Higher-order comparative reward processing is affected by noninvasive stimulation of the ventromedial prefrontal cortex.

A crucial skill, especially in rapidly changing environments, is to be able to learn efficiently from prior rewards or losses and apply this acquired knowledge in upcoming situations. Often, we must weigh the risks of different options and decide whether an option is worth the risk or whether we should choose a safer option. The ventromedial prefrontal cortex (vmPFC) is suggested as a major hub for basic but also higher-order reward processing. Dysfunction in this region has been linked to cognitive risk factors for depression and behavioral addictions, including reduced optimism and feedback learning. Here, we test whether modulations of vmPFC excitability via noninvasive transcranial direct current stimulation (tDCS) can alter reward anticipation and reward processing. In a financial gambling task, participants chose between a higher and a lower monetary risk option and eventually received feedback whether they won or lost. Simultaneously feedback on the unchosen option was presented as well. Behavioral and magnetoencephalographic correlates of reward processing were evaluated in direct succession of either excitatory or inhibitory tDCS of the vmPFC. We were able to show modulated reward approach behavior (expectancy of greater reward magnitudes) as well as altered reevaluation of received feedback by vmPFC tDCS as indicated by modified choice behavior following the feedback. Thereby, tDCS not only influenced early, rather basic reward processing, but it also modulated higher-order comparative feedback evaluation of gains and losses relative to alternative outcomes. The neural results underline this idea, as stimulation-driven modulations of the basic reward-related effect occurred at rather early time intervals and were followed by stimulation effects related to comparative reward processing. Importantly, behavioral ratings were correlated with neural activity in left frontal areas. Our results imply a dual function of the vmPFC consisting of approaching reward (as indicated by more risky choices) and elaborately evaluating outcomes. In addition, our data suggest that vmPFC activity is associated with adaptive decision-making in the future via modulated behavioral adaptation or reinforcement learning.

Excitatory stimulation of the ventromedial prefrontal cortex reduces cognitive gambling biases via improved feedback learning.

Humans are subject to a variety of cognitive biases, such as the framing-effect or the gambler's fallacy, that lead to decisions unfitting of a purely rational agent. Previous studies have shown that the ventromedial prefrontal cortex (vmPFC) plays a key role in making rational decisions and that stronger vmPFC activity is associated with attenuated cognitive biases. Accordingly, dysfunctions of the vmPFC are associated with impulsive decisions and pathological gambling. By applying a gambling paradigm in a between-subjects design with 33 healthy adults, we demonstrate that vmPFC excitation via transcranial direct current stimulation (tDCS) reduces the framing-effect and the gambler's fallacy compared to sham stimulation. Corresponding magnetoencephalographic data suggest improved inhibition of maladaptive options after excitatory vmPFC-tDCS. Our analyses suggest that the underlying mechanism might be improved reinforcement learning, as effects only emerge over time. These findings encourage further investigations of whether excitatory vmPFC-tDCS has clinical utility in treating pathological gambling or other behavioral addictions.

Non-invasive stimulation reveals ventromedial prefrontal cortex function in reward prediction and reward processing.

Introduction: Studies suggest an involvement of the ventromedial prefrontal cortex (vmPFC) in reward prediction and processing, with reward-based learning relying on neural activity in response to unpredicted rewards or non-rewards (reward prediction error, RPE). Here, we investigated the causal role of the vmPFC in reward prediction, processing, and RPE signaling by transiently modulating vmPFC excitability using transcranial Direct Current Stimulation (tDCS). Methods: Participants received excitatory or inhibitory tDCS of the vmPFC before completing a gambling task, in which cues signaled varying reward probabilities and symbols provided feedback on monetary gain or loss. We collected self-reported and evaluative data on reward prediction and processing. In addition, cue-locked and feedback-locked neural activity via magnetoencephalography (MEG) and pupil diameter using eye-tracking were recorded. Results: Regarding reward prediction (cue-locked analysis), vmPFC excitation (versus inhibition) resulted in increased prefrontal activation preceding loss predictions, increased pupil dilations, and tentatively more optimistic reward predictions. Regarding reward processing (feedback-locked analysis), vmPFC excitation (versus inhibition) resulted in increased pleasantness, increased vmPFC activation, especially for unpredicted gains (i.e., gain RPEs), decreased perseveration in choice behavior after negative feedback, and increased pupil dilations. Discussion: Our results support the pivotal role of the vmPFC in reward prediction and processing. Furthermore, they suggest that transient vmPFC excitation via tDCS induces a positive bias into the reward system that leads to enhanced anticipation and appraisal of positive outcomes and improves reward-based learning, as indicated by greater behavioral flexibility after losses and unpredicted outcomes, which can be seen as an improved reaction to the received feedback.

