Good moments to stimulate the brain - A randomized controlled double-blinded study on anodal transcranial direct current stimulation of the ventromedial prefrontal cortex on two different time points in a two-day fear conditioning paradigm.

It is assumed that extinction learning is a suitable model for understanding the mechanisms underlying exposure therapy. Furthermore, there is evidence that non-invasive brain stimulation (NIBS) can elevate extinction learning by enhancing frontal brain activity and therefore NIBS can augment symptom reduction during exposure therapy in phobias. But, the underlying processes are still not well established. Open questions arise from NIBS time points and electrode placement, among others. Therefore, we investigated in a 2-day fear conditioning experiment, whether anodal transcranial direct current stimulation (tDCS) of the ventromedial prefrontal cortex (vmPFC) modulates either fear memory consolidation or dampened fear reaction during fear extinction. Sixty-six healthy participants were randomly assigned either to a group that received tDCS after fear acquisition (and before fear memory consolidation), to a group that received tDCS directly before fear extinction, or to a control group that never received active stimulation (sham). Differential skin conductance response (SCR) to CS+ vs. CS- was significantly decreased in both tDCS-groups compared to sham group. Our region of interest, the vmPFC, was stimulated best focally with a lateral anode position and a cathode on the contralateral side. But this comes along with a slightly lateral stimulation of vmPFC depending on whether anode is placed left or right. To avoid unintended effects of stimulated sides the two electrode montages (anode left or right) were mirror-inverted which led to differential effects in SCR and electrocortical (mainly late positive potential [LPP]) data in our exploratory analyses. Results indicated that tDCS-timing is relevant for fear reactions via disturbed fear memory consolidation as well as fear expression, and this depends on whether vmPFC is stimulated with either left- or right-sided anode electrode montage. Electrocortical data can shed more light on the underlying neural correlates and exaggerated LPP seems to be associated with disturbed fear memory consolidation and dampened SCR to CS+ vs. CS-, but solely in the right anode electrode montage. Further open questions addressing where and when to stimulate the prefrontal brain in the course of augmenting fear extinction are raised.

Effects of Differential Strategies of Emotion Regulation.

Patients suffering from mental disorders, especially anxiety disorders, are often impaired by inadequate emotional reactions. Specific aspects are the insufficient perception of their own emotional states and the use of dysfunctional emotion regulation strategies. Both aspects are interdependent. Thus, Cognitive Behavioral Therapy (CBT) comprises the development and training of adequate emotion regulation strategies. Traditionally, reappraisal is the most common strategy, but strategies of acceptance are becoming more important in the course of advancing CBT. Indeed, there is evidence that emotion regulation strategies differ in self-reported effectiveness, psychophysiological reactions, and underlying neural correlates. However, comprehensive comparisons of different emotion regulation strategies are sparse. The present study, therefore, compared the effect of three common emotion regulation strategies (reappraisal, acceptance, and suppression) on self-reported effectiveness, recollection, and psychophysiological as well as electroencephalographic dimensions. Twenty-nine healthy participants were instructed to either reappraise, accept, suppress, or passively observe their upcoming emotional reactions while anxiety- and sadness-inducing pictures were presented. Results showed a compelling effect of reappraisal on emotional experience, skin conductance response, and P300 amplitude. Acceptance was almost as effective as reappraisal, but led to increased emotional experience. Combining all results, suppression was shown to be the least effective but significantly decreased emotional experience when thoughts and feelings had to be suppressed. Moreover, results show that greater propensity for rumination differentially impairs strategies of emotion regulation.

Modulation of sustained fear by transcranial direct current stimulation (tDCS) of the right inferior frontal cortex (rIFC).

Downregulation of emotional responses to threat is strongly associated with frontal cortex functions. Additionally pathological anxiety has been proposed to be associated with the altered frontal control. Understanding the frontal regulation of both initial and sustained fear responses seems to be crucial for further research on the treatment of anxiety disorders. Therefore, this study aims to examine the effects of transcranial direct current stimulation (tDCS) over the right inferior frontal cortex (rIFC) on the subjects' psychophysiological responses as measured by skin conductance reaction (SCR) during a sustained threat paradigm. 80 participants were randomly assigned to an anodal and sham stimulation group in a double-blinded manner. Indicated by visual cues, participants anticipated the temporally unpredictable occurrence of aversive or neutral auditory stimuli. We found a significant interaction effect of condition x tDCS for SCR during the sustained threat. Post-hoc tests revealed a significant reduction in SCR during sustained fear in verum stimulated group. The results confirm that tDCS of the rIFC attenuates sustained fear. This supports the suggested role of the rIFC in psychophysiological emotional regulation and the potential use of tDCS to enhance these effects.

Phasic and sustained brain responses in the amygdala and the bed nucleus of the stria terminalis during threat anticipation.

