The Effects of tDCS on the Neuronal Mechanisms of Cognitive Control in Schizophrenia

University of California, Davis6 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Interventions

Transcranial Direct Current StimulationDEVICE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

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.