A 5-min paradigm to evoke robust emotional reactivity in neuroimaging studies.

The advent of the Research Domain Criteria (RDoC) approach to funding translational neuroscience has highlighted a need for research that includes measures across multiple task types. However, the duration of any given experiment is quite limited, particularly in neuroimaging contexts, and therefore robust estimates of multiple behavioral domains are often difficult to achieve. Here we offer a "turn-key" emotion-evoking paradigm suitable for neuroimaging experiments that demonstrates strong effect sizes across widespread cortical and subcortical structures. This short series could be easily added to existing fMRI protocols, and yield a reliable estimate of emotional reactivity to complement research in other behavioral domains. This experimental adjunct could be used to enable an initial comparison of emotional modulation with the primary behavioral focus of an investigator's work, and potentially identify new relationships between domains of behavior that have not previously been recognized.

Noninvasive stimulation of the ventromedial prefrontal cortex modulates rationality of human decision-making.

The framing-effect is a bias that affects decision-making depending on whether the available options are presented with positive or negative connotations. Even when the outcome of two choices is equivalent, people have a strong tendency to avoid the negatively framed option. The ventromedial prefrontal cortex (vmPFC) is crucial for rational decision-making, and dysfunctions in this region have been linked to cognitive biases, impulsive behavior and gambling addiction. Using a financial decision-making task in combination with magnetoencephalographic neuroimaging, we show that excitatory compared to inhibitory non-invasive transcranial direct current stimulation (tDCS) of the vmPFC reduces framing-effects while improving the assessment of loss-probabilities, ultimately leading to increased overall gains. Behavioral and neural data consistently suggest that this improvement in rational decision-making is predominately due to an attenuation of biases towards negative affect (loss-aversion and risk-aversion). These findings recommend further research towards clinical applications of vmPFC-tDCS as in addictive disorders.

Transcranial Direct Current Stimulation of the Ventromedial Prefrontal Cortex Modulates Perceptual and Neural Patterns of Fear Generalization.

BACKGROUND: Overgeneralization of fear is a pathogenic marker of anxiety and stress-related disorders and has been linked with perceptual discrimination deficits, reduced fear inhibition, and prefrontal hyporeactivity to safety-signaling stimuli. We aimed to examine whether behavioral and neural patterns of fear generalization are influenced by the fear-inhibiting ventromedial prefrontal cortex (vmPFC). METHODS: Three groups of healthy participants received excitatory (n = 27), inhibitory (n = 26), or sham (n = 26) transcranial direct current stimulation of the vmPFC after a fear conditioning phase and before a fear generalization phase. We obtained, as dependent variables, fear ratings and unconditioned stimulus-expectancy ratings, perceptual aspects of fear generalization (perceptual discrimination), pupil dilations, and source estimations of event-related fields elicited by conditioned and generalization stimuli. RESULTS: After inhibitory (compared with excitatory and sham) vmPFC stimulation, we observed reduced performance in perceptual discrimination and less negative inhibitory gradients in frontal structures at midlatency and late time intervals. Fear and unconditioned stimulus-expectancy ratings as well as pupil dilation remained unaffected by stimulation. CONCLUSIONS: These findings reveal a causal contribution of vmPFC reactivity to generalization patterns and suggest that vmPFC hyporeactivity consequent on inhibitory vmPFC stimulation may serve as a model for pathological processes of fear generalization (reduced discrimination, impaired fear inhibition via frontal brain structures). This encourages further basic and clinical research on the potential of targeted brain stimulation to modulate fear generalization and overgeneralization.

