Patients with Ventromedial Prefrontal Lesions Show an Implicit Approach Bias to Angry Faces.

Damage to the ventromedial PFC (VMPFC) can cause maladaptive social behavior, but the cognitive processes underlying these behavioral changes are still uncertain. Here, we tested whether patients with acquired VMPFC lesions show altered approach-avoidance tendencies to emotional facial expressions. Thirteen patients with focal VMPFC lesions and 31 age- and gender-matched healthy controls performed an implicit approach-avoidance task in which they either pushed or pulled a joystick depending on stimulus color. Whereas controls avoided angry faces, VMPFC patients displayed an incongruent response pattern characterized by both increased approach and reduced avoidance of angry facial expressions. The approach bias was stronger in patients with higher self-reported impulsivity and disinhibition and in those with larger lesions. We further used linear ballistic accumulator modeling to investigate latent parameters underlying approach-avoidance decisions. Controls displayed negative drift rates when approaching angry faces, whereas VMPFC lesions abolished this pattern. In addition, VMPFC patients had weaker response drifts than controls during avoidance. Finally, patients showed reduced drift rate variability and shorter nondecision times, indicating impulsive and rigid decision-making. Our findings thus suggest that VMPFC damage alters the pace of evidence accumulation in response to social signals, eliminating a default, protective avoidant bias and facilitating a dysfunctional approach behavior.

Alleviating social avoidance: effects of single dose testosterone administration on approach-avoidance action.

Testosterone is an important regulator of social-motivational behavior and is known for its dominance-enhancing and social-anxiolytic properties. However, to date no studies have systematically investigated the causal effect of testosterone on actual social approach-avoidance behavior in humans. The present study sets out to test the effects of testosterone administration in healthy female volunteers using an objective implicit measure of social motivational behavior: the social Approach-Avoidance Task, a reaction time task requiring participants to approach or avoid visually presented emotional (happy, angry, and neutral) faces. Participants showed significantly diminished avoidance tendencies to angry faces after testosterone administration. Testosterone did not affect approach-avoidance tendencies to social affiliation (happy) faces. Thus, a single dose testosterone administration reduces automatic avoidance of social threat and promotes relative increase of threat approach tendencies in healthy females. These findings further the understanding of the neuroendocrine regulation of social motivational behavior and may have direct treatment implications for social anxiety, characterized by persistent social avoidance.

High-frequency repetitive transcranial magnetic stimulation to the cerebellum and implicit processing of happy facial expressions.

BACKGROUND: Previous research has demonstrated that the cerebellum is involved in emotive and cognitive processes. Furthermore, recent findings suggest high-frequency repetitive transcranial magnetic stimulation (rTMS) to the cerebellum has mood-improving properties. We sought to further explore the effects of cerebellar high-frequency rTMS on implicit processing of emotional stimuli and mood. METHODS: In a double-blind, crossover study, 15 healthy volunteers received 15 minutes of 20 Hz (5 s on, 5 s off) rTMS over the medial cerebellum, occipital cortex or sham in a randomized counterbalanced order on 3 consecutive days. A masked emotional faces response task measured implicit emotional processing of happy, fearful and neutral facial expressions. We used positive and negative affect scales to evaluate rTMS-related changes in mood. RESULTS: High-frequency rTMS over the cerebellum was associated with significant increases in masked emotional responses to happy facial expressions only. We observed no changes in consciously experienced mood. LIMITATIONS: Although the sham rTMS served as our baseline measurement, additional pre-rTMS data showing that reaction time increases immediately after cerebellar rTMS would have made our results more compelling. CONCLUSION: The results replicate and extend previous findings by establishing a direct relation between the cerebellum and emotive information-processing. The parallel between the present effects of high-frequency cerebellar rTMS and short-term antidepressant therapy regarding the change in implicit processing of positive stimuli in the absence of mood changes is notable and warrants further research.

Exogenous testosterone affects early threat processing in socially anxious and healthy women.

Testosterone plays an important role in social threat processing. Recent evidence suggests that testosterone administration has socially anxiolytic effects, but it remains unknown whether this involves early vigilance or later, more sustained, processing-stages. We investigated the acute effects of testosterone administration on social threat processing in 19 female patients with Social Anxiety Disorder (SAD) and 19 healthy controls. Event-related potentials (ERPs) were recorded during an emotional Stroop task with subliminally presented faces. Testosterone induced qualitative changes in early ERPs (<200ms after stimulus onset) in both groups. An initial testosterone-induced spatial shift reflected a change in the basic processing (N170/VPP) of neutral faces, which was followed by a shift for angry faces suggesting a decrease in early threat bias. These findings suggest that testosterone specifically affects early automatic social information processing. The decreased attentional bias for angry faces explains how testosterone can decrease threat avoidance, which is particularly relevant for SAD.

Moral fixations: The role of moral integrity and social anxiety in the selective avoidance of social threat.

