Emotional Face Processing Task Research Articles

Alterations in Neural Activation During Facial Emotion Processing in Adolescent Male Participants With Klinefelter Syndrome.

Klinefelter syndrome (KS) is the most common sex-chromosome aneuploidy (47,XXY), affecting 1 in 500 male participants. The phenotype of male participants with KS includes both physical features, such as tall stature and testicular insufficiency, and behavioral alterations, including difficulties in social functioning, anxiety, and depression. Studies examining underlying neural alterations associated with the behavioral phenotype, however, are sparse. We aimed to address this gap in knowledge using functional magnetic resonance imaging in conjunction with an emotion processing paradigm. Functional magnetic resonance imaging was conducted on 38 children and adolescents with KS ( Mage = 12.85, SD = 2.45) and 47 typical developing (control) boys ( Mage = 12.04, SD = 1.82) as they completed a facial emotion processing task. Group differences in activation occurring during the processing of angry versus neutral faces were examined while controlling for age. The results indicated that relative to typically developing boys, boys with KS exhibited anomalous increases in activation of frontal, temporal, and occipital cortices. Within the KS group, secondary analyses indicated that greater activation in these regions was associated with more internalizing symptoms (e.g., anxiety, depression, withdrawn behaviors) and greater social impairments (e.g., social cognition, social communication, social motivation, social communication and interaction, functional communication). The findings from this study indicate a possible neural correlation for difficulties in social and emotional function in KS and add to a growing body of research aimed at increasing our understanding of neural biomarkers in this condition. Future studies that examine the influence of testosterone-replacement therapy on these differences are warranted.

Adjunctive cognitive training with exposure enhances fear and neural outcomes in social anxiety

Exposure-based cognitive behavioral therapy (CBT) is the gold standard for treating social anxiety disorder (SAD), yet response is not universal. CBT is thought to operate via extinction-related learning during exposure, which in turn relies on cognitive processes such as working memory. The present proof-of-concept study investigates the potential for training working memory to improve anxiety related outcomes following exposure. Thirty-three adults with elevated social anxiety were randomized to complete a working memory training or sham training condition. Post-training, participants completed a working memory assessment, speech exposure session, and two fMRI tasks. Participants who received working memory training demonstrated lower distress ratings by the end of the speech exposures and better performance on the fMRI working memory task than those in sham. Working memory training completers had greater neural activation in frontoparietal regions during an in-scanner working memory task and exhibited less neural activation in the fusiform gyrus in response to an emotional face processing task than those in sham. Adding working memory training to exposure procedures could strengthen functioning of frontoparietal regions and alter emotional processing - key mechanisms implicated in extinction learning. Findings provide preliminary evidence that training working memory in conjunction with exposure may enhance exposure success.

EEG alpha band functional connectivity reveals distinct cortical dynamics for overt and covert emotional face processing

Current knowledge regarding how the focus of our attention during face processing influences neural responses largely comes from neuroimaging studies reporting on regional brain activations. The present study was designed to add novel insights to this research by studying how attention can differentially impact the way cortical regions interact during emotional face processing. High-density electroencephalogram was recorded in a sample of fifty-two healthy participants during an emotional face processing task. The task required participants to either attend to the expressions (i.e., overt processing) or attend to a perceptual distractor, which rendered the expressions task-irrelevant (i.e., covert processing). Functional connectivity in the alpha band was estimated in source space and modeled using graph theory to quantify whole-brain integration and segregation. Results revealed that overt processing of facial expressions is linked to reduced cortical segregation and increased cortical integration, this latter specifically for negative expressions of fear and sadness. Furthermore, we observed increased communication efficiency during overt processing of negative expressions between the core and the extended face processing systems. Overall, these findings reveal that attention makes the interaction among the nodes involved in face processing more efficient, also uncovering a connectivity signature of the prioritized processing mechanism of negative expressions, that is an increased cross-communication within the nodes of the face processing network.

