Oxytocin differentially modulates amygdala responses during top-down and bottom-up aversive anticipation

Oxytocin (OT) is a neuropeptide that modulates social behaviors and the social brain. The effects of OT on the social brain can be tracked by assessing the neural activity in the resting and task states, providing a system-level framework for characterizing state-based functional relationships of its distinct effect. Here, we contribute to this framework by examining how OT modulates social brain network correlations during the resting and task states using fMRI. Firstly, we investigated network activation, followed by analyzing the relationship between networks and individual differences measured by the Positive and Negative Affect Schedule and the Big-Five scales. Subsequently, we evaluated functional connectivity in both states. Finally, the relationship between networks across the states was represented by the predictive power of networks in the resting state for task-evoked activity. The difference in predicted accuracy between subjects displayed individual variations in this relationship. Our results showed decreased dorsal default mode network (DDMN) for OT group in the resting state. Additionally, only in the OT group, the activity of the DDMN in the resting state had the largest predictive power for task-evoked activation of the precuneus network (PN). The results also demonstrated OT reduced individual variation of PN, specifically, the difference of accuracy between predicting a subject's own and others' PN task activation. These findings suggest a distributed but modulatory effect of OT on the association between resting brain networks and task-dependent brain networks, showing increased DDMN to PN connectivity after OT administration, which may support OT-induced distributed processing during task performance.

Loneliness has been associated with detrimental effects on mental and physical health and is increasingly recognized as a critical public health issue which may be further exacerbated by societal challenges such as increasing urbanization, an aging society as well as the COVID-19 pandemic. We here review recent findings on the neurocognitive mechanisms and brain alterations that underpin social disconnectedness, therapeutic approaches for chronic loneliness and how these lines of research can be integrated to improve the efficacy of loneliness interventions in healthy individuals and patients with mental disorders.

There has been growing interest in using pharmacological fMRI to identify novel treatments for fear, yet these models are limited with respect to determining process-specific effects on the actual subjective experience of fear which represents the key symptom why patients seek treatment. Combining a selective angiotensin II type 1 receptor (ATR1) antagonist with a fear vigilance fMRI paradigm and neurofunctional decoding in n = 87 individuals we demonstrate that AT1R blockade selectively reduces the neurofunctional reactivity to fear-inducing visual oddballs in terms of attenuating dorsolateral prefrontal activity and amygdala-ventral anterior cingulate (vACC) communication, and further show that the observed effect is due to reduced subjective fear, but not threat or non-specific negative affect, using a decoding analysis. Our findings demonstrate a highly specific role of AT1R in subjective fear experience and demonstrate the feasibility of a precision approach to the affective characterization of novel receptor targets for fear in humans.