for depression, on the one hand, and as protective indicators of well-being, on the other hand. Previous results from EEG-ERP studies investigating the time-course of self-referential emotional processing are introduced, summarized, and discussed with respect to the specificity of depression-related processing and the importance of EEG-ERP-based experimental testing for well-being and the prevention and treatment of depressive disorders.

Cold Cognition as Predictor of Treatment Response to rTMS; A Retrospective Study on Patients With Unipolar and Bipolar Depression

BackgroundCognitive impairments are prevalent in patients with unipolar and bipolar depressive disorder (UDD and BDD, respectively). Considering the fact assessing cognitive functions is increasingly feasible for clinicians and researchers, targeting these problems in treatment and using them at baseline as predictors of response to treatment can be very informative.MethodIn a naturalistic, retrospective study, data from 120 patients (Mean age: 33.58) with UDD (n = 56) and BDD (n = 64) were analyzed. Patients received 20 sessions of bilateral rTMS (10 Hz over LDLPFC and 1 HZ over RDLPFC) and were assessed regarding their depressive symptoms, sustained attention, working memory, and executive functions, using the Beck Depression Inventory (BDI-II) and Neuropsychological Test Automated Battery Cambridge, at baseline and after the end of rTMS treatment course. Generalized estimating equations (GEE) and logistic regression were used as the main statistical methods to test the hypotheses.ResultsFifty-three percentage of all patients (n = 64) responded to treatment. In particular, 53.1% of UDD patients (n = 34) and 46.9% of BDD patients (n = 30) responded to treatment. Bilateral rTMS improved all cognitive functions (attention, working memory, and executive function) except for visual memory and resulted in more modulations in the working memory of UDD compared to BDD patients. More improvements in working memory were observed in responded patients and visual memory, age, and sex were determined as treatment response predictors. Working memory, visual memory, and age were identified as treatment response predictors in BDD and UDD patients, respectively.ConclusionBilateral rTMS improved cold cognition and depressive symptoms in UDD and BDD patients, possibly by altering cognitive control mechanisms (top-down), and processing negative emotional bias.

Interoception Dysfunction Contributes to the Negative Emotional Bias in Major Depressive Disorder.

BackgroundPrevious research studies have demonstrated that impaired interoception is involved in emotional information processing in major depressive disorder (MDD). Heartbeat-evoked potential (HEP) amplitudes, an index for interoception, could be manipulated by emotional faces in healthy people. Considering negative emotional bias is the core characteristic in MDD, we hypothesized that interoception dysfunction was associated with the negative emotional bias in MDD.MethodsAn electroencephalogram (EEG) study under an emotional faces task was applied to explore the relationship between interoception and emotional bias. HEPs before emotional faces stimuli were used to predict the late positive potential (LPP) amplitudes and it worked as an index of emotional bias. Twenty-seven patients with MDD and 27 healthy controls (HCs) participated in this study. Source analysis gave an auxiliary description for results in sensory level.ResultsMajor depressive disorders (MDDs) had poor performance in the heartbeat count task (HCT) and attenuate HEP average amplitudes (455–550 ms). Compared with HCs, cluster-based permutation t-tests revealed that MDDs had attenuated LPP amplitudes (300–1,000 ms) over centroparietal regions and enhanced LPP amplitudes over frontocentral regions. Furthermore, abnormal attenuated HEPs could predict aberrant LPPs under sad face stimuli in MDDs, which could be associated with the dysfunction of the anterior cingulate cortex (ACC) and right insula.ConclusionMediated by ACC and insula, interoception dysfunction contributes to the negative emotional bias of MDD, highlighting the importance of interoception in the disorder.

Assessing Interpersonal Relationships in Medical Education: the Connection Index.

The relationship between a resident physician and his/her supervising attending is foundational to graduate medical education and may impact the clinical learning environment and resident well-being. This paper focuses on how to measure connection between a resident and their clinical supervisor. Connection includes the subdomains of psychological safety, empathy, educational alliance, and feedback. After reviewing the literature, the authors designed the 12-item, 7-point Connection Index (CI12) to quantitatively measure connections between a resident and his/her supervisor during a 6-month period (supervision dyad), and based on educational alliance, empathy, psychological safety, and effective feedback. A 9-criteria evaluation framework was applied to assess its reliability and validity on a sample of psychiatry residents at a residency program, July 2016 through June 2018. Out of a total possible number of 50 residents, 100% participated to rate 41 supervisors over 201 supervision dyads; the CI12 satisfied all eight of the eight testable criteria, including high scalability (H = 0.78), consistency (alpha = 0.98), test-retest validity (ICC = 0.95), and construct validity where CI12 was found to have statistically significant correlations with outcomes measures (greater connection was associated with less negative emotional experiences, less mistreatment or bias, less burnout, and higher attendance to supervision sessions). The authors showed the CI12 can be a valid and reliable instrument to quantify whether a resident and his/her supervisor connects during a 6-month supervision with respect to empathy, psychological safety, educational alliance, and feedback. We recommend assessing connections as part of the overall evaluation of a resident's experience with the clinical learning environment.