Guilt by Association: Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders

Guilt by Association: Inflammation and Shared Genetic Risk Between Stress-Related and Immune Disorders

Atypical oscillatory dynamics during emotional face processing in paediatric obsessive–compulsive disorder with MEG

Children and youth with obsessive–compulsive disorder (OCD) demonstrate difficulties with social, emotional and cognitive functions in addition to the core diagnosis of obsessions and compulsions. This is the first magnetoencephalography (MEG) study to examine whole-brain neurophysiological functional connectivity of emotional face processing networks in paediatric OCD. Seventy-two participants (OCD: n = 36; age 8–17 yrs; typically developing controls: n = 36, age 8–17 yrs) completed an implicit emotional face processing task in the MEG. Functional connectivity networks in canonical frequency bands were compared between groups, and within OCD and control groups between emotions (angry vs. happy). Between groups, participants with OCD showed increased functional connectivity in the gamma band to angry faces, suggesting atypical perception of angry faces in OCD. Within groups, the OCD group showed greater engagement of the beta band, suggesting the over-use of top-down processing when perceiving happy versus angry emotions, while controls engaged in bottom-up gamma processing, also greater to happy faces. Over-activation of top-down processing has been linked to difficulties modifying one’s cognitive set. Findings establish altered patterns of neurophysiological connectivity in children with OCD, and are striking in their oscillatory specificity. Our results contribute to a greater understanding of the neurobiology of the disorder, and are foundational for the possibility of alternative targets for intervention.

The genetics of ME: A commentary on Hajdarevic et al.

Depression is characterized by altered neurobiological responses to threat and inflammation may be involved in the development and maintenance of symptoms. However, the mechanistic pathways underlying the relationship between the neural underpinnings of threat, inflammation and depressive symptoms remain unknown.Twenty participants with major depressive disorder (MDD) and 17 healthy controls (HCs) completed this study. Peripheral blood mononuclear cells (PBMCs) were collected and stimulated ex vivo with lipopolysaccharide (LPS). We then measured a broad array of secreted proteins and performed principal component analysis to compute an aggregated immune reactivity score. Subjects completed a well-validated emotional face processing task during functional magnetic resonance imaging (fMRI). Amygdala activation was measured during perception of threat for the main contrast of interest: fear > happy face. Participants completed the Mood and Anxiety Symptom Questionnaire (MASQ) and the Perceived Stress Scale (PSS). Correlation analyses between amygdala activation, the aggregate immune score, and symptom were computed across groups. A mediation analysis was also performed across groups to further explore the relationship between these three variables.In line with our hypotheses and with prior work, the MDD group showed greater amygdala activation in response to threat compared to the HC group [t35 = -2.038, p = 0.049]. Internal consistency of amygdala activation to threat was found to be moderate. Response to an ex vivo immune challenge was greater in MDD than HC based on the computed immune reactivity score (PC1; t35 = 2.674, p = 0.011). Amygdala activation was positively correlated with the immune score (r = 0.331, p = 0.045). Moreover, higher amygdala activation was associated with greater anxious arousal measured by the MASQ (r = 0.390, p = 0.017). Exploring the role of stress, we found that higher perceived stress was positively associated with both inflammatory response (r = 0.367, p = 0.026) and amygdala response to threat (r = 0.325, p = 0.050). Mediation analyses showed that perceived stress predicted anxious arousal, but neither inflammation nor amygdala activation fully accounted for the effect of perceived stress on anxious arousal.These data highlight the potential importance of threat circuitry hyperactivation in MDD, consistent with prior reports. We found that higher levels of inflammatory biomarkers were associated with higher amygdala activation, which in turn was associated with anxious arousal. Future research utilizing larger sample sizes are needed to replicate these preliminary results.

Exaggerated amygdala response to threat and association with immune hyperactivity in depression

