A Trial of Cognitive Training in Euthymic Bipolar Disorder

Study Overview
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Brief Summary
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Bipolar disorder (BD) is characterized by extreme changes in mood and emotion dysregulation. Mood changes are episodic in nature, with distinct periods of mania, depression, and asymptomatic periods of euthymia. In addition to impairments in mood, cognitive impairments are a common feature of the disorder. These cognitive impairments persist during periods of euthymia and are associated with negative clinical and psychosocial outcomes. Specifically, individuals with BD show impairments in executive functions. Recent studies show that emotion regulation can be down-regulated by taxing executive functions, and it can be improved with working memory training, a specific component of executive functions. These initial studies show that emotion regulation is under executive control in healthy individuals; however, the nature of this relationship is not well understood in populations that are affected by impairments in both executive control and emotion regulation. Previous work on cognitive training has not targeted specific cognitive domains with an emphasis on understanding the underlying mechanisms that promote change. Moreover, well-controlled randomized control trial (RCT) studies are needed in order to provide high quality evidence to inform the efficacy of cognitive training interventions for psychiatric populations. The aim of the proposed study is to use a commercially available cognitive training program to study the effects of working memory training on cognitive, clinical, and psychosocial outcomes in patients with BD. We hypothesize that training working memory will lead to improvements in cognitive and emotional functioning, leading to downstream changes that will positively impact untrained outcomes, such as mood and community functioning.

Official Title
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A Randomized Control Trial of Cognitive Training in Euthymic Bipolar Disorder

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Behavioral: Working memory training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Age between 18 and 65 years Clinically diagnosed with bipolar disorder I or bipolar disorder II and currently in a euthymic state Normal, or corrected to normal, vision and hearing Able to provide informed consent Exclusion Criteria: Meeting Diagnostic and Statistical Manual 5th edition (DSM-5) diagnostic criteria for a current major depressive episode, manic episode, or hypomanic episode Past electroconvulsive therapy (ECT) Past Transcranial Magnetic Stimulation therapy (TMS) Past 3 month history of substance abuse Diagnosed with a medical condition known to affect cognition (e.g., endocrine disease) Score less than 70 on the Wechsler Abbreviated Scale of Intelligence (WASI)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive training<br>The neurocognitive training program will be provided by an online platform called BrainGymmer (https://www.braingymmer.com/en/brain-games/). The experimental group will complete the working memory training, which involves three games: N-back, Multi-Memory, and Moving Memory. These games are designed to engage processes involving updating and manipulation of information. All of the training games provided by BrainGymmer are adaptive, meaning that the level of difficulty increases as users develop expertise on a given task. Participants randomized to the cognitive training arm will complete the training games for 30 minutes per day, 5 days a week, for a total of 10 weeks. | Behavioral: Working memory training<br>* The neurocognitive training program will be provided by an online platform called BrainGymmer (https://www.braingymmer.com/en/brain-games/). The experimental group will complete the working memory training, which involves three games: N-back, Multi-Memory, and Moving Memory. These games are designed to engage processes involving updating and manipulation of information. All of the training games provided by BrainGymmer are adaptive, meaning that the level of difficulty increases as users develop expertise on a given task. Participants randomized to the cognitive training arm will complete the training games for 30 minutes per day, 5 days a week, for a total of 10 weeks.<br>|
| No Intervention: Control<br>The control group will wait 10-weeks, during which they will receive treatment-as-usual (TAU), which might involve pharmacotherapy, psychotherapy, or both. After the 10-week waiting period, participants will complete post-testing assessments. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Working memory capacity | Measured with the Automated Operation Span task (AOSPAN), Wechsler Adult Intelligence Scale (WAIS-IV) Digit Span and Maintenance and Manipulation task | Change from baseline to post-assessment (after 10 weeks of training) | 
| Emotion regulation | Measured with the Emotional Stroop task and Emotional N-back task | Change from baseline to post-assessment (after 10 weeks of training) | 
| Fluid intelligence | Measured with the Raven's Progressive Matrices (RPM) task | Change from baseline to post-assessment (after 10 weeks of training) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression symptom severity | Measured with the 17-item Hamilton Rating Scale for Depression (HRDS-17) | Change from baseline to post-assessment (after 10 weeks of training) | 
| Manic symptom severity | Measured with the Young Mania Rating Scale (YMRS) | Change from baseline to post-assessment (after 10 weeks of training) | 
| Community functioning | Measured with the Functioning Assessment Short Test (FAST) | Change from baseline to post-assessment (after 10 weeks of training) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive training, Working memory, Emotion regulation