Mod of Cognitive Flexibility by tDCS, Tyrosine Polymorphisms in the COMT Gene

Study Overview
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Brief Summary
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The current study would examine whether increases in endogenous dopaminergic activity via tyrosine and the (presumed) excitation of these by anodal tDCS of the dlPFC could causally be related to cognitive flexibility as measured by task switching and reversal learning. Additionally, the study will test whether the Val158Met-polymorphism in the catechol- O-methyltransferase (COMT) gene could also predict the effect of TYR supplementation, as this gene is involved in DA degradation in the prefrontal cortex.

Official Title
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Modulation of Cognitive Flexibility by Transcranial Direct Current Stimulation, Tyrosine Administration and Polymorphisms in the COMT Gene

Conditions
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Modulation of Cognitive Flexibility by Transcranial Direct Current Stimulation, Tyrosine Administration and Polymorphisms in the COMT Gene

Intervention / Treatment
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* Combination Product: tdcs (sham/anodal) + drug (placebo/tyrosine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Either male or female Between 18 and 30 years You are in good health You agree to fast overnight prior to testing Exclusion Criteria: • Are suffering from cardiac, hepatic, renal, neurological disorders Damaged or diseased skin on your face and scalp, or a sensitive scalp A history of alcohol or drug addiction, or severe psychiatric illness Drug treatment which may lower seizure threshold (i.e. epilepsy) Pregnancy Sleep deprivation (less than 6 hours a day) A history of migraine or headaches A history of taking antidepressants A history of taking tyrosine supplements

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: tDCS sham + placebo<br>tDCS= transcranial direct current stimulation drugs= placebo (cellulose [2 grams]) | Combination Product: tdcs (sham/anodal) + drug (placebo/tyrosine)<br>* tDCS= A DC Stimulator Plus (neuroConn, Germany) with one 5 cm x 7 cm rubber electrode (anode) and a 10 cm x 10 cm (cathode; reference electrode), encased in saline soaked sponges will be used. The anode will be positioned over the left dlPFC, centered on F3 in the 10e20 electroencephalography (EEG) system, while the cathode on the contralateral supraorbital ridge (Fp2).Current will be delivered at 1.5mA for 20 min plus 30 s fade in/fade out periods.For sham stimulation, the current will be faded in over 30 s, at 1.5mA and then will be switched off. Drugs= 2.0 g of L-Tyrosine and 2.0 g of the placebo microcrystalline cellulose will be dissolved in 400ml of orange juice as per previously published protocols.<br>|
| Experimental: tDCS sham + tyrosine<br>tDCS= transcranial direct current stimulation drugs= tyrosine (2 grams) | Combination Product: tdcs (sham/anodal) + drug (placebo/tyrosine)<br>* tDCS= A DC Stimulator Plus (neuroConn, Germany) with one 5 cm x 7 cm rubber electrode (anode) and a 10 cm x 10 cm (cathode; reference electrode), encased in saline soaked sponges will be used. The anode will be positioned over the left dlPFC, centered on F3 in the 10e20 electroencephalography (EEG) system, while the cathode on the contralateral supraorbital ridge (Fp2).Current will be delivered at 1.5mA for 20 min plus 30 s fade in/fade out periods.For sham stimulation, the current will be faded in over 30 s, at 1.5mA and then will be switched off. Drugs= 2.0 g of L-Tyrosine and 2.0 g of the placebo microcrystalline cellulose will be dissolved in 400ml of orange juice as per previously published protocols.<br>|
| Experimental: tDCS anodal + placebo<br>tDCS= anodal transcranial direct current stimulation of the dorsolateral prefrontal cortex drugs= placebo (cellulose [2 grams]) | Combination Product: tdcs (sham/anodal) + drug (placebo/tyrosine)<br>* tDCS= A DC Stimulator Plus (neuroConn, Germany) with one 5 cm x 7 cm rubber electrode (anode) and a 10 cm x 10 cm (cathode; reference electrode), encased in saline soaked sponges will be used. The anode will be positioned over the left dlPFC, centered on F3 in the 10e20 electroencephalography (EEG) system, while the cathode on the contralateral supraorbital ridge (Fp2).Current will be delivered at 1.5mA for 20 min plus 30 s fade in/fade out periods.For sham stimulation, the current will be faded in over 30 s, at 1.5mA and then will be switched off. Drugs= 2.0 g of L-Tyrosine and 2.0 g of the placebo microcrystalline cellulose will be dissolved in 400ml of orange juice as per previously published protocols.<br>|
| Experimental: tDCS anodal +tyrosine<br>tDCS= anodal transcranial direct current stimulation of the dorsolateral prefrontal cortex drugs= tyrosine (2 grams) | Combination Product: tdcs (sham/anodal) + drug (placebo/tyrosine)<br>* tDCS= A DC Stimulator Plus (neuroConn, Germany) with one 5 cm x 7 cm rubber electrode (anode) and a 10 cm x 10 cm (cathode; reference electrode), encased in saline soaked sponges will be used. The anode will be positioned over the left dlPFC, centered on F3 in the 10e20 electroencephalography (EEG) system, while the cathode on the contralateral supraorbital ridge (Fp2).Current will be delivered at 1.5mA for 20 min plus 30 s fade in/fade out periods.For sham stimulation, the current will be faded in over 30 s, at 1.5mA and then will be switched off. Drugs= 2.0 g of L-Tyrosine and 2.0 g of the placebo microcrystalline cellulose will be dissolved in 400ml of orange juice as per previously published protocols.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wisconsin Card Sorting Test (WCST) performance | Measuring change in perseverative errors in the WCST | Measured twice in each session (4 arms): at time 0 and 80 minutes into testing. | 
| Probabilistic Reversal Learning (PRL) performance | Measuring change in reversal errors in the WCST | Measured twice in each session (4 arms): at time 0 and 80 minutes into testing. | 
| Flanker Task performance | Measuring change in conflict cost (defined as the difference in reaction time between congruent and incongruent responses) | Measured twice in each session (4 arms): at time 0 and 80 minutes into testing. |