Post-Traumatic Stress Disorder
Conditions
Keywords
PTSD, Neurofeedback
Brief summary
The primary purpose of this study is to investigate the efficacy of neurofeedback (NF) of real-time functional magnetic resonance imaging (rt-fMRI) data of the amygdala with regards to the reduction of post-traumatic stress disorder (PTSD) symptoms. A secondary purpose of this study is to use fMRI as a method of investigating brain function in individuals with PTSD. This study approach provides a tool for probing the neurobiology of PTSD by (1) testing the critical role of the amygdala in this disorder, and by (2) examining how amygdala connectivity is related to both amygdala regulation and clinical symptoms.
Detailed description
In pursuit of the overarching goals of this study, the investigators aim to: * determine if an experimental feedback intervention increases control over the region of interest (the amygdala) more than a control feedback intervention in which participants receive feedback that is unassociated with their PTSD symptoms. * determine if an experimental feedback intervention results in clinical improvements in PTSD symptoms relative to a control feedback intervention, and examine whether these improvements correlate with improved control over the amygdala. * determine if an experimental feedback intervention results in changes in resting state connectivity to the amygdala, and whether these changes correlate with symptom improvement and an improved ability to regulate the amygdala.
Interventions
DEVICEExperimental Feedback
Feedback is presented in the form of a line graph that is updated every 2 seconds throughout the scan to indicate activity in the target area. A red diamond will indicate periods of symptom provocation, during which participants are exposed to symptom-provoking auditory stimuli in the form of personalized trauma scripts and sound clips. A blue arrow will indicate periods of down-regulation, where participants will try to bring the feedback line down as much as possible (by trying to decrease their fear/anxiety). The investigators believe that this feedback may help participants learn to control their PTSD symptoms. Participants will attend a total of 18 feedback scans over the course of 3 sessions.
DEVICEControl Feedback
Feedback is presented in the form of a line graph that is updated every 2 seconds throughout the scan to indicate activity in the target area. A red diamond will indicate periods of symptom provocation, during which participants are exposed to symptom-provoking auditory stimuli in the form of personalized trauma scripts and sound clips. A blue arrow will indicate periods of down-regulation, where participants will try to bring the feedback line down as much as possible (by trying to decrease their fear/anxiety). The investigators do not believe this feedback can help participants' PTSD symptoms. Participants will attend a total of 18 feedback scans over the course of 3 sessions.
Sponsors
VA Connecticut Healthcare System
National Institute of Mental Health (NIMH)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants will be blind to group assignment (experimental feedback intervention or control feedback intervention). The outcome assessor will be blind to group assignment.
Intervention model description
Participants will receive either an experimental feedback intervention or a control feedback intervention. Participants who receive the control feedback intervention will be offered to return to receive the experimental feedback intervention upon completion of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ages 18 and up * Diagnosis of chronic PTSD, as established by the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V; CAPS-5) * Ability to give signed, informed consent in English * Normal or corrected-to-normal vision * Participants who are on a stable dose of selective serotonin reuptake inhibitor (SSRI) antidepressants for 2 months (3 months if they are on sertraline), or who have been un-medicated for at least 2 months, will be allowed to participate in this study * At the time of recruitment, patients must have no intention of changing their medication or psychotherapy during the 2.5-month period of the intervention * Research group must be able to identify a trauma-related target region in or immediately adjacent to the amygdala
Exclusion criteria
* Any primary psychiatric diagnosis of a current major mood disorder, psychotic disorder, autism, mental retardation, or DSM-5 substance use disorder of mild or greater severity (2 or more symptoms) in the past 30 days. Comorbid mood and anxiety disorders will be permitted if they are not the primary focus of clinical attention * Any history of psychosis or mania * Active suicidality within past year, or history of suicide attempt in past 2 years * Any contraindication to MRI scanning (severe claustrophobia, ferromagnetic metal in body, etc.) * Pregnancy * Any unstable medical or neurological condition * Any history of severe past drug dependence (i.e., a focus of clinical attention or a cause of substantial social or occupational difficulty) * Any history of brain surgery, of penetrating, neurovascular, infectious, or other major brain injury, of epilepsy, or of other major neurological abnormality (including a history of traumatic brain injury \[TBI\] with loss of consciousness for more than 24 hours or posttraumatic amnesia for more than 7 days) * Significant