Dopamine Dorsolateral Prefrontal Cortex Behavioural Flexibility
Condition: Cognitive Change
Study type: Interventional

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.
    


Intervention name(s): Cathodal Transcranial direct current stimulation; L-Tyrosine; Transcranial direct current stimulation (sham); Cellulose (placebo)
Intervention type(s): Device; Dietary Supplement; Device; Dietary Supplement
Intervention description(s): Cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex; Administration of 2 grams tyrosine; Sham tDCS; Administration of 2 grams cellulose
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science