How the Dorsolateral Prefrontal Cortex Controls Affective Processing in Absence of Visual Awareness – Insights From a Combined EEG-rTMS Study

The dorsolateral prefrontal cortex (DLPFC) plays a key role in the modulation of affective processing. However, its specific role in the regulation of neurocognitive processes underlying the interplay of affective perception and visual awareness has remained largely unclear. Using a mixed factorial design, this study investigated effects of inhibitory continuous theta-burst stimulation (cTBS) of the right DLPFC (rDLPFC) compared to an Active Control condition on behavioral (N = 48) and electroencephalographic (N = 38) correlates of affective processing in healthy Chinese participants. Event-related potentials (ERPs) in response to passively viewed subliminal and supraliminal negative and neutral natural scenes were recorded before and after cTBS application. We applied minimum-norm approaches to estimate the corresponding neuronal sources. On a behavioral level, we found evidence for reduced emotional interference by, and less negative and aroused ratings of negative supraliminal stimuli following rDLPFC inhibition. We found no evidence for stimulation effects on self-reported mood or the behavioral discrimination of subliminal stimuli. On a neurophysiological level, rDLPFC inhibition relatively enhanced occipito-parietal brain activity for both subliminal and supraliminal negative compared to neutral images (112–268 ms; 320–380 ms). The early onset and localization of these effects suggests that rDLPFC inhibition boosts automatic processes of “emotional attention” independently of visual awareness. Further, our study reveals the first available evidence for a differential influence of rDLPFC inhibition on subliminal versus supraliminal neural emotion processing. Explicitly, our findings indicate that rDLPFC inhibition selectively enhances late (292–360 ms) activity in response to supraliminal negative images. We tentatively suggest that this differential frontal activity likely reflects enhanced awareness-dependent down-regulation of negative scene processing, eventually leading to facilitated disengagement from and less negative and aroused evaluations of negative supraliminal stimuli

Brief learning induces a memory bias for arousing-negative words: an fMRI study in high and low trait anxious persons

Eden AS, Dehmelt V, Bischoff M, et al. Brief learning induces a memory bias for arousing-negative words: an fMRI study in high and low trait anxious persons. Frontiers in Psychology. 2015;6: 1226.Persons suffering from anxiety disorders display facilitated processing of arousing and negative stimuli, such as negative words. This memory bias is reflected in better recall and increased amygdala activity in response to such stimuli. However, individual learning histories were not considered in most studies, a concern that we meet here. Thirty-four female persons (half with high-, half with low trait anxiety) participated in a criterion-based associative word-learning paradigm, in which neutral pseudowords were paired with aversive or neutral pictures, which should lead to a valence change for the negatively paired pseudowords. After learning, pseudowords were tested with fMRI to investigate differential brain activation of the amygdala evoked by the newly acquired valence. Explicit and implicit memory was assessed directly after training and in three follow-ups at 4-day intervals. The behavioral results demonstrate that associative word-learning leads to an explicit (but no implicit) memory bias for negatively linked pseudowords, relative to neutral ones, which confirms earlier studies. Bilateral amygdala activation underlines the behavioral effect: Higher trait anxiety is correlated with stronger amygdala activation for negatively linked pseudowords than for neutrally linked ones. Most interestingly, this effect is also present for negatively paired pseudowords that participants could not remember well. Moreover, neutrally paired pseudowords evoked higher amygdala reactivity than completely novel ones in highly anxious persons, which can be taken as evidence for generalization. These findings demonstrate that few word-learning trials generate a memory bias for emotional stimuli, indexed both behaviorally and neurophysiologically. Importantly, the typical memory bias for emotional stimuli and the generalization to neutral ones is larger in high anxious persons

Pons to Posterior Cingulate Functional Projections Predict Affective Processing Changes in the Elderly Following Eight Weeks of Meditation Training

Evidence indicates meditation facilitates affective regulation and reduces negative affect. It also influences resting-state functional connectivity between affective networks and the posterior cingulate (PCC)/precuneus, regions critically implicated in self-referential processing. However, no longitudinal study employing active control group has examined the effect of meditation training on affective processing, PCC/precuneus connectivity, and their association. Here, we report that eight-week meditation, but not relaxation, training ‘neutralized’ affective processing of positive and negative stimuli in healthy elderly participants. Additionally, meditation versus relaxation training increased the positive connectivity between the PCC/precuneus and the pons, the direction of which was largely directed from the pons to the PCC/precuneus, as revealed by dynamic causal modeling. Further, changes in connectivity between the PCC/precuneus and pons predicted changes in affective processing after meditation training. These findings indicate meditation promotes self-referential affective regulation based on increased regulatory influence of the pons on PCC/precuneus, which new affective-processing strategy is employed across both resting state and when evaluating affective stimuli. Such insights have clinical implications on interventions on elderly individuals with affective disorders

Self-guided digital treatment with virtual reality for panic disorder and agoraphobia