hearing loss or severe sensory impairment * Any psychotropic medication other than a stable dose of selective serotonin reuptake inhibitors (SSRIs) * Any change in accepted psychotropic medication within the past 2 months * Active engagement in cognitive-behavioral therapy or any evidence-based PTSD psychotherapy (Cognitive Processing Therapy \[CPT\], Prolonged Exposure \[PE\], Eye Movement Desensitization and Reprocessing \[EMDR\]) initiated within the past 3 months; continuation of established maintenance supportive therapy will be permitted * Enrollment in another research study testing an experimental/clinical/behavioral intervention intended to affect symptoms initiated within the last 2 months, or intended enrollment within the next 2.5 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Control Over the Amygdala | baseline; 30 day-day follow up | Control over the amygdala will be defined as the change in the blood-oxygen-level dependent (BOLD) signal in the target area (an individually-localized region of interest (ROI) in the amygdala) during down-regulation blocks following symptom provocation relative to rest. Investigators will assess the magnitude of change in control over the amygdala to trauma reminders from baseline to 30-day post treatment follow-up. This measure is based on beta values, which are unitless |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvements in PTSD Symptoms | Baseline; 30-day follow-up | Clinical improvement will be defined as the change from baseline at the post-intervention assessments (based on the past-month Clinician-Administered PTSD scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V ) \[CAPS-5\]). Score ranges from 0 - no PTSD symptoms to a maximum of 80. Higher score is associated with increase severity of PTSD. A change in CAPS score of more than 5 points over the course of treatment is considered a meaningful change and a change of 10 point or more is considered to be a clinically meaningful change. |
| Number of Participants With Changes in Resting State Connectivity to the Amygdala | Baseline; 60 days follow up. | The number of participants with a significant whole brain change in seed region connectivity to the amygdala from pre- to post-intervention will be assessed in the blood-oxygen-level dependent (BOLD) signal collected during resting state runs. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental Feedback Intervention Participants receive real-time feedback during fMRI scans that the investigators believe may help them learn to control their PTSD symptoms.
Experimental Feedback: Feedback is presented in the form of a line graph that is updated every 2 seconds throughout the scan to indicate activity in the target area. A red diamond will indicate periods of symptom provocation, during which participants are exposed to symptom-provoking auditory stimuli in the form of personalized trauma scripts and sound clips. A blue arrow will indicate periods of down-regulation, where participants will try to bring the feedback line down as much as possible (by trying to decrease their fear/anxiety). The investigators believe that this feedback may help participants learn to control their PTSD symptoms.
Participants will attend a total of 18 feedback scans over the course of 3 sessions. | 14 |
| Control Feedback Intervention Participants receive real-time feedback during fMRI scans that the investigators do not believe can help their PTSD symptoms.
Control Feedback: Feedback is presented in the form of a line graph that is updated every 2 seconds throughout the scan to indicate activity in the target area. A red diamond will indicate periods of symptom provocation, during which participants are exposed to symptom-provoking auditory stimuli in the form of personalized trauma scripts and sound clips. A blue arrow will indicate periods of down-regulation, where participants will try to bring the feedback line down as much as possible (by trying to decrease their fear/anxiety). The investigators do not believe this feedback can help participants' PTSD symptoms.
Participants will attend a total of 18 feedback scans over the course of 3 sessions. | 11 |
| Total | 25 |
Baseline characteristics
| Characteristic | Total | Experimental Feedback Intervention | Control Feedback Intervention |
|---|---|---|---|
| Additional Diagnoses Agoraphobia without History of Panic Disorder | 1 Participants | 1 Participants | 0 Participants |
| Additional Diagnoses Body Dysmorphic Disorder | 4 Participants | 2 Participants | 2 Participants |
| Additional Diagnoses Dysthymic Disorder | 0 Participants | 0 Participants | 0 Participants |
| Additional Diagnoses Generalized Anxiety Disorder | 4 Participants | 2 Participants | 2 Participants |
| Additional Diagnoses Major Depressive Disorder(MDD) | 10 Participants | 5 Participants | 5 Participants |
| Additional Diagnoses MDD in full remission | 7 Participants | 5 Participants | 2 Participants |
| Additional Diagnoses MDD in partial remission | 4 Participants | 2 Participants | 2 Participants |
| Additional Diagnoses Obsessive-Compulsive Disorder | 3 Participants | 3 Participants | 0 Participants |
| Additional Diagnoses Panic Disorder with Agoraphobia | 2 Participants | 1 Participants | 1 Participants |
| Additional Diagnoses Panic Disorder without Agoraphobia | 4 Participants | 1 Participants | 3 Participants |
| Additional Diagnoses Phobia of Heights | 1 Participants | 0 Participants | 1 Participants |
