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.
Phase:
N/A
Details
Lead Sponsor:
Donders Centre for Cognitive Neuroimaging
Collaborators:
Max Planck Institute for Psycholinguistics Radboud University Medical Center