Dopamine Dorsolateral Prefrontal Cortex Behavioural Flexibility

NCT03068884 | Completed

• 1 other identifier: SheffieldHallamAquili2017
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Behavioural or cognitive flexibility (BF) is an essential ability which allows an organism to adaptively change responses in accordance with feedback of results. In humans, this ability is disrupted among those who suffer a variety of neurological and psychiatric conditions including Parkinson's disease, schizophrenia, addiction, obsessive compulsive disorder and autism. Additionally, there is evidence of substantial individual differences in BF within the healthy population. Two known neurobiological mechanisms which relate to BF performance are variation in dopamine (DA) and serotonin (SE) function. One particular brain regions which has been heavily implicated in BF is the prefrontal cortex (PFC), with the dorsolateral PFC receiving a largely DA innervation and the dorsomedial PFC a SE input. Studies have demonstrated that damage to parts of PFC including the orbitofrontal cortex (OFC), for example, impairs reversal learning (a form of BF) whereas lesions of the dorsolateral PFC affect attentional set-shifting (another measure of BF). In humans, putative augmentation of DA efflux via administration of the DA and norepinephrine precursor tyrosine has been shown to improve task-switching performance, and inhibitory control suggesting a causal role of DA in regulating BF. Similarly, putative depletion of serotonin neurotransmission via tryptophan depletion procedures has been shown to reduce the BOLD response during performance monitoring and increase perseverative behaviour. One important strategy (in humans) to observe whether the PFC is causally involved in BF performance, is by reversible electrical stimulation of the PFC, so that PFC cells could be inhibited or excited while a participant is performing a BF task. In recent years, several laboratories have taken advantage of a relatively new technology known as transcranial direct current stimulation (tDCS) to study the relationship between brain function and behaviour. Using this technique, increases or decreases in cortical excitability are partly determined by the polarity of the stimulation; increases occur under the anode electrode whereas decreases occur under the negatively charged cathode. Using this approach, several studies have shown that anodal and cathodal stimulation over the PFC can have a number of effects on BF performance, with general improvements during anodal stimulation and impairments during cathodal. If this is the case, one important step that remains to be understood is whether dopamine and serotonin are causally related to these outcomes when neurons of the dLPFC/dMPFC are either excited or inhibited via tDCS. Thus, the specific novelty of this study rests in combining a psychopharmacological approach (i.e. tyrosine/tryptophan loading) with selective neuroanatomical (i.e. dorsolateral/dorsomedial prefrontal cortex) inhibition of cells via tDCS while participants are performing BF tasks. By doing so, we will be able to establish whether increased dopaminergic/serotonergic output to the PFC is a necessary requirement for BF performance.

Conditions

Cognitive Change

Outcome Measures

Primary Outcomes (2)

• Wisconsin Card Sorting task

  Total Number of errors (e.g. 1-200)

  2 hours for each of the four conditions

• Probabilistic reversal learning task

  Mean Errors per reversal (e.g. 1-20)

  2 hours for each of the four conditions

Study Arms (4)

Tdcs sham

SHAM COMPARATOR

Dietary Supplement: L-Tyrosine; Dietary Supplement: Cellulose (placebo)

Placebo

PLACEBO COMPARATOR

Device: Cathodal Transcranial direct current stimulation; Device: Transcranial direct current stimulation (sham)

Tdcs cathodal

EXPERIMENTAL

Dietary Supplement: L-Tyrosine; Dietary Supplement: Cellulose (placebo)

Tyrosine

EXPERIMENTAL

Device: Cathodal Transcranial direct current stimulation; Device: Transcranial direct current stimulation (sham)

Interventions

Cathodal Transcranial direct current stimulation DEVICE

Cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex

Placebo; Tyrosine

L-Tyrosine DIETARY_SUPPLEMENT

Administration of 2 grams tyrosine

Tdcs cathodal; Tdcs sham

Transcranial direct current stimulation (sham) DEVICE

Sham tDCS

Placebo; Tyrosine

Cellulose (placebo) DIETARY_SUPPLEMENT

Administration of 2 grams cellulose

Tdcs cathodal; Tdcs sham

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged between 18 and 30 years
• In good health
• Agrees to fast overnight prior to testing

You may not qualify if:

• Presence of cardiac, hepatic, renal, or neurological disorders
• Presence of damaged or diseased skin on your face and scalp, or a sensitive scalp
• A history of alcohol or drug addiction, or severe psychiatric illness
• Taking drugs which may lower seizure threshold (i.e. epilepsy)
• In a state of pregnancy
• Having slept less than 6 hours the night before testing
• A history of migraine or headaches
• A history of taking antidepressants
• A history of taking tyrosine supplements

Sponsors & Collaborators

• Sheffield Hallam University: lead

Study Sites (1)

Psychology laboratories

Sheffield, Yorkshire, S10 2BQ, United Kingdom

Location

MeSH Terms

Interventions

Transcranial Direct Current Stimulation; Tyrosine; Cellulose

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Glucans; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Luca Aquili, Ph.D.

  Sheffield Hallam University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2017
• First Posted: March 3, 2017
• Study Start: March 1, 2017
• Primary Completion: December 31, 2017
• Study Completion: January 31, 2018
• Last Updated: February 22, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)