Increased early motivational response to food in adolescent anorexia nervosa revealed by magnetoencephalography.

BACKGROUND: It remains unclear to what extent reduced nutritional intake in anorexia nervosa (AN) is a consequence of a reduced motivational response to food. Although self-reports typically suggest AN patients have a reduced appetitive response, behavioral and neurophysiological measures have revealed evidence for both increased and reduced attentional biases towards food stimuli. The mechanisms influencing food perception in AN, might be clarified using time-sensitive magnetoencephalography (MEG) to differentiate the early (more automatic processing) stages from the late (more controlled) stages. METHODS: MEG was recorded in 22 partially weight-restored adolescent AN patients and 29 age- and gender-matched healthy control (HC) participants during a rapid serial visual presentation paradigm using 100 high-calorie food, 100 low-calorie food, and 100 non-food pictures. Neural sources of event-related fields were estimated using the L2-Minimum-Norm method and analyzed in early (50-300 ms) and late (350-500 ms) time intervals. RESULTS: AN patients rated high-calorie food as less palatable and reported overall less food craving than HC participants. Nevertheless, in response to food pictures AN patients showed relative increased neural activity in the left occipito-temporal and inferior frontal regions in the early time interval. No group differences occurred in the late time interval. CONCLUSIONS: MEG results speak against an overall reduced motivational response to food in AN. Instead, relative increased early food processing in the visual cortex suggests greater motivated attention. A greater appetitive response to food might be an adaptive mechanism in a state of undernourishment. Yet, this relative increased food processing in AN was no longer present later, arguably reflecting rapid downregulation.

Repeated noninvasive stimulation of the ventromedial prefrontal cortex reveals cumulative amplification of pleasant compared to unpleasant scene processing: A single subject pilot study.

The ventromedial prefrontal cortex (vmPFC) is a major hub of the reward system and has been shown to activate specifically in response to pleasant / rewarding stimuli. Previous studies demonstrate enhanced pleasant cue reactivity after single applications of transcranial direct current stimulation (tDCS) to the vmPFC. Here we present a pilot case study in which we assess the cumulative impact of multiple consecutive vmPFC-tDCS sessions on the processing of visual emotional stimuli in an event-related MEG recording design. The results point to stable modulation of increased positivity biases (pleasant > unpleasant stimulus signal strength) after excitatory vmPFC stimulation and a reversed pattern (pleasant < unpleasant) after inhibitory stimulation across five consecutive tDCS sessions. Moreover, cumulative effects of these emotional bias modulations were observable for several source-localized spatio-temporal clusters, suggesting an increase in modulatory efficiency by repeated tDCS sessions. This pilot study provides evidence for improvements in the effectiveness and utility of a novel tDCS paradigm in the context of emotional processing.

Fear generalization of implicit conditioned facial features - Behavioral and magnetoencephalographic correlates.

