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Per request of the study PI (fyi: NOT due to adverse events).
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The purpose of this study is to better understand the neural correlates of cognitive control (CC) deficits in schizophrenia and determine how these mechanisms can be modulated by transcranial direct current stimulation (tDCS). CC is a critical neurocognitive process that is required for flexible, directed thought and action based on goals and intentions. Identifying and developing paradigms to improve CC is therefore a mental health priority. Current theories of CC postulate that recruitment of the dorsolateral prefrontal cortex (DLPFC) is essential for this process by maintaining high-level information that it can then use to orchestrate patterns of activation in other brain networks to support optimal performance. tDCS is a safe, noninvasive method of modulating regional brain excitability via brief (15-20 m) application of a weak (1-2 mA) current. The goal of the proposed experiments is to combine tDCS with functional magnetic resonance imaging (fMRI) to test the hypotheses that 1) acute tDCS over the DLPFC can improve performance during a CC task (the dot pattern expectancy (DPX) variant of the AX-Continuous Performance Task) in schizophrenia patients and healthy control subjects, and 2) acute tDCS over the DLPFC can increase recruitment of the DLPFC during the DPX. Effects of tDCS on brain functional connectivity (during CC as well as during the resting state) will also be examined, as well as effects on an episodic memory task. The current study will be the first to use functional magnetic resonance imaging (fMRI) to examine the effects of tDCS on the neuronal mechanisms of CC in schizophrenia, and has potentially important implications for therapeutic development for this treatment refractory yet disabling aspect of the illness.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sham Followed by Experimental Stimulation | Other | Sham stimulation administered followed by 24-48 hour washout, then experimental stimulation. Experimental Intervention. 20 minutes of 2 mA direct current stimulation over the dorsolateral prefrontal cortex Placebo Comparator. 1 minute of 2 mA direct current stimulation over the dorsolateral prefrontal cortex followed by 19 minutes of sham stimulation. |
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| Experimental Stimulation Followed by Sham | Other | Experimental stimulation administered followed by 24-48 hour washout, then sham stimulation. Experimental Intervention. 20 minutes of 2 mA direct current stimulation over the dorsolateral prefrontal cortex Placebo Comparator. 1 minute of 2 mA direct current stimulation over the dorsolateral prefrontal cortex followed by 19 minutes of sham stimulation. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial Direct Current Stimulation | Device | In tDCS, saline-soaked electrodes are temporary affixed to the scalp and connected to a battery-powered current generator. A weak (2 mA) constant current is then briefly applied (~20 minutes) to stimulate the targeted brain area (e.g. the DLPFC). To control for placebo effects, the study will utilize a sham stimulation protocol that consists of very brief constant stimulation (~1 minute). Subjects usually cannot discern the difference between the sham and experimental stimulation protocols due to habituation. |
| Measure | Description | Time Frame |
|---|---|---|
| Dorsolateral Prefrontal Cortex Response | Blood oxygen level-dependent response of the dorsolateral prefrontal cortex during a cognitive control task (Dot-Probe Expectancy Task) | Assessment will begin immediately following stimulation and last for up to an hour. |
| Behavioral Response | Cognitive control-related performance (d-prime context) associated with the task (Dot-Probe Expectancy Task). The d-prime context index was calculated by computing a d-prime index from hits on AX trials and false alarms on BX trials as Z(H) - Z(F), with H representing hits on AX trials, F representing false alarms on BX trials, and Z representing the z-transform of a value. Positive d-prime values indicate more cognitive control, and negative values indicate less cognitive control. | Assessment will begin immediately following stimulation and last for up to an hour. |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Cameron Carter, M.D. | University of California, Davis | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Imaging Research Center, University of California Davis Medical Center | Sacramento | California | 95817 | United States |
Select data from this study may be submitted to the National Institute of Mental Health Data Archive (NDA). NDA is a data repository run by the National Institute of Mental Health (NIMH) that allows researchers studying mental illness to collect and share de-identified information with each other. The data repository is accessible only to qualified investigators. All subject data will be de-identified (subject names will not be used) and each subject will have a separate identifier called a Global Unique Identifier (GUID) to remove any possibility that "the identities of the subjects cannot be readily ascertained or otherwise associated with the data by the repository staff or secondary data users" (45 Code of Federal Regulations, 46.102).
