Neural substrates of human fear generalization: A 7T-fMRI investigation.

Fear generalization - the tendency to interpret ambiguous stimuli as threatening due to perceptual similarity to a learned threat - is an adaptive process. Overgeneralization, however, is maladaptive and has been implicated in a number of anxiety disorders. Neuroimaging research has indicated several regions sensitive to effects of generalization, including regions involved in fear excitation (e.g., amygdala, insula) and inhibition (e.g., ventromedial prefrontal cortex). Research has suggested several other small brain regions may play an important role in this process (e.g., hippocampal subfields, bed nucleus of the stria terminalis [BNST], habenula), but, to date, these regions have not been examined during fear generalization due to limited spatial resolution of standard human neuroimaging. To this end, we utilized the high spatial resolution of 7T fMRI to characterize the neural circuits involved in threat discrimination and generalization. Additionally, we examined potential modulating effects of trait anxiety and intolerance of uncertainty on neural activation during threat generalization. In a sample of 31 healthy undergraduate students, significant positive generalization effects (i.e., greater activation for stimuli with increasing perceptual similarity to a learned threat cue) were observed in the visual cortex, thalamus, habenula and BNST, while negative generalization effects were observed in the dentate gyrus, CA1, and CA3. Associations with individual differences were underpowered, though preliminary findings suggested greater generalization in the insula and primary somatosensory cortex may be correlated with self-reported anxiety. Overall, findings largely support previous neuroimaging work on fear generalization and provide additional insight into the contributions of several previously unexplored brain regions.

Modulation of the startle reflex across time by unpleasant pictures distinguishes dysphoric from non-dysphoric women.

While several investigators have examined differences in affective startle modulation between individuals with and without Major Depressive Disorder, fewer researchers have evaluated the time course of this response, particularly in dysphoric individuals. The purpose of this study was to evaluate emotion modulation of the startle reflex during and after the presentation of affective pictures in dysphoric and non-dysphoric women. Dysphoric subjects showed attenuated startle for unpleasant compared to neutral pictures 1.5s post-stimulus onset relative to non-dysphoric subjects and potentiated startle for unpleasant compared to neutral pictures 3s post-stimulus offset. These findings extend the literature on the time course of affective startle modulation in dysphoria, and mirror results of studies in which other psychophysiological responses were examined in this population with regard to negative emotion.

Stability of emotion-modulated startle during short and long picture presentation.

Following reports on improved test-retest reliability of emotion-modulated startle during a 6-s picture presentation when different pictures are presented at each assessment (Larson et al., 2000) and data suggesting that brief picture presentations also elicit affective blink modulation (Codispoti, Bradley, & Lang, 2001), we assessed test-retest reliability of blink modulation during brief picture presentations. At two acoustic startle sessions (4 weeks apart) subjects viewed different IAPS pictures for either 6 s (long group) or 300 ms (short), with emotion modulation assessed at three different points in time during and following picture viewing. Group ANOVAs revealed emotion modulation for both short and long groups. In addition, comparable and, in some cases, greater stability of emotion modulation was found for short compared to long picture presentations. Stability was generally low for individual probe times for both groups.