Dopamine Dorsolateral Prefrontal Cortex Behavioural Flexibility

NCT ID: NCT03068884

Last Updated: 2018-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2018-01-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Tdcs sham

Group Type: SHAM_COMPARATOR

L-Tyrosine

Intervention Type: DIETARY_SUPPLEMENT

Administration of 2 grams tyrosine

Cellulose (placebo)

Intervention Type: DIETARY_SUPPLEMENT

Administration of 2 grams cellulose

Placebo

Group Type: PLACEBO_COMPARATOR

Cathodal Transcranial direct current stimulation

Intervention Type: DEVICE

Cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex

Transcranial direct current stimulation (sham)

Intervention Type: DEVICE

Sham tDCS

Tdcs cathodal

Group Type: EXPERIMENTAL

L-Tyrosine

Intervention Type: DIETARY_SUPPLEMENT

Administration of 2 grams tyrosine

Cellulose (placebo)

Intervention Type: DIETARY_SUPPLEMENT

Administration of 2 grams cellulose

Tyrosine

Group Type: EXPERIMENTAL

Cathodal Transcranial direct current stimulation

Intervention Type: DEVICE

Cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex

Transcranial direct current stimulation (sham)

Intervention Type: DEVICE

Sham tDCS

Interventions

Cathodal Transcranial direct current stimulation

Cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex

Intervention Type: DEVICE

L-Tyrosine

Administration of 2 grams tyrosine

Intervention Type: DIETARY_SUPPLEMENT

Transcranial direct current stimulation (sham)

Sham tDCS

Intervention Type: DEVICE

Cellulose (placebo)

Administration of 2 grams cellulose

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sheffield Hallam University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luca Aquili, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Sheffield Hallam University

Locations

Psychology laboratories

Sheffield, Yorkshire, United Kingdom

Countries

United Kingdom

Other Identifiers

SheffieldHallamAquili2017

Identifier Type: -

Identifier Source: org_study_id