Evaluation of Neurofeedback for Posttraumatic Stress Disorder Related to Refugee Experiences Using Self-Report and Cognitive ERP Measures.

Background. Neurofeedback holds promise as an intervention for the psychophysiological dysfunction found in posttraumatic stress disorder (PTSD). Few empirical studies have assessed the efficacy of neurofeedback for PTSD, and none in individuals with refugee trauma. A proposed mechanism for neurofeedback efficacy in PTSD is through remediating deficits in cognitive control. We assessed pre- and postchanges in symptoms and neurocognitive functioning of refugee clients participating in a neurofeedback intervention for PTSD. Methods. Clinical data for 13 adult refugees with chronic PTSD who participated in neurofeedback combined with trauma counseling (NFT) was compared with 13 adult refugees placed on a waitlist to receive neurofeedback. Waitlist clients continued to receive trauma counseling alone (TC). NFT was additionally assessed pre- and posttherapy for changes in event-related potentials (ERPs) and behavioral indices of cognitive control using a visual continuous performance task (VCPT). Comparison VCPT data from healthy controls (HC) was available from the Human Brain Index database. Results. Posttherapy, NFT had significantly lower symptoms of trauma, anxiety, and depression compared with TC. NFT demonstrated an increased P3 amplitude and improved behavioral performance suggesting a normalization of cognitive control. Conclusions. These preliminary observations are consistent with a possible benefit of neurofeedback for remediating PTSD. This may be achieved at least partially by an improvement in cognitive control. Further confirmation of the effectiveness of the treatment now requires a randomized controlled trial that considers issues such as placebo response, nonspecific therapist effects, and duration of treatment.

Characterizing neurocognitive markers of familial risk for depression using multi-modal imaging, behavioral and self-report measures.

BACKGROUND: Major depressive disorder (MDD) is associated with poorer behavioral performance in domains of working memory and associated cognitive systems for cognitive control and attention. Functional neuroimaging studies show altered functioning in MDD in frontal executive control circuits implicated in these cognitive processes. It is not yet known whether poor cognitive performance involving these circuits is part of the familial risk for MDD, and we addressed this issue using a multi-modal imaging, behavioral and self-report approach in unaffected first-degree relatives of parent probands with MDD. METHODS: 72 unaffected adult first-degree relatives of probands with MDD (mean age 30.5 ± 13.4 years) with and 66 case-wise matched non-relative controls underwent functional magnetic resonance imaging during performance of 'n-back' working memory task, a Go/No-go task assessing cognitive control and an Auditory Oddball test of selective attention. Groups were compared on imaging data analyzed voxel wise with a focus on dorsolateral prefrontal cortex, anterior cingulate cortex and insula regions of interest, and on corresponding behavioral accuracy and reaction time data. Symptoms were assessed using self-report scales. RESULTS: Relatives were distinguished by comparatively decreased activation in the left dorsolateral prefrontal cortex (DLPFC) during updating of working memory. Behaviorally, relatives also showed more errors of omission during working memory updating. DLPFC hypo-activation was associated with greater depressive symptom severity. CONCLUSIONS: Deficits in cognitive processing may be part of the profile of familial risk for depression, preceding illness onset, specifically in the domain of working memory.

Reduced safety processing during aversive social conditioning in psychosis and clinical risk.

Social impairment occurs across the psychosis spectrum, but its pathophysiology remains poorly understood. Here we tested the hypothesis that reduced differential responses (aversive vs. neutral) in neural circuitry underpinning aversive conditioning of social stimuli characterizes the psychosis spectrum. Participants age 10-30 included a healthy control group (HC, analyzed n = 36) and a psychosis spectrum group (PSY, n = 71), including 49 at clinical risk for psychosis and 22 with a frank psychotic disorder. 3T fMRI utilized a passive aversive conditioning paradigm, with neutral faces as conditioned stimuli (CS) and a scream as the unconditioned stimulus. fMRI conditioning was indexed as the activation difference between aversive and neutral trials. Analysis focused on amygdala, ventromedial prefrontal cortex, and anterior insula, regions previously implicated in aversive and social-emotional processing. Ventromedial prefrontal cortex activated more to neutral than aversive CS; this "safety effect" was driven by HC and reduced in PSY, and correlated with subjective emotional ratings following conditioning. Insula showed the expected aversive conditioning effect, and although no group differences were found, its activation in PSY correlated with anxiety severity. Unexpectedly, amygdala did not show aversive conditioning; its activation trended greater for neutral than aversive CS, and did not differ significantly based on group or symptom severity. We conclude that abnormalities in social aversive conditioning are present across the psychosis spectrum including clinical risk, linked to a failure of safety processing. Aversive and safety learning provide translational paradigms yielding insight into pathophysiology of psychosis risk, and providing potential targets for therapeutic and preventative interventions.