Acquired fear responses often generalize from conditioned stimuli (CS) towards perceptually similar, but harmless generalization stimuli (GS). Knowledge on similarities between CS and GS may be explicit or implicit. Employing behavioral measures and whole-head magnetoencephalography, we here investigated the neurocognitive mechanisms underpinning implicit fear generalization. Twenty-nine participants underwent a classical conditioning procedure in which 32 different faces were either paired with an aversive scream (16 CS+) or remained unpaired (16 CS-). CS+ and CS- faces systematically differed from each other regarding their ratio of eye distance and mouth width. High versus low values on this "threat-related feature (TF)" implicitly predicted the presence or absence of the aversive scream. In pre- and post-conditioning phases, all CS and 32 novel GS faces were presented. 16 GS+ â€‹faces shared the TF of the 16 CS+ â€‹faces, while 16 â€‹GS- faces shared the TF of the 16 CS- faces. Behavioral tests confirmed that participants were fully unaware of TF-US contingencies. CS+ â€‹compared to CS- faces revealed higher unpleasantness, arousal and US-expectancy ratings. A generalization of these behavioral fear responses to GS+ â€‹compared to GS- faces was observed by trend only. Source-estimations of event-related fields showed stronger neural responses to both CS+ and GS+ â€‹compared to CS- and GS- in anterior temporal (<100 â€‹ms) and temporo-occipital (<150 â€‹ms; 553-587 â€‹ms) ventral brain regions. Reverse effects were found in dorsal frontal areas (<100 â€‹ms; 173-203 â€‹ms; 257-290 â€‹ms). Neural data also revealed selectively enhanced responses to CS+ â€‹but not GS+ â€‹stimuli in occipital regions (110-167 â€‹ms; 330-413 â€‹ms), indicating perceptual discrimination. Our data suggest that the prioritized perceptual analysis of threat-associated conditioned faces in ventral networks rapidly generalizes to novel faces sharing threat-related features. This generalization process occurs in absence of contingency awareness and may thus contribute to implicit attentional biases. The coexisting perceptual discrimination suggests that fear generalization is not a mere consequence of insufficient stimulus discrimination but rather an active, integrative process.

Noninvasive Stimulation of the Ventromedial Prefrontal Cortex Indicates Valence Ambiguity in Sad Compared to Happy and Fearful Face Processing.

The ventromedial prefrontal cortex (vmPFC) is known to be specifically involved in the processing of stimuli with pleasant, rewarding meaning to the observer. By the use of non-invasive transcranial direct current stimulation (tDCS), it was previously possible to show evidence for this valence specificity and to modulate the impact of the vmPFC on emotional network processing. Prior results showed increased neural activation during pleasant relative to unpleasant stimulus processing after excitatory compared to inhibitory vmPFC-tDCS. As dysfunctional vmPFC activation patterns are associated with major depressive disorder (MDD), tDCS of this region could render an attractive application in future therapy. Here, we investigated vmPFC-tDCS effects on sad compared to happy face processing, as sad faces are often used in the study of mood disorders. After counterbalanced inhibitory or excitatory tDCS, respectively, healthy participants viewed happy and sad faces during magnetoencephalography (MEG) recording. In addition, tDCS effects on an interpretational bias of ambiguous happy-sad face morphs and an attentional bias of a dot-probe task with happy and sad faces as emotional primes were investigated. Finally, in conjoint analyses with data from a previous sibling study (happy and fearful faces) we examined whether excitatory vmPFC-tDCS would reveal a general increase in processing of pleasant stimuli independent of the type of unpleasant stimuli applied (sad vs. fearful faces). MEG and behavioral results showed that happy faces promoted a relative positivity bias after excitatory compared to inhibitory tDCS, visible in left orbitofrontal cortex and in the emotion-primed dot-probe task. A converse pattern in the MEG data during sad face processing suggests the possible involvement of an empathy network and thus significantly differed from neuronal processing of fearful face processing. Implications for the bearing of vmPFC modulation on emotional face processing and the impact of specific unpleasant face expressions are discussed.

Identity and expression processing during classical conditioning with faces.

In classical conditioning, conditioned responses (CRs) to aversively paired (CS+) relative to unpaired (CS-) face images are often interpreted in terms of the specific individual displayed in the CS + face image having adopted an aversive emotional connotation. This interpretation requires conditioning to rely on an association between CS + face identity and the occurrence of the aversive event (UCS). Here, we tested this requirement assuming that if an association between CS + face identity and UCS occurrence is established, CRs to originally conditioned face images should transfer to novel images of same-identity faces. Forty-eight participants underwent MultiCS conditioning with eight neutral faces as CSs and electric shock as UCS. Central, peripheral, evaluative, and behavioral CRs signaled successful emotional learning (as reported in Pastor et al., 2015). Behavioral and EEG responses of consecutive passive viewing showed enhanced reactions to novel angry and happy expressions of previously shocked CS + versus nonshocked CS- identities, indicating successful CR transfer within the dimension of face identity. Investigating the nature of CR transfer, EEG revealed an interaction of identity and expression information during face processing that followed emotional congruency (i.e., stronger reactions to congruent angry CS + and happy CS- vs. incongruent angry CS- and happy CS + compounds). While correlates of transfer appeared in late and midlatency time intervals, the congruency interaction became significant within the first 100 ms of face processing. Our results suggest conditioning to rely on an association of UCS occurrence with CS + identity and point to fast dynamic interrelations between identity and expression processing.

