Pilot Study Using an NMDA Antagonist to Modulate Transcranial Direct Current Stimulation (tDCS) Effects on Sensory Discrimination

Study Overview
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Brief Summary
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Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a very weak constant current to temporarily excite the brain area of interest via small electrodes placed on the scalp. Currently, tDCS is being used as a tool to investigate mental processes (cognition) and motor function (movement) in healthy controls and to treat neurological (i.e. stroke) and psychiatric (i.e. depression and dementia) patients. tDCS has been found to improve motor processes and cognitive performance, including attention and memory functions. This study will attempt to examine the effects of tDCS on a specific aspect of short term memory to sounds measured from electrical activity (EEG) from the top of the scalp. This study will also assess the effect of a drug, dextromethorphan (DMO), commonly found in cough syrup, which is thought to regulate tDCS treatment through brain receptors. The study involves four laboratory test sessions. EEG assessments will be done in two sessions involving 'anodal' tDCS stimulation (to temporarily excite cortical activity locally), one session with DMO treatment and one with placebo treatment, and two sessions involving 'sham' tDCS stimulation (device is turned off), with the same DMO and placebo treatments. These findings will contribute to our understanding of the brain chemistry involved in tDCS treatment and its effects on cognitive abilities.

Official Title
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A Pilot Study Using an NMDA Antagonist to Modulate Transcranial Direct Current Stimulation (tDCS) Effects on Auditory Sensory Memory Processing

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: Direct Current Stimulation
* Drug: Dextromethorphan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, medication free Non-smoker Right-handed Exclusion Criteria: Any current or past Axis I or Axis II disorder including a current or recent history of alcohol/substance abuse A clinically significant medical illness or organic brain disorder known to cause psychosis or cognitive impairment Any neurological diagnosis (including epilepsy) Recent head trauma (<6 months) Metallic implants or any electrical device (e.g., pacemaker) in the body Major learning disability Body mass index >38kg/m¬2 Use of illicit drugs Abnormal hearing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Direct Current Stimulation active<br>Electrodes will be placed on the scalp overlying the left auditory cortex (anodal electrode) and on the contralateral forehead above the orbit (reference/cathode). Stimulation will be applied using a battery-driven constant-current regulator (Oasis Pro, Edmonton). In active tDCS sessions, the DC current will be initially increased in a ramp-like fashion over 10 s until reaching 2 mA and will be similarly decreased at the end of stimulation. In active tDCS, stimulation will be maintained for a total of 20 minutes. This will occur in two separate sessions, occurring within weeks. | Device: Direct Current Stimulation<br>* Comparison between active Direct Current Stimulation (2 mA, 20 minutes) and Sham stimulation (the device is set up, but only turned on for 30 seconds). Conductive saline-soaked rubber electrodes super-imposed on sponge plates will be placed on the scalp overlying the left auditory cortex (anodal electrode) and on the contralateral forehead above the orbit (reference/cathode). Stimulation will be applied using a battery-driven constant-current regulator (Oasis Pro, Edmonton). In active tDCS sessions, the DC current will be initially increased in a ramp-like fashion over 10 s until reaching 2 mA and will be similarly decreased at the end of stimulation. In active tDCS, stimulation will be maintained for a total of 20 minutes. This will occur in two separate sessions, occurring within weeks. For 'sham' stimulation, the device will only be turned on for 30 seconds. This will occur in two separate sessions, occurring within weeks.<br>|
| Sham Comparator: Direct Current Stimulation sham<br>In sham sessions, the device will have the same placement and intensity, but will only be turned on for 30 seconds. The DC current will be initially increased in a ramp-like fashion over 10 s until reaching 2 mA and will be similarly decreased at the end of stimulation. This will occur in two separate sessions, occurring within weeks. | Device: Direct Current Stimulation<br>* Comparison between active Direct Current Stimulation (2 mA, 20 minutes) and Sham stimulation (the device is set up, but only turned on for 30 seconds). Conductive saline-soaked rubber electrodes super-imposed on sponge plates will be placed on the scalp overlying the left auditory cortex (anodal electrode) and on the contralateral forehead above the orbit (reference/cathode). Stimulation will be applied using a battery-driven constant-current regulator (Oasis Pro, Edmonton). In active tDCS sessions, the DC current will be initially increased in a ramp-like fashion over 10 s until reaching 2 mA and will be similarly decreased at the end of stimulation. In active tDCS, stimulation will be maintained for a total of 20 minutes. This will occur in two separate sessions, occurring within weeks. For 'sham' stimulation, the device will only be turned on for 30 seconds. This will occur in two separate sessions, occurring within weeks.<br>|
| Active Comparator: NMDA antagonist active<br>Dextromethorphan (DMO), a non-competitive NMDA antagonist, will be delivered in the form of generic Life Brand Clear Cough Syrup DM (Trillium Healthcare Products Inc, Brockville, ON). Each subject will receive a dose of 50 ml DM with no-sugar cranberry juice (100 ml) to drink. This same dose will be delivered in two separate sessions, occurring within weeks. | Drug: Dextromethorphan<br>* Comparison between Dextromethorphan and a no-sugar placebo. Dextromethorphan (DMO), a non-competitive NMDA antagonist, will be delivered in the form of generic Life Brand Clear Cough Syrup DM (Trillium Healthcare Products Inc, Brockville, ON), which has high dose of DMO (15 mg/5 ml) with no other major additives. Each subject will receive a dose of 50 ml DM with no-sugar cranberry juice (100 ml) to drink from a mug, while wearing a nose plug. This same dose will be delivered in two separate sessions, occurring within weeks. Each subject will receive a dose of a placebo (150 ml of no-sugar cranberry juice) to drink from a mug, while wearing a nose plug. This same dose will be delivered in two separate sessions, occurring within weeks.<br>* Other names: Life Brand Clear Cough Syrup DM;|
| Placebo Comparator: NMDA antagonist placebo<br>Each subject will receive a dose of a placebo (150 ml of no-sugar cranberry juice) to drink. This same dose will be delivered in two separate sessions, occurring within weeks. | Drug: Dextromethorphan<br>* Comparison between Dextromethorphan and a no-sugar placebo. Dextromethorphan (DMO), a non-competitive NMDA antagonist, will be delivered in the form of generic Life Brand Clear Cough Syrup DM (Trillium Healthcare Products Inc, Brockville, ON), which has high dose of DMO (15 mg/5 ml) with no other major additives. Each subject will receive a dose of 50 ml DM with no-sugar cranberry juice (100 ml) to drink from a mug, while wearing a nose plug. This same dose will be delivered in two separate sessions, occurring within weeks. Each subject will receive a dose of a placebo (150 ml of no-sugar cranberry juice) to drink from a mug, while wearing a nose plug. This same dose will be delivered in two separate sessions, occurring within weeks.<br>* Other names: Life Brand Clear Cough Syrup DM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMN ERP amplitudes as a measure of sensory processing changes | Acute effects of DMO (vs. placebo) and tDCS (vs. sham) on MMN-indexed auditory sensory memory processing | 1 year | 
| Adverse Events Scores as measure of treatment side effects | Adverse Events and self-reported symptoms after treatment | 1 year |