Prefrontal Cortical Engagement Through Non-Invasive Brain Stimulation in Schizophrenia

Cognitive impairments in schizophrenia are the most debilitating aspect of the illness and poorly treated by current medications. This study investigates transcranial direct current stimulation (tDCS) - a safe, noninvasive weak electrical current delivery to stimulate brain function - as a novel therapeutic for cognition in schizophrenia. Integrating neurostimulation, electrophysiology and neuroimaging, this project aims to study tDCS effects on cognition by verifying therapeutic target engagement, evaluating the tolerability of tDCS sessions, and optimizing treatment parameters.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Psychosis
• Intervention / Treatment: Device: transcranial direct current stimulation

Detailed Description

Cognitive deficits are a strong predictor of functional outcome in schizophrenia, yet poorly remediated by current treatments. Disturbances in dorsolateral prefrontal cortex (DLPFC) function underlie core impairments such as in cognitive control and thus represent a critical target for novel therapeutics. Initial studies indicate transcranial direct-current stimulation (tDCS) may be effective in reducing symptoms due to DLPFC dysfunction. While tDCS potentially represents an exciting, novel therapeutic advance, a number of basic questions should be addressed prior to conducting larger-scale clinical trials, including: verifying therapeutic target engagement, optimizing treatment parameters, and evaluating for meaningful clinical effects. Recent studies employing tDCS to enhance prefrontal cortical function in schizophrenia applied stimulating electrodes over the left frontal scalp region, putatively targeting the left DLPFC. However, explicit confirmation of such target engagement is lacking. Further, EEG studies have demonstrated close links of frontal cortical gamma oscillations to cognitive control processes but modulation of this critical physiologic process has not been investigated. Accordingly, the primary aim of this study is to employ multimodal imaging to explicitly test for the assumed DLPFC engagement (fMRI) and modulation of frontal gamma activity (EEG) by tDCS. This study will also investigate the optimization of tDCS application parameters. Analogous to dose-finding investigations in drug studies, we will conduct a parametric investigation of optimal current strengths. Also, while there is extensive evidence for tolerability of single session tDCS, confirmation of feasibility of multisession optimized protocols in schizophrenia is lacking and so will be explicitly evaluated.

In summary, a successful outcome of this study would provide tDCS the sound mechanistic and methodologic basis for more definitive testing in large-scale clinical trials as a highly innovative therapeutic intervention for cognitive impairments in schizophrenia.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ages 18-35 years;
2. within first five years of antipsychotic treatment;
3. on stable doses of antipsychotic medication for at least one month;
4. Clinically stable as defined by Clinical Global Impression-Severity scale (CGI-S) less than or equal to 4 (moderately ill);
5. Mild to severe cognitive impairment in MATRICS Consensus Cognitive Battery (composite scores <40);
6. DSM-5 MINI 7.0.2 criteria for schizophrenia or schizoaffective by patient SCID

Exclusion Criteria:

1. Mental retardation as defined by pre-morbid IQ by Wechsler Test of Adult Reading at screening <70 or Spanish Word Accentuation Test;
2. significant head injury;
3. History of severe medical or neurological illnesses
4. pregnancy or postpartum (<6 weeks after delivery or miscarriage);
5. inability to provide informed consent;
6. significant color blindness that affects task performance;
7. Positive urine drug screen (exception for marijuana) or presence of substance use disorder within 1 month;
8. Currently on benzodiazepines or mood stabilizers affecting GABA

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 2.5mA; Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation.	Device: transcranial direct current stimulation; transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.
EXPERIMENTAL: 2.0mA; Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation.	Device: transcranial direct current stimulation; transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.
EXPERIMENTAL: 1.5mA; Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation.	Device: transcranial direct current stimulation; transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.
SHAM_COMPARATOR: 0mA; This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms.	Device: transcranial direct current stimulation; transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tDCS Engagement of DLPFC Activity Indexed by fMRI BOLD Imaging	Change from Baseline to week 1 as measured by modulation of fMRI BOLD signal in DLPFC in the context of cognitive control task performance.	1 week
tDCS Engagement of DLPFC Activity Indexed by Modulation of Frontal Cortical Gamma Oscillations	Change from Baseline to week 1 as measured by EEG frontal gamma oscillations in the context of cognitive control task performance	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimal tDCS Strength for DLPFC Engagement	Change from baseline to 1 week in DLPFC engagement across conditions (1.5 vs 2.0 vs 2.5 mA)	1 Week
Tolerability and Feasibility of Multi-session tDCS in Schizophrenia	The percentage of participants able to complete the full study.	1 week

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Raymond Cho, M.D., M.Sc., Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (ACTUAL): June 1, 2019
• Study Completion (ACTUAL): June 1, 2019

Study Registration Dates

• First Submitted: November 23, 2016
• First Submitted That Met QC Criteria: November 23, 2016
• First Posted (ESTIMATE): November 29, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 25, 2020
• Last Update Submitted That Met QC Criteria: November 4, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: tDCS; EEG; cognitive control; gamma oscillations
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: H-41815

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be open to sharing after primary findings of study have been published

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes