Fear and Avoidance in PTSD Patients

Official title

Neural Correlates of Active Avoidance Learning and Their Interactions With Fear Extinction Mechanisms in PTSD Patients

Overview

The purpose of this research study is to study how the brain learns to avoid certain stimuli or situations using an experimental paradigm. The big goal is to measure brain responses and subject's feelings and expectations when they are learning to actively avoid experimental stimuli, and how fear extinction learning and monetary cost can change how and when subjects are to avoid.

Detailed description

This study aims to study the neural correlates of avoidance learning using a recently validated conditioning and active avoidance paradigm (CAAP). The overarching objective is to measure the neural correlates of active avoidance, and how fear extinction learning and monetary cost modulate these avoidance responses. Participants will include healthy controls (HC), trauma-exposed healthy controls (TEHC), and participants with post-traumatic stress disorder (PTSD). Avoidance is common and often hinders the progression and success of extinction-based exposure therapy in PTSD. The data to be gathered in this study will enable us to probe neural mechanisms of avoidance, extinction, and decision-making to avoid or not, in addition to understanding the impact of cost on avoidance decision-making. These data will provide a more integrated platform for the understanding of the mechanisms of avoidance in both trauma-exposed healthy controls and PTSD psychopathology, which has important implications for treatment.

Interventions

• Behavioral Fear Conditioning
  Participants will be administered increasing intensities of mild electric shock via electrodes connected to the foot. New Biopac stimulators that can deliver higher shock intensity, provided participants agreement will be used to assure adequate conditioning levels. Stimulation is measures in milliamps (mA), and each delivered stimulation will be 0.5 seconds long (500 milliseconds). To colored (blue, red, \& yellow) light stimuli (CS). The light stimulus is followed by a shock or no shock depend
• Other Avoidance conditioning
  Via button pressing. Only one stimulus-CS will enable control over experiencing the shock: the participant can press the button during the first 2 seconds of the light presentation to avoid the shock.
• Other Pavlovian fear extinction learning
  After avoidance conditioning, the CS+ associated with avoidance responding appears with no button to press and no shock is administered.
• Other Willingness to pay to avoid shock
  On the next day, participants receive a monetary stipend to use to pay to guarantee that they are not to receive any shocks if they press a button from the CS+. This and all previously described experimental phases noted above will occur inside of the fMRI scanner.

Primary outcome measures

• Skin Conductance Response (SCR) [Time frame: Experimental Day 1, Experimental Day 2]
• Functional MRI (fMRI) responses [Time frame: Experimental Day 1, Experimental Day 2]

Eligibility criteria

Inclusion criteria

• 18 - 70 years of age
• Female or Male
• Inclusion Criteria: PTSD Subjects

a. Diagnosis of current PTSD

• Inclusion Criteria: Trauma-exposed healthy controls (TEHC)

• SCID diagnosis consistent with no current psychiatric disorders, and no current PTSD
• History of trauma exposure
• Inclusion Criteria: Healthy controls (HC)

• SCID diagnosis consistent with no current psychiatric disorders ("Axis I" disorders).
• No history of trauma exposure
• Willing and able to provide informed consent.

Exclusion Criteria for ALL subjects:

• History of neurologic disease (e.g. tic disorder)
• Current significant suicidal ideation, plan or intent or suicidal behavior in past 6 months based on CSSRS or Self-injurious behavior that involves suicidal intent, requires medical attention, or occurs daily
• History of seizure or significant head trauma
• History of the serious/significant psychiatric diagnosis ("Axis I" disorders)
• Use of neuroleptics within one year prior to study
• Current substance use (assessed by urine toxicology; positive urine toxicology screen for any substance, with the exception of THC). Per PI judgement and approval: if urine toxicology is positive for a substance, participant may be eligible to proceed with study provided their urine toxicology (or saliva test for THC) is negative at experimental visit(s)
• Pregnancy (to be ruled out by urine ß-HCG)
• Metallic implants or devices contraindicating magnetic resonance imaging
• High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or the informed consent process

Additional exclusion criteria for Trauma-exposed healthy controls (TEHC) group and Healthy controls (HC) group:

• Current psychiatric diagnosis ("Axis I" diagnoses)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• UTHealth Houston — Houston

Identifiers

NCT: NCT04770584 · HSC-MS-23-0495 · R01MH123736

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