Amygdala and anterior cingulate cortex activation during affective startle modulation: a PET study of fear

Abstract

The human startle response is modulated by emotional experiences, with startle potentiation associated with negative affect. We used positron emission tomography with 15O‐water to study neural networks associated with startle modulation by phobic fear in a group of subjects with specific snake or spider phobia, but not both, during exposure to pictures of their feared and non‐feared objects, paired and unpaired with acoustic startle stimuli. Measurement of eye electromyographic activity confirmed startle potentiation during the phobic as compared with the non‐phobic condition. Employing a factorial design, we evaluated brain correlates of startle modulation as the interaction between startle and affect, using the double subtraction contrast (phobic startle vs. phobic alone) vs. (non‐phobic startle vs. non‐phobic alone). As a result of startle potentiation, a significant increase in regional cerebral blood flow was found in the left amygdaloid–hippocampal region, and medially in the affective division of the anterior cingulate cortex (ACC). These results provide evidence from functional brain imaging for a modulatory role of the amygdaloid complex on startle reactions in humans. They also point to the involvement of the affective ACC in the processing of startle stimuli during emotionally aversive experiences. The co‐activation of these areas may reflect increased attention to fear‐relevant stimuli. Thus, we suggest that the amygdaloid area and the ACC form part of a neural system dedicated to attention and orientation to danger, and that this network modulates startle during negative affect.

Neural processing of threat cues in social environments

“…Because the stimuli and motor responses in Experiment 1 were identical for these comparisons, any differential activity caused by automatic emotional responses to stimuli should be eliminated. Even the contrast between potentially dangerous and safe situations in Experiment 2 did not show any activation increase in the neural system usually associated with emotional responses (e.g., the amygdala, anterior cingulate cortex, and orbitalfrontal cortex) [Carlsson et al, 2004;Carretie et al, 2005;Morris et al, 1996;Pissiota et al, 2003]. Thus, our findings indicate that detection and evaluation of evolutionary unprepared threats in social situations do not necessarily involve the emotion-related neural system and that the processing of threat signals can be independent of the affective network in the absence of overt threat cues (such as fearful faces or snakes).…”

“…These responses are most pronounced in snake-or spiderfearful subjects. Angry or fearful faces also elicit increased activity in the amygdala and anterior cingulate [Morris et al, 1996;Pissiota et al, 2003]. In addition, males and females appear to show differential neural activity to images associated with potential danger, though the direction of these effects do not necessarily fit with the idea that females are more sensitive to threat signals.…”

Evaluating Behavior in Mouse Models of the Behavioral Variant of Frontotemporal Dementia: Which Test for Which Symptom?

“…Interestingly, this observational fear learning is enhanced when the demonstrator is a cagemate, showing that this behavior is dependent of social connection. Moreover, this observational fear learning is dependent on the ACC and the amygdala [52], 2 structures involved in the recognition of fear in humans [53,54] and particularly defective in FTD [18,35]. This paradigm is used in autism modeling but could also be highly relevant for FTD, given the proximity of the behavior and the correspondence of the brain structures involved.…”

Generalization of conditioned fear-potentiated startle in humans: Experimental validation and clinical relevance

“…Whereas SCR is highly sensitive to attentional processes (e.g., Filion, Dawson, Schell, & Hazlett, 1991) and reflects increases in general sympathetic arousal, attentional effects on FPS-though present-may well be smaller than emotional effects (e.g., Bocker, Baas, Kenemans, & Verbaten, 2004) and FPS is more valence specific (for a review, see Lang, Bradley, & Cuthbert, 1998). Additionally, the construct validity of FPS as a measure of fear is supported by the central role played by amygdala-based "fear circuits" in the potentiation of startle in both rodents (e.g., Hitchcock & Davis, 1986) and humans (e.g., Pissiota et al, 2003). Because of these advantages, FPS is increasingly used to measure psychophysiological correlates of pathologic anxiety and to test the anxiolytic properties of pharmaceutical compounds (for a review, see Grillon, in press).…”