| Additional Diagnoses Social Phobia | 8 Participants | 5 Participants | 3 Participants |
| Additional Diagnoses Stratification: high re-experiencing (vs low) | 16 Participants | 9 Participants | 7 Participants |
| Age, Customized | 44.67 years STANDARD_DEVIATION 14.31 | 40.2 years STANDARD_DEVIATION 14.27 | 50.36 years STANDARD_DEVIATION 12.78 |
| Clinician-Administered PTSD scale for Diagnostic and Statistical Manual of Mental Disorders, (CAPS-5 | 36.36 score STANDARD_DEVIATION 8.93 | 33.71 score STANDARD_DEVIATION 7.99 | 39.73 score STANDARD_DEVIATION 9.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 11 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Medication Status Anticonvulsant | 2 Participants | 0 Participants | 2 Participants |
| Medication Status Antidepressants | 9 Participants | 7 Participants | 2 Participants |
| Medication Status Medical Marijuana/Cannabinoids (CBD Oil) | 4 Participants | 1 Participants | 3 Participants |
| Medication Status No psychiatric medication | 8 Participants | 4 Participants | 4 Participants |
| Medication Status Stimulants | 1 Participants | 1 Participants | 0 Participants |
| Medication Status Unknown | 1 Participants | 1 Participants | 0 Participants |
| PTSD Checklist for DSM-5 (PCL-5) | 45.20 score STANDARD_DEVIATION 13.555 | 43.43 score STANDARD_DEVIATION 13.42 | 47.45 score STANDARD_DEVIATION 14.03 |
| Race/Ethnicity, Customized White | 25 Participants | 14 Participants | 11 Participants |
| Region of Enrollment United States | 25 participants | 14 participants | 11 participants |
| Sex: Female, Male Female | 21 Participants | 11 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 12 |
| other Total, other adverse events | 0 / 15 | 0 / 12 |
| serious Total, serious adverse events | 0 / 15 | 0 / 12 |
Outcome results
Primary
Change in Control Over the Amygdala
Control over the amygdala will be defined as the change in the blood-oxygen-level dependent (BOLD) signal in the target area (an individually-localized region of interest (ROI) in the amygdala) during down-regulation blocks following symptom provocation relative to rest. Investigators will assess the magnitude of change in control over the amygdala to trauma reminders from baseline to 30-day post treatment follow-up. This measure is based on beta values, which are unitless
Time frame: baseline; 30 day-day follow up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Feedback Intervention | Change in Control Over the Amygdala | -0.279 unitless | Standard Error 0.146 |
| Control Feedback Intervention | Change in Control Over the Amygdala | 0.202 unitless | Standard Error 0.167 |
p-value: 0.047t-test, 2 sided
Secondary
Improvements in PTSD Symptoms
Clinical improvement will be defined as the change from baseline at the post-intervention assessments (based on the past-month Clinician-Administered PTSD scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V ) \[CAPS-5\]). Score ranges from 0 - no PTSD symptoms to a maximum of 80. Higher score is associated with increase severity of PTSD. A change in CAPS score of more than 5 points over the course of treatment is considered a meaningful change and a change of 10 point or more is considered to be a clinically meaningful change.
Time frame: Baseline; 30-day follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Feedback Intervention | Improvements in PTSD Symptoms | 8.786 Average CAPS change score | Standard Deviation 9.744 |
| Control Feedback Intervention | Improvements in PTSD Symptoms | 10.545 Average CAPS change score | Standard Deviation 13.441 |
Secondary
Improvements in PTSD Symptoms
Clinical improvement will be defined as the change from baseline at the post-intervention assessments (based on the past-month Clinician-Administered PTSD scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V ) \[CAPS-5\]). Score ranges from 0 - no PTSD symptoms to a maximum of 80. Higher score is associated with increase severity of PTSD. A change in CAPS score of more than 5 points over the course of treatment is considered a meaningful change and a change of 10 point or more is considered to be a clinically meaningful change.
Time frame: Baseline; 60-day follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Feedback Intervention | Improvements in PTSD Symptoms | 13.286 Average change in CAPS scores | Standard Deviation 9.934 |
| Control Feedback Intervention | Improvements in PTSD Symptoms | 9.364 Average change in CAPS scores | Standard Deviation 13.246 |
Secondary
Number of Participants With Changes in Resting State Connectivity to the Amygdala
The number of participants with a significant whole brain change in seed region connectivity to the amygdala from pre- to post-intervention will be assessed in the blood-oxygen-level dependent (BOLD) signal collected during resting state runs.
Time frame: Baseline; 60 days follow up.
Population: Due to the COVID-19 suspension of human subject research, resting state date for 60-day post treatment were not available for 4 participants in the experiential group and 1 subject in the control group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Feedback Intervention | Number of Participants With Changes in Resting State Connectivity to the Amygdala | 0 number of participants with change |
| Control Feedback Intervention | Number of Participants With Changes in Resting State Connectivity to the Amygdala | 0 number of participants with change |