The Role of the Anterolateral Prefrontal Cortex in the Regulation of Defensive Responses: A TMS study

Abstract

After the termination of threat, defensive responses should be reduced to prevent chronic anxiety. Previous neuroimaging research has shown that the anterolateral prefrontal cortex (alPFC) might play a role in the downregulation of fear after threat offset. By temporarily inhibiting neural activity of the alPFC, we explore the role of this area in the downregulation of defensive responses. Healthy participants (N=30) completed an instructed fear task before and after receiving active (right alPFC) and control (vertex) continuous theta burst stimulation (cTBS). During all four fear tasks, fear potentiated startle, subjective fear measures, skin conductance response and electroencephalogram were measured. Previous results have shown that startle magnitudes were increased after cTBS stimulation of the right alPFC. Against expectations, this was found both during and after presentation of the threat cue, rather than specifically after cue offset. The current study failed to replicate these findings and found no significant difference following active versus control stimulation on any measures. These results raise concern regarding the impact of the cTBS on the brain itself. However, significant results were found for subjects who received active stimulation in the first session. In addition, the combination of the former and current startle datasets (N=51) yielded significant results, indicating that the effect of alPFC suppression on the downregulation of startle magnitudes is not entirely absent. Due to unclear outcomes and methodological concerns, the nature of the failed replication is unclear. More research with sufficient sample sizes should be done to provide clear conclusions regarding the remaining questions.