Dopamine Dorsolateral Prefrontal Cortex Behavioural Flexibility

Cognitive Change Clinical Trial

Official title:

Dopaminergic Contribution to Behavioural Flexibility as Modulated by Transcranial Direct-current Stimulation of the Dorsolateral Prefrontal Cortex

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03068884
• Other study ID #: SheffieldHallamAquili2017
• Status: Completed
• Phase: N/A
• First received: February 21, 2017
• Last updated: February 20, 2018
• Start date: March 1, 2017
• Est. completion date: January 31, 2018

Study information

• Verified date: February 2018
• Source: Sheffield Hallam University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 31, 2018
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Change

Intervention

Device:
• Cathodal Transcranial direct current stimulation
Cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex

Dietary Supplement:
• L-Tyrosine
Administration of 2 grams tyrosine

Device:
• Transcranial direct current stimulation (sham)
Sham tDCS

Dietary Supplement:
• Cellulose (placebo)
Administration of 2 grams cellulose

Locations

Country	Name	City	State
United Kingdom	Psychology laboratories	Sheffield	Yorkshire

Sponsors (1)

Lead Sponsor	Collaborator
Sheffield Hallam University

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Wisconsin Card Sorting task	Total Number of errors (e.g. 1-200)	2 hours for each of the four conditions
Primary	Probabilistic reversal learning task	Mean Errors per reversal (e.g. 1-20)	2 hours for each of the four conditions