Restoration of Cognitive Function With TDCS and Training in Serious Mental Illness

Study Overview
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Brief Summary
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Development of interventions that can effectively target and remediate the cognitive and functional impairment associated with serious mental illness is a treatment priority. Transcranial direct current stimulation (tDCS) is a safe, non-invasive neuromodulation technique that is capable of stimulating brain activity to facilitate learning. The primary objective of this study is to evaluate the pairing of two therapeutic techniques, cognitive remediation and tDCS, as a cognitively enhancing intervention. This study is designed to test the hypotheses that cognitive remediation paired with tDCS will be more efficacious than cognitive remediation delivered with sham stimulation and that intervention-induced cognitive change will be sustainable. To examine the incremental benefit of pairing tDCS with cognitive remediation, clinically stable outpatients between the ages of 18-65 who have a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder will be enrolled in a double-blind, double-baseline, sham-controlled clinical trial. Participants will be randomized in a 1:1 ratio to receive either tDCS or sham stimulation concurrent with working memory focused cognitive remediation. Training will be offered to participants in a small group format. Training will consist of 48 sessions, with 2-3 sessions scheduled in a week. Each training session will last 2 hours. One hour will be spent completing cognitive exercises that require working memory skills on a computer. TDCS or sham stimulation will be offered concurrent with the first 20 minutes of training with a StarStim neuromodulator. One mA of anodal stimulation will be applied to the left dorsal lateral prefrontal cortex and the cathodal electrode will be placed in the contralateral supraorbital position. Upon completion of working memory training, participants will transition to a 45-minute bridging group focus on application of cognitive skills in everyday life. To assess intervention-induced change, working memory, other aspects of cognition, functional capacity, community functioning, and symptom severity will be assessed pre- and post-intervention. Sustainability of intervention-induced change will be assessed with an assessment session 6 weeks post-intervention. Mixed effect, repeated measure ANOVAS will be used to analyze intervention-induced change.

Official Title
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Restoration of Cognitive Function With TDCS and Training in Serious Mental Illness

Conditions
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Schizophrenia, Bipolar Disorder, Schizo Affective Disorder

Intervention / Treatment
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* Device: TDCS
* Device: Sham Stimulation
* Behavioral: Cognitive Remediation
* Behavioral: Bridging Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants are eligible for the study if they have a diagnosis of schizophrenia, schizoaffective disorder, or bipolar I disorder and are clinically stable at the time of enrollment defined as not severely depressed or acutely manic and no hospitalizations or antipsychotic medication changes in the four weeks prior to enrollment Exclusion Criteria: Met criteria for a severe alcohol or substance use disorder in the last 6 months Met criteria for a mild alcohol or substance use disorder in the last month A history of head injury or neurological disease that has compromised cognitive functioning Ability to speak English is not sufficient to understand study procedures Diagnosis of learning disability, mental retardation, or pervasive developmental disorder Diagnosis of a medical condition that is incompatible with tDCS procedures Participant does not demonstrate understanding of study procedures during the consent process A documented history of behavioral problems that prevent participation in a group intervention Participated in a study of tDCS or cognitive remediation in the previous 12 months