Noninvasive stimulation of the ventromedial prefrontal cortex modulates emotional face processing.

The ventromedial prefrontal cortex (vmPFC) is associated with emotional states that can be characterized as positive affect. Moreover, a variety of psychiatric disorders that are associated with disturbed reactions toward reward- or safety-signaling stimuli reveal functional or structural anomalies within this area. Thus, neuromodulation of this region via transcranial direct current stimulation (tDCS) offers an attractive opportunity to noninvasively influence pleasant emotional and reward processing. Recent experiments revealed hemodynamic and electrophysiological evidence for valence specific modulations of emotional scene processing after excitatory and inhibitory tDCS of the vmPFC. Here, we identified that tDCS modulation of vmPFC during emotional face processing results in effects convergent with scene processing, in that excitatory tDCS increased neural reactivity during happy compared to fearful face perception, whereas inhibitory stimulation led to a converse effect. In addition, behavioral data (affect identification of ambiguous expressive faces) revealed a bias toward preferential processing of happy compared to fearful faces after excitatory compared to after inhibitory stimulation. These results further support the vmPFC as an appropriate target for noninvasive neuromodulation of an appetitive processing network in patients suffering from disturbed cognition of reward- and safety-signaling stimuli. It should however be noted that electrophysiological pre-tDCS differences at earlier time intervals of emotional face and scene processing appeared amplified by tDCS, which remains to be investigated.

Noninvasive Stimulation of the Ventromedial Prefrontal Cortex Enhances Pleasant Scene Processing.

Depressive patients typically show biased attention towards unpleasant and away from pleasant emotional material. Imaging studies suggest that dysfunctions in a distributed neural network, including the ventromedial prefrontal cortex (vmPFC), are associated with this processing bias. Accordingly, changes in vmPFC activation should mediate changes in processing of emotional stimuli. Here, we investigated the effect of inhibitory and excitatory transcranial direct current stimulation (tDCS) of the vmPFC on emotional scene processing in two within-subject experiments using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). Both studies showed that excitatory relative to inhibitory tDCS amplifies processing of pleasant compared to unpleasant scenes in healthy participants. This modulatory effect occurred in a distributed network including sensory and prefrontal cortex regions and was visible during very early to late processing stages. Findings are discussed with regard to neurophysiological models of emotional processing. The convergence of stimulation effects across independent groups of healthy participants and complementary neuroimaging methods (fMRI, MEG) provides a basis for further investigation of a potentially therapeutic use of this novel stimulation approach in patients with depression or other affective disorders.

An evil face? Verbal evaluative multi-CS conditioning enhances face-evoked mid-latency magnetoencephalographic responses.

Humans have a remarkable capacity for rapid affective learning. For instance, using first-order US such as odors or electric shocks, magnetoencephalography (MEG) studies of multi-CS conditioning demonstrate enhanced early (<150 ms) and mid-latency (150-300 ms) visual evoked responses to affectively conditioned faces, together with changes in stimulus evaluation. However, particularly in social contexts, human affective learning is often mediated by language, a class of complex higher-order US. To elucidate mechanisms of this type of learning, we investigate how face processing changes following verbal evaluative multi-CS conditioning. Sixty neutral expression male faces were paired with phrases about aversive crimes (30) or neutral occupations (30). Post conditioning, aversively associated faces evoked stronger magnetic fields in a mid-latency interval between 220 and 320 ms, localized primarily in left visual cortex. Aversively paired faces were also rated as more arousing and more unpleasant, evaluative changes occurring both with and without contingency awareness. However, no early MEG effects were found, implying that verbal evaluative conditioning may require conceptual processing and does not engage rapid, possibly sub-cortical, pathways. Results demonstrate the efficacy of verbal evaluative multi-CS conditioning and indicate both common and distinct neural mechanisms of first- and higher-order multi-CS conditioning, thereby informing theories of associative learning.

