Prefrontal tDCS Attenuates Self-Referential Attentional Deployment: A Mechanism Underlying Adaptive Emotional Reactivity to Social-Evaluative Threat

Social-evaluative threat (SET) – a situation in which one could be negatively evaluated by others – elicits profound (psycho)physiological reactivity which, if chronically present and not adaptively regulated, has deleterious effects on mental and physical health. Decreased self-awareness and increased other-awareness are understood to be an adaptive response to SET. Attentional deployment – the process of selectively attending to certain aspects of emotional stimuli to modulate emotional reactivity – is supported by fronto-parietal and fronto-limbic networks, with the dorsolateral prefrontal cortex being a central hub. The primary aim of the current study was to investigate the effects of active (versus sham) prefrontal transcranial direct current stimulation (tDCS) on self and other-attentional deployment during the exposure to a SET context. Seventy-four female participants received active or sham tDCS and were subsequently exposed to a rigged social feedback paradigm. In this paradigm a series of social evaluations were presented together with a photograph of the supposed evaluator and a self- photograph of the participant, while gaze behavior (time to first fixation, total fixation time) and skin conductance responses (SCRs; a marker of emotional reactivity) were measured. For half of the evaluations, participants could anticipate the valence (negative or positive) of the evaluation a priori. Analyses showed that participants receiving active tDCS were (a) slower to fixate on their self-photograph, (b) spent less time fixating on their self-photograph, and (c) spent more time fixating on the evaluator photograph. During unanticipated evaluations, active tDCS was associated with less time spent fixating on the evaluation. Furthermore, among those receiving active tDCS, SCRs were attenuated as a function of slower times to fixate on the self-photograph. Taken together, these results suggest that in a context of SET, prefrontal tDCS decreases self-attention while increasing other-attention, and that attenuated self-referential attention specifically may be a neurocognitive mechanism through which tDCS reduces emotional reactivity. Moreover, the results suggest that tDCS reduces vigilance toward stimuli that possibly convey threatening information, corroborating past research in this area.

Neural sensitivity to peer rejection predicts increases in depressive symptoms among anxious adolescents

Objective: The goal of this study was to examine whether neural sensitivity to peer rejection, a potent form of social evaluative threat in adolescence, conveys risk for depression among anxious youth. We hypothesized that brain activation in regions that process affective salience in response to rejection from virtual peers would predict depressive symptoms one year later and would be associated with ecological momentary assessment (EMA) reports of real-world peer connectedness. Method: Participants were 38 adolescents ages 11-16 (50% female) with a history of anxiety, recruited from a previous clinical trial. The present study was a prospective naturalistic follow-up of depressive symptoms assessed 2 years (Wave 2) and 3 years (Wave 3) following treatment. At Wave 2, participants completed the Chatroom Interact Task during neuroimaging and 16 days of EMA. Results: Controlling for depressive and anxiety symptoms at Wave 2, subgenual anterior cingulate (sgACC;\ \beta=.39, p=.010) and nucleus accumbens activation (NAcc;\beta=.30, p=.041) to peer rejection (vs. acceptance) predicted depressive symptoms at Wave 3. SgACC activation to rejection (vs. acceptance) was highly correlated with EMA reports of connectedness with peers in daily life (r=-.71, p<.001). Conclusion: Findings suggest that elevated sgACC and NAcc activation to rejection may serve as a risk factor for the development of depressive symptoms among anxious youth, perhaps by promoting vigilance or reactivity to potential social evaluative threats and subsequent avoidance behaviors. SgACC activation to simulated rejection appears to have implications for understanding how adolescents experience their daily social environments in ways that could contribute to depressive symptoms.

Threat-induced hippocampal connectivity fingerprints do not generalize to psychosocial stress

Stress is an everyday experience and maladaptive responses play a crucial role in the etiology of affective disorders. Despite its ubiquity, the neural underpinnings of subjective stress experiences have not yet been elucidated, particularly at an individual level. In an important advance, Goldfarb et al.1 showed recently that subjective stress and arousal levels in response to threatening stimuli were successfully predicted based on changes in hippocampal connectivity during the task using a machine learning approach. Crucially, stress responses were predicted by interpretable hippocampal connectivity networks, shedding new light on the role of the hippocampus in regulating stress reactivity2. However, the authors induced stress by displaying aversive pictures, while stress research often relies on the extensively validated Trier social stress task (TSST)3. The TSST incorporates crucial factors such as unpredictability of success and the social-evaluative threat of the stressor thereby eliciting cortisol responses more robustly compared to threatening images4. Towards generalization, cross validation within a sample as conducted by Goldfarb et al.1 or independent replications are important steps, but the generalizability to different stressors allows to draw broader conclusions about the potential use of hippocampal connectivity to predict subjective stress5. Arguably, translating these findings to clinical applications would require a broad generalization of the results or the prediction algorithm to psychosocial stress. Here, we assessed the predictive performance of Goldfarb et al’s1 algorithm for subjective stress in an independent sample using an MR adaption of the TSST6,7. In line with Goldfarb et al.1, we observed robust stress-induced changes in hippocampal connectivity. However, the spatial correlation of the changes in connectivity was low indicating little convergence across alleged stress paradigms. Critically, stress-induced changes of hippocampal connectivity were not robustly predictive of subjective stress across a multiverse of analyses based on connectivity changes. Collectively, this indicates that the generalizability of the reported stress connectivity fingerprint to other stressors is limited at best, suggesting that specific tasks might require tailored algorithms to robustly predict stress above chance levels.

Neuroendocrine responses to a psychosocial stress test for larger groups of participants: comparison of two test exposures

Objective. Individual stress tests characterized by social evaluative threat and uncontrollability are known to elicit strong neuroendocrine responses. We tested whether a psychosocial stressor submitted to a larger group of participants (up to 60) may elicit comparable stress responses. Methods. A total of 59 adult subjects (33 women, 26 men) participated in the study, whereas 24 of them suffered from allergy and 35 were healthy. The stress test consisted of a distraction stress task followed by a speech task, in which the participants were randomly subjected to questions related to a topic that they had to prepare as well as arithmetic questions in front of their peers and a committee that responded in standardized and non-supporting manner. State and trait anxiety inventory (STAI) for anxiety state was administrated before and after the test and salivary samples taking. The test was repeated after five months. Results. The results showed that the shared psychosocial stress application in a larger group of subjects was prosperous. The larger group test (LGST) resulted in an enhanced subjectively experienced stress and an intensive sympathetic nervous system activation, reflected by elevated salivary alpha-amylase activity and the heart rate. The cortisol increment after exposure to the stress test was not significant. Repeated exposure to the test failed to reproduce the original stress responses with exception of the heart rate rise. Conclusions. In a larger group of subjects, the psychosocial stress test did elicit stress responses similar to the individual stress tests. Our data indicate that the above-mentioned stress test is apparently not an appropriate approach for the repeated use.