Language & Cognitive Control

Catecholamine (CA) neurotransmitters, such as dopamine (DA) and noradrenaline (NA), have long been implicated playing a critical role in cognitive functions, such as working memory (WM), inhibition, learning, and decision making. Recent evidence from neurodegenerative patients and the healthy population suggested that CA also influences language processing. However, the question of what kind of influence that CA might exert on language is still open. Some previous studies have shown that CA can enhance semantic processing. In a recent study it was observed that CA agonists (i.e., methylphenidate) enhance participant's sensitivity to semantically incongruent information even when language processing was actually goal-irrelevant. On the other hand, the processing of semantically congruent information was enhanced while language processing was the goal. Moreover, consistent with some previous findings that there is a relation between participants' baseline characteristics and MPH effects, it was observed that participants with lower WM capacity benefited more from receiving methylphenidate. These results shed light on the relation between CA and language processing, but also lead to further questions, such as whether the interaction between CA and semantic processing is language-specific or mediated by the relation between CA and more general cognitive functions (e.g., WM, inhibition), and whether CA also has an influence on other aspects of language processing, such as syntactic processing. The present study aimed to further investigate the nature of the relation between CA and language processing by administrating methylphenidate (MPH) to healthy participants. MPH is an indirect CA agonist, which is the most commonly prescribed drug for attention deficit/hyperactivity disorder (ADHD). Previous studies have shown that MPH can efficiently increase the extracellular levels of CA in the brain by blocking their reuptake.

Objective: The primary objectives are: 1) to further investigate the effect of CA on semantic processing. The study plans to examine whether MPH interacts with processing of sentence context constraints via its influence on cognitive control operations. 2) To investigate the effects of MPH on syntactic processing. More specifically, the study is interested in whether MPH has an influence on revising syntactically temporarily ambiguous sentences.

A secondary objective is to further examine the relation between MPH effects and the baseline characteristics of individual participants.

Study design: This study will use a within-subject, double-blind, placebo-controlled, randomized, crossover design.

Study population: Approximately 40 healthy native Dutch speakers between 18 and 45 years old will be recruited. All subjects will have to complete one screening session and two separate testing sessions within three different days at the Donders Centre for Cognitive Neuroimaging (DCCN).

Intervention: Participants will either orally receive a 20mg methylphenidate or placebo capsule in each of the two testing sessions. Methylphenidate has been approved for clinical use in the Netherlands and the drug can be administered safely without any relevant risk of serious adverse events.

Main study parameters: Primary study parameters will include sentence comprehension capacity, attention and processing speed. In addition, several other measures will be included to monitor participants' baseline characteristics (e.g. working memory capacity, vocabulary size) and the general modulation effects of MPH (e.g. heart rate, blood pressure, subjective feeling).

Hypotheses:

Based on the previous finding that methylphenidate improves cognitive stability while it impairs flexible updating, the hypothesis is that methylphenidate will hinder participants' performance in resolving syntactic ambiguity, which requires an immediate updating and revising of an initial interpretation. This should be reflected in event-related potential (ERP) measures related to revision, namely the P600 effect is predicted to be reduced in the drug condition compared to placebo.


Eligibility Criteria:
Inclusion Criteria:

* Native Dutch speakers
* Right-handed

Exclusion Criteria:

* Current (or history of) psychiatric disorder (e.g., psychosis, mania, severe depressive disorder)
* Current (or history of) neurological disorder (e.g. m. Parkinson, epilepsy)
* Current (or history of) endocrine / metabolic disorder
* Current (or history of) cardiac or vascular disorder
* Current (or history of) blood illness (e.g. severe anaemia, porphyria)
* Current (or history of) stomach or gastrointestinal tract disease
* History of autonomic failure (e.g., vasovagal reflex syncope)
* Experience of irregular sleep-wake rhythm
* Current (or history of) obstructive respiratory disease
* Current (or history of) clinically significant renal or hepatic disease
* (Recent treatment of) glaucoma
* Current (or history of) drug addiction (e.g. opiate, (meth)amphetamine, lysergic acid diethylamide, cocaine, solvents or barbiturate) or alcohol dependence
* One first degree or two or more second degree family members with a recent treatment of sudden death or ventricular arrhythmia
* Problems swallowing or problems with the oesophagus
* Frequent experience of headrush (vertigo)
* Current experience of an acute serious infection
* First degree family member with schizophrenia or bipolar disorder
* Abnormal hearing or (uncorrected) vision
* Use of psychotropic medication or recreational drugs weekly or more over a period of more than three months in the last 6 months
* Cannabis usage for the last 6 months
* Strong smoking behaviour starting at more than 1 package of cigarettes per week
* Hypersensitivity for e.g. beta blockers or methylphenidate
* Uncontrolled hypertension, defined as diastolic blood pressure at rest \>95 mmHg or systolic blood pressure at rest \>180 mmHg
* Irregular sleep/wake rhythm (e.g. regular nightshifts or cross timeline travel)
* Possible pregnancy or breastfeeding/ inadequate anticonception (for women)
* Lactose intolerance (because the placebo pill will be a lactose product)
* Language related disabilities (e.g. dyslexia, stuttering)
* Daily intense physical training