No abstract

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.

These results suggested that the age-related impairment of the inhibitory process could already occur around the age of 50 years and consist in an increase of the activity in the left prefrontal and parietal cortex before increasing more and becoming bilateral around the age of 60 years.

Human models of anxiety are useful to develop new effective anxiolytics. The objective of this study was to use functional magnetic resonance imaging (fMRI) to test the hypothesis that a single dose of lorazepam modifies brain activation during an anxiety challenge. Eighteen healthy male subjects underwent fMRI associated with a challenge based on the anticipation of aversive electrical stimulations after pretreatment, either with placebo or with 1.0 mg of oral lorazepam. Anxiety was rated before fMRI and after, referring to the threat condition periods, using State Trait Anxiety Inventory (STAI) and Hamilton scales. The conditioning procedure induced anxiety, as indicated by clinical rating score changes. Lorazepam did not modify anxiety rating as compared to placebo. Lorazepam reduced cerebral activity in superior frontal gyrus, anterior insula/inferior frontal gyrus and cingulate gyrus. The current finding provides the first evidence of the modulatory effects of an established anxiolytic agent on brain activation related to anticipatory anxiety.

In many patients, there is a good concordance between fMRI and brain functions suggested by EP and metabolic activity demonstrated with PET. In few others, fMRI can be integrated in the early evaluation of brain functions to further augment our capacity for a proper evaluation of brain functions in critically ill patients.