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The ‘core’ regions of the default mode network (DMN) – the medial prefrontal cortex (MPFC), the posterior cingulate cortex (PCC), and inferior parietal lobules (IPL) – show consistent engagement across mental states that involve self-oriented processing. Precisely how these regions interact in support of such processes remains an important unanswered question. In the current functional magnetic resonance imaging (fMRI) study, we examined dynamic interactions of the ‘core-self’ DMN regions during two forms of self-referential cognition: direct self-appraisal (thinking about oneself) and reflected self-appraisal (thinking about oneself from a third-person perspective). One-hundred and eleven participants completed our dual self-appraisal task during fMRI, and general linear models were used to characterize common and distinct neural responses to these conditions. Informed by these results, we then applied dynamic causal modelling to examine causal interactions among the ‘core-self’ regions, and how they were specifically modulated under the influence of direct and reflected self-appraisal. As a primary observation, this network modelling revealed a distinct inhibitory influence of the left IPL on the PCC during reflected compared to direct self-appraisal, which was accompanied by evidence of greater activation in both regions during the reflected self-appraisal condition. We suggest that the greater engagement of posterior DMN regions during reflected self-appraisal is a function of the higher-order processing needed for this form of self-appraisal, with the left IPL supporting abstract self-related processes including episodic memory retrieval and shifts of perspective. Overall, we show that core DMN regions interact in functionally unique ways in support of self-referential processes, even when these processes are inter-related. Further characterization of DMN functional interactions across self-related mental states is likely to inform a deeper understanding of how this brain network orchestrates the self.

Threat learning elicits robust changes across multiple affective domains, including changes in autonomic indices and subjective reports of fear and anxiety. It has been argued that the underlying causes of such changes may be dissociable at a neural level, but there is currently limited evidence to support this notion. To address this, we examined the neural mediators of trial-by-trial skin conductance responses (SCR), and subjective reports of anxious arousal and valence in participants (n = 27; 17 females) performing a threat reversal task during ultra-high field functional magnetic resonance imaging. This allowed us to identify brain mediators during initial threat learning and subsequent threat reversal. Significant neural mediators of anxious arousal during threat learning included the dorsal anterior cingulate, anterior insula cortex (AIC), and ventromedial prefrontal cortex (vmPFC), subcortical regions including the amygdala, ventral striatum, caudate and putamen, and brain-stem regions including the pons and midbrain. By comparison, autonomic changes (SCR) were mediated by a subset of regions embedded within this broader circuitry that included the caudate, putamen and thalamus, and two distinct clusters within the vmPFC. The neural mediators of subjective negative valence showed prominent effects in posterior cortical regions and, with the exception of the AIC, did not overlap with threat learning task effects. During threat reversal, positive mediators of both subjective anxious arousal and valence mapped to the default mode network; this included the vmPFC, posterior cingulate, temporoparietal junction, and angular gyrus. Decreased SCR during threat reversal was positively mediated by regions including the mid cingulate, AIC, two sub-regions of vmPFC, the thalamus, and the hippocampus. Our findings add novel evidence to support distinct underlying neural processes facilitating autonomic and subjective responding during threat learning and threat reversal. The results suggest that the brain systems engaged in threat learning mostly capture the subjective (anxious arousal) nature of the learning process, and that appropriate responding during threat reversal is facilitated by participants engaging self- and valence-based processes. Autonomic changes (SCR) appear to involve distinct facilitatory and regulatory contributions of vmPFC sub-regions.

Responding flexibly to sources of threat and safety is critical to the adaptive regulation of emotions, including fear. At a neural systems level, such flexibility is thought to rely on an extended neural circuitry involving the dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortices (vmPFC), although precisely how this occurs remains unclear. Using a novel fear reversal task and functional magnetic resonance imaging (fMRI), we examined the neural correlates of threat and safety reversal learning and their associations with individual differences in anxious responding in a large sample of healthy adolescents and young adults. Overall, participants demonstrated successful threat and safety reversal learning, as indexed by subjective ratings. At a whole-brain level, threat reversal was associated with significant activation of the bilateral anterior insular cortex and dACC, in particular its rostral subregion. Conversely, safety reversal led to significant activation of the anterior vmPFC, together with posterior mid-line regions. Further analyses of regional responses suggested a more selective role for the rostral dACC in threat signal updating, as well as a direct association of its activity with participants’ change in subjective anxious arousal to the reversed threat. Taken together, our findings complement existing neurocircuitry models of human fear regulation, particularly regarding the importance of midline cortical regions, and provide further insights into their specific contribution to flexible threat-safety signal processing. In particular, our results suggest that rostral dACC function may be more centrally involved in regulating levels of anxious arousal when flexibility is required. They also raise important questions regarding the vmPFC’s role in safety learning, particularly involving its hypothesized subregional contributions to response inhibitory versus stimulus value processing functions.