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.

Meditation-induced neuroplastic changes of the prefrontal network are associated with reduced valence perception in older people.

BACKGROUND: Neuroplastic underpinnings of meditation-induced changes in affective processing are largely unclear. METHODS: We included healthy older participants in an active-controlled experiment. They were involved a meditation training or a control relaxation training of eight weeks. Associations between behavioral and neural morphometric changes induced by the training were examined. RESULTS: The meditation group demonstrated a change in valence perception indexed by more neutral valence ratings of positive and negative affective images. These behavioral changes were associated with synchronous structural enlargements in a prefrontal network involving the ventromedial prefrontal cortex and the inferior frontal sulcus. In addition, these neuroplastic effects were modulated by the enlargement in the inferior frontal junction. In contrast, these prefrontal enlargements were absent in the active control group, which completed a relaxation training. Supported by a path analysis, we propose a model that describes how meditation may induce a series of prefrontal neuroplastic changes related to valence perception. These brain areas showing meditation-induced structural enlargements are reduced in older people with affective dysregulations. CONCLUSION: We demonstrated that a prefrontal network was enlarged after eight weeks of meditation training. Our findings yield translational insights in the endeavor to promote healthy aging by means of meditation.

Effects of vicarious pain on self-pain perception: investigating the role of awareness.

The observation of pain in others may enhance or reduce self-pain, yet the boundary conditions and factors that determine the direction of such effects are poorly understood. The current study set out to show that visual stimulus awareness plays a crucial role in determining whether vicarious pain primarily activates behavioral defense systems that enhance pain sensitivity and stimulate withdrawal or appetitive systems that attenuate pain sensitivity and stimulate approach. We employed a mixed factorial design with the between-subject factors exposure time (subliminal vs optimal) and vicarious pain (pain vs no pain images), and the within-subject factor session (baseline vs trial) to investigate how visual awareness of vicarious pain images affects subsequent self-pain in the cold-pressor test. Self-pain tolerance, intensity and unpleasantness were evaluated in a sample of 77 healthy participants. Results revealed significant interactions of exposure time and vicarious pain in all three dependent measures. In the presence of visual awareness (optimal condition), vicarious pain compared to no-pain elicited overall enhanced self-pain sensitivity, indexed by reduced pain tolerance and enhanced ratings of pain intensity and unpleasantness. Conversely, in the absence of visual awareness (subliminal condition), vicarious pain evoked decreased self-pain intensity and unpleasantness while pain tolerance remained unaffected. These findings suggest that the activation of defense mechanisms by vicarious pain depends on relatively elaborate cognitive processes, while - strikingly - the appetitive system is activated in highly automatic manner independent from stimulus awareness. Such mechanisms may have evolved to facilitate empathic, protective approach responses toward suffering individuals, ensuring survival of the protective social group.

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.

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

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.

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.

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.

Have we met before? Neural correlates of emotional learning in women with social phobia.

BACKGROUND: Altered memory processes are thought to be a key mechanism in the etiology of anxiety disorders, but little is known about the neural correlates of fear learning and memory biases in patients with social phobia. The present study therefore examined whether patients with social phobia exhibit different patterns of neural activation when confronted with recently acquired emotional stimuli. METHODS: Patients with social phobia and a group of healthy controls learned to associate pseudonames with pictures of persons displaying either a fearful or a neutral expression. The next day, participants read the pseudonames in the magnetic resonance imaging scanner. Afterwards, 2 memory tests were carried out. RESULTS: We enrolled 21 patients and 21 controls in our study. There were no group differences for learning performance, and results of the memory tests were mixed. On a neural level, patients showed weaker amygdala activation than controls for the contrast of names previously associated with fearful versus neutral faces. Social phobia severity was negatively related to amygdala activation. Moreover, a detailed psychophysiological interaction analysis revealed an inverse correlation between disorder severity and frontolimbic connectivity for the emotional > neutral pseudonames contrast. LIMITATIONS: Our sample included only women. CONCLUSION: Our results support the theory of a disturbed cortico limbic interplay, even for recently learned emotional stimuli. We discuss the findings with regard to the vigilance-avoidance theory and contrast them to results indicating an oversensitive limbic system in patients with social phobia.

How 'love' and 'hate' differ from 'sleep': using combined electro/magnetoencephalographic data to reveal the sources of early cortical responses to emotional words.

Emotional words--as symbols for biologically relevant concepts--are preferentially processed in brain regions including the visual cortex, frontal and parietal regions, and a corticolimbic circuit including the amygdala. Some of the brain structures found in functional magnetic resonance imaging are not readily apparent in electro- and magnetoencephalographic (EEG; MEG) measures. By means of a combined EEG/MEG source localization procedure to fully exploit the available information, we sought to reduce these discrepancies and gain a better understanding of spatiotemporal brain dynamics underlying emotional-word processing. Eighteen participants read high-arousing positive and negative, and low-arousing neutral nouns, while EEG and MEG were recorded simultaneously. Combined current-density reconstructions (L2-minimum norm least squares) for two early emotion-sensitive time intervals, the P1 (80-120 ms) and the early posterior negativity (EPN, 200-300 ms), were computed using realistic individual head models with a cortical constraint. The P1 time window uncovered an emotion effect peaking in the left middle temporal gyrus. In the EPN time window, processing of emotional words was associated with enhanced activity encompassing parietal and occipital areas, and posterior limbic structures. We suggest that lexical access, being underway within 100 ms, is speeded and/or favored for emotional words, possibly on the basis of an "emotional tagging" of the word form during acquisition. This gives rise to their differential processing in the EPN time window. The EPN, as an index of natural selective attention, appears to reflect an elaborate interplay of distributed structures, related to cognitive functions, such as memory, attention, and evaluation of emotional stimuli.

Early prefrontal brain responses to the Hedonic quality of emotional words--a simultaneous EEG and MEG study.

The hedonic meaning of words affects word recognition, as shown by behavioral, functional imaging, and event-related potential (ERP) studies. However, the spatiotemporal dynamics and cognitive functions behind are elusive, partly due to methodological limitations of previous studies. Here, we account for these difficulties by computing combined electro-magnetoencephalographic (EEG/MEG) source localization techniques. Participants covertly read emotionally high-arousing positive and negative nouns, while EEG and MEG were recorded simultaneously. Combined EEG/MEG current-density reconstructions for the P1 (80-120 ms), P2 (150-190 ms) and EPN component (200-300 ms) were computed using realistic individual head models, with a cortical constraint. Relative to negative words, the P1 to positive words predominantly involved language-related structures (left middle temporal and inferior frontal regions), and posterior structures related to directed attention (occipital and parietal regions). Effects shifted to the right hemisphere in the P2 component. By contrast, negative words received more activation in the P1 time-range only, recruiting prefrontal regions, including the anterior cingulate cortex (ACC). Effects in the EPN were not statistically significant. These findings show that different neuronal networks are active when positive versus negative words are processed. We account for these effects in terms of an "emotional tagging" of word forms during language acquisition. These tags then give rise to different processing strategies, including enhanced lexical processing of positive words and a very fast language-independent alert response to negative words. The valence-specific recruitment of different networks might underlie fast adaptive responses to both approach- and withdrawal-related stimuli, be they acquired or biological.