Fear learning sculpts functional brain connectivity at rest beyond the traditional fear network

Neuroscientific research has identified specific brain networks involved in the acquisition of fear memories. Using functional magnetic resonance imaging to assess changes in resting-state functional connectivity (RSFC) induced by fear acquisition, single brain regions from these networks have been linked to fear memory consolidation. However, previous studies merely examined RSFC changes within restricted sets of brain regions or without a proper control group, leaving our knowledge about fear consolidation outside of traditional fear networks incomplete. Here, an experimental group of 98 and a control group of 28 individuals, free of self-reported psychiatric or neurological disorders, participated in a differential fear conditioning paradigm using visual stimuli and electrical stimulation. Fear responses were quantified by skin conductance responses. RSFC changes were analyzed across 360 cortical and 16 subcortical brain regions, constituting a total of 70,500 functional connections. Subsequent to fear acquisition, we identified 21 functional connections, involving 35 individual brain regions, that exhibited significant RSFC changes in the experimental compared to the control group. Importantly, these connections were not restricted to traditional fear networks but also comprised various frontal, visual, premotor, and somatosensory regions. Overall, our findings highlight the importance of employing a proper control group and indicate that fear memory consolidation is a complex process that integrates relevant information across the entire brain. Brain regions recruited for this task presumably depend on the modality of acquired fear memories, which demands an update regarding the components of established fear networks.