Negative bias effects during audiovisual emotional processing in major depression disorder.

Aberrant affective neural processing and negative emotional bias are trait‐marks of major depression disorders (MDDs). However, most research on biased emotional perception in depression has only focused on unimodal experimental stimuli, the neural basis of potentially biased emotional processing of multimodal inputs remains unclear. Here, we addressed this issue by implementing an audiovisual emotional task during functional MRI scanning sessions with 37 patients with MDD and 37 gender‐, age‐ and education‐matched healthy controls. Participants were asked to distinguish laughing and crying sounds while being exposed to faces with different emotional valences as background. We combined general linear model and psychophysiological interaction analyses to identify abnormal local functional activity and integrative processes during audiovisual emotional processing in MDD patients. At the local neural level, MDD patients showed increased bias activity in the ventromedial prefrontal cortex (vmPFC) while listening to negative auditory stimuli and concurrently processing visual facial expressions, along with decreased dorsolateral prefrontal cortex (dlPFC) activity in both the positive and negative visual facial conditions. At the network level, MDD exhibited significantly decreased connectivity in areas involved in automatic emotional processes and voluntary control systems during perception of negative stimuli, including the vmPFC, dlPFC, insula, as well as the subcortical regions of posterior cingulate cortex and striatum. These findings support a multimodal emotion dysregulation hypothesis for MDD by demonstrating that negative bias effects may be facilitated by the excessive ventral bottom‐up negative emotional influences along with incapability in dorsal prefrontal top‐down control system.

Recall and Self-Relevance of Emotional Words Predict Subjective Self-Evaluation of Cognition in Patients with MTLE with or without Depressive Symptoms.

We examined whether word processing is associated with subjective self-evaluation of cognition in patients with mesial temporal lobe epilepsy (MTLE) as a function of their depressive symptoms. MTLE patients with (MTLE +d, N = 28) or without (MTLE -d, N = 11) depression were compared to pair-matched healthy control participants on free recall and self-relevance ratings of emotionally valenced words. Correlation and hierarchical analyses were conducted to investigate whether the subjective self-evaluation of cognition in MTLE patients is predicted by the negative emotional bias reflected in task performance. MTLE +d patients endorsed as self-relevant fewer positive words and more negative words than the MTLE -d patients and healthy participants. They also self-evaluated their cognition poorer than the MTLE -d patients. Analyses indicated that recall and self-endorsement of emotional words predicted both self-evaluation of cognition as well as epilepsy duration. Our findings indicate that negative self-relevance emotional bias is observed in MTLE patients and is predictive of subjective self-evaluation of cognition. Application of brief behavioral tasks probing emotional functions could be valuable for clinical research and practice in the patients with MTLE.

Altered effective connectivity of the extended face processing system in depression and its association with treatment response: findings from the YoDA-C randomized controlled trial.

Depression is commonly associated with fronto-amygdala dysfunction during the processing of emotional face expressions. Interactions between these regions are hypothesized to contribute to negative emotional processing biases and as such have been highlighted as potential biomarkers of treatment response. This study aimed to investigate depression associated alterations to directional connectivity and assess the utility of these parameters as predictors of treatment response. Ninety-two unmedicated adolescents and young adults (mean age 20.1; 56.5% female) with moderate-to-severe major depressive disorder and 88 healthy controls (mean age 19.8; 61.4% female) completed an implicit emotional face processing fMRI task. Patients were randomized to receive cognitive behavioral therapy for 12 weeks, plus either fluoxetine or placebo. Using dynamic causal modelling, we examined functional relationships between six brain regions implicated in emotional face processing, comparing both patients and controls and treatment responders and non-responders. Depressed patients demonstrated reduced inhibition from the dlPFC to vmPFC and reduced excitation from the dlPFC to amygdala during sad expression processing. During fearful expression processing patients showed reduced inhibition from the vmPFC to amygdala and reduced excitation from the amygdala to dlPFC. Response was associated with connectivity from the amygdala to dlPFC during sad expression processing and amygdala to vmPFC connectivity during fearful expression processing. Our study clarifies the nature of face processing network alterations in adolescents and young adults with depression, highlighting key interactions between the amygdala and prefrontal cortex. Moreover, these findings highlight the potential utility of these interactions in predicting treatment response.

