Brain Changes in Fear
|First Submitted Date||October 22, 2002|
|First Posted Date||October 23, 2002|
|Last Update Posted Date||October 19, 2017|
|Start Date||October 15, 2002|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures||Not Provided|
|Original Primary Outcome Measures||Not Provided|
|Change History||Complete list of historical versions of study NCT00047853 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures||Not Provided|
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||Brain Changes in Fear|
|Official Title||fMRI Investigation of Explicit Cue and Contextual Fear|
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.
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 Design||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
All screening procedures described in this section are conducted under screening protocol 01-M-0254. Subjects must meet the following inclusion criteria in order to participate in the study:
Subjects will be excluded from the study if they meet the following exclusion criteria:
ADDITIONAL EXCLUSION CRITERIA FOR PATIENTS:
Patients who would be unable to comply with study procedures or assessments
Specific phobia patients carrying a diagnosis of generalized anxiety disorder
Patients who are currently on psychotropic medications with the exception that PTSD patients currently taking SSRI s, benzodiazepines, or tricyclic antidepressants will be included. (Patients who are required to be free of all psychotropics must be off medication for 2 weeks, 6 weeks for fluoxetine. Additionally, PTSD patients on psychotropics other than SSRI s, benzodiazepines, or tricyclic antidepressants must be off medication for 2 weeks prior to testing. Patients will not be taken off medications for the purpose of the study)
Patients will be excluded if they have a current or past history of any psychotic disorder, bipolar disorder, delirium, dementia, amnestic disorder, cognitive disorder not otherwise specified, any of the pervasive developmental disorders, or mental retardation
ADDITIONAL EXCLUSION CRITERIA FOR THE STUDY INVOLVING ALPRAZOLAM:
Adverse reactions to benzodiazepines
History of angioedema
High or low blood pressure
History of fainting
A first degree relative with a history of mania, schizophrenia, or other psychoses
|Ages||18 Years to 50 Years (Adult)|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries||United States|
|Removed Location Countries|
|Other Study ID Numbers||020321
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )|
|Study Sponsor||National Institute of Mental Health (NIMH)|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||September 27, 2017|