Amygdala-related electrical fingerprint is modulated with neurofeedback training and correlates with deep-brain activation: proof-of-concept in borderline personality disorder.

BACKGROUND: The modulation of brain circuits of emotion is a promising pathway to treat borderline personality disorder (BPD). Precise and scalable approaches have yet to be established. Two studies investigating the amygdala-related electrical fingerprint (Amyg-EFP) in BPD are presented: one study addressing the deep-brain correlates of Amyg-EFP, and a second study investigating neurofeedback (NF) as a means to improve brain self-regulation. METHODS: Study 1 combined electroencephalography (EEG) and simultaneous functional magnetic resonance imaging to investigate the replicability of Amyg-EFP-related brain activation found in the reference dataset (N = 24 healthy subjects, 8 female; re-analysis of published data) in the replication dataset (N = 16 female individuals with BPD). In the replication dataset, we additionally explored how the Amyg-EFP would map to neural circuits defined by the research domain criteria. Study 2 investigated a 10-session Amyg-EFP NF training in parallel to a 12-weeks residential dialectical behavior therapy (DBT) program. Fifteen patients with BPD completed the training, N = 15 matched patients served as DBT-only controls. RESULTS: Study 1 replicated previous findings and showed significant amygdala blood oxygenation level dependent activation in a whole-brain regression analysis with the Amyg-EFP. Neurocircuitry activation (negative affect, salience, and cognitive control) was correlated with the Amyg-EFP signal. Study 2 showed Amyg-EFP modulation with NF training, but patients received reversed feedback for technical reasons, which limited interpretation of results. CONCLUSIONS: Recorded via scalp EEG, the Amyg-EFP picks up brain activation of high relevance for emotion. Administering Amyg-EFP NF in addition to standardized BPD treatment was shown to be feasible. Clinical utility remains to be investigated.

Survey on Open Science Practices in Functional Neuroimaging.

Replicability and reproducibility of scientific findings is paramount for sustainable progress in neuroscience. Preregistration of the hypotheses and methods of an empirical study before analysis, the sharing of primary research data, and compliance with data standards such as the Brain Imaging Data Structure (BIDS), are considered effective practices to secure progress and to substantiate quality of research. We investigated the current level of adoption of open science practices in neuroimaging and the difficulties that prevent researchers from using them. Email invitations to participate in the survey were sent to addresses received through a PubMed search of human functional magnetic resonance imaging studies that were published between 2010 and 2020. 283 persons completed the questionnaire. Although half of the participants were experienced with preregistration, the willingness to preregister studies in the future was modest. The majority of participants had experience with the sharing of primary neuroimaging data. Most of the participants were interested in implementing a standardized data structure such as BIDS in their labs. Based on demographic variables, we compared participants on seven subscales, which had been generated through factor analysis. Exploratory analyses found that experienced researchers at lower career level had higher fear of being transparent and researchers with residence in the EU had a higher need for data governance. Additionally, researchers at medical faculties as compared to other university faculties reported a more unsupportive supervisor with regards to open science practices and a higher need for data governance. The results suggest growing adoption of open science practices but also highlight a number of important impediments.

An Investigation of Awareness and Metacognition in Neurofeedback with the Amygdala Electrical Fingerprint.

Awareness theory posits that individuals connected to a brain-computer interface can learn to estimate and discriminate their brain states. We used the amygdala Electrical Fingerprint (amyg-EFP) - a functional Magnetic Resonance Imaging-inspired Electroencephalogram surrogate of deep brain activation - to investigate whether participants could accurately estimate their own brain activation. Ten participants completed up to 20 neurofeedback runs and estimated their amygdala-EFP activation (depicted as a thermometer) and confidence in this rating during each trial. We analysed data using multilevel models, predicting the real thermometer position with participant rated position and adjusted for activation during the previous trial. Hypotheses on learning regulation and improvement of estimation were not confirmed. However, participant ratings were significantly associated with the amyg-EFP signal. Higher rating accuracy also predicted higher subjective confidence in the rating. This proof-of-concept study introduces an approach to study awareness with fMRI-informed neurofeedback and provides initial evidence for metacognition in neurofeedback.

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist).

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.

fMRI neurofeedback in emotion regulation: A literature review.

