Neuroimaging Memories of Fear and Safety in the Human Brain

The purpose of this research is to use functional magnetic resonance imaging (fMRI) to investigate how the brain forms associations between neutral and negative stimuli. The ultimate goal is to understand the neural systems involved in regulating negative emotional responses to fearful stimuli.

This study uses functional magnetic resonance imaging (fMRI) to investigate how the brain forms associations between neutral stimuli and a mildly uncomfortable electrical stimulation to the wrist. Referred to as Pavlovian fear conditioning. The goal is to compare brain activity between individuals with posttraumatic stress disorder (PTSD) and healthy control subjects without PTSD. PTSD is characterized by excessive fear and anxiety, including in harmless situations. The data here will help us better understand dysregulation in neural circuitry involved in fear recovery, which has implications for improving treatment.

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.