Language & Cognitive Control
Condition: Language; Methylphenidate of Undetermined Intent
Study type: Interventional

Summary: 
      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.
    


Intervention name(s): Methylphenidate 20 Mg Oral Tablet; Placebo; Language Task; Rest Recording; Go/No-Go Task; Processing Speed; Operation Span; Reading Span; Barratt Impulsiveness Scale
Intervention type(s): Drug; Drug; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral
Intervention description(s): 20mg methylphenidate or placebo capsule - one per session (counterbalanced) approximately 1 week apart; 20mg methylphenidate or placebo capsule - one per session (counterbalanced) approximately 1 week apart; The core part of the experiment is the language task, in which the aim is to investigate two critical aspects of language processing: semantic and syntactic processing. In this task, participants will be asked to read a list of sentences.; Brain activity in the EEG is recorded at rest with eyes open and eyes closed to obtain baseline measures of alpha power as a proxy for attention and control under conditions of drug and placebo.; A Go/No-Go task will be implemented in the study design to investigate the functional properties of spatial selective attention and response inhibition. An adapted cued Go/No-Go paradigm from Randall & Smith (2011) will be employed.; A speeded button response task will be included to measure participants' general processing speed. In this task, participants will be instructed to respond to a simple shape presented in the centre of the screen as fast and accurately as possible through pressing a corresponding button.; In the operation span task, participants are instructed to solve math operations (e.g., (1*2) +1=?) as soon as possible and then remember a single letter. This to-be-remembered letter is followed by either another math-word combination or a recall screen, which will show up at the end of each set. When the recall screen is presented, participants have to recall all the letters in the correct order they were presented. The experimental trials contain three sets at each set size (i.e., the number of math-word pairs), with set sizes ranging from 3 to 7 items. This results in a total of 75 sets with 75 letters and 75 math problems. The order of set sizes is random for each participant. Participants' operation span will be evaluated by the total number of letters recalled in the correct serial position regardless of whether the entire trial was recalled correctly.; Participants are instructed to judge whether a presented sentence makes sense or not. After each sentence, a to-be-remembered letter will be shown on the screen, which is followed by either another sentence-word combination or the final recall screen. The set size ranges from 3 to 7 items. At the end of each set of sentences, participants will be required to recall all the letters in the current set in order. There will be a total of 75 letters and 75 sentence judgements. The order of the set sizes will be at random for each participant. Participants' performance will be evaluated by calculating the total number of correctly recalled letter sets.; The Barratt impulsiveness scale (BIS-11) will be used in the experiment to measure participants' trait impulsivity. Participants will be required to rate themselves on 30 items that are related to attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness.
Intervention MeSH terms: Methylphenidate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Cognitive Control; Language Processing; Reading; Methylphenidate; Catecholaminergic Neurotransmitters