Social aversive conditioning in youth at clinical high risk for psychosis and with psychosis: An ERP study.

BACKGROUND: Social cognition and emotion processing are compromised in schizophrenia. Disruptions in these domains may also be present during the psychosis-risk state. Aversive conditioning is an established translational research paradigm to investigate affective reactivity and learning. Using an aversive conditioning ERP paradigm with social cues, we examined whether psychosis patients and at-risk youths differentially respond to aversively conditioned faces. METHODS: Participants (ages 10-30) were enrolled into three demographically-matched groups: clinical risk for psychosis (CR, n = 32), psychosis (PS, n = 26), and healthy control (HC, n = 33). EEGs were recorded during a delay aversive conditioning task in which three neutral faces were paired with an aversive tone at 100%, 50% and 0% contingencies. Analysis focused on group differences in ERP peaks representing visual processing (occipital P120), emotional valence (frontal VPP), and directed attention (parietal-occipital P300), for dimensions of aversiveness (100% vs. 0%) and unpredictability (50% vs. 100% + 0%). RESULTS: HC, but not CR or PS, showed increased P300 amplitude to aversive vs. non-aversive conditioned stimuli. CR, but not PS or HC, showed increased VPP amplitude to unpredictable vs. predictable stimuli. CONCLUSIONS: PS and CR both fail to allocate appropriate salience to social cues that are predictably aversive. CR, but not PS exhibit heightened emotional reactivity to social cues that are of uncertain salience. Clinical risk for schizophrenia may involve neural abnormalities distinct from both healthy and fully-established disease states.

Electrocortical reactivity to negative and positive facial expressions in individuals with a family history of major depression.

Facial expressions signaling threat and mood-congruent loss have been used to probe abnormal neural reactivity in major depressive disorder (MDD) and may be implicated in genetic vulnerability to MDD. This study investigated electro-cortical reactivity to facial expressions in 101 unaffected, adult first-degree relatives of probands with MDD and non-relative controls (n = 101). We investigated event-related potentials (ERPs) to five facial expressions of basic emotion: fear, anger, disgust, sadness and happiness under both subliminal (masked) and conscious (unmasked) presentation conditions, and the source localization of group differences. In the conscious condition, controls showed a distinctly positive-going shift in responsive to negative versus happy faces, reflected in a greater positivity for the VPP frontally and the P300 parietally, and less negativity for the N200. By contrast, relatives showed less differentiation of emotions, reflected in less VPP and P300 positivity, particularly for anger and disgust, which produced an enhanced N200 for sadness. These group differences were consistently source localized to the anterior cingulate cortex. The findings contribute new evidence for neural disruptions underlying the differentiation of salient emotions in familial risk for depression. These disruptions occur to the appraisal (∼200 ms post-stimulus) through to the context evaluation (∼300 ms+ post-stimulus) phases of emotion processing, consistent with theories that risk for depression involves biased or attenuated processing of emotion.

Profiling risk for depressive disorder by circuit, behavior and self-report measures of emotion function.

BACKGROUND: Major depressive disorder (MDD) is characterized by maladaptions in affective brain circuitry and in emotion regulation. It remains unknown whether these maladaptions characterize first-degree relatives of probands who are unaffected yet have a higher risk of developing MDD. METHODS: Participants were 72 unaffected first-degree relatives of probands with MDD and 66 matched non-relative controls. We investigated brain circuit function and self-reported emotion regulation strategies for reappraisal and suppression. During functional magnetic resonance imaging, we probed circuitry relevant to both negative and positive valence systems using facial expressions signaling potential threat, sadness and happiness, presented under both conscious and subliminal viewing conditions. We compared groups using a statistically controlled region of interest (ROI) approach including the amygdala, insula, anterior cingulate cortex (ACC), ventromedial prefrontal cortex and dorsolateral prefrontal cortex. We also used a data-driven cluster analytic approach for characterizing the relatives by their brain function profiles. RESULTS: As a group, relatives were distinguished by hyper-reactivity of the pregenual ACC during subliminal viewing of threat-related expressions but hypo-activation of the amygdala, insula and dorsal ACC during explicit viewing of the same threat-related expressions and sadness. When considered individually, this brain function profile characterized two-thirds of relatives, and these relatives were also less likely to use reappraisal to regulate negative emotion. LIMITATIONS: The design was cross-sectional and therefore does not provide direct evidence as to the trait- (versus state-) like profile observed in relatives. CONCLUSIONS: Familial risk for MDD may involve a disruption to the normal recruitment of neural circuits for appraising salient emotions, both implicit and explicit. Interventions targeting reappraisal strategies for regulating negative emotion may serve to buffer this risk.

