Brain Changes in Fear
Condition: Anxiety Disorders; Fear
MeSH terms: Anxiety Disorders
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      This protocol examines the neurobiology of fear and anxiety using various approaches. 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. 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 threat
      (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 and learning of threat cues in the amygdala,
      the visual and auditory systems, and motivation/reward systems. This will be investigated by
      means of event-related magneto-encephalography (MEG) and fMRI measurements using various
      paradigms. Finally, a last project will examine how pharmacologic manipulation of
      gamma-aminobutyric acid (GABA) levels with the benzodiazepine alprazolam affects the
      relationship between GABA concentration (quantified with magnetic resonance spectroscopy,
      MRS), visual- and auditory-induced gamma oscillations (measured with MEG), and fMRI BOLD
      response.
    

Intervention name(s): Shock device; Acoustic startle
Intervention type(s): Device; Device
Intervention description(s): Electric shock stimulus; Acoustic startle for MEG only
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Stress; Fear; Anxiety; Neuroimaging; Unpredictability; Healthy Volunteer; HV