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Predictability of threat is one of the key modulators of neural activity in fear and anxiety-related threat processes and there is a considerable number of studies focusing on the exact contribution of centromedial amygdala and Bed nucleus of stria terminalis (BNST) in animals as well as in humans. In this research field, some studies already investigated the differential involvement of both areas during temporally predictable and unpredictable threat processes in humans. However, these studies showed several limitations e.g. small sample size, no predictable threat conditions, no separation of anticipation and confrontation processes, which should be addressed in future studies. Furthermore, evidence for group-based inter-individual differences of amygdala and BNST activity during predictable and unpredictable threat processes have not been studied extensively.
Several studies suggest a relevant role of the amygdala and BNST activity in phobic processes in patients with specific phobia, but no study so far has investigated the exact contribution of centromedial amygdala (CM) and BNST during temporally predictable and unpredictable threat processes in specific phobia.
This thesis consisted of three studies and aimed to evaluate the exact contribution of CM and BNST during temporally predictable and unpredictable threat anticipation and confrontation with the use of an optimized functional magnetic resonance imaging (fMRI) paradigm, which aimed to solve methodological limitations of recent studies. Study 1 used a large sample of healthy participants who were grouped based on NPSR1 genotype, and study 2 and study 3 used a sample of patients with spider phobia. In sum, the results of all three studies indicated, that BNST is more relevant for anticipation processes as compared to the CM. Contrary, during the confrontation phase the CM displays a greater relevance for threat confrontation processes.
In recent years, various studies have investigated the extent to which treatment success can be predicted in patients with anxiety disorders based on pre-treatment fMRI activity. Therefore, this was investigated for the first time in study 3 in patients with spider phobia during temporally predictable and unpredictable threat processes. Results indicated that independent of temporal predictability lower anterior cingulate cortex (ACC) activity during threat anticipation and engaged BNST during threat confrontation might be benefitting factors for successful therapy response in spider phobia.
Cognitive views of the psychopathology of anxiety propose that attentional biases toward threatening information play a substantial role in the disorders’ etiology and maintenance. For healthy subjects, converging evidence show that threatening stimuli attract attention and lead to enhanced activation in visual processing areas. It is assumed that this preferential processing of threat occurs at a preattentive level and is followed by fast attentional engagement. High-anxious individuals show augmented tendencies to selectively attend toward fear-relevant cues (Mathews, 1990) and exhibit elevated neural processing of threatening cues compared to non-anxious individuals (Dilger et al., 2003). Regarding attentional biases in high-anxious subjects, it remains unanswered up to now whether initial engagement of attention toward threat or difficulties to disengage from threat is an underlying mechanism. Furthermore, little is known whether the preferential (attentive) processing of threatening cues does influence perceptional outcomes of anxious subjects. In order to directly study separate components of attentional bias the first study of this dissertation was a combined reaction time and eye-tracking experiment. Twenty one spider phobic patients and 21 control participants were instructed to search for a neutral target while ignoring task-irrelevant abrupt-onset distractor circles which contained either a small picture of a spider (phobic), a flower (non-phobic, but similar to spiders in shape), a mushroom (non-phobic, and not similar to spiders in shape), or small circles with no picture. As expected, patients’ reaction times to targets were longer on trials with spider distractors. However, analyses of eye movements revealed that this was not due to attentional capture by spider distractors; patients more often fixated on all distractors with pictures. Instead, reaction times were delayed by longer fixation durations on spider distractors. This result does not support automatic capture of attention by phobic cues but suggests that phobic patients fail to disengage attention from spiders. To assess whether preferential processing of phobic cues differentially affects visual perception in phobic patients compared to healthy controls, the second study of this dissertation used a binocular rivalry paradigm, where two incompatible pictures were presented to each eye. These pictures cannot be merged to a meaningful percept and temporarily, one picture predominates in conscious perception whereas the other is suppressed. 23 spider phobic patients and 20 non-anxious control participants were shown standardized pictures of spiders or flowers, each paired with a neutral pattern under conditions of binocular rivalry. Their task was to continuously indicate the predominant percept by key presses. Analyses show that spider phobic patients perceived the spider picture more often and longer as dominant compared to non-anxious control participants. Thus, predominance of phobic cues in binocular rivalry provides evidence that preferential processing of fear-relevant cues in the visual system actually leads to superior perception. In combination both studies support the notion that phobic patients process phobic cues preferentially within the visual system resulting in enhanced attention and perception. At early stages of visual processing, this is mainly reflected by delayed attentional disengagement and across time, preferential processing leads to improved perception of threat cues.