People derive their sense of belonging from perceptions of being a moral person. Research moreover suggests that social cues of rejection rapidly influence visual scanning, and result in avoidant gaze behavior, especially in socially anxious individuals. With the current eye-tracking experiment, we therefore examined whether moral integrity threats and affirmations influence selective avoidance of social threat, and how this varies with individual differences in social anxiety. Fifty-nine participants retrieved a memory of a past immoral, moral, or neutral act. Next, participants passively viewed angry, happy, and neutral faces, while we recorded how often they first fixated on the eyes. In addition, we administered the Liebowitz Social Anxiety Scale (1987). Participants first fixated less on angry eyes compared to happy or neutral eyes when their moral integrity was threatened, and this selective avoidance was enhanced with increasing social anxiety. Following a moral affirmation, however, participants no longer selectively avoided the eyes of angry faces, regardless of individual differences in social anxiety. The results thus suggest that both low and high socially anxious people adjust their social gaze behavior in response to threats and affirmations of their moral integrity, pointing to the importance of the social context when considering affective processing biases.

Single dose testosterone administration alleviates gaze avoidance in women with Social Anxiety Disorder.

Gaze avoidance is one of the most characteristic and persistent social features in people with Social Anxiety Disorder (SAD). It signals social submissiveness and hampers adequate social interactions. Patients with SAD typically show reduced testosterone levels, a hormone that facilitates socially dominant gaze behavior. Therefore we tested as a proof of principle whether single dose testosterone administration can reduce gaze avoidance in SAD. In a double-blind, within-subject design, 18 medication-free female participants with SAD and 19 female healthy control participants received a single dose of 0.5mg testosterone and a matched placebo, at two separate days. On each day, their spontaneous gaze behavior was recorded using eye-tracking, while they looked at angry, happy, and neutral facial expressions. Testosterone enhanced the percentage of first fixations to the eye-region in participants with SAD compared to healthy controls. In addition, SAD patients' initial gaze avoidance in the placebo condition was associated with more severe social anxiety symptoms and this relation was no longer present after testosterone administration. These findings indicate that single dose testosterone administration can alleviate gaze avoidance in SAD. They support theories on the dominance enhancing effects of testosterone and extend those by showing that effects are particularly strong in individuals featured by socially submissive behavior. The finding that this core characteristic of SAD can be directly influenced by single dose testosterone administration calls for future inquiry into the clinical utility of testosterone in the treatment of SAD.

Testosterone biases the amygdala toward social threat approach.

Testosterone enhances amygdala reactions to social threat, but it remains unclear whether this neuroendocrine mechanism is relevant for understanding its dominance-enhancing properties; namely, whether testosterone biases the human amygdala toward threat approach. This pharmacological functional magnetic-resonance imaging study shows that testosterone administration increases amygdala responses in healthy women during threat approach and decreases it during threat avoidance. These findings support and extend motivational salience models by offering a neuroendocrine mechanism of motivation-specific amygdala tuning.

Salivary testosterone: associations with depression, anxiety disorders, and antidepressant use in a large cohort study.

OBJECTIVE: Low circulating levels of testosterone have been associated with major depression, but there is more limited evidence for differences in patients with anxiety disorders. The use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants is associated with sexual side effects, warranting testing for interactions with testosterone. METHODS: Data are from 722 male and 1380 female participants of The Netherlands Study of Depression and Anxiety (NESDA), who were recruited from the community, general practice care, and specialized mental health care. Depressive and anxiety diagnoses were assessed using the DSM-IV Composite International Diagnostic Interview. To smooth the episodic secretion, the four morning saliva samples per participant and the two evening samples were pooled before testosterone analysis. RESULTS: Morning median testosterone levels were 25.2 pg/ml in men and 16.2 pg/ml in women, with lower evening levels of 18.2 and 14.1 pg/ml, respectively. Significant determinants of testosterone levels were sex, age, time of the day, use of contraceptives, and smoking status. Female patients with a current (1-month) depressive disorder (effect size 0.29; P=0.002), generalized anxiety disorder (0.25; P=0.01), social phobia (0.30; P<0.001), and agoraphobia without panic disorder (0.30; P=0.02) had lower salivary testosterone levels than female controls. Higher testosterone levels were found in male and female participants using SSRIs than in non-users (effect size 0.26; P<0.001). CONCLUSION: Salivary testosterone levels are lower in female patients with a depressive disorder, generalized anxiety disorder, social phobia, and agoraphobia as compared to female controls. SSRIs may increase salivary testosterone in men and women.

A case of illusory own-body perceptions after transcranial magnetic stimulation of the cerebellum.

Illusory own-body perceptions are 'body in space' misinterpretations of the brain and belong to the class of out-of-body experiences wherein the angular gyrus seems importantly implicated. In the present study additional cerebellum involvement in illusory own-body perceptions was investigated in a healthy young female right-handed volunteer. Transcranial magnetic stimulation (TMS) was applied over the cerebellum. Placebo cerebellum TMS and occipital TMS served as control conditions. Illusory own-body perceptions accompanied by electric brain activity over the somatosensory cortex were only observed after cerebellum TMS. The data provide the first evidence that the cerebellum might be involved in a neuronal network underlying illusory own-body perceptions.