OBJECTIVES: Emotion regulation is one of the most prevalent objectives for real-time fMRI neurofeedback (rt-fMRI-NF) studies. The existing studies differ in a number of methodological parameters. This study provides a literature review of the main parameters and results of studies using rt-fMRI-NF for emotion regulation enhancement. METHOD: A search of the Web of Science database up through November 8, 2018, identified 144 articles written in English, 89 of which were excluded as irrelevant for this study. The remaining 51 original studies and four secondary analyses of previously published original studies were included in the literature review. The selection of target brain areas, target populations, emotion regulation protocols, NF presentation, control group types, and emotion regulation instructions were examined in relation to achieved brain regulation and changes in cognitive or clinical outcomes. Study results were evaluated in terms of their statistical robustness. RESULTS: The results show that healthy people are able to regulate their brain activity in the presence of rt-fMRI-NF from various brain regions related to emotion regulation, including the amygdala, anterior insula, and anterior cingulate cortex. The regulation of brain activity using rt-fMRI-NF from prefrontal-limbic connectivity or from individually navigated brain areas is feasible as well. Most studies that used a control group show that rt-fMRI-NF actually induces some effects on brain regulation, cognitive variables, and clinical variables. Generally, the success of ROI regulation during NF training is related to the combination of target brain region, the type of emotion regulation task, and the population undergoing the training. In terms of patient groups, the strongest support for the beneficial effects of rt-fMRI-NF has been shown in increased positive emotion experiencing in patients with depression and in decreased anxiety in patients with anxiety disorders. Symptom reduction following NF training has been also reported in patients with PTSD, BPD, and schizophrenia, but direct comparisons with control groups in these studies makes it impossible to evaluate the added value of NF. Studies often do not report all the relevant analyses for evaluating NF success and many studies lack statistical robustness. CONCLUSIONS: Overall, rt-fMRI-NF seems a promising tool for emotion regulation enhancement with the potential to induce long-term symptom reduction in patients with various mental disorders. Preplanning of statistical analyses, careful interpretations of the results, and evaluations of the NF effect on symptom reduction in patient groups is recommended.

Current progress in real-time functional magnetic resonance-based neurofeedback: Methodological challenges and achievements.

Neurofeedback (NF) is a research and clinical technique, characterized by live demonstration of brain activation to the subject. The technique has become increasingly popular as a tool for the training of brain self-regulation, fueled by the superiority in spatial resolution and fidelity brought along with real-time analysis of fMRI (functional magnetic resonance imaging) data, compared to the more traditional EEG (electroencephalography) approach. NF learning is a complex phenomenon and a controversial discussion on its feasibility and mechanisms has arisen in the literature. Critical aspects of the design of fMRI-NF studies include the localization of neural targets, cognitive and operant aspects of the training procedure, personalization of training, and the definition of training success, both through neural effects and (for studies with therapeutic aims) through clinical effects. In this paper, we argue that a developmental perspective should inform neural target selection particularly for pediatric populations, and different success metrics may allow in-depth analysis of NF learning. The relevance of the functional neuroanatomy of NF learning for brain target selection is discussed. Furthermore, we address controversial topics such as the role of strategy instructions, sometimes given to subjects in order to facilitate learning, and the timing of feedback. Discussion of these topics opens sight on problems that require further conceptual and empirical work, in order to improve the impact that fMRI-NF could have on basic and applied research in future.

Monitoring and control of amygdala neurofeedback involves distributed information processing in the human brain.

Brain-computer interfaces provide conscious access to neural activity by means of brain-derived feedback ("neurofeedback"). An individual's abilities to monitor and control feedback are two necessary processes for effective neurofeedback therapy, yet their underlying functional neuroanatomy is still being debated. In this study, healthy subjects received visual feedback from their amygdala response to negative pictures. Activation and functional connectivity were analyzed to disentangle the role of brain regions in different processes. Feedback monitoring was mapped to the thalamus, ventromedial prefrontal cortex (vmPFC), ventral striatum (VS), and rostral PFC. The VS responded to feedback corresponding to instructions while rPFC activity differentiated between conditions and predicted amygdala regulation. Control involved the lateral PFC, anterior cingulate, and insula. Monitoring and control activity overlapped in the VS and thalamus. Extending current neural models of neurofeedback, this study introduces monitoring and control of feedback as anatomically dissociated processes, and suggests their important role in voluntary neuromodulation.

Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: A preliminary analysis.

Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.

The neurobiology of emotion regulation in posttraumatic stress disorder: Amygdala downregulation via real-time fMRI neurofeedback.

