An interventional study of Working Memory Training and Sham Training in Post-Traumatic Stress Disorders, Stress Disorders, Traumatic and Post Traumatic Stress Disorder, sponsored by VA Office of Research and Development. Recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-10-09.
Sponsored by VA Office of Research and Development · Not applicable, Interventional, and Other
The proposed study will test whether a working memory training (WMT) program improves fear extinction learning and its underlying neural circuitry in Veterans with posttraumatic stress disorder (PTSD). WMT is designed to improves the ability to maintain task-relevant information in mind. The project will further validate the relationship between working memory and fear extinction using novel computational and multivariate analyses that link to specific PTSD symptoms. If WMT can enhance fear extinction learning, then WMT may be a powerful adjunctive treatment that can enhance exposure therapy outcomes or be leveraged as a stand-alone treatment. This project supports the Department of Veteran Affairs mission of developing viable targets of treatment for Veterans with PTSD.
Posttraumatic stress disorder (PTSD) is prevalent, debilitating, and associated with significant levels of functional impairment in Veterans seeking care at the VA. Despite evidence that current treatments for PTSD are effective, a substantial portion of individuals maintain elevated PTSD symptoms after first line treatments. Mechanistic insight and tools that improve the neurocognitive and affective mechanisms that underlie successful clinical outcomes from evidence-based psychotherapies, like prolonged exposure, are highly needed. One of the most prominent mechanisms associated with therapeutic symptom reduction in PTSD is fear extinction. Indeed, extinction learning is a key theoretical treatment target in exposure-based therapies for PTSD. Fear extinction learning is not only an emotional process, but relies on an individual's cognitive control abilities, including working memory (WM). Under a WM framework, high WM ability offers the ability of an individual to adjudicate the competition between threat and extinction memory expression as they repeatedly encounter feared cues that are no longer threatening. Consistent with this hypothesis, previous investigations show replicable findings that variation in WM ability is associated with laboratory measures of fear extinction learning. The investigators have previously shown that psychophysiological and neural measures of fear extinction is a construct malleable to treatment. In civilian populations a brief WM training (WMT) designed to boost WM was effective in reducing anxiety during a speech exposure and was is effective in enhancing behavioral and neural markers of WM ability. These findings raise the intriguing possibility for the mechanistic link between WM and extinction, and that enhancing WM ability through WMT may also improve fear extinction learning success in Veterans with PTSD.
The current proposal aims to answer these questions. In a between-group design, Veterans diagnosed with PTSD will complete 8-sessions of working memory training (WMT) or sham-training (ST) over a four-week period. At pre- and post-training, Veterans will complete a standard fear acquisition \& extinction learning task in addition to tasks assaying WM capacity and cognitive control. The investigators will identify whether WMT modulates behavior, psychophysiological, and neural changes in extinction learning. The investigators will further test the conceptual link between WM and extinction in Veterans with PTSD by testing whether neural circuits associated with high WM capacity and extinction learning are linked. The project is expected to determine if a cognitive control training program targeting WM capacity shows the potential to enhance behavioral and neural markers of fear extinction, mechanisms that are clearly integral to current PTSD treatments. These aims support the VA mission of testing and evaluating innovative treatment targets for PTSD. Results will provide a mechanistic foundation for future clinical trials that test whether adding WMT prior to or in conjunction with exposure based psychotherapies will improve clinical outcomes and further clarify existing mechanistic and neurobiological models of PTSD and its treatment for Veterans.
2,682 studies on the registry are indexed under Stress Disorders, Post-Traumatic; 601 are open to participants now.
This study's planned enrollment of 120 is above the median of 69 across 2,196 interventional studies indexed under Stress Disorders, Post-Traumatic.
Browse Stress Disorders, Post-Traumatic studies →VA Office of Research and Development is the lead sponsor of 1,771 studies on the registry; 392 are open to participants now.
Of its 213 completed or terminated interventional studies of FDA-regulated products, 185 (87%) have results posted.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Computer-administered working memory training program. WMT is a modified working memory capacity task designed to train working memory functioning. WMT is designed to contain high interference across trials and is adaptive to performance. As participants improve working memory, the task becomes more difficult.
Behavioral: Working Memory Training
The Sham condition requires participants to complete a similar computer task for the same length of time. The Sham Training is a modified working memory capacity task designed to place less demands on working memory.
Other: Sham Training
Computer-administered working memory training program. WMT is a modified working memory capacity task designed to train working memory functioning. WMT is designed to contain high interference across trials and is adaptive to performance. As participants improve working memory, the task becomes more difficult.
