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

The Effects of Transcranial Direct Current Stimulation on the Neuronal Mechanisms of Cognitive Control in Schizophrenia

Stimulation did not show any evidence of the anticipated effect after 6 participants completed the study. Study was thus halted.

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.

Schizophrenia, Transcranial Direct Current Stimulation, tDCS, Cognitive Control, fMRI, Dorsolateral Prefrontal Cortex

Placebo Comparator. 0.5-1 minutes of 2 mA direct current stimulation over the dorsolateral prefrontal cortex followed by 19-19.5 minutes of sham 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.

Blood oxygen level-dependent response of the dorsolateral prefrontal cortex during a cognitive control task (Dot-Probe Expectancy Task)

Cognitive control-related performance (d-prime context) associated with the task (Dot-Probe Expectancy Task)

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

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).