Armita Golkar

Distinct Contributions of the Dorsolateral Prefrontal and Orbitofrontal Cortex during Emotion Regulation

The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC) and the lateral orbitofrontal cortex (OFC) contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task.

Are fear memories erasable?-reconsolidation of learned fear with fear-relevant and fear-irrelevant stimuli

Recent advances in the field of fear learning have demonstrated that a single reminder exposure prior to extinction training can prevent the return of extinguished fear by disrupting the process of reconsolidation. These findings have however proven hard to replicate in humans. Given the significant implications of preventing the return of fear, the purpose of the present study was to further study the putative effects of disrupting reconsolidation. In two experiments, we assessed whether extinction training initiated within the reconsolidation time window could abolish the return of fear using fear-relevant (Experiment 1) or fear-irrelevant (Experiment 2) conditioned stimuli (CS). In both experiments, participants went through conditioning, extinction, and reinstatement testing on three consecutive days, with one of two reinforced CS being reactivated 10 min prior to extinction. We found that a single reminder exposure prior to extinction training did not prevent the return of extinguished fear responding using either fear-relevant or fear-irrelevant CSs. Our findings point to the need to further study the specific parameters that enable disruption of reconsolidation.

5-HTTLPR and COMTval158met genotype gate amygdala reactivity and habituation

Amygdala reactivity is a heritable trait, potentiated in affective disorders and associated with both the 5-HTTLPR and the COMTval158met polymorphism. Fifty-four healthy volunteers selected a priori based on gender and 5-HTTLPR/rs25531 and COMTval158met genotypes performed a passive viewing task of angry facial expressions using fMRI. Amygdala reactivity and habituation were investigated using the a priori anatomical region of interest (ROI) approach. Furthermore, salivary cortisol and skin conductance responses were recorded. We observed an effect of 5-HTTLPR on right amygdala reactivity (s-carrier>l/l) and COMTval158met on left amygdala reactivity (met/met>val-carrier). We provide preliminary evidence that different amygdala habituation curves may partly underlie the differences between 5-HTTLPR and not COMT genotype groups. Further, exploratory analyses find no evidence for additive or interaction effects. Our results support that 5-HTTLPR s-carriers and COMT met/met carriers may be more sensitive to the detection of biologically and socially relevant information and suggest a mechanism behind this for the 5-HTTLPR.

Don’t fear ‘fear conditioning’: Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear

HighlightsOriginates from discussions on replicability and researchers degrees of freedom.Aims at stimulating discussions on methods applied in fear conditioning research.Addresses critical issues on terminology, design, methods, analysis.Serves as comprehensive compendium and critical evaluation of read‐out measures.Highlights methodological considerations when studying individual differences. ABSTRACT The so‐called ‘replicability crisis’ has sparked methodological discussions in many areas of science in general, and in psychology in particular. This has led to recent endeavours to promote the transparency, rigour, and ultimately, replicability of research. Originating from this zeitgeist, the challenge to discuss critical issues on terminology, design, methods, and analysis considerations in fear conditioning research is taken up by this work, which involved representatives from fourteen of the major human fear conditioning laboratories in Europe. This compendium is intended to provide a basis for the development of a common procedural and terminology framework for the field of human fear conditioning. Whenever possible, we give general recommendations. When this is not feasible, we provide evidence‐based guidance for methodological decisions on study design, outcome measures, and analyses. Importantly, this work is also intended to raise awareness and initiate discussions on crucial questions with respect to data collection, processing, statistical analyses, the impact of subtle procedural changes, and data reporting specifically tailored to the research on fear conditioning.

5-HT7 receptor stimulation by 8-OH-DPAT counteracts the impairing effect of 5-HT1A receptor stimulation on contextual learning in mice

The principal 5-HT(1A) receptor agonist 8-Hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) impairs several different types of learning. Besides 5-HT(1A) receptors, 8-OH-DPAT stimulates 5-HT(7) receptors, but it is not known whether 5-HT(7) receptors contribute to the impairments. The 5-HT(7) receptor antagonist (2R)-1-[(3-Hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl] pyrrolidine (SB-269970) was combined with 8-OH-DPAT to dissociate 5-HT(1A) from 5-HT(7) receptor-mediated effects, in the passive avoidance task for emotional learning. SB-269970 intensified impairments caused by 8-OH-DPAT. SB-269970 alone had no effect on memory performance, but moderately decreased retention under suboptimal learning conditions. These findings indicate that 5-HT(7) receptor stimulation by 8-OH-DPAT counteracts 5-HT(1A) receptor-mediated impairments in hippocampal-dependent contextual learning.

