Modulation of Cognitive Flexibility by Tyrosine Depletion and Transcranial Direct Current Stimulation

The dorsolateral prefrontal cortex (dlPFC) and dopamine (DA) have been implicated in the control of cognitive flexibility. However, while a great deal of what it is know regarding a causative relationship between cognitive flexibility and its neuronal underpinning comes from animal studies, human data have largely been correlational (i.e. imaging investigations). In a recent study, the current research group examined whether putative increases in dopamine levels through tyrosine administration and blockage of these by cathodal (i.e. inhibitory) transcranial direct current stimulation (tDCS) of the dlPFC could be causally related to cognitive flexibility as measured by task switching and reversal learning.

The next step involves finding a way of lowering dopamine concentrations while anodal (i.e. excitatory) stimulation of the dlPFC is applied and cognitive flexibility measured. One experimental approach to reduce global DA synthesis and transmission is through acute phenylalanine and tyrosine depletion (APTD). This dietary intervention involves the administration of an amino-acid mixture lacking in tyrosine and phenylalanine, which can be used to selectively lower DA synthesis in humans.

Study Overview

• Status: Completed
• Conditions: Cognitive Flexibility
• Intervention / Treatment: Combination product: Sham tDCS and balanced drink; Combination product: Sham tDCS and tyrosine depleted drink; Combination product: Anodal tDCS and balanced drink; Combination product: Anodal tDCS and tyrosine depleted drink

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2BQ
      • Department of Psychology labs

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Either male or female
• You are aged 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, or 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
• Are in drug treatment which may lower seizure threshold (i.e. epilepsy)
• You are pregnant
• Slept less than 6 hours prior to coming to the lab
• Suffer from phenylketonuria
• A history of or current experience of migraine or headaches
• A history of or current use of antidepressants
• A history of or current use of tyrosine supplements
• Consume more than five beverages containing caffeine per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: tDCS sham + balanced drink	Combination product: Sham tDCS and balanced drink; Transcranial direct current stimulation (sham) of the dlPFC in combination with a drink containing both tyrosine and phenylalanine.
Experimental: tDCS sham + tyrosine depleted drink	Combination product: Sham tDCS and tyrosine depleted drink; Transcranial direct current stimulation (sham) of the dlPFC in combination with a tyrosine and phenylalanine free product.
Experimental: tDCS anodal + balanced drink	Combination product: Anodal tDCS and balanced drink; Transcranial direct current stimulation (anodal) of the dlPFC in combination with a drink containing both tyrosine and phenylalanine.
Experimental: tDCS anodal +tyrosine depleted drink	Combination product: Anodal tDCS and tyrosine depleted drink; Transcranial direct current stimulation (anodal) of the dlPFC in combination with a tyrosine and phenylalanine free product.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognitive flexibility performance	Measured using Wisconsin Card Sorting Test	Measured over 5 hours four times.1st measurement taken at baseline (i.e. time 0). 2nd measurement taken 120 minutes after measurement 1. 3rd measurement taken 220 minutes after measurement 1. 4th measurement taken 270 minutes after measurement 1.
Change in cognitive flexibility performance	Measured using Probabilistic Reversal Learning	Measured over 5 hours. 1st measurement taken at baseline (i.e. time 0). 2nd measurement taken 120 minutes after measurement 1. 3rd measurement taken 220 minutes after measurement 1. 4th measurement taken 270 minutes after measurement 1.

Collaborators and Investigators

• Sponsor: Sheffield Hallam University

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2018
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: February 20, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (Actual): March 12, 2018

Study Record Updates

• Last Update Posted (Actual): September 11, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: SheffieldHallamAquili2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No