BackgroundDepression is characterized by altered neurobiological responses to threat and inflammation may be involved in the development and maintenance of symptoms. However, the mechanistic pathways underlying the relationship between the neural underpinnings of threat, inflammation and depressive symptoms remain unknown. MethodsTwenty participants with major depressive disorder (MDD) and 17 healthy controls (HCs) completed this study. Peripheral blood mononuclear cells (PBMCs) were collected and stimulated ex vivo with lipopolysaccharide (LPS). We then measured a broad array of secreted proteins and performed principal component analysis to compute an aggregated immune reactivity score. Subjects completed a well-validated emotional face processing task during functional magnetic resonance imaging (fMRI). Amygdala activation was measured during perception of threat for the main contrast of interest: fear > happy face. Participants completed the Mood and Anxiety Symptom Questionnaire (MASQ) and the Perceived Stress Scale (PSS). Correlation analyses between amygdala activation, the aggregate immune score, and symptom were computed across groups. A mediation analysis was also performed across groups to further explore the relationship between these three variables. ResultsIn line with our hypotheses and with prior work, the MDD group showed greater amygdala activation in response to threat compared to the HC group [t35 = -2.038, p = 0.049]. Internal consistency of amygdala activation to threat was found to be moderate. Response to an ex vivo immune challenge was greater in MDD than HC based on the computed immune reactivity score (PC1; t35 = 2.674, p = 0.011). Amygdala activation was positively correlated with the immune score (r = 0.331, p = 0.045). Moreover, higher amygdala activation was associated with greater anxious arousal measured by the MASQ (r = 0.390, p = 0.017). Exploring the role of stress, we found that higher perceived stress was positively associated with both inflammatory response (r = 0.367, p = 0.026) and amygdala response to threat (r = 0.325, p = 0.050). Mediation analyses showed that perceived stress predicted anxious arousal, but neither inflammation nor amygdala activation fully accounted for the effect of perceived stress on anxious arousal. ConclusionThese data highlight the potential importance of threat circuitry hyperactivation in MDD, consistent with prior reports. We found that higher levels of inflammatory biomarkers were associated with higher amygdala activation, which in turn was associated with anxious arousal. Future research utilizing larger sample sizes are needed to replicate these preliminary results.

Neural alterations of emotion processing in atypical trajectories of psychotic-like experiences

The aim of this study was to investigate the neural bases of facial emotion processing before the onset of clinical psychotic symptoms in youth belonging to well-defined developmental trajectories of psychotic-like experiences (PLEs). A unique sample of 86 youths was recruited from a population-based sample of over 3800 adolescents who had been followed from 13 to 17 years of age. Three groups were identified based on validated developmental trajectories: a control trajectory with low and decreasing PLEs, and two atypical trajectories with moderate to elevated baseline PLEs that subsequently decreased or increased. All had functional magnetic resonance imaging data collected during a facial emotion processing task. Functional activation and connectivity data were analyzed for different contrasts. The increasing PLE trajectory displayed more positive psychotic symptoms while the decreasing trajectory exhibited more negative symptoms relative to the control group. During face processing, both atypical trajectories displayed decreased activations of the right inferior frontal gyrus (IFG), while the increasing trajectory displayed a negative signal in the precentral gyrus. The increasing PLE trajectory also displayed impaired connectivity between the amygdala, ventromedial prefrontal cortex, and cerebellum, and between the IFG, precuneus, and temporal regions, while the decreasing trajectory exhibited reduced connectivity between the amygdala and visual regions during emotion processing. Both atypical PLE trajectories displayed alterations in brain regions involved in attention salience. While the increasing trajectory with more positive symptoms exhibited dysconnectivity in areas that influence emotion salience and face perception, the decreasing trajectory with more negative symptoms had impairments in visual information integration areas. These group-specific features might account for the differential symptom expression.

Context-dependent amygdala-prefrontal connectivity in youths with autism spectrum disorder

BackgroundThe amygdala-prefrontal cortex circuit is involved in processing socio-emotional cues and may partially mediate social impairment in autism spectrum disorder (ASD). Past task-based fMRI studies in ASD indicate a mix of hypo- and hyper-connectivity in response to socio-emotional stimuli whereas resting state studies report hypoconnectivity between these regions. However, it is still unknown whether ASD-related alterations in amygdala-prefrontal circuitry are present across socio-emotional tasks and resting state contexts within the same sample or instead, depend on context. MethodASD (n = 47) and typically developing individuals (TD; n = 72) underwent fMRI during an implicit emotional face processing task and during rest, and whole-brain amygdala connectivity was calculated to determine patterns that differed by context and diagnosis. ResultsRelative to TD, the ASD group demonstrated weaker left amygdala connectivity with the medial frontal gyrus and the left superior frontal gyrus during rest, but stronger connectivity during task. Furthermore, across both contexts, ASD vs. TD had stronger right amygdala connectivity with the left insula/superior temporal gyrus. ConclusionFindings suggest some alterations in amygdala connectivity of ASD may depend on context while others are pervasive across task and rest conditions. Understanding context-dependent brain alterations in ASD may help disambiguate the mechanisms subserving social impairment and provide targets for treatment.