Healthy individuals maintain adaptive stimulus evaluation under predictable and unpredictable threat.

The anxiety inducing paradigms such as the threat-of-shock paradigm have provided ample data on the emotional processing of predictable and unpredictable threat, but little is known about the processing of aversive, threat-irrelevant stimuli in these paradigms. We investigated how the predictability of threat influences the neural visual processing of threat-irrelevant fearful and neutral faces. Thirty-two healthy individuals participated in an NPU-threat test, consisting of a safe or neutral condition (N) and a predictable (P) as well as an unpredictable (U) threat condition, using audio-visual threat stimuli. In all NPU-conditions, we registered participants' brain responses to threat-irrelevant faces via magnetoencephalography. The data showed that increasing unpredictability of threat evoked increasing emotion regulation during face processing predominantly in dorsolateral prefrontal cortex regions during an early to mid-latency time interval. Importantly, we obtained only main effects but no significant interaction of facial expression and conditions of different threat predictability, neither in behavioral nor in neural data. Healthy individuals with average trait anxiety are thus able to maintain adaptive stimulus evaluation processes under predictable and unpredictable threat conditions.

Magnetoencephalographic Correlates of Emotional Processing in Major Depression Before and After Pharmacological Treatment.

BACKGROUND: In major depressive disorder (MDD), electrophysiological and imaging studies suggest reduced neural activity in the parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were analyzed for the first time in a pre-/post-treatment design by means of magnetoencephalography (MEG), allowing for detecting temporal dynamics of brain activation. METHODS: Twenty-five medication-free Caucasian in-patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant, unpleasant, and neutral pictures. Fifteen patients were followed-up with a second MEG session after 4 weeks of antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. The clinical course of depression was assessed using the Hamilton Depression scale. RESULTS: Prior to treatment, an overall neocortical hypoactivation during emotional processing, particularly at the parietal regions and areas at the right temporoparietal junction, as well as abnormal valence-specific reactions at the right parietal and bilateral dorsolateral prefrontal cortex (dlPFC) regions were observed in patients compared to controls. These effects occurred <150 ms, suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at the right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy. CONCLUSIONS: The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto-parieto-temporal network, possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success.

Facing Challenges in Differential Classical Conditioning Research: Benefits of a Hybrid Design for Simultaneous Electrodermal and Electroencephalographic Recording.

Several challenges make it difficult to simultaneously investigate central and autonomous nervous system correlates of conditioned stimulus (CS) processing in classical conditioning paradigms. Such challenges include, for example, the discrepant requirements of electroencephalography (EEG) and electrodermal activity (EDA) recordings with regard to multiple repetitions of conditions and sufficient trial duration. Here, we propose a MultiCS conditioning set-up, in which we increased the number of CSs, decreased the number of learning trials, and used trials of short and long durations for meeting requirements of simultaneous EEG-EDA recording in a differential aversive conditioning task. Forty-eight participants underwent MultiCS conditioning, in which four neutral faces (CS+) were paired four times each with aversive electric stimulation (unconditioned stimulus) during acquisition, while four different neutral faces (CS-) remained unpaired. When comparing after relative to before learning measurements, EEG revealed an enhanced centro-posterior positivity to CS+ vs. CS- during 368-600 ms, and subjective ratings indicated CS+ to be less pleasant and more arousing than CS-. Furthermore, changes in CS valence and arousal were strong enough to bias subjective ratings when faces of CS+/CS- identity were displayed with different emotional expression (happy, angry) in a post-experimental behavioral task. In contrast to a persistent neural and evaluative CS+/CS- differentiation that sustained multiple unreinforced CS presentations, electrodermal differentiation was rapidly extinguished. Current results suggest that MultiCS conditioning provides a promising paradigm for investigating pre-post-learning changes under minimal influences of extinction and overlearning of simple stimulus features. Our data also revealed methodological pitfalls, such as the possibility of occurring artifacts when combining different acquisition systems for central and peripheral psychophysiological measures.