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| ID | Title | Description |
|---|---|---|
| FG000 | Sham First, Then Experimental Stimulation | Sham: Very brief 2 mA constant stimulation (~1 minute). Experimental: 20 minutes of 2 mA direct current stimulation over the dorsolateral prefrontal cortex. Transcranial Direct Current Stimulation: In tDCS, saline-soaked electrodes are temporary affixed to the scalp and connected to a battery-powered current generator. A weak (2 mA) constant current is then briefly applied (~20 minutes) to stimulate the targeted brain area (e.g. the DLPFC). To control for placebo effects, the study will utilize a sham stimulation protocol that consists of very brief constant stimulation (~1 minute). Subjects usually cannot discern the difference between the sham and experimental stimulation protocols due to habituation. In this arm, sham was given first, followed by a washout period of 24-48 hours, followed by the experimental TDCS stimulation. |
| FG001 | Experimental Stimulation First, Then Sham | Experimental: 20 minutes of 2 mA direct current stimulation over the dorsolateral prefrontal cortex Sham: Very brief 2 mA constant stimulation (~1 minute). Transcranial Direct Current Stimulation: In tDCS, saline-soaked electrodes are temporary affixed to the scalp and connected to a battery-powered current generator. A weak (2 mA) constant current is then briefly applied (~20 minutes) to stimulate the targeted brain area (e.g. the DLPFC). To control for placebo effects, the study will utilize a sham stimulation protocol that consists of very brief constant stimulation (~1 minute). Subjects usually cannot discern the difference between the sham and experimental stimulation protocols due to habituation. In this arm, the experimental TDCS stimulation was given first, followed by a washout period of 24-48 hours, followed by sham. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sham Stimulation (1-20 Minutes) |
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| Washout (24-48 Hours) |
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| Experimental Stimulation (1-20 Minutes) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Sham Followed by Experimental Stimulation | This study will use a crossover design. In this arm, the sham stimulation is followed by a 24-48 hour washout period, followed by experimental stimulation. Experimental Intervention: 20 minutes of 2 mA direct current stimulation over the dorsolateral prefrontal cortex Sham: 1 minute fo 2 mA direct current stimulation over the dorsolateral prefrontal cortex Transcranial Direct Current Stimulation: In tDCS, saline-soaked electrodes are temporary affixed to the scalp and connected to a battery-powered current generator. A weak (2 mA) constant current is then briefly applied (~20 minutes) to stimulate the targeted brain area (e.g. the DLPFC). To control for placebo effects, the study will utilize a sham stimulation protocol that consists of very brief constant stimulation (~1 minute). Subjects usually cannot discern the difference between the sham and experimental stimulation protocols due to habituation. The study will use a crossover design. To control for placebo effects, the study will utilize a sham stimulation protocol that consists of very brief constant stimulation (~1 minute). Subjects usually cannot discern the difference between the sham and experimental stimulation protocols due to habituation. I |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dorsolateral Prefrontal Cortex Response | Blood oxygen level-dependent response of the dorsolateral prefrontal cortex during a cognitive control task (Dot-Probe Expectancy Task) | Posted | Mean | Standard Deviation | beta weights of DLPFC fMRI activations | Assessment will begin immediately following stimulation and last for up to an hour. |
|
3 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sham Stimulation | The sham stimulation protocol consists of very brief constant stimulation (~1 minute 20 mA). |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tiffany T . Norris | University of CA Davis Health | 916-703-9193 | ttnorris@ucdavis.edu |
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 23, 2019 | Apr 22, 2024 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D065908 | Transcranial Direct Current Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
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Sham Stimulation followed by Direct Current Stimulation or Vice-Versa
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| NOT COMPLETED |
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| NOT COMPLETED |
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| BG001 | Experimental Stimulation Followed by Sham | This study will use a crossover design. In this arm, the experimental stimulation is followed by a 24-48 hour washout period, followed by sham stimulation. Experimental Intervention: 20 minutes of 2 mA direct current stimulation over the dorsolateral prefrontal cortex Sham: 1 minute fo 2 mA direct current stimulation over the dorsolateral prefrontal cortex Transcranial Direct Current Stimulation: In tDCS, saline-soaked electrodes are temporary affixed to the scalp and connected to a battery-powered current generator. A weak (2 mA) constant current is then briefly applied (~20 minutes) to stimulate the targeted brain area (e.g. the DLPFC). To control for placebo effects, the study will utilize a sham stimulation protocol that consists of very brief constant stimulation (~1 minute). Subjects usually cannot discern the difference between the sham and experimental stimulation protocols due to habituation. The study will use a crossover design. To control for placebo effects, the study will utilize a sham stimulation protocol that consists of very brief constant stimulation (~1 minute). Subjects usually cannot discern the difference between the sham and experimental stimulation protocols due to habituation. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
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|
| Primary | Behavioral Response | Cognitive control-related performance (d-prime context) associated with the task (Dot-Probe Expectancy Task). The d-prime context index was calculated by computing a d-prime index from hits on AX trials and false alarms on BX trials as Z(H) - Z(F), with H representing hits on AX trials, F representing false alarms on BX trials, and Z representing the z-transform of a value. Positive d-prime values indicate more cognitive control, and negative values indicate less cognitive control. | Posted | Mean | Standard Deviation | d-prime context | Assessment will begin immediately following stimulation and last for up to an hour. |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Experimental Stimulation | 20 minutes 2 mA transcranial direct current stimulation. | 0 | 6 | 0 | 6 | 0 | 6 |
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| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |