Extinction of cognitively conditioned fear in Borderline Personality Disorder

Aims: Despite the prominent role of emotion dysregulation in theoretical accounts of BPD, so far only few imaging studies have examined emotion dysregulation in BPD. Learning to combine a previously neutral stimulus with a possible aversive event by means of verbal instruction is an everyday experience humans encounter. Symbolically acquired fear results in physiological fear responses and functional neuroimaging data comparable to the responses in classical fear conditioning. This study aims to investigate the neural underpinnings of extinction learning in female borderline patients to test the hypothesis of different emotion regulation during the extinction process.

Methods: We explored the neural mechanisms of fear extinction by means of an instructed fear conditioning task (Phelps et al. 2001). Prior to scanning, the participants determined the level of electrodermal stimulation said to be received during the scan session via a standardized dial-up procedure. The scanning session consisted of a „threat condition“, about which subjects were told that an electrodermal stimulation could occur at any time and a „safety condition“, during which participants knew they would not receive any stimulation. Threat and safety were signified by the presentation of easily-distinguishable coloured squares. The expression of fear responses was controlled by measuring the skin conductance response (SCR). As no stimulation was given at any time during the experiment, extinction processes were recorded throughout the scanning session. So far, 14 female patients with borderline personality disorder and 14 matched healthy controls have been included.

Results: In the debriefing, all subjects indicated that they expected to receive a stimulation during the presentation of the threat stimulus until some point in time when expectancy was starting to decrease. Interaction analysis (group x condition x time) of brain regions (ROI) previously shown to be associated with extinction processes revealed stronger activation of the lateral amygdalae in the patient group compared to controls, regardless of stimulus type. In both groups, the amygdala response to the threat stimulus was largest at the beginning of the scanning procedure, but, in the patient group, the decline of activation turned out to be less pronounced over the extinction period. As hypothesized, all control subjects revealed a stronger activation of the (lateral) orbitofrontal cortex (OFC) during extinction, possibly indicating the change of stimulus value that is encoded. Patients did not show comparable activity increase, indicating failure of stimulus value reversal.

Conclusion: Analyses confirmed a hyperactivity of the amygdala in borderline patients suggesting a more general responsiveness to threat stimuli. Furthermore, activations of the lateral OFC and amygdala differed between groups throughout the extinction process indicating a failure of frontolimbic regulatory mechanisms.