Effects of cognitive-behavioral therapy on brain responses to subliminal and supraliminal threat and their functional significance in specific phobia.

BACKGROUND: Neurocircuitry models of anxiety disorders suggest dysregulated mechanisms encompassing both automatic and elaborate threat processing. However, the extent to which these processes might be differentially modified by psychotherapy and the neural basis of such changes are unknown. We examined the effects of cognitive-behavioral therapy (CBT) in patients with anxiety disorder on brain responses to subliminal and supraliminal threat. METHODS: 3-Tesla functional magnetic resonance imaging was used to assess neural responses to disorder-related stimuli, presented during two backward-masking conditions employed to manipulate stimulus awareness. In 28 spider-phobic patients randomly assigned to a therapy group or a waiting-list control group scanning was performed before and after completing CBT or a waiting period. Scanning was performed one time in 16 healthy control subjects. Self-report and behavioral measures were used to relate CBT-mediated brain activation changes with symptom improvement. RESULTS: Untreated patients demonstrated abnormal hyperactivation in the amygdala, fusiform gyrus, insula, anterior cingulate cortex, and dorsomedial prefrontal cortex. Successful CBT was reflected in an overall downregulation in these fear circuitry structures, especially in the right amygdala and anterior cingulate cortex, with reductions in amygdala responsiveness associated with self-reported symptom improvement. However, subliminal threat induced a pattern of right-lateralized hyperactivation in the amygdala and fusiform gyrus that was subject to intersession habituation across groups without showing significant sensitivity to CBT. CONCLUSIONS: These results challenge prevailing models that emphasize a role for amygdala automaticity in the maintenance of anxiety. Our results suggest CBT-related changes in neural activation associated with fear responses to consciously perceived threat.

Awareness modulates responses of the amygdala and the visual cortex to highly arousing visual threat.

It is still a matter of debate under which conditions the neural processing of emotional stimuli can occur without conscious awareness. Using functional magnetic resonance imaging, we investigated brain responses to highly arousing threat-related versus neutral pictures which were presented very briefly during two backward-masking conditions resulting in either subliminal or supraliminal stimulus processing. Signal detection analysis confirmed the successful experimental manipulation of awareness that effectively prevented stimulus recognition during the subliminal condition. Participants showed stronger responses of the amygdala and extrastriate visual cortex during the supraliminal, but not during the subliminal condition. These results suggest that the processing of highly arousing visual threat requires conscious awareness during backward masking. This contradicts the assumption of pervasive neural responses to emotional stimuli.

Vigilance for threat interacts with amygdala responses to subliminal threat cues in specific phobia.

BACKGROUND: The amygdala has been strongly implicated in the processing of threat-relevant information in specific phobia. However, there is an ongoing debate as to whether the amygdala may also be engaged outside of conscious stimulus awareness. Furthermore, considering that sustained vigilance for threat constitutes a crucial characteristic of specific phobias, we hypothesized a possible role of this symptom in modulating amygdala sensitivity to disorder-relevant cues. Using event-related functional magnetic resonance imaging, we examined responses of the amygdala to subliminal and supraliminal phobogenic stimuli in spider-phobic subjects and whether these responses might be specifically associated with disorder-related hypervigilance. METHODS: Eighteen female spider-phobic subjects and 18 healthy female control subjects were exposed to pictures of spiders and phobia-irrelevant objects, presented briefly during two backward-masking conditions used to manipulate stimulus awareness. Brain activation data were analyzed as a function of subjects' perceptual performance on each single trial and were tested for correlations with different components of the phobic symptomatology, such as vigilance, as assessed by self-report scales. RESULTS: Compared with control subjects, phobic participants showed stronger responses of both amygdalae to consciously perceived spiders versus nonspider targets, whereas during unconscious stimulus processing, enhanced activation was only apparent in the right amygdala. Moreover, the intensity of disorder-related vigilance was positively correlated with right amygdala activation specifically during the subliminal condition. CONCLUSIONS: These findings provide evidence for unconscious threat processing in specific phobia, with the magnitude of amygdala responses specifically potentiated by sustained hypervigilance for threat. Aberrations in this vigilance system may be critically involved in anxiety disorders.

Amygdala activation to threat under attentional load in individuals with anxiety disorder.

BACKGROUND: Previous studies in healthy subjects have shown that strong attentional distraction prevents the amygdala from responding to threat stimuli. Here, we investigated the effects of attentional load on amygdala activation to threat-related stimuli in individuals suffering from an anxiety disorder. METHODS: During functional magnetic resonance imaging, spider-phobicand healthy control subjects were presented with phobia-related and neutral stimuli while performing a distraction task with varying perceptual load (high vs low). RESULTS: Our data revealed a pattern of simultaneously increased amygdala and visual cortical activation to threat vs neutral pictures in phobic individuals, compared with controls, occurring regardless of attentional load. CONCLUSIONS: These results suggest that, in contrast to studies in healthy subjects, amygdala activation to clinically relevant threat stimuli is more resistant to attentional load.

Neural representation of anxiety and personality during exposure to anxiety-provoking and neutral scenes from scary movies.

Some people search for intense sensations such as being scared by frightening movies while others do not. The brain mechanisms underlying such inter-individual differences are not clear. Testing theoretical models, we investigated neural correlates of anxiety and the personality trait sensation seeking in 40 subjects who watched threatening and neutral scenes from scary movies during functional magnetic resonance imaging. Threat versus neutral scenes induced increased activation in anterior cingulate cortex, insula, thalamus, and visual areas. Movie-induced anxiety correlated positively with activation in dorsomedial prefrontal cortex, indicating a role for this area in the subjective experience of being scared. Sensation seeking-scores correlated positively with brain activation to threat versus neutral scenes in visual areas and in thalamus and anterior insula, i.e. regions involved in the induction and representation of arousal states. For the insula and thalamus, these outcomes were partly due to an inverse relation between sensation seeking scores and brain activation during neutral film clips. These results support models predicting cerebral hypoactivation in high sensation seekers during neutral stimulation, which may be compensated by more intense sensations such as watching scary movies.