Amygdala dysregulation has been shown to be central to the pathophysiology of posttraumatic stress disorder (PTSD) representing a critical treatment target. Here, amygdala downregulation was targeted using real-time fMRI neurofeedback (rt-fMRI-nf) in patients with PTSD, allowing us to examine further the regulation of emotional states during symptom provocation. Patients (n = 10) completed three sessions of rt-fMRI-nf with the instruction to downregulate activation in the amygdala, while viewing personalized trauma words. Amygdala downregulation was assessed by contrasting (a) regulate trials, with (b) viewing trauma words and not attempting to regulate. Training was followed by one transfer run not involving neurofeedback. Generalized psychophysiological interaction (gPPI) and dynamic causal modeling (DCM) analyses were also computed to explore task-based functional connectivity and causal structure, respectively. It was found that PTSD patients were able to successfully downregulate both right and left amygdala activation, showing sustained effects within the transfer run. Increased activation in the dorsolateral and ventrolateral prefrontal cortex (PFC), regions related to emotion regulation, was observed during regulate as compared with view conditions. Importantly, activation in the PFC, rostral anterior cingulate cortex, and the insula, were negatively correlated to PTSD dissociative symptoms in the transfer run. Increased functional connectivity between the amygdala- and both the dorsolateral and dorsomedial PFC was found during regulate, as compared with view conditions during neurofeedback training. Finally, our DCM analysis exploring directional structure suggested that amygdala downregulation involves both top-down and bottom-up information flow with regard to observed PFC-amygdala connectivity. This is the first demonstration of successful downregulation of the amygdala using rt-fMRI-nf in PTSD, which was critically sustained in a subsequent transfer run without neurofeedback, and corresponded to increased connectivity with prefrontal regions involved in emotion regulation during the intervention. Hum Brain Mapp 38:541-560, 2017. © 2016 Wiley Periodicals, Inc.

fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity.

Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: p<.05 at cluster-level). Task-dependent increases in amygdala-vmPFC connectivity were predicted by picture arousal (ß=.59, p<.05). A dynamic causal modeling analysis with Bayesian model selection aimed at further characterizing the underlying causal structure and favored a bottom-up model assuming predominant information flow from the amygdala to the vmPFC (xp=.90). The results were complemented by the observation of task-dependent alterations in functional connectivity of the vmPFC with the visual cortex and the ventrolateral PFC in the experimental group (Condition t-contrast: p<.05 at cluster-level). Taken together, the results underscore the potential of amygdala fMRI neurofeedback to influence functional connectivity in key networks of emotion processing and regulation. This may be beneficial for patients suffering from severe emotion dysregulation by improving neural self-regulation.

Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated?

An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first- (single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-of-interest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success.

Incision and stress regulation in borderline personality disorder: neurobiological mechanisms of self-injurious behaviour.

BACKGROUND: Patients with borderline personality disorder frequently show non-suicidal self-injury (NSSI). In these patients, NSSI often serves to reduce high levels of stress. AIMS: Investigation of neurobiological mechanisms of NSSI in borderline personality disorder. METHOD: In total, 21 women with borderline personality disorder and 17 healthy controls underwent a stress induction, followed by either an incision into the forearm or a sham treatment. Afterwards participants underwent resting-state functional magnetic resonance imaging while aversive tension, heart rate and heart rate variability were assessed. RESULTS: We found a significant influence of incision on subjective and objective stress levels with a stronger decrease of aversive tension in the borderline personality disorder group following incision than sham. Amygdala activity decreased more and functional connectivity with superior frontal gyrus normalised after incision in the borderline personality disorder group. CONCLUSIONS: Decreased stress levels and amygdala activity after incision support the assumption of an influence of NSSI on emotion regulation in individuals with borderline personality disorder and aids in understanding why these patients use self-inflicted pain to reduce inner tension.

Transient and sustained BOLD signal time courses affect the detection of emotion-related brain activation in fMRI.