Chronotype and time of day effects on verbal and facial emotional Stroop task performance in adolescents

ABSTRACT This study investigated chronotype and time of day effects on lexical and facial emotion processing tasks and explored relationships with sleep quality and mental health outcomes. Participants were 351 Taiwanese adolescents (204 males) aged 13 to 16 years of age who completed both a Facial-Emotional Stroop and a Lexical-Emotional Stroop task at 08:00–10:00 am or at 14:00–16:00 pm. Chronotype was measured using the Morningness-Eveningness Questionnaire (MEQ) and grouped into Morning (n = 46), Intermediate (n = 248) or Evening types (n = 57). Participants completed validated measures of sleep quality (PSQI) and mental health difficulties (DASS-21). The study observed independent effects of time of day and chronotype on the Facial-Emotional Stroop task. Independent of chronotype group, delayed reaction times to anger stimuli were observed in adolescents tested in the morning. Younger adolescents with an Evening chronotype showed delayed responses to anger faces independent of the time of testing. Facial-Emotional Stroop task performance correlated with reported sleep quality and mental health only in Evening chronotypes, with attenuated responses to anger versus neutral stimuli associated with poorer sleep quality and worse mental health outcomes. An exploratory simple mediation analysis indicated that the relationship between attenuated responses to anger and greater mental health difficulties was fully mediated by poorer sleep quality. This study provides evidence of diurnal and chronotype-related variation in facial threat-related processing in typical adolescent development. It also indicates how social emotional processing is vulnerable to sleep disruptions and is linked to the greater mental health problems observed in adolescents with an eveningness profile.

Deficits in facial emotional valence processing in older people with subjective memory complaints: Behavioral and electrophysiological evidence.

Subjective memory complaints (SMCs), which occur in the absence of clinical memory deficits, may precede mild cognitive impairment (MCI) or Alzheimer's disease (AD). Some studies have reported a deficit in facial emotion processing in people with MCI or AD. However, it is unclear whether this deficit is also present in older people with SMCs. The present study used behavioral measurements and event-related potentials (ERPs) to investigate the facial emotion processing of 41 older people with SMCs and 38 without SMCs. The task contained 204 images displaying facial emotions (positive, negative, and neutral). In terms of behavior, our results showed that participants with SMCs were slower and less accurate than controls. In terms of ERPs, the N170latency was longer in men with SMCs than in controls, whereas no differences were observed between groups in the P300 and late positive potential (LPP) latencies or amplitudes. Moreover, in participants with SMCs, higher P300 and LPP amplitudes were related to better performance on working memory, psychomotor speed, and attention. Additionally, women were faster and more accurate than men on the facial emotion-processing task. In sum, these results suggest that older people with SMCs may have deficits in the processing of facial expressions of emotion. However, this deficit seems to affect the structural encoding of faces, rather than the late stages of processing.

Facial emotion processing and language during early-to-middle childhood development: An event related potential study

Facial emotion processing (FEP) is critical to social cognitive ability. Developmentally, FEP rapidly improves in early childhood and continues to be fine-tuned throughout middle childhood and into adolescence. Previous research has suggested that language plays a role in the development of social cognitive skills, including non-verbal emotion recognition tasks. Here we investigated whether language is associated with specific neurophysiological indicators of FEP. One hundred and fourteen children (4–12 years) completed a language assessment and a FEP task including stimuli depicting anger, happiness, fear, and neutrality. EEG was used to record key event related potentials (ERPs; P100, N170, LPP at occipital and parietal sites separately) previously shown to be sensitive to faces and facial emotion. While there were no main effects of language, the P100 latency to negative expressions appeared to increase with language, while LPP amplitude increased with language for negative and neutral expressions. These findings suggest that language is linked to some early physiological indicators of FEP, but this is dependent on the facial expression. Future studies should explore the role of language in later stages of neural processing, with a focus on processes localised to ventromedial prefrontal regions.

Developmental changes within the extended face processing network: A cross‐sectional functional magnetic resonance imaging study

In the field of face processing, the so-called "core network" has been intensively researched. Its neural activity can be reliably detected in children and adults using functional magnetic resonance imaging (fMRI). However, the core network's counterpart, the so-called "extended network," has been less researched. In the present study, we compared children's and adults' brain activity in the extended system, in particular in the amygdala, the insula, and the inferior frontal gyrus (IFG). Using fMRI, we compared the brain activation pattern between children aged 7-9 years and adults during an emotional face processing task. On the one hand, children showed increased activity in the extended face processing system in relation to adults, particularly in the left amygdala, the right insula, and the left IFG. On the other hand, lateralization indices revealed a "leftward bias" in children's IFG compared to adults. These results suggest that brain activity associated with face processing is characterized by a developmental decrease in activity. They further show that the development is associated with a rightward migration of face-related IFG activation, possibly due to the competition for neural space between several developing brain functions ("developmental competition hypothesis").

Childhood maltreatment results in altered deactivation of reward processing circuits in depressed patients: A functional magnetic resonance imaging study of a facial emotion recognition task

Importance and objectivesChildhood adversity is a strong risk factor for the development of various psychopathologies including major depressive disorder (MDD). However, not all depressed patients experience early life trauma. Functional magnetic resonance imaging (fMRI) studies using facial emotion processing tasks have documented altered blood-oxygen-level-dependent (BOLD) responses in specific cortico-limbic networks both in MDD patients and in individuals with a history of childhood maltreatment (CM). Therefore, a history of maltreatment may represent a key modulating factor responsible for the altered processing of socio-affective stimuli. To test this hypothesis, we recruited MDD patients with and without of maltreatment history to study the long-term consequences of childhood trauma and examined the impact of CM on brain activity using a facial emotion recognition fMRI task. MethodsMDD patients with childhood maltreatment (MDD + CM, n = 21), MDD patients without maltreatment (MDD, n = 19), and healthy controls (n = 21) matched for age, sex and intelligence quotient underwent fMRI while performing a block design facial emotion matching task with images portraying negative emotions (fear, anger and sadness). The history of maltreatment was assessed with the 28-item Childhood Trauma Questionnaire. ResultsBoth MDD and MDD + CM patients displayed impaired accuracy to recognize sad faces. Analysis of brain activity revealed that MDD + CM patients had significantly reduced negative BOLD signals in their right accumbens, subcallosal cortex, and anterior paracingulate gyrus compared to controls. Furthermore, MDD + CM patients had a significantly increased negative BOLD response in their right precentral and postcentral gyri compared to controls. We found little difference between MDD and MDD + CM patients, except that MDD + CM patients had reduced negative BOLD response in their anterior paracingulate gyrus relative to the MDD group. ConclusionsOur present data provide evidence that depressed patients with a history of maltreatment are impaired in facial emotion recognition and that they display altered functioning of key reward-related fronto-striatal circuits during a facial emotion matching task.

Correlations between facial emotion processing and biochemical abnormalities in untreated adolescent patients with major depressive disorder: A proton magnetic resonance spectroscopy study

BackgroundStudies show that disturbances of the fronto-striato-thalamic-cerebellar circuit could be correlated to facial emotion processing (FEP) biases in major depressive disorder (MDD). Nevertheless, the underlying mechanism of natural metabolism-emotion relationships in adolescent MDD remains unclear. MethodsThirty-seven adolescent patients with MDD and 30 healthy controls completed FEP tasks using the Chinese Facial Affective Picture System (CAFPS). Proton magnetic resonance spectroscopy (1H-MRS) was also used to obtain ratios of N-acetylaspartate (NAA) /creatine (Cr) and choline (Cho) /Cr ratios in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), putamen, thalamus and cerebellum. Correlations between abnormal neurometabolic ratios and FEP were also computed. ResultsCompared with the control group, the MDD group had significantly lower accuracy and perception intensity of happiness, and significantly higher accuracy of disgust and perception intensity of sad and fearful faces in FEP tasks. Compared to healthy controls, adolescent patients with MDD showed significantly lower NAA/Cr ratios in the left PFC, higher NAA/Cr ratios in the right thalamus, and higher Cho/Cr ratios in the right putamen, although there were no significant differences in metabolites in the ACC and cerebellum between two groups. In the MDD group, NAA/Cr ratios of the right thalamus were negatively correlated with happy reaction time and positively correlated with sad, anger, and fear intensity; Cho/Cr ratios in the right putamen were positively correlated with fear reaction time. ConclusionsOur findings suggest that FEP bias may exist in adolescents with MDD, while the impairment of FEP may be associated with abnormal metabolites in the fronto-striato-thalamic circuit.