A review on human reinstatement studies: an overview and methodological challenges

In human research, studies of return of fear (ROF) phenomena, and reinstatement in particular, began only a decade ago and recently are more widely used, e.g., as outcome measures for fear/extinction memory manipulations (e.g., reconsolidation). As reinstatement research in humans is still in its infancy, providing an overview of its stability and boundary conditions and summarizing methodological challenges is timely to foster fruitful future research. As a translational endeavor, clarifying the circumstances under which (experimental) reinstatement occurs may offer a first step toward understanding relapse as a clinical phenomenon and pave the way for the development of new pharmacological or behavioral ways to prevent ROF. The current state of research does not yet allow pinpointing these circumstances in detail and we hope this review will aid the research field to advance in this direction. As an introduction, we begin with a synopsis of rodent work on reinstatement and theories that have been proposed to explain the findings. The review however mainly focuses on reinstatement in humans. We first describe details and variations of the experimental setup in reinstatement studies in humans and give a general overview of results. We continue with a compilation of possible experimental boundary conditions and end with the role of individual differences and behavioral and/or pharmacological manipulations. Furthermore, we compile important methodological and design details on the published studies in humans and end with open research questions and some important methodological and design recommendations as a guide for future research.

Amygdala-dependent fear conditioning in humans is modulated by the BDNFval66met polymorphism

The brain-derived neurotrophic factor (BDNF) is critically involved in neuroplasticity, as well as the acquisition, consolidation, and retention of hippocampal- and amygdala-dependent learning. A common functional A-->G single nucleotide polymorphism (BDNFval66met) in the prodomain of the human BDNF gene is associated with abnormal intracellular trafficking and reduced activity-dependent BDNF release. We studied the effect of BDNFval66met in an aversive differential fear conditioning, and a delayed extinction paradigm in 57 healthy participants. Pictures of male faces were used as stimuli and fear learning was quantified by fear potentiated startle (FPS) and skin conductance responses (SCR). Aware BDNF met-carriers show a deficit in amygdala-dependent fear conditioning as indicated by an absence of FPS responses in the last acquisition block. This deficit was maintained in the first block of extinction. No genotype differences were found in conditioned SCR discrimination. These data provide evidence for the involvement of BDNF signaling in human amygdala-dependent learning. We suggest that the BDNF met-allele may have a protective effect for the development of affective pathologies that may be mediated via reduced synaptic plasticity induced by negative experience.

In Your Face: Risk of Punishment Enhances Cognitive Control and Error-Related Activity in the Corrugator Supercilii Muscle

Cognitive control is needed when mistakes have consequences, especially when such consequences are potentially harmful. However, little is known about how the aversive consequences of deficient control affect behavior. To address this issue, participants performed a two-choice response time task where error commissions were expected to be punished by electric shocks during certain blocks. By manipulating (1) the perceived punishment risk (no, low, high) associated with error commissions, and (2) response conflict (low, high), we showed that motivation to avoid punishment enhanced performance during high response conflict. As a novel index of the processes enabling successful cognitive control under threat, we explored electromyographic activity in the corrugator supercilii (cEMG) muscle of the upper face. The corrugator supercilii is partially controlled by the anterior midcingulate cortex (aMCC) which is sensitive to negative affect, pain and cognitive control. As hypothesized, the cEMG exhibited several key similarities with the core temporal and functional characteristics of the Error-Related Negativity (ERN) ERP component, the hallmark index of cognitive control elicited by performance errors, and which has been linked to the aMCC. The cEMG was amplified within 100 ms of error commissions (the same time-window as the ERN), particularly during the high punishment risk condition where errors would be most aversive. Furthermore, similar to the ERN, the magnitude of error cEMG predicted post-error response time slowing. Our results suggest that cEMG activity can serve as an index of avoidance motivated control, which is instrumental to adaptive cognitive control when consequences are potentially harmful.

Recognizing Masked Threat: Fear Betrays, But Disgust You Can Trust

If emotions guide consciousness, people may recognize degraded objects in center view more accurately if they either fear the objects or are disgusted by them. Therefore, we studied whether recognition of spiders and snakes correlates with individual differences in spider fear, snake fear, and disgust sensitivity. Female students performed a recognition task with pictures of spiders, snakes, flowers, and mushrooms as well as blanks. Pictures were backward masked to reduce picture visibility. Signal detection analyses showed that recognition of spiders and snakes was correlated with disgust sensitivity but not with fear of spiders or snakes. Further, spider fear correlated with the tendency to misinterpret blanks as threatening (response bias). These findings suggest that effects on recognition and response biases to emotional pictures vary for different emotions and emotional traits. Whereas fear may induce response biases, disgust may facilitate recognition.

Other People as Means to a Safe End Vicarious Extinction Blocks the Return of Learned Fear

Information about what is dangerous and safe in the environment is often transferred from other individuals through social forms of learning, such as observation. Past research has focused on the observational, or vicarious, acquisition of fears, but little is known about how social information can promote safety learning. To address this issue, we studied the effects of vicarious-extinction learning on the recovery of conditioned fear. Compared with a standard extinction procedure, vicarious extinction promoted better extinction and effectively blocked the return of previously learned fear. We confirmed that these effects could not be attributed to the presence of a learning model per se but were specifically driven by the model’s experience of safety. Our results confirm that vicarious and direct emotional learning share important characteristics but that social-safety information promotes superior down-regulation of learned fear. These findings have implications for emotional learning, social-affective processes, and clinical practice.