Mapping Neural Circuit Biotypes to Symptoms and Behavioral Dimensions of Depression and Anxiety

BackgroundDespite tremendous advances in characterizing human neural circuits that govern emotional and cognitive functions impaired in depression and anxiety, we lack a circuit-based taxonomy for depression and anxiety that captures transdiagnostic heterogeneity and informs clinical decision making. MethodsWe developed and tested a novel system for quantifying 6 brain circuits reproducibly and at the individual patient level. We implemented standardized circuit definitions relative to a healthy reference sample and algorithms to generate circuit clinical scores for the overall circuit and its constituent regions. ResultsIn new data from primary and generalizability samples of depression and anxiety (N = 250), we demonstrated that overall disconnections within task-free salience and default mode circuits map onto symptoms of anxious avoidance, loss of pleasure, threat dysregulation, and negative emotional biases—core characteristics that transcend diagnoses—and poorer daily function. Regional dysfunctions within task-evoked cognitive control and affective circuits may implicate symptoms of cognitive and valence-congruent emotional functions. Circuit dysfunction scores also distinguished response to antidepressant and behavioral intervention treatments in an independent sample (n = 205). ConclusionsOur findings articulate circuit dimensions that relate to transdiagnostic symptoms across mood and anxiety disorders. Our novel system offers a foundation for deploying standardized circuit assessments across research groups, trials, and clinics to advance more precise classifications and treatment targets for psychiatry.

Acute Time-Locked Alpha Frequency Subthalamic Stimulation Reduces Negative Emotional Bias in Parkinson’s Disease

BackgroundEmotional processing is a core cognitive process cutting across neuropsychiatric disorders. Understanding the neurophysiological features underlying depressive symptoms and their sensitivity to modulation is critical to modifying emotional bias. The subthalamic nucleus (STN), targeted in Parkinson’s disease, shows a late alpha desynchronization to affective stimuli. We targeted this alpha desynchronization using a novel stimulation protocol asking if brief alpha (10 Hz) frequency stimulation time-locked to unpleasant imagery might influence subjective emotion. MethodsA total of 27 patients with Parkinson’s disease were recruited. The first study tested patients (n = 16) on affective stimuli with STN local field potential recordings assessed bilaterally without stimulation. In the second study, patients (n = 24) were tested on two affective tasks comparing negative and neutral stimuli paired with acute right-STN stimulation, with one of the negative conditions stimulated briefly for 1 second at either 130 Hz or 10 Hz. The subjects rated valence and arousal of negative and neutral stimuli. ResultsWe confirmed greater alpha desynchronization in both negative and positive affect relative to neutral in the right STN. Using acute stimulation of the right STN, we show a critical interaction effect between ratings, stimulation, and frequency; alpha frequency stimulation increased the subjective pleasantness of negative imagery, particularly with ventromedial contacts. Higher depression scores were associated with a positive bias to 10-Hz but not 130-Hz stimulation. ConclusionsWe highlight the potential of brief alpha frequency subthalamic stimulation to reduce negative emotional bias. This finding provides mechanistic insights underlying subjective emotional valence and has implications for the management of depression using neuromodulation.

Regulatory Effects of Reward Anticipation and Target on Attention Processing of Emotional Stimulation.

Studies suggest that reward and emotion are interdependent. However, there are discrepancies regarding the interaction between these variables. Some researchers speculate that the inconsistent findings may be due to different targets being used. Although reward and emotion both affect attention, it is not clear whether their impacts are independent. This study examined the impact of reward anticipation on emotion processing for different targets. A cue-target paradigm was used, and behavior and eye-tracking data were recorded in an emotion or sex recognition task under the conditions of reward and non-reward anticipation. The results showed that when the target was related to the emotional attribute of the stimulus, the reward promoted the processing target information, thereby generating reward-oriented attention. When the target was unrelated to the emotional attributes of the stimulus, the reward did not promote the processing target information, and at the same time, individuals had negative emotional biases toward the emotional faces. The results revealed that, in addition to affecting the attention to emotional faces independently, the target regulated the promotion of reward anticipation to emotional attention and attention bias toward negative stimuli.

The impact of five nights of sleep restriction on emotional reactivity.

An inadequate amount of sleep can negatively affect emotional processing, causing behavioural and neurofunctional changes. However, unlike the condition of total sleep deprivation, which has been extensively studied, the effects of prolonged sleep restriction have received less attention. In this study, we evaluated, for the first time, the effects of five nights of sleep restriction (5hr a night) on emotional reactivity in healthy subjects. Forty-two subjects were selected to participate, over two consecutive weeks, in two experimental conditions in counterbalanced order. The subjects were tested the morning after five nights of regular sleep and after five consecutive nights of sleep restriction. During the test, participants evaluated valence and arousal of 90 images selected from the International Affective Picture System. The subjects perceived pleasant and neutral pictures in a more negative way in the sleep-restriction condition compared to the sleep condition. This effect survived after removing the contribution of mood changes. In contrast, there was no significant difference between conditions for ratings of unpleasant pictures. These results provide the first evidence that an inadequate amount of sleep for five consecutive nights determines an alteration of the evaluation of pleasant and neutral stimuli, imposing a negative emotional bias. Considering the pervasiveness of insufficient sleep in modern society, our results have potential implications for daily life, as well as in clinical settings.

Sex differences in emoji use, familiarity, and valence

Emojis (particularly smiley emojis, ☺) are increasingly used in computer-mediated communication as well as in applied domains within marketing, healthcare, and psychology. The emotional negativity bias in the facial emotion processing literature posits that women are more sensitive to negative facial emotion than are men. Given the similarity in neural processing between human faces and smiley emojis, women may likewise view negative smiley emojis as more negative than do men. Moreover, the familiarity of the emoji and the participants' overall emoji use may increase the positivity of the emoji. To investigate these potential influences of sex, familiarity, and emoji use on the valence of smiley emojis, we assessed the familiarity and the perceived valence for 70 iOS facial emojis in a large sample (N = 299; 163 women) of United States college students (Mage = 19.66, SDage = 2.72). Results indicated higher emoji usage and familiarity ratings for women than for men. In assessing valence we found higher overall positive ratings for men than for women. Consistent with the emotional negativity bias, this sex difference was limited to the negative smiley emojis with no sex difference in valence for the positive emojis. The obtained sex differences in smiley emojis’ use, familiarity, and valence are an important consideration in the selection of such stimuli in future studies.

Emotional recognition training modifies neural response to emotional faces but does not improve mood in healthy volunteers with high levels of depressive symptoms.

There is demand for new, effective and scalable treatments for depression, and development of new forms of cognitive bias modification (CBM) of negative emotional processing biases has been suggested as possible interventions to meet this need. We report two double blind RCTs, in which volunteers with high levels of depressive symptoms (Beck Depression Inventory ii (BDI-ii) > 14) completed a brief course of emotion recognition training (a novel form of CBM using faces) or sham training. In Study 1 (N = 36), participants completed a post-training emotion recognition task whilst undergoing functional magnetic resonance imaging to investigate neural correlates of CBM. In Study 2 (N = 190), measures of mood were assessed post-training, and at 2-week and 6-week follow-up. In both studies, CBM resulted in an initial change in emotion recognition bias, which (in Study 2) persisted for 6 weeks after the end of training. In Study 1, CBM resulted in increases neural activation to happy faces, with this effect driven by an increase in neural activity in the medial prefrontal cortex and bilateral amygdala. In Study 2, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias at either 2 or 6-week follow-ups. CBM of emotion recognition has effects on neural activity that are similar in some respects to those induced by Selective Serotonin Reuptake Inhibitors (SSRI) administration (Study 1), but we find no evidence that this had any later effect on self-reported mood in an analogue sample of non-clinical volunteers with low mood (Study 2).

Mapping Neural Circuit Biotypes to Symptoms and Behavioral Dimensions of Depression and Anxiety

Background: Despite tremendous advances in characterizing human brain circuits that govern emotional and cognitive functions that are impaired in depression and anxiety, we lack a circuitbased taxonomy that captures transdiagnostic heterogeneity and informs clinical decision making. Methods: We develop and test a novel system for quantifying six brain circuits reproducibly and at the individual patient level. We implement standardized circuit definitions relative to a healthy reference group, and algorithms to generate circuit function and dysfunction scores for the overall circuit and its constituent regions. Outcomes: In primary and generalizability samples of depression and anxiety (n=251) we demonstrate that overall disconnections within task-free salience and default mode circuits map onto symptoms of anxious avoidance, loss of pleasure, threat dysregulation, and negative emotional biases – core characteristics that transcend diagnoses – and poorer daily function. Regional dysfunctions within task-evoked cognitive control and affective circuits implicate more specific cognitive symptoms and valence-congruent behavioral disruptions. Circuit dysfunction scores also predict response to pharmacological and behavioral therapies in an independent sample (n=207). Interpretation: Our findings articulate circuit dimensions that parse the heterogeneity of depression and anxiety and have direct clinical translational significance. Our novel system offers a foundation for deploying standardized circuit assessments across research groups, trials and clinics to advance more precise classifications and treatment targets for psychiatry. Funding: This work was supported by the National Institutes of Health [grant numbers R01MH101496 (LMW), UH2HL132368 (JM, LMW), F32MH108299 (ANG-P), T32MH019938 (TMB), and K23MH113708 (TMB)]. Declaration of Interests: LMW declares US Pants. App. 10/034,645 and 15/820,338: Systems and methods for detecting complex networks in MRI image data. ANG-P, TMB, ZS, KAG, SLF, ASK, BRS, and BHG declare no competing interests. Ethics Approval Statement: All procedures were approved by the Stanford University Institutional Review Board (IRB 27937 and 41837) or Western Sydney Area Health Service Human Research Ethics Committee. All participants provided written informed consent prior to study procedures.