Investigating how the brain processes fear and safety memories

Localizing and Modulating Competing Memories of Fear and Safety in the Human Brain

This study looks at how the brains of people with PTSD respond to fear and safety to see if it can help us find better treatments for the condition.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: University of Texas at Austin (Academic / other)
• Locations: 2 sites (Austin, Texas and 1 other locations)
• Trial ID: NCT04975009 on ClinicalTrials.gov

What this trial studies

This research uses functional magnetic resonance imaging (fMRI) to explore how the brain creates associations between neutral stimuli and negative experiences, specifically focusing on fear conditioning. The study compares brain activity in individuals with posttraumatic stress disorder (PTSD) to healthy control subjects to understand the neural mechanisms that regulate emotional responses to fear. By examining these differences, the research aims to shed light on the dysregulation of neural circuits involved in fear recovery, which could inform future treatment strategies for PTSD and related conditions.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with PTSD as well as healthy control subjects without any psychiatric disorders.

Not a fit: Patients with significant medical illnesses, neurological disorders, or those who have a history of severe psychiatric conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatments for individuals suffering from PTSD and anxiety disorders.

How similar studies have performed: Other studies using neuroimaging to investigate fear conditioning have shown promising results, indicating that this approach is both relevant and potentially impactful.

Eligibility criteria

Inclusion Criteria (All study populations):

1. Volunteers with a major medical illness or a neurological disorder (e.g., Parkinson's Disease), or neurological abnormality including significant head trauma (loss of consciousness \> 5 min).
2. A positive pregnancy test in female volunteers.
3. Benzodiazepines, tested using urine tox screen.
4. For the healthy subjects, exclusion is meeting criteria for either PTSD, or any other psychiatric disorder, or any prior psychiatric hospitalizations.
5. For the healthy subjects, exclusion is prior use of a psychotropic medication for longer than 1 month.
6. History of moderate to severe cannabis use disorder.
7. Magnetic Resonance Imaging (MRI) exclusions: Claustrophobia; tattoos above the shoulders; permanent eyeliner or permanent; artificial eyebrows; cardiac pacemaker; metal fragments in eye, skin, or body, including shrapnel; heart valve replacement; brain clips; venous umbrella; being a sheet-metal worker or welder; lifetime history of aneurysm surgery; intracranial bypass, renal, or aortic clips; prosthetic devices such as middle ear, eye, joint, or penile implants; joint replacements; non-removable hearing aid, neurostimulator, or insulin pump; shunts/stents; metal mesh/coil implants; metal plate/pin/screws/wires; or any other metal implants.

Inclusion Criteria (PTSD populations):

1. Meet diagnostic criteria for PTSD, as assessed by standard diagnostic instruments.
2. Participants with PTSD are eligible if they meet diagnostic criteria for current PTSD. This is determined by the presence of a Criterion A event in addition to a severity score of 2 or greater on 1 symptom in clusters B and C and on 2 symptoms in clusters D and E, in addition to meeting criteria F and G. The specific form of trauma is not considered for inclusion/exclusion.
3. Volunteers in the patient group, but not healthy control group, may also meet criteria for a mood disorder (except for bipolar affective disorder, see exclusions below), as well as other anxiety disorders (panic disorder, agoraphobia, social phobia, generalized anxiety disorder, or obsessive compulsive disorder). Including these comorbidities is essential because of the high frequency of co-occurring mood and anxiety disorders with PTSD.

Exclusion Criteria (all participants):

1. Volunteers with a major medical illness or a neurological disorder (e.g., Parkinson's Disease), or neurological abnormality including significant head trauma (loss of consciousness \> 5 min).
2. A positive pregnancy test in female volunteers.
3. Benzodiazepines, tested using urine tox screen.
4. For the healthy subjects, exclusion is meeting criteria for either PTSD, or any other psychiatric disorder, or any prior psychiatric hospitalizations.
5. For the healthy subjects, exclusion is prior use of a psychotropic medication for longer than 1 month.
6. History of moderate to severe cannabis use disorder.
7. MRI exclusions: Claustrophobia; tattoos above the shoulders; permanent eyeliner or permanent; artificial eyebrows; cardiac pacemaker; metal fragments in eye, skin, or body, including shrapnel; heart valve replacement; brain clips; venous umbrella; being a sheet-metal worker or welder; lifetime history of aneurysm surgery; intracranial bypass, renal, or aortic clips; prosthetic devices such as middle ear, eye, joint, or penile implants; joint replacements; non-removable hearing aid, neurostimulator, or insulin pump; shunts/stents; metal mesh/coil implants; metal plate/pin/screws/wires; or any other metal implants.

Exclusion Criteria (PTSD group):

* 1. Volunteers meeting DSM-5 criteria for history of or current psychotic or bipolar affective disorders, a current eating disorder (bulimia, anorexia nervosa), or dissociative identity disorder.

  2. Volunteers meeting DSM-5 criteria for another substance use disorder, with the exception of caffeine or nicotine, within the past 12 months.

  3. Individuals considered an immediate suicide risk based on the Columbia Suicide Severity Scale (C-SSRS) or who would likely require hospitalization during the course of the study.

  4. Participants must be stable on medication.

Where this trial is running

Austin, Texas and 1 other locations

• The University of Texas at Austin — Austin, Texas, United States (Recruiting)
• Biomedical Imaging Center — Austin, Texas, United States (Recruiting)

Conditions Fear Anxiety; PTSD; Pavlovian conditioning; Fear Conditioning; Neuroimaging