The purpose of this study is to use brain imaging technology to investigate brain changes in people exposed to predictable versus unpredictable unpleasant stimuli. Unpleasant events that can be predicted evoke a response of fear, whereas unpredictable, unpleasant stimuli cause chronic anxiety not associated with a specific event. Information gained from this study may help in the development of more effective treatments for anxiety disorders.

When confronted with fearful events, people eventually develop fear of specific cues that were associated with these events as well as to the environmental context in which the fearful event occurred. Evidence suggests that cued fear and contextual fear model different aspects of anxiety. However, studies that examine the way the brain affects expression of contextual fear have not been conducted. This study will use magnetic resonance imaging (MRI) or Magneto-encephalography (MEG) to compare the brain activity underlying fear brought on by predictable and unpredictable aversive stimuli.

During fear conditioning in which a phasic explicit cue (e.g., a light) is repeatedly associated with an aversive unconditioned stimulus (e.g., a shock), the organism develops fear to the explicit cue as well as to the environmental context in which the experiment took place. Experimental evidence suggests that cued fear and contextual fear model different aspects of anxiety. Studies in patients indicated that contextual fear may model an aspect that is especially relevant to anxiety disorders (Grillon et al.,1994, 1998a,b; 1999). However, the neural basis for the expression of contextual fear has not previously been elucidated in human imaging studies.

One important determinant of contextual fear is predictability: contextual fear increases when a treat (e.g., electric shock) is unpredictable, as opposed to when the threat is predictable. The aim of this study is to compare the neural substrates underlying fear evoked by predictable versus unpredictable shocks. Animal studies have indicated that conditioned responses to predictably cued threat and to less explicit threat are separate processes mediated by distinct brain structures. Psychophysiological data suggest that the proposed procedure can differentiate between these two responses. Hence, we anticipate that this procedure will allow us to compare brain correlates of these responses in humans.

Another objective is to study effects of threat of shock on processing of threat cues in the amygdala and the visual system. This will be investigated by means of event-related magneto-encephalography (MEG), electro-encephalography, and fMRI measurements.

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• INCLUSION CRITERIA:

Male or female volunteers ages 18-40 years old.

Judged to be in good physical and psychiatric health on the basis of medical history, a clinical MRI scan, and physical examination.

Able to understand procedures and agree to participate in the study by giving written informed consent.

EXCLUSION CRITERIA:

Clinically significant organ disease, e.g., cardiovascular.

Clinically significant abnormalities in physical examination.

Any medical condition that increases risk for fMRI (e.g. pacemaker, metallic foreign body in eye).

History of any disease, which in the investigators' opinion may confound the results of the study, including, but not limited to, history of organic mental disorders, seizure, or mental retardation.

Lifetime history of substance dependence, or substance abuse within past 1 year.

Current Axis I psychiatric disorders as identified with the Structured Clinical Interview for DSM-IV-TR axis disorders, non-patient edition (SCID-np).

Past bipolar depression and any history of psychosis or delusional disorders.

Psychotropic medication within 4 weeks of scanning.

Pregnancy, i.e., a positive beta-HCG urine test.

Current or past history of cubital tunnel syndrome or carpal tunnel syndrome.