Also known as: WMT
The Sham condition requires participants to complete a similar computer task for the same length of time. The Sham Training is a modified working memory capacity task designed to place less demands on working memory.
Also known as: Sham
Behavioral Threat Expectancy Ratings During Extinction Performance
Threat Expectancy Ratings. Behavioral ratings will be collected during the extinction learning task. Responses will be on scale of 1- 4. High scores reflect greater threat expectancy. It is expected that the working memory training group (WMT) will have lower threat expectancy ratings during extinction learning than the Sham group.
Time frame: Baseline, Approximately 5 or 6 weeks
Extinction Electrodermal Activity Response
Electrodermal Activity Response. Responses are measured in microsiemens and time-locked to the CS+ trials during extinction learning. It is expected that the working memory training group (WMT) will have lower electrodermal activity responses during extinction learning than the Sham group.
Time frame: Baseline, Approximately 5 or 6 weeks
Extinction Blood Oxygen Level Dependent (BOLD) Response
Functional Magnetic Resonance Imaging (fMRI) will be used to measure Blood Oxygen Level Dependent (BOLD) Response during the Extinction task. BOLD response during the extinction task conditions are measured using % signal change from baseline BOLD activity with higher scores indicating greater activation. It is expected that the working memory training group (WMT) will have greater changes in BOLD responses during extinction learning than the Sham group.
Time frame: Baseline, Approximately 5 or 6 weeks
Working Memory Task Blood Oxygen Level Dependent (BOLD) Response
Functional Magnetic Resonance Imaging (fMRI) will be used to measure Blood Oxygen Level Dependent (BOLD) Response during a working memory capacity task while undergoing functional MRI. BOLD response to the task conditions is measured using % signal change with higher scores indicating greater activation.
Time frame: Baseline, Approximately 5 or 6 weeks
Working memory capacity change detection task
This behavioral task measures the number of visual items maintained in working memory and is a measure of working memory capacity. This task will use simple geometric shapes as stimuli. Scores are measured using percent accuracy (o - 100%) and a measure of working memory capacity (K-score range: 0 - 6 in this task). High scores indicate greater accuracy and working memory capacity.
Time frame: Baseline, Approximately 5 or 6 weeks
Affective working memory task
An affective working memory task. A behavioral task, the affective working memory task measures working memory capacity - how many stimuli are stored in working memory) and include conditions with an emotional distractors. Scores are measured using percent accuracy (range: 0-100%) and a measure of working memory capacity (K-score range: 0 - 2 in this task). High scores indicate greater accuracy and working memory capacity. Reaction time (in milliseconds) will also be collected. High Reaction time indicates slower or more impaired working memory ability.
Time frame: Baseline, Approximately 5 or 6 weeks
Flanker Task
This behavioral task measures cognitive and motor inhibition. Stimuli consist of arrows presented at the center of a computer screen. Reaction Time (in milliseconds) for button presses will be the primary variable. High scores indicate slower reaction time to make the required behavioral response. The investigators will also measure accuracy, with high scores indicating higher accuracy and will be scored as percent correct (range: 0-100%)
Time frame: Baseline, Approximately 5 or 6 weeks
Affective stop signal task
This behavioral task measures cognitive and motor inhibitory control and will include affective stimuli. Primary outcome variables will be reaction time (in milliseconds) and accuracy (0 to 100%). High reaction time indicates slow inhibitory control on stop signal trials.
Time frame: Baseline, Approximately 5 or 6 weeks
PTSD Checklist for DSM-5 (PCL-5)
Self-reported Posttraumatic Stress Disorder (PTSD) symptoms will be measured using the PTSD Checklist for DSM-5 (PCL-5).The total score ranges from 0-80, with higher scores indicating higher severity.
Time frame: Baseline, Approximately 5 or 6 weeks
PHQ-9 (Patient Health Questionnaire-9)
Depression symptoms will be measured using the PHQ-9 (Patient Health Questionnaire-9). Scores range from 0 - 27. Higher scores indicating higher depression symptoms and severity.
Time frame: Baseline, Approximately 5 or 6 weeks
General Anxiety Disorder 7 (GAD-7)
Anxiety symptoms will be measured with the General Anxiety Disorder 7 (GAD-7). The total score ranges from 0-21. High scores indicate higher levels of anxiety symptoms.
Time frame: Baseline, Approximately 5 or 6 weeks
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Clinician-rated Posttraumatic Stress Disorder (PTSD) symptoms and PTSD diagnostic status will be measured using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Symptom severity ranges from 0 - 80. High scores indicate greater PTSD symptom severity.
Time frame: Baseline, Approximately 5 or 6 weeks
Plan to share: No
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