Rapid prefrontal cortex activation towards aversively paired faces and enhanced contingency detection are observed in highly trait-anxious women under challenging conditions.

Relative to healthy controls, anxiety-disorder patients show anomalies in classical conditioning that may either result from, or provide a risk factor for, clinically relevant anxiety. Here, we investigated whether healthy participants with enhanced anxiety vulnerability show abnormalities in a challenging affective-conditioning paradigm, in which many stimulus-reinforcer associations had to be acquired with only few learning trials. Forty-seven high and low trait-anxious females underwent MultiCS conditioning, in which 52 different neutral faces (CS+) were paired with an aversive noise (US), while further 52 faces (CS-) remained unpaired. Emotional learning was assessed by evaluative (rating), behavioral (dot-probe, contingency report), and neurophysiological (magnetoencephalography) measures before, during, and after learning. High and low trait-anxious groups did not differ in evaluative ratings or response priming before or after conditioning. High trait-anxious women, however, were better than low trait-anxious women at reporting CS+/US contingencies after conditioning, and showed an enhanced prefrontal cortex (PFC) activation towards CS+ in the M1 (i.e., 80-117 ms) and M170 time intervals (i.e., 140-160 ms) during acquisition. These effects in MultiCS conditioning observed in individuals with elevated trait anxiety are consistent with theories of enhanced conditionability in anxiety vulnerability. Furthermore, they point towards increased threat monitoring and detection in highly trait-anxious females, possibly mediated by alterations in visual working memory.

Cognitive emotion regulation in children: Reappraisal of emotional faces modulates neural source activity in a frontoparietal network.

Emotion regulation has an important role in child development and psychopathology. Reappraisal as cognitive regulation technique can be used effectively by children. Moreover, an ERP component known to reflect emotional processing called late positive potential (LPP) can be modulated by children using reappraisal and this modulation is also related to children's emotional adjustment. The present study seeks to elucidate the neural generators of such LPP effects. To this end, children aged 8-14 years reappraised emotional faces, while neural activity in an LPP time window was estimated using magnetoencephalography-based source localization. Additionally, neural activity was correlated with two indexes of emotional adjustment and age. Reappraisal reduced activity in the left dorsolateral prefrontal cortex during down-regulation and enhanced activity in the right parietal cortex during up-regulation. Activity in the visual cortex decreased with increasing age, more adaptive emotion regulation and less anxiety. Results demonstrate that reappraisal changed activity within a frontoparietal network in children. Decreasing activity in the visual cortex with increasing age is suggested to reflect neural maturation. A similar decrease with adaptive emotion regulation and less anxiety implies that better emotional adjustment may be associated with an advance in neural maturation.

Rapid plasticity in the prefrontal cortex during affective associative learning.

MultiCS conditioning is an affective associative learning paradigm, in which affective categories consist of many similar and complex stimuli. Comparing visual processing before and after learning, recent MultiCS conditioning studies using time-sensitive magnetoencephalography (MEG) revealed enhanced activation of prefrontal cortex (PFC) regions towards emotionally paired versus neutral stimuli already during short-latency processing stages (i.e., 50 to 80 ms after stimulus onset). The present study aimed at showing that this rapid differential activation develops as a function of the acquisition and not the extinction of the emotional meaning associated with affectively paired stimuli. MEG data of a MultiCS conditioning study were analyzed with respect to rapid changes in PFC activation towards aversively (electric shock) paired and unpaired faces that occurred during the learning of stimulus-reinforcer contingencies. Analyses revealed an increased PFC activation towards paired stimuli during 50 to 80 ms already during the acquisition of contingencies, which emerged after a single pairing with the electric shock. Corresponding changes in stimulus valence could be observed in ratings of hedonic valence, although participants did not seem to be aware of contingencies. These results suggest rapid formation and access of emotional stimulus meaning in the PFC as well as a great capacity for adaptive and highly resolving learning in the brain under challenging circumstances.