Finanziert im Rahmen der DEAL-Verträge durch die Universitätsbibliothek SiegenBackground Cognitive behavioral therapy is the first-line treatment for patients with panic disorder (PD) and agoraphobia (AG). Yet, many patients remain untreated due to limited treatment resources. Digital self-guided short-term treatment applications may help to overcome this issue. While some therapeutic applications are already supported by health insurance companies, data on their efficacy is limited. The current study investigates the effect of self-guided digital treatment comprising psychoeducation and virtual reality exposure therapy (VRET). Methods Thirty patients diagnosed with PD, AG, or panic disorder with agoraphobia (PDA) will be randomly assigned to either the experimental group (EG) or the control group (CG). Participants of both groups will undergo baseline diagnostics in the first two sessions. The subsequent treatment for the EG consists of a self-guided 6-week phase of application-based psychoeducation, one therapy session preparing for the VRET, and 4 weeks of application-based self-guided VRET. To control for the potential effects of the therapy session with the therapist, the CG will receive relaxation and stress-reduction training instead. All patients will then undergo a closing session which terminates with the post-assessment (~ 10 weeks after baseline assessment) and a follow-up assessment 6 weeks following the closing session. Symptom severity (primary outcome) will be assessed at baseline, interim, post-treatment, and follow-up. Additionally, remission status (secondary outcome) will be obtained at follow-up. Both measures will be compared between the groups. Discussion The current study aims at providing insights into the efficacy of short-term treatment applications including psychoeducation and self-guided VRET. If successful, this approach might be a feasible and promising way to ease the burden of PD, AG, and PDA on the public health system and contribute to a faster access to treatment

Self-guided virtual reality therapy for social anxiety disorder

Finanziert im Rahmen der DEAL-Verträge durch die Universitätsbibliothek SiegenBackground Social anxiety disorder (SAD) is a highly prevalent mental disorder associated with enormous stress and suffering. Cognitive behavior therapy (CBT) is the first-line treatment for SAD, yet its accessibility is often constrained with long waiting times. Digital therapeutic applications, including psychoeducation and self-guided behavioral experiments in virtual reality (VR), could facilitate access and reduce waiting times. The study aims to investigate if ultra-short-time therapy involving self-guided digital therapeutic applications with VR components can reduce the severity of SAD. Methods Forty SAD patients will participate in this randomized controlled trial. Half will get access to a self-guided, digital therapeutic application with exposure-based behavioral experiments in VR, while the other half will receive a control treatment. Both treatments include four therapeutic appointments. Changes in the severity of SAD will be measured after each appointment and on a 6-week follow-up assessment and will be compared between groups, with the change in SAD measured at baseline- and post-assessment as primary outcome. Discussion Self-guided digital therapeutic applications including ultra-short-time therapy combined with VR could help reduce the waiting time for patients and relieve the health system. The results of this study may inform psychotherapists regarding the potential of self-guided digital therapeutic applications including exposure-based behavioral experiments in VR for SAD and will provide important insight for future research on VR therapy

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

Of 'disgrace' and 'pain'--corticolimbic interaction patterns for disorder-relevant and emotional words in social phobia.

Limbic hyperactivation and an impaired functional interplay between the amygdala and the prefrontal cortex are discussed to go along with, or even cause, pathological anxiety. Within the multi-faceted group of anxiety disorders, the highly prevalent social phobia (SP) is characterized by excessive fear of being negatively evaluated. Although there is widespread evidence for amygdala hypersensitivity to emotional faces in SP, verbal material has rarely been used in imaging studies, in particular with an eye on disorder-specificity. Using functional magnetic resonance imaging (fMRI) and a block design consisting of (1) overall negative, (2) social-phobia related, (3) positive, and (4) neutral words, we studied 25 female patients with social phobia and 25 healthy female control subjects (HC). Results demonstrated amygdala hyperactivation to disorder-relevant but not to generally negative words in SP patients, with a positive correlation to symptom severity. A functional connectivity analysis revealed a weaker coupling between the amygdala and the left middle frontal gyrus in patients. Symptom severity was negatively related to connectivity strength between the amygdala and the ventromedial prefrontal and orbitofrontal cortex (Brodmann Area 10 and 11). The findings clearly support the view of a hypersensitive threat-detection system, combined with disorder-related alterations in amygdala-prefrontal cortex connectivity in pathological anxiety

Paradigm.

<p>(A) The procedure consisted of assessments of behavior and of neuronal activity via Magnetoencephalography (MEG). For behavior, participants completed subjective (SAM) ratings of hedonic valence and emotional arousal of all conditioned stimuli (CSs) before and after conditioning as well as an affective priming and a CS-US matching task. MEG recordings were acquired, while participants underwent MultiCS conditioning. (B) MultiCS conditioning consisted of three phases: a pre-learning, a learning, and a post-learning phase. During the learning phase, half of the CS faces were paired (CS+; solid frame) with an aversive electric stimulation (US), while the other half remained unpaired (CS−; dashed frame). During pre- and post-learning phases, all CSs were shown without US presentations.</p

Evaluative results.

<p>Visualization of the change in hedonic valence for aversively paired (CS+; solid line) and unpaired (CS−; dotted line) faces across sessions (i.e., before and after MultiCS conditioning).</p