Schizophrenia
Conditions
Keywords
Schizophrenia, Transcranial Direct Current Stimulation, tDCS, Cognitive Control, fMRI, Dorsolateral Prefrontal Cortex
Brief summary
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.
Interventions
DEVICETranscranial 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.
Sponsors
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Sham Stimulation followed by Direct Current Stimulation or Vice-Versa
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Sufficient English literacy so as to be able to understand and complete cognitive tasks. * The ability to give valid informed consent. * Diagnosis of schizophrenia, schizophreniform or schizoaffective disorder (for patient group) * Stable outpatient or partial hospital status (for patient group)
Exclusion criteria
* Psychiatric medication changes in the prior month (for patient group) * No psychiatric medication changes anticipated in the upcoming month (for patient group) * Intelligence Quotient (IQ) \< 70; IQ will be measured by administering the Wechsler Abbreviated Scale of Intelligence (WASI) test. * People under the age of 18 * Pregnant Women * Prisoners * Pacemakers * Implanted brain stimulators * Implanted defibrillator * Metallic implants * Skin damage or skin conditions such as eczema at the sites where electrodes will be placed * Dreadlocks or other hair styles hindering the placement of tDCS electrodes * Cranial pathologies * Head trauma * Epilepsy * Mental retardation * Neurological disorders * Uncorrected vision problems that would hinder cognitive testing (this also pertains to subjects with color blindness in tasks where discriminating colored objects/items is necessary for successful performance). * Other than nicotine, no subjects reporting substance dependence in the past six months and no substance abuse in the past month
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dorsolateral Prefrontal Cortex Response | Assessment will begin immediately following stimulation and last for up to an hour. | Blood oxygen level-dependent response of the dorsolateral prefrontal cortex during a cognitive control task (Dot-Probe Expectancy Task) |
| Behavioral Response | Assessment will begin immediately following stimulation and last for up to an hour. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 3 |
| 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. | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Sham Followed by Experimental Stimulation | Experimental Stimulation Followed by Sham | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Continuous | 21 years STANDARD_DEVIATION 3 | 21 years STANDARD_DEVIATION 3 | 21 years STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 6 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
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.
Time frame: Assessment will begin immediately following stimulation and last for up to an hour.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Stimulation | Behavioral Response | 3.35 d-prime context | Standard Deviation 0.25 |
| Experimental Stimulation | Behavioral Response | 3.12 d-prime context | Standard Deviation 0.91 |
Primary
Dorsolateral Prefrontal Cortex Response
Blood oxygen level-dependent response of the dorsolateral prefrontal cortex during a cognitive control task (Dot-Probe Expectancy Task)
Time frame: Assessment will begin immediately following stimulation and last for up to an hour.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sham Stimulation | Dorsolateral Prefrontal Cortex Response | 1.46 beta weights of DLPFC fMRI activations | Standard Deviation 0.76 |
| Experimental Stimulation | Dorsolateral Prefrontal Cortex Response | 1.49 beta weights of DLPFC fMRI activations | Standard Deviation 2.08 |