The Course of Disease in Major Depressive Disorder Is Associated With Altered Activity of the Limbic System During Negative Emotion Processing

BackgroundBrain functional alterations during emotion processing in patients with major depressive disorder (MDD) compared with healthy control subjects (HCs) are frequently reported. However, evidence for functional correlates of emotion processing with regard to MDD trajectories is scarce. This study investigates the role of lifetime disease course for limbic brain activation during negative emotional face processing in patients with MDD. MethodsIn a large sample of patients with MDD (n = 333; 58.55% female) and HCs (n = 333; 60.06% female), brain activation was investigated during a negative emotional face-processing task within a cross-sectional design. Differences between HC and MDD groups were analyzed. Previous disease course, characterized by 2 components, namely hospitalization and duration of illness, was regressed on brain activation of the amygdala, (para-)hippocampus, and insula in patients with MDD. ResultsPatients with MDD showed increased activation in the amygdala, insula, and hippocampus compared with HCs (all p values corrected for familywise error [pFWE] < .045). The hospitalization component showed negative associations with brain activation in the bilateral insula (right: pFWE = .026, left: pFWE = .019) and (para-)hippocampus (right: pFWE = .038, left: pFWE = .031). No significant association was found for the duration of illness component (all pFWE > .057). ConclusionsThis study investigated negative emotion processing in a large sample of patients with MDD and HCs. Our results confirm limbic hyperactivation in patients with MDD during negative emotion processing; however, this hyperactivation may resolve with a more severe lifetime disease course in the insula and (para-)hippocampus—brain regions involved in emotion processing and regulation. These findings need further replication in longitudinal studies.

Seeing sadness: Comorbid effects of loneliness and depression on emotional face processing.

Background/ObjectiveLoneliness and depression are highly comorbid, and both are associated with social processing deficits. However, there is a paucity of research aimed at differentiating emotional face‐processing deficits that are comorbid to loneliness and depression versus those attributable to loneliness or depression only.Methods502 participants were recruited and screened for loneliness (UCLA Loneliness Scale) and depression (Beck Depression Inventory). Of those, seventy‐seven took part in a fully crossed 2 (loneliness; low/high) * 2 (depression; low/high) factorial between‐subjects design study to assess individual and comorbid effects of loneliness and depression on a computerized morphed facial emotion processing task.ResultsComorbidity was confirmed by a significant positive correlation between loneliness and depression. On the emotion processing task, loneliness was associated with an increased accuracy for sad faces and decreased accuracy for fearful faces and depression with decreased accuracy in identifying happy faces. Comorbid loneliness and depression resulted in an increased misattribution of neutral faces as sad, an effect that was also seen in those who were either only lonely or only depressed.ConclusionThis if the first study to tease out comorbid versus independent effects of loneliness and depression on social information processing. To the extent that emotional biases may act as risk factors for detrimental outcomes, our findings highlight the importance of treating both loneliness and depression.

The effects of FAAH inhibition on the neural basis of anxiety-related processing in healthy male subjects: a randomized clinical trial

Acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), prolongs the regulatory effects of endocannabinoids and reverses the stress-induced anxiety state in a cannabinoid receptor-dependent manner. However, the neural systems underlying this modulation are poorly understood. A single site, randomized, double-blind, placebo-controlled, parallel study was conducted with 43 subjects assigned to receive once daily dosing of either placebo (n = 21) or JNJ-42165279 (100 mg) (n = 22) for 4 consecutive days. Pharmacodynamic effects were assessed on the last day of dosing and included evaluation of brain activation patterns using BOLD fMRI during an (1) emotion face-processing task, (2) inspiratory breathing load task, and (3) fear conditioning and extinction task. JNJ-42165279 attenuated activation in the amygdala, bilateral anterior cingulate, and bilateral insula during the emotion face-processing task consistent with effects previously observed with anxiolytic agents. Higher levels of anandamide were associated with greater attenuation in bilateral anterior cingulate and left insula. JNJ-42165279 increased the activation during anticipation of an aversive interoceptive event in the anterior cingulate and bilateral anterior insula and right inferior frontal cortex. JNJ-42165279 did not affect fear conditioning or within-session extinction learning as evidenced by a lack of differences on a subjective and neural circuit level. Taken together, these results support the hypothesis that JNJ-42165279 at this dose shares some effects with existing anxiolytic agents in dampening response to emotional stimuli but not responses to conditioned fear.

