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While animal research on fear conditioning suggests crucial involvement of the amygdala, this has not been corroborated in humans when using subtractive neuroimaging methodology. Correlation analyses might be more able to reveal relations between individual differences in conditionability and central neural activity. Hence, we performed a directed search for amygdalar participation in human fear conditioning by correlating central and autonomic nervous activity. [15O]Butanol positron emission tomography evaluated regional cerebral blood flow (rCBF) in six subjects before and after aversive conditioning to visual snake stimuli. Non-specific electrodermal fluctuations (EDA) were recorded simultaneously. A significant positive correlation was obtained between conditioned EDA and conditioned rCBF in the right amygdala (r = 0.75, p < 0.05), supporting involvement of the amygdala in human fear conditioning.

We investigated central nervous system correlates of simple phobic fear. Regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) in eight volunteers with symptomatic spider phobia that were exposed to visual phobogenic and neutral stimuli. Diazepam (0.1 mg/kg body weight i.v.) or placebo was administered under double-blind conditions after initial PET scans. The PET scans were then repeated. The presence of fear was confirmed by rating procedures and increased number of nonspecific electrodermal fluctuations and by higher heart rate during phobic than during neutral stimulation. Phobic as compared to neutral stimulation elevated the regional to whole brain (relative) CBF in the secondary visual cortex but reduced relative rCBF in the hippocampus, prefrontal, orbitofrontal, temporopolar, and posterior cingulate cortex. Diazepam treatment did not affect the relative rCBF or the subjective or physiological fear indices. The observed rCBF pattern replicates our previous findings in snake phobics (M. Fredrikson et al. [1993] Psychophysiology, 30, 127-131; G. Wik et al. [1993] Psychiatry Research (Neuroimaging), 50, 15-24) and indicates that fear and anxiety affect cortical areas outside the classic limbic system areas.

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To investigate CNS habituation (i.e. response decrement due to stimulus repetition) the present study used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in eight healthy women during two repetitions of complex visual stimuli. Repeated visual stimulation resulted in neural habituation bilaterally in the secondary visual cortex and in the right medial temporal cortex including the amygdala and the hippocampus. Regional CBF in the left thalamus was elevated as a function of repeated stimuli presentations. Thus, repeated presentation of complex visual stimuli result in rCBF habituation in later stages of the visual processing chain. The elevated neural activity in the thalamus might be associated with interruption of further neural transmission related to suppression of non-meaningful behavior.