Non Invasive Brain Stimulation for PTSD

Study Overview
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Brief Summary
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This study is designed to identify changes in the brain that underlie symptoms of combat-related PTSD using brain imaging (fMRI). Then, the investigators will administer mild electrical stimulation to the side of the head (using a method called tDCS) in an attempt to reduce the symptoms of PTSD.

Detailed Description
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Being involved in combat is a horrific experience that substantially increases the risk of developing posttraumatic stress disorder (PTSD). Although several effective treatments have been identified for PTSD a substantial number of patients (up to 50%) continue to experience symptoms. The field of neuroscience has revealed that patients with PTSD demonstrate altered functioning within, and interactions between, several brain regions; findings that are consistent with animal models of chronic stress. Despite this evidence, existing treatments are generally not designed using this neuroanatomical knowledge. The central premise of the proposed study is that neuroscientifically-based information can be used to develop more precise and effective treatments. Transcranial direct current stimulation (tDCS) will be used in an attempt to correct the dysfunctional brain regions (and communication between these regions), with the expectation that this modulation will result in symptom improvement. The primary goals of the study are to verify the maladaptive brain networks and then establish evidence that tDCS modulates these networks. Subsequent studies, performed during the later study years, will examine dose-response relationships and synergistic effects of tDCS and existing treatments. Outcome will be assessed using a multi-method approach that includes functional connectivity using resting-state functional magnetic resonance imaging data, neuropsychological tests, and self-report measures of emotional functioning. The combined results will provide vital methodological, mechanistic, and practical information necessary for a formal clinical trial of tDCS in PTSD.

Official Title
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Non-invasive Brain Stimulation for Post-Traumatic Stress Disorder

Conditions
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Posttraumatic Stress Disorder (PTSD)

Intervention / Treatment
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* Device: Active tDCS
* Device: Sham tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Combat Veteran - both Veterans with and without PTSD will be included at different points in this study Right-handed Between the ages 18-88 Stable on medications for a minimum of 2 weeks Exclusion Criteria: a history of neurological disease (e.g., dementia, epilepsy, stroke, moderate - severe traumatic brain injury) severe Axis I diagnoses (e.g., bipolar disorder, schizophrenia) presence of Axis II disorders current alcohol or drug abuse/dependence (in the past 8 weeks) participants will also be excluded if they are not MRI compatible (assessed using the guidelines of the American College of Radiology) Imminent risk of harm to self or others history of HIV or sickle cell anemia, as these can cause neuropsychological issues .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 88 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: active tDCS<br>Investigators will use cathodal tDCS to inhibit the brain regions that may be associated with symptoms of PTSD (temporal cortex). Active tDCS will be provided at 2 miliamps (mA) for 20 minutes (with gradual increase and withdraw of stimulation during the first and last minute). | Device: Active tDCS<br>* Participants will be randomized into active or sham stimulation in the first tDCS session. Participants will then have the option to complete 9 additional session of tDCS which will be active tDCS or a combination of active and sham tDCS in a non-randomized manner over two consecutive weeks. Each session will last 1 - 2 hours.<br>* Other names: HD-tDCS;|
| Sham Comparator: sham tDCS<br>Participants randomized to the sham condition will receive stimulation during the first and final minutes of the 20 minute period (with gradual increase and removal of current during that time). | Device: Sham tDCS<br>* Participants will be randomized into active or sham stimulation in the first tDCS session. Participants will then have the option to complete 9 additional session of tDCS which will be active tDCS or a combination of active and sham tDCS in a non-randomized manner over two consecutive weeks. Each session will last 1 - 2 hours.<br>* Other names: fake tDCS;|
| No Intervention: Combat Controls<br>Participants without PTSD will undergo neuropsychological testing and a single fMRI scan. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Connectivity changes as assessed by fMRI images | Investigators will use the fMRI images taken from before and after tDCS to determine if the treatment intervention contributed to any changes within the neural networks associated with the symptoms of PTSD. | Pre and post tDCS; typically within 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic changes as assessed by structured questionnaires (PCL-C) | PTSD checklist | Pre and post tDCS; typically within 4 weeks | 
| Symptomatic changes as assessed by structured questionnaires (CAPS) | Clinician administered PTSD Scale | Pre and post tDCS; typically within 4 weeks | 
| Symptomatic changes as assessed by structured questionnaires (Hamilton Depression Rating Scale) | Current symptoms of depression | Pre and post tDCS; typically within 4 weeks | 
| Symptomatic changes as assessed by structured questionnaires (State-trait anxiety inventory) | current symptoms of anxiety | Pre and post tDCS; typically within 4 weeks | 
| Cognitive changes as assessed by Neuropsychological testing | Verbal (HVLT) and visuospatial memory (object-location association test) | Pre and post tDCS; typically within 4 weeks | 
| Cognitive changes as assessed by Neuropsychological testing | Working memory (n-back) | Pre and post tDCS; typically within 4 weeks | 
| Cognitive changes as assessed by Neuropsychological testing | inhibitory control (go/no-go; flanker task; pattern comparison task) | Pre and post tDCS; typically within 4 weeks | 
| Cognitive changes as assessed by Neuropsychological testing | Executive functioning (Dimensional change card sort) | Pre and post tDCS; typically within 4 weeks |