Language & Cognitive Control

Donders Centre for Cognitive Neuroimaging36 enrolled

Overview

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.

Interventions

Methylphenidate 20 Mg Oral TabletDRUG

20mg methylphenidate or placebo capsule - one per session (counterbalanced) approximately 1 week apart

PlaceboDRUG

20mg methylphenidate or placebo capsule - one per session (counterbalanced) approximately 1 week apart

Language TaskBEHAVIORAL

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.

Rest RecordingBEHAVIORAL

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.

Go/No-Go TaskBEHAVIORAL

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.

Processing SpeedBEHAVIORAL

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.

Operation SpanBEHAVIORAL

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.

Reading SpanBEHAVIORAL

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.

Barratt Impulsiveness ScaleBEHAVIORAL

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Language Task ERP Drug Session

This measure will assess the P600 ERP effect (amplitude difference between correct and syntactic ambiguity conditions) just after the target word in the sentences being read.

Time frame: First or second testing session depending on which session corresponds to the session where the drug was administered.

Language Task ERP Placebo Session

This measure will assess the P600 ERP effect (amplitude difference between correct and syntactic ambiguity conditions) just after the target word in the sentences being read.