Eye gaze patterns and functional brain responses during emotional face processing in adolescents with conduct disorder

BackgroundConduct disorder (CD) is characterized by severe aggressive and antisocial behavior. Initial evidence suggests neural deficits and aberrant eye gaze pattern during emotion processing in CD; both concepts, however, have not yet been studied simultaneously. The present study assessed the functional brain correlates of emotional face processing with and without consideration of concurrent eye gaze behavior in adolescents with CD compared to typically developing (TD) adolescents. Methods58 adolescents (23CD/35TD; average age = 16 years/range = 14–19 years) underwent an implicit emotional face processing task. Neuroimaging analyses were conducted for a priori-defined regions of interest (insula, amygdala, and medial orbitofrontal cortex) and using a full-factorial design assessing the main effects of emotion (neutral, anger, fear), group and the interaction thereof (cluster-level, p < .05 FWE-corrected) with and without consideration of concurrent eye gaze behavior (i.e., time spent on the eye region). ResultsAdolescents with CD showed significant hypo-activations during emotional face processing in right anterior insula compared to TD adolescents, independent of the emotion presented. In-scanner eye-tracking data revealed that adolescents with CD spent significantly less time on the eye, but not mouth region. Correcting for eye gaze behavior during emotional face processing reduced group differences previously observed for right insula. ConclusionsAtypical insula activation during emotional face processing in adolescents with CD may partly be explained by attentional mechanisms (i.e., reduced gaze allocation to the eyes, independent of the emotion presented). An increased understanding of the mechanism causal for emotion processing deficits observed in CD may ultimately aid the development of personalized intervention programs.

Interferon and anti-TNF therapies differentially modulate amygdala reactivity which predicts associated bidirectional changes in depressive symptoms

A third of patients receiving Interferon-α (IFN-α) treatment for Hepatitis-C develop major depressive disorder (MDD). Conversely, anti-Tumor Necrosis Factor (TNF) therapies improve depression providing key empirical support for the “inflammatory theory” of depression. Heightened amygdala reactivity (particularly to negatively valanced stimuli) is a consistent finding within MDD; can predict treatment efficacy and reverses following successful treatment. However, whether IFN-α and anti-TNF enhance/attenuate depressive symptoms through modulation of amygdala emotional reactivity is unknown. Utilizing a prospective study design, we recruited 30 patients (mean 48.0 ± 10.5 years, 21 male) initiating IFN-α treatment for Hepatitis-C and 30 (mean 50.4 ± 15.7 years, 10 male) anti-TNF therapy for inflammatory arthritis. All completed an emotional face-processing task during fMRI and blood sampling before and after their first IFN-α (4-h) or anti-TNF (24-h) injection and follow-up psychiatric assessments for 3 months of treatment. IFN-α significantly increased depression symptoms (Hamilton Depression Rating Scale HAM-D) at 4 weeks (p < 0.001) but not 4-h after first dose (p > 0.1). Conversely, anti-TNF significantly improved depressive symptoms (Hospital Anxiety and Depression Rating Scale HADS) at both 24-h (P = 0.015) and 12 weeks (p = 0.018). In support of our a-priori hypothesis, both IFN-α and anti-TNF significantly modulated amygdala reactivity with IFN-α acutely enhancing right amygdala responses to sad (compared with neutral) faces (p = 0.032) and anti-TNF conversely decreasing right amygdala reactivity (across emotional valence) (p = 0.033). Furthermore, these changes predicted IFN-induced increases in HAM-D 4 weeks later (R2 = 0.17, p = 0.022) and anti-TNF-associated decreases in HADS at 24-h (R2 = 0.23, p = 0.01) suggesting that actions of systemic inflammation on amygdala emotional reactivity play a mechanistic role in inflammation-associated depressive symptoms.