PURPOSE: To evaluate the reproducibility of neural activations induced by an anticipatory anxiety provocation challenge in healthy volunteers.

MATERIALS AND METHODS: Fourteen healthy male volunteers participated in two separate functional MRI (fMRI) sessions in which they underwent a paradigm based on anticipation of aversive transcutaneous electrical nerve stimulations. This paradigm consisted of alternating presentation of red circles associated with the likelihood that aversive stimuli may be given and blue circles during which the subjects knew that no shock could be given. Anxiety state was compared before the fMRI sessions and during the threat periods using clinical scales (Hamilton, STAI-Y1), the Bond and Lader Visual Analogue Scale, and self-rating scales of apprehension and stimulus aversivity.

RESULTS: The selected paradigm induced anticipatory anxiety of moderate intensity as suggested by clinical scales and apprehension rating, without any habituation to the somatosensory stimulus across sessions. Compared to rest periods, threat of the aversive stimulus induced clear brain activation in anticipatory anxiety-related areas: frontal/prefrontal cortex, insula, lentiform nucleus, temporal pole, and cingulate cortex. Anxiety symptoms and cerebral activity were reproducible across sessions.

CONCLUSION: The fMRI paradigm and its assessment method include all criteria to speed up the evaluation and the development of new anxiolytics.