Language & Cognitive Control

Not Applicable

Completed

• Conditions: Methylphenidate of Undetermined Intent; Language
• Interventions: Drug: Methylphenidate 20 Mg Oral Tablet; Drug: Placebo; Behavioral: Operation Span; Behavioral: Language Task; Behavioral: Reading Span; Behavioral: Rest Recording; Behavioral: Barratt Impulsiveness Scale; Behavioral: Go/No-Go Task; Behavioral: Processing Speed

• Registration Number: NCT05272397
• Lead Sponsor: Donders Centre for Cognitive Neuroimaging

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-11-26
• Primary Completion: 2021-12-02
• Study Completion: 2021-12-02
• Status Verified: 2022-02
• Study First Submitted: 2022-02-07
• Study First Submitted QC: 2022-02-28
• Study First Posted: 2022-03-09
• Last Update Submitted: 2022-03-21
• Last Update Posted: 2022-04-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Drug Session	Methylphenidate 20 Mg Oral Tablet	In this arm of the study participants receive the drug (Methylphenidate - 20mg), administered prior to completion of the primary and secondary tasks for the study. Electroencephalography (EEG) is measured for the duration of the primary and secondary tasks. Participants complete both arms of the study, and the order in which participants are assigned to this and the other arm of the study is randomized.
Drug Session	Language Task	In this arm of the study participants receive the drug (Methylphenidate - 20mg), administered prior to completion of the primary and secondary tasks for the study. Electroencephalography (EEG) is measured for the duration of the primary and secondary tasks. Participants complete both arms of the study, and the order in which participants are assigned to this and the other arm of the study is randomized.
Placebo Session	Go/No-Go Task	In this arm of the study participants receive the a placebo, administered prior to completion of the primary and secondary tasks for the study. Electroencephalography (EEG) is measured for the duration of the primary and secondary tasks. Participants complete both arms of the study, and the order in which participants are assigned to this and the other arm of the study is randomized.
Drug Session	Processing Speed	In this arm of the study participants receive the drug (Methylphenidate - 20mg), administered prior to completion of the primary and secondary tasks for the study. Electroencephalography (EEG) is measured for the duration of the primary and secondary tasks. Participants complete both arms of the study, and the order in which participants are assigned to this and the other arm of the study is randomized.
Placebo Session	Rest Recording	In this arm of the study participants receive the a placebo, administered prior to completion of the primary and secondary tasks for the study. Electroencephalography (EEG) is measured for the duration of the primary and secondary tasks. Participants complete both arms of the study, and the order in which participants are assigned to this and the other arm of the study is randomized.
Placebo Session	Placebo	In this arm of the study participants receive the a placebo, administered prior to completion of the primary and secondary tasks for the study. Electroencephalography (EEG) is measured for the duration of the primary and secondary tasks. Participants complete both arms of the study, and the order in which participants are assigned to this and the other arm of the study is randomized.
Intake Session	Barratt Impulsiveness Scale	In this arm of the study participants are screened for suitability to participate in the experiment based on specified inclusion and exclusion criteria. They also complete some baseline tasks to assess working memory capacity, impulsiveness, and subjective mood.
Drug Session	Rest Recording	In this arm of the study participants receive the drug (Methylphenidate - 20mg), administered prior to completion of the primary and secondary tasks for the study. Electroencephalography (EEG) is measured for the duration of the primary and secondary tasks. Participants complete both arms of the study, and the order in which participants are assigned to this and the other arm of the study is randomized.
Drug Session	Go/No-Go Task	In this arm of the study participants receive the drug (Methylphenidate - 20mg), administered prior to completion of the primary and secondary tasks for the study. Electroencephalography (EEG) is measured for the duration of the primary and secondary tasks. Participants complete both arms of the study, and the order in which participants are assigned to this and the other arm of the study is randomized.
Placebo Session	Language Task	In this arm of the study participants receive the a placebo, administered prior to completion of the primary and secondary tasks for the study. Electroencephalography (EEG) is measured for the duration of the primary and secondary tasks. Participants complete both arms of the study, and the order in which participants are assigned to this and the other arm of the study is randomized.
Intake Session	Reading Span	In this arm of the study participants are screened for suitability to participate in the experiment based on specified inclusion and exclusion criteria. They also complete some baseline tasks to assess working memory capacity, impulsiveness, and subjective mood.
Placebo Session	Processing Speed	In this arm of the study participants receive the a placebo, administered prior to completion of the primary and secondary tasks for the study. Electroencephalography (EEG) is measured for the duration of the primary and secondary tasks. Participants complete both arms of the study, and the order in which participants are assigned to this and the other arm of the study is randomized.
Intake Session	Operation Span	In this arm of the study participants are screened for suitability to participate in the experiment based on specified inclusion and exclusion criteria. They also complete some baseline tasks to assess working memory capacity, impulsiveness, and subjective mood.

Primary Outcome Measures

Name	Time	Method
Language Task ERP Drug Session	First or second testing session depending on which session corresponds to the session where the drug was administered.	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.
Language Task ERP Placebo Session	First or second testing session depending on which session corresponds to the session where the placebo was administered.	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.
Language Task Alpha Power Drug Session	First or second testing session depending on which session corresponds to the session where the drug was administered.	This measure will assess the alpha power effect (relative power difference between high and low sentence constraint conditions in the alpha frequency band, 8-12 Hz) just before the target word in the sentences being read.
Language Task Alpha Power Placebo Session	First or second testing session depending on which session corresponds to the session where the placebo was administered.	This measure will assess the alpha power effect (relative power difference between high and low sentence constraint conditions in the alpha frequency band, 8-12 Hz) just before the target word in the sentences being read.

Secondary Outcome Measures

Name	Time	Method
Default Mode Alpha Power Placebo Session	First or second testing session depending on which session corresponds to the session where the placebo was administered.	This measure will assess alpha power (8-12 Hz) at rest (relative difference between alpha power measured over the duration of the eyes open to that measured over the duration of the eyes closed recordings).
Go-NoGo Task Alpha Power Placebo Session	First or second testing session depending on which session corresponds to the session where the placebo was administered.	This measure will assess alpha power (8-12 Hz) at response and no-response cues to obtain a measure of attentional control.
Go-NoGo Task Alpha Power Drug Session	First or second testing session depending on which session corresponds to the session where the placebo was administered.	This measure will assess alpha power (8-12 Hz) at response and no-response cues to obtain a measure of attentional control.
Default Mode Alpha Power Drug Session	First or second testing session depending on which session corresponds to the session where the placebo was administered.	This measure will assess alpha power (8-12 Hz) at rest (relative difference between alpha power measured over the duration of the eyes open to that measured over the duration of the eyes closed recordings).

Trial Locations

Locations (1)

Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging; 🇳🇱 Nijmegen, Gelderland, Netherlands