A tremendous amount of effort has been dedicated to unravel the functional neuroanatomy of the processing and regulation of emotion, resulting in a well-described picture of limbic, para-limbic and prefrontal regions involved. Studies applying functional magnetic resonance imaging (fMRI) often use the block-wise presentation of stimuli with affective content, and conventionally model brain activation as a function of stimulus or task duration. However, there is increasing evidence that regional brain responses may not always translate to task duration and rather show stimulus onset-related transient time courses. We assume that brain regions showing transient responses cannot be detected in block designs using a conventional fMRI analysis approach. At the same time, the probability of detecting these regions with conventional analyses may be increased when shorter stimulus timing or a more intense stimulation during a block is used. In a within-subject fMRI study, we presented aversive pictures to 20 healthy subjects and investigated the effect of experimental design (i.e. event-related and block design) on the detection of brain activation in limbic and para-limbic regions of interest of emotion processing. In addition to conventional modeling of sustained activation during blocks of stimulus presentation, we included a second response function into the general linear model (GLM), suited to detect transient time courses at block onset. In the conventional analysis, several regions like the amygdala, thalamus and periaqueductal gray were activated irrespective of design. However, we found a positive BOLD response in the anterior insula (AI) in event-related but not in block-design analyses. GLM analyses suggest that this difference may result from a transient response pattern which cannot be captured by the conventional fMRI analysis approach. Our results indicate that regions with a transient response profile like the AI can be missed in block designs if analyses do not account for transient responses. This may bias conclusions from empirical reports and meta-analyses towards an underestimation of these regions and their role in emotion and emotion regulation. The cognitive processes underlying differential time courses are discussed.

Sharing brain imaging data in the Open Science era: how and why?

The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption. Therefore, we provide practical advice on how to overcome the technical barriers. We also call for a harmonised application of the General Data Protection Regulation across EU countries. Finally, we suggest the development of a system that makes data count by recognising the generation and sharing of data as a highly valuable contribution to the community.

Neurofeedback through the lens of reinforcement learning.

Despite decades of experimental and clinical practice, the neuropsychological mechanisms underlying neurofeedback (NF) training remain obscure. NF is a unique form of reinforcement learning (RL) task, during which participants are provided with rewarding feedback regarding desired changes in neural patterns. However, key RL considerations - including choices during practice, prediction errors, credit-assignment problems, or the exploration-exploitation tradeoff - have infrequently been considered in the context of NF. We offer an RL-based framework for NF, describing different internal states, actions, and rewards in common NF protocols, thus fashioning new proposals for characterizing, predicting, and hastening the course of learning. In this way we hope to advance current understanding of neural regulation via NF, and ultimately to promote its effectiveness, personalization, and clinical utility.

Aversive anticipations modulate electrocortical correlates of decision-making and reward reversal learning, but not behavioral performance.

Predicting the consequences of one's own decisions is crucial for organizing future behavior. However, when reward contingencies vary frequently, flexible adaptation of decisions is likely to depend on the situation. We examined the effects of an instructed threat context on choice behavior (i.e., reversal learning) and its electrocortical correlates. In a probabilistic decision-making task, 30 participants had to choose between two options that were either contingent on monetary gains or losses. Reward contingencies were reversed after reaching a probabilistic threshold. Decision-making and reversal learning were examined with two contextual background colors, which were instructed as signals for threat-of-shock or safety. Self-report data confirmed the threat context as more unpleasant, arousing, and threatening relative to safety condition. However, against our expectations, behavioral performance was comparable during the threat and safety conditions (i.e., errors-to-criterion, number of reversal, error rates, and choice times). Regarding electrocortical activity, feedback processing changed throughout the visual processing stream. The feedback-related negativity (FRN) reflected expectancy-driven processing (unexpected vs. congruent losses and gains), and the threat-selective P3 component revealed non-specific discrimination of gains vs. losses. Finally, the late positive potentials (LPP) showed strongly valence-specific processing (unexpected and congruent losses vs. gains). Thus, regardless of contextual threat, early and late cortical activity reflects an attentional shift from expectation- to outcome-based feedback processing. Findings are discussed in terms of reward, threat, and reversal-learning mechanisms with implications for emotion regulation and anxiety disorders.

Feasibility and utility of amygdala neurofeedback.

Amygdala NeuroFeedback (NF) have the potential of being a valuable non-invasive intervention tool in many psychiatric disporders. However, the feasibility and best practices of this method have not been systematically examined. The current article presents a review of amygdala-NF studies, an analytic summary of study design parameters, and examination of brain mechanisms related to successful amygdala-NF performance. A meta-analysis of 33 publications showed that real amygdala-NF facilitates learned modulation compared to control conditions. In addition, while variability in study dsign parameters is high, these design choices are implicitly organized by the targeted valence domain (positive or negative). However, in most cases the neuro-behavioral effects of targeting such domains were not directly assessed. Lastly, re-analyzing six data sets of amygdala-fMRI-NF revealed that successful amygdala down-modulation is coupled with deactivation of the posterior insula and nodes in the Default-Mode-Network. Our findings suggest that amygdala self-modulation can be acquired using NF. Yet, additional controlled studies, relevant behavioral tasks before and after NF intervention, and neural 'target engagement' measures are critically needed to establish efficacy and specificity. In addition, the fMRI analysis presented here suggest that common accounts regarding the brain network involved in amygdala NF might reflect unsuccessful modulation attempts rather than successful modulation.

