Involvement of the alPFC in electroencephalographic processes that underlie fear processing and fear downregulation: a TMS-EEG study

Abstract

Layman’s Summary: After a threat has disappeared, it is necessary to downregulate fear to prevent chronic anxiety. A frontal brain area called the anterolateral prefrontal cortex (alPFC) has been found to be involved in regulating emotional behavior and downregulating fear. Studies that record electrical brain activity have found that brainwaves in the theta range (4 to 8 Hz) measured in the frontal middle brain areas are associated with fear processing. Theta brainwaves measured in these locations have been found to originate in a brain region called the dorsomedial PFC (dmPFC), which is involved in fear expression. However, theta brainwaves originating in the alPFC have been found to be involved in the process of regulating social emotional behavior. In our study, we used brain stimulation that decreases the activity in the targeted brain area. By targeting the alPFC, we can directly study the causal involvement of this brain area in downregulating fear and the underlying electrical activity involved in this process. We recruited 30 healthy participants that completed a task, in which they were instructed that they may receive an electric shock when they are presented with one cue (threat cue), whereas they would never receive an electric shock when presented with another cue (safe cue). Against our expectations, we did not find any effect of the brain stimulation on theta brainwaves. During the presentation of the cue, there was no difference between the threatening and the safe cue in the theta brainwaves. However, we did find a difference between these conditions in slower brainwave band called delta (0.5 to 4 Hz). The threatening condition induced stronger delta brainwaves than the safe condition. Delta brainwaves have been found to play a role in emotional processing and therefore, the stronger delta during threatening versus the safe cue can be explained by stronger emotional processing elicited by the threatening stimulus. After the cue disappeared, we did find a difference between the threatening and the safe cue in theta brainwaves, with the threatening condition having stronger theta waves than the safe condition. However, it is unclear whether this theta increase represents the process of fear downregulation, or the ongoing process of fear expression elicited by the preceding threat cue. Moreover, it is not clear whether the lack of effect of the brain stimulation on theta brainwaves was observed because the stimulated region (alPFC) was insufficiently involved in fear processing, or the decreased alPFC activity caused by the stimulation was not captured by brainwaves, or if the effect of cTBS on the brain was too weak.