Neurofeedback as an adjunct therapy for treatment of chronic posttraumatic stress disorder related to refugee trauma and torture experiences: two case studies.

OBJECTIVE: The objective of this study was to describe the use of neurofeedback for refugee-related chronic posttraumatic stress disorder (PTSD) in two case studies. METHODS: We describe the assessment and application of neurofeedback integrated into the treatment of two clients with chronic PTSD. We include details of our treatment schedule, symptoms and quantitative electrophysiological data for each case. Results All clients achieved significant reduction in symptoms of PTSD and improvement in daily functioning post-neurofeedback therapy. Quantitative electroencephalogric (EEG) measures indicate a normalisation of EEG markers relating to trauma, including overarousal at rest and working memory function. Conclusions Neurofeedback as an adjunct to trauma-informed therapy may help to remediate chronic PTSD relating to refugee experiences. If replicated then improvements demonstrated in this population would be generalisable to all chronic PTSD.

Using multiple methods to characterize the phenotype of individuals with a family history of major depressive disorder.

BACKGROUND: Unaffected relatives (URs) of individuals with major depressive disorder (MDD) are biologically more vulnerable to depression. We compare healthy URs and controls at the level of phenotype (symptoms and functioning) and endophenotype (negative emotion bias), and further investigate the interrelation between these and the contribution of environmental early life stress. METHODS: URs (n=101), identified using Family History Screen interview methods and matched controls completed written and interview questions assessing symptoms of depression and anxiety, negative cognitive style, life functioning and early life stress. Biases in emotion processing were measured using a facial expression of emotion identification paradigm. RESULTS: Compared to controls, URs reported higher levels of depression and anxiety, a stronger negative cognitive bias, and poorer functioning and lower satisfaction with life. URs were slower to correctly identify fear and sad facial expressions. A slower response time to identify sad faces was correlated with lower quality of life in the social domain. Early life stress (ELS) did not contribute significantly to any outcome. LIMITATIONS: The methodology relies on accurate reporting of participants' own psychiatric history and that of their family members. The degree of vulnerability varies among URs. CONCLUSIONS: A family history of depression accounts for subtle differences in symptom levels and functioning without a necessary role of ELS. A negative emotion bias in processing emotion may be one vulnerability marker for MDD. Biological markers may affect functioning measures before symptoms at the level of experience.

Negative biases and risk for depression; integrating self-report and emotion task markers.

BACKGROUND: Negativity biases and their impact on reactivity to negative emotion are implicated in the mechanisms of risk for depression. The aim of this study was to determine whether self-reported negativity bias is related to objective cognitive measures of emotional reactivity. METHODS: A previously established Web self-report measure of negativity bias was used to assess 1,080 volunteers from the Brain Resource International Database (overseen by the nonprofit BRAINnet Foundation). We identified matched subgroups of "High Risk" (n = 216) and "Low Risk" (n = 216) participants using a psychometric high-risk method, which classified High Risk as the sample's top 30% of negativity bias scores and Low Risk as the bottom 30%. These subsamples also completed the WebNeuro cognitive tasks for assessing both conscious and nonconscious reactions to facial emotions. Task performance was quantified by accuracy, reaction time, and misidentification errors. RESULTS: The High Risk (high negativity bias) subgroup was distinguished by greater reactivity to negative emotion in both conscious and nonconscious processing. The High Risk profile was reflected in higher accuracy for sadness (nonconsciously) and disgust (consciously), and more frequent misidentification of neutral as anger (consciously). CONCLUSIONS: These results are consistent with seminal theories that a systematic cognitive negativity bias produces a hyper-reactivity to negative emotion, which can impact nonconscious as well as conscious processing. The results provide a step toward objective markers of risk for depression that would help the community act regarding preventative programs. Replication in patient samples is warranted.