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a double-blind, double-baseline, sham-controlled study in which participants are randomized to receive either tDCS or sham stimulation concurrent with cognitive training.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TDCS<br>TDCS offered concurrent with working memory focused cognitive training | Device: TDCS<br>* 1 mA of anodal stimulation will be applied to the left dorsal lateral cortex (F3) concurrent with working memory focused cognitive training for 20 minutes<br>* Other names: Transcranial Direct Current Stimulation;Behavioral: Cognitive Remediation<br>* Participants complete 60 minutes of computer-based cognitive training. All tasks are adaptable in terms of difficulty and require working memory skills. Sessions always begin with N-back and complex span tasks completed concurrent with tDCS or sham stimulation. Other tasks selected from Happy Neuron software and experimental working memory tasks are used throughout the protocol.<br>Behavioral: Bridging Group<br>* Participants complete 45 minutes of activities and discussion to practice engaging cognitive skills through performance of everyday activities and to learn strategies to use cognitive abilities most effectively. Curriculum generated from Action-based Cognitive Remediation and Compensatory Cognitive Training intervention manuals.<br>|
| Sham Comparator: Sham<br>Sham stimulation offered concurrent with working memory focused cognitive training | Device: Sham Stimulation<br>* Participants will receive 20 seconds of 1 mA anodal stimulation applied to the left dorsal lateral cortex (F3) concurrent with working memory focused cognitive training to mimic the effect of the active condition<br>* Other names: Sham;Behavioral: Cognitive Remediation<br>* Participants complete 60 minutes of computer-based cognitive training. All tasks are adaptable in terms of difficulty and require working memory skills. Sessions always begin with N-back and complex span tasks completed concurrent with tDCS or sham stimulation. Other tasks selected from Happy Neuron software and experimental working memory tasks are used throughout the protocol.<br>Behavioral: Bridging Group<br>* Participants complete 45 minutes of activities and discussion to practice engaging cognitive skills through performance of everyday activities and to learn strategies to use cognitive abilities most effectively. Curriculum generated from Action-based Cognitive Remediation and Compensatory Cognitive Training intervention manuals.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Working Memory Capacity Composite Score | This is a measure of one core component of working memory. Proportion correct average from Change Detection and Change Localization Tasks. Score ranges from 0.00 to 1.00, with a higher score indicating better performance | Total score at Baseline, 4 months, and 5.5 months | 
| Goal Maintenance Composite Score | This is a measure of one core component of working memory. Performance on the Dot Pattern Expectancy Task and AX-Continuous Performance Task was measured with d prime. D Prime is a measure of response accuracy that takes into account both hit rate and false alarm rate. This measure of response accuracy ranges from -4.546 to 4.546, with a higher score indicating better performance. A score of 0 indicates chance level performance. D prime scores reflecting overall performance on the Dot Pattern Expectancy Task and the AX-Continuous Performance Task were averaged. The resulting d prime score reflects performance on the goal maintenance component of working memory. | D Prime at Baseline, 4 months, and 5.5 months | 
| Interference Control Composite Score | This is a measure of one core component of working memory. Performance on Rotation and Reading Complex Span Tasks was measured with z-scores. Scores range from -3 to 3, with a higher positive score indicating better performance. A score of 0 represents the sample mean at the baseline assessment. The z-scores reflecting overall performance on Rotation and Reading Span Tasks were averaged to create one z-score that reflects performance on the interference control component of working memory. | Z-score at Baseline, 4 months, and 5.5 months | 
| The University of California San Diego Performance-Based Skills Assessment Total Score | This is a performance-based measure of functional capacity to perform activities of daily living. This measure has two scales, measuring financial and communication skills. The two scales are summed to create a total score. The Total score ranges from 0-100, with a higher score indicating better performance. | Total score at Baseline, 4 months, and 5.5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First-Episode Social Functioning Scale Actual Performance Total Score | Total score summed from Actual Performance subscales 1-5. This is a self-report measure of social and community functioning in the past 3 months. Scores reflect the frequency with which participants report engaging in a behavior. Total score ranges from 20-80, with a higher score indicating better social functioning in the community. | Total score at Baseline, 4 months, and 5.5 months | 
| Novel N-Back Task D Prime Score | This is a working memory task. The number and picture n-back tasks are novel versions of the training tasks used in this protocol. D-prime, a measure of response accuracy that takes into account hit rate and false alarm rate was used to measure overall performance on each task. This measure of performance accuracy ranges from -4.546 to 4.546, with a higher, positive score indicating better performance. A score of 0 indicates chance level performance. D prime scores from the number and picture task were average to create one d prime measure that reflects performance on novel, untrained n-back measures. Improvement on these tasks would indicate generalization of learning from the trained tasks. | D prime at Baseline, 4 months, and 5.5 months | 
| Complex Span Task Z-score | This is a working memory task. This measure is an indicator of whether participants were able to improve on a task procedurally similar to the training tasks. Rotation and Reading complex span tasks are novel versions of training tasks. A z-score was used to measure performance on each task. Z-scores range from -3 to 3, with a higher positive score indicating better performance. A score of 0 represents the sample mean at the baseline assessment. Z-scores from the Rotation and Reading span tasks were averaged to create one measure of working memory. Improvement on this task would indicate generalization of learning from the training. | Z-score at Baseline, 4 months, and 5.5 months | 
| MATRICS Consensus Cognitive Battery Processing Speed Subscale and the Reasoning and Problem-Solving Subscale T-score Average | Two subscales from the MATRICS Consensus Cognitive Battery, the Processing Speed subscale and the Reasoning and Problem-Solving subscale, were averaged to create a composite that reflects performance on cognitive functions closely related to working memory. Performance on each subscale was measured with a T-score. T-scores range from 0-100. A score of 50 reflects the population mean, with a standard deviation of 10. On each subscale, a higher score indicated better performance in the cognitive domain. Improvement on this composite T-score would indicate generalization of training gains to untrained cognitive domains. | T-score at Baseline, 4 months, and 5.5 months | 
| Brief Psychiatric Rating Scale Total Score | This is a 24-item measure of psychiatric symptom severity. Each item is rated on a 1-7 scale, with a higher score indicating that the symptom is more severe. Brief Psychiatric Rating Scale Total score can range from 24-168, with a higher score indicating the presence of more severe psychiatric symptoms. | Total score at Baseline, 4 months, and 5.5 months | 
| Brief Negative Symptom Severity Scale Total Score | This is a 13-item scale that measures the severity of negative symptoms. Each item is rated from 0-6, with a higher score indicating that the symptom is more severe. Brief Negative Symptom Severity Scale Total score can range from 0 to 78, with a higher score indicating more severe negative symptoms | Total score at Baseline, 4 months, and 5.5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, tdcs, working memory, cognitive remediation, cognition, serious mental illness