Brain Changes in Fear
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|ClinicalTrials.gov Identifier: NCT00047853|
Recruitment Status : Recruiting
First Posted : October 23, 2002
Last Update Posted : March 12, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Anxiety Disorders Fear||Device: Shock device Device: Acoustic startle||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1872 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||fMRI Investigation of Explicit Cue and Contextual Fear|
|Actual Study Start Date :||November 4, 2002|
|Estimated Primary Completion Date :||September 30, 2029|
|Estimated Study Completion Date :||September 30, 2029|
Experimental: Acoustic startle
loud noises with MEG only
Device: Acoustic startle
Acoustic startle for MEG only
Experimental: Threat of shock
threat of electric shock
Device: Shock device
Electric shock stimulus
- event-related magnetic fields [ Time Frame: End of study visit ]Magnetoencephalography (MEG) a neuroimaging technique employed in the current protocol to measure the event-related magneticfields produced by electrical activity in the brain
- event-related haemodynamic response [ Time Frame: End of study visit ]Functional magnetic resonance imaging (fMRI), measuring the event-related haemodynamic response related to neural activity in the brain.
- Self-reported measures of anxiety, level of risk, and CSUS contingency awareness. [ Time Frame: End of study visit ]Self-reported measures of anxiety, level of risk, and CSUS contingency awareness.
- Psychophysiological measures [ Time Frame: End of study visit ]Psychophysiological measures of anxious arousal including the skinconductance response (SCR), heart rate, respiration, and EMG measures of the fearpotentiation of the startle reflex.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00047853
|Contact: Marilla Geraci, R.N.||(301) email@example.com|
|Contact: Christian Grillon, Ph.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Christian Grillon, Ph.D.||National Institute of Mental Health (NIMH)|