Several lines of evidence suggest that the amygdala and the bed nucleus of the stria terminalis (BNST) are differentially involved in phasic and sustained fear. Even though, results from neuroimaging studies support this distinction, a specific effect of a temporal dissociation with phasic responses to onset versus sustained responses during prolonged states of threat anticipation has not been shown yet. To explore this issue, we investigated brain activation during anticipation of threat in 38 healthy participants by means of functional magnetic resonance imaging. Participants were presented different visual cues indicated the temporally unpredictable occurrence of a subsequent aversive or neutral stimulus. During the onset of aversive versus neutral anticipatory cues, results showed a differential phasic activation of amygdala, anterior cingulate cortex (ACC), and ventrolateral prefrontal cortex (PFC). In contrast, activation in the BNST and other brain regions, including insula, dorsolateral PFC, ACC, cuneus, posterior cingulate cortex, and periaqueductal grey was characterized by a sustained response during the threat versus neutral anticipation period. Analyses of functional connectivity showed phasic amygdala response as positively associated with activation, mainly in sensory cortex areas whereas sustained BNST activation was negatively associated with activation in visual cortex and positively correlated with activation in the insula and thalamus. These findings suggest that the amygdala is responsive to the onset of cues signaling the unpredictable occurrence of a potential threat while the BNST in concert with other areas is involved in sustained anxiety. Furthermore, the amygdala and BNST are characterized by distinctive connectivity patterns during threat anticipation.

Neural correlates of emotional interference in social anxiety disorder.

Disorder-relevant but task-unrelated stimuli impair cognitive performance in social anxiety disorder (SAD); however, time course and neural correlates of emotional interference are unknown. The present study investigated time course and neural basis of emotional interference in SAD using event-related functional magnetic resonance imaging (fMRI). Patients with SAD and healthy controls performed an emotional stroop task which allowed examining interference effects on the current and the succeeding trial. Reaction time data showed an emotional interference effect in the current trial, but not the succeeding trial, specifically in SAD. FMRI data showed greater activation in the left amygdala, bilateral insula, medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (ACC), and left opercular part of the inferior frontal gyrus during emotional interference of the current trial in SAD patients. Furthermore, we found a positive correlation between patients' interference scores and activation in the mPFC, dorsal ACC and left angular/supramarginal gyrus. Taken together, results indicate a network of brain regions comprising amygdala, insula, mPFC, ACC, and areas strongly involved in language processing during the processing of task-unrelated threat in SAD. However, specifically the activation in mPFC, dorsal ACC, and left angular/supramarginal gyrus is associated with the strength of the interference effect, suggesting a cognitive network model of attentional bias in SAD. This probably comprises exceeded allocation of attentional resources to disorder-related information of the presented stimuli and increased self-referential and semantic processing of threat words in SAD.

Neural correlates of self-focused attention in social anxiety.

Socially anxious individuals tend to shift their attention away from external socially threatening cues and instead become highly self-focused. Such heightened self-focused attention has been suggested to be involved in the development and maintenance of social anxiety disorder. This study used functional magnetic resonance imaging to investigate the neural correlates of self-focused attention in 16 high socially anxious (HSA) and 16 low socially anxious (LSA) individuals. Participants were instructed to focus their attention either inwardly or outwardly during a simulated social situation. Results indicate hyperactivation of medial prefrontal cortex (mPFC), temporo-parietal junction (TPJ) and temporal pole during inward vs outward attention in HSA compared with LSA participants. Furthermore, activation of mPFC, right anterior insula, TPJ and posterior cingulate cortex was positively correlated with the trait of self-focused attention in HSA subjects. Results highlight the prominent role of the mPFC and other cortical structures in abnormal self-focused attention in social anxiety. Finally, findings for the insula suggest increased processing of bodily states that is related to the amount of habitual self-focused attention in social anxiety.

Area-dependent time courses of brain activation during video-induced symptom provocation in social anxiety disorder.

BACKGROUND: Previous functional imaging studies using symptom provocation in patients with social anxiety disorder (SAD) reported inconsistent findings, which might be at least partially related to different time-dependent activation profiles in different brain areas. In the present functional magnetic resonance imaging study, we used a novel video-based symptom provocation design in order to investigate the magnitude and time course of activation in different brain areas in 20 SAD patients and 20 healthy controls. RESULTS: The disorder-related videos induced increased anxiety in patients with SAD as compared to healthy controls. Analyses of brain activation to disorder-related versus neutral video clips revealed amygdala activation during the first but not during the second half of the clips in patients as compared to controls. In contrast, the activation in the insula showed a reversed pattern with increased activation during the second but not during the first half of the video clips. Furthermore, a cluster in the anterior dorsal anterior cingulate cortex showed a sustained response for the entire duration of the videos. CONCLUSIONS: The present findings suggest that different regions of the fear network show differential temporal response patterns during video-induced symptom provocation in SAD. While the amygdala is involved during initial threat processing, the insula seems to be more involved during subsequent anxiety responses. In accordance with cognitive models of SAD, a medial prefrontal region engaged in emotional-cognitive interactions is generally hyperactivated.

Brain activation during anticipatory anxiety in social anxiety disorder.

Exaggerated anticipatory anxiety during expectation of performance-related situations is an important feature of the psychopathology of social anxiety disorder (SAD). The neural basis of anticipatory anxiety in SAD has not been investigated in controlled studies. The current study used functional magnetic resonance imaging (fMRI) to investigate the neural correlates during the anticipation of public and evaluated speaking vs a control condition in 17 SAD patients and 17 healthy control subjects. FMRI results show increased activation of the insula and decreased activation of the ventral striatum in SAD patients, compared to control subjects during anticipation of a speech vs the control condition. In addition, an activation of the amygdala in SAD patients during the first half of the anticipation phase in the speech condition was observed. Finally, the amount of anticipatory anxiety of SAD patients was negatively correlated to the activation of the ventral striatum. This suggests an association between incentive function, motivation and anticipatory anxiety when SAD patients expect a performance situation.