The effects of transient receptor potential cation channel inhibition by BI 1358894 on cortico-limbic brain reactivity to negative emotional stimuli in major depressive disorder.

Abnormal emotional processing in major depressive disorder (MDD) has been associated with increased activation to negative stimuli in cortico-limbic brain regions. The authors investigated whether treatment with BI 1358894, a small-molecule inhibitor of the transient receptor potential cation channel subfamily C leads to attenuated activity in these areas in MDD patients. 73 MDD patients were randomized to receive a single oral dose of BI 1358894 (100 mg), citalopram (20 mg), or matching placebo. Brain responses to emotional faces and scenes were investigated using functional magnetic resonance imaging. Primary endpoints were BOLD signal changes in response to negative faces in cortico-limbic brain regions, i.e. bilateral amygdala (AMY), dorsolateral prefrontal cortex, anterior insula (AI), and anterior cingulate cortex. Secondary endpoints were BOLD signal changes in response to negative scenes. For each region, separate ANOVA models were computed for the comparison of treatments (BI 1358894 or citalopram) vs. placebo. The adjusted treatment differences in the % BOLD signal changes in the faces task showed that BI 1358894 induced signal reduction in bilateral AMY and left AI. In the scenes task, BI 1358894 demonstrated significant signal reduction in bilateral AMY, AI, anterior cingulate cortex and left dorsolateral prefrontal cortex. Citalopram failed to induce any significant reductions in BOLD signal in both tasks. BI 1358894-mediated inhibition of the transient receptor potential cation channel subfamily resulted in strong signal reduction in cortico-limbic brain regions, thereby supporting development of this mechanism of action for MDD patients.

Single-Dose Effects of Citalopram on Neural Responses to Affective Stimuli in Borderline Personality Disorder: A Randomized Clinical Trial.

BACKGROUND: Psychiatric medication that has a soothing effect on limbic responses to affective stimuli could improve affective instability symptoms as observed in borderline personality disorder (BPD). The objective of this study was to investigate whether citalopram versus placebo reduces the response of the affective neural circuitry during an emotional challenge. METHODS: A total of 30 female individuals with a BPD diagnosis participated in a placebo-controlled, double-blind crossover trial design. Three hours after oral drug intake, individuals with BPD viewed affective pictures while undergoing functional magnetic resonance imaging. Blood oxygen level-dependent responses to images of negative affective scenes and faces showing negative emotional expressions were assessed in regions of interest (amygdala, anterior cingulate cortex, anterior insula, dorsolateral prefrontal cortex). Blood perfusion at rest was assessed with arterial spin labeling. RESULTS: The neural response to pictures showing negative affective scenes was not significantly affected by citalopram (n = 23). Citalopram significantly reduced the amygdala response to pictures of faces with negative affective expressions (n = 25, treatment difference left hemisphere: -0.06 ± 0.16, p < .05; right hemisphere: -0.06 ± 0.17, p < .05). We observed no significant effects of citalopram on the other regions. The drug did not significantly alter blood perfusion at rest. CONCLUSIONS: Citalopram can alter the amygdala response to affective stimuli in BPD, which is characterized by overly responsive affective neural circuitry.

Threat rapidly disrupts reward reversal learning.

Threat changes cognition and facilitates adaptive coping. However, when threat becomes overwhelming, it may be deleterious to mental health, especially for vulnerable individuals. Flexible decision-making was probed with a reward reversal task to investigate how well healthy participants (N = 34) can adapt to changes in reward contingency when they expect adverse events (i.e., electric shocks). In comparison to a safe control condition, the threat of shock significantly impaired reward reversal learning. Moreover, enhanced self-reported threat ratings and elevated skin conductance levels support the successful induction of stressful and aversive apprehensions. The findings are in line with literature showing the stress-induced inhibition of goal-directed behavior at the advantage of a reflexive (habitual) response style. Notably, reversal learning was rapidly restored with the omission of threat through several cycles of threat and safety contexts within one experimental session. These results extend the literature and illuminate the immediate consequence of a sustained threatening stressor (and its removal) on decision-making. Better knowledge of the immediate effects of anticipatory anxiety on behavior could improve understanding of psychopathology and may be informative for the development of effective therapy for anxiety and emotion dysregulation.