The Interaction of Cognitive Control Mechanisms and Language Processing: An Investigation With Methylphenidate
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Language Task Alpha Power Placebo Session
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Native Dutch speakers
- •Right-handed
排除标准
- •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
研究组 & 干预措施
Drug Session
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.
干预措施: Language Task (Behavioral)
Placebo Session
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.
干预措施: Go/No-Go Task (Behavioral)
Drug Session
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.
干预措施: Processing Speed (Behavioral)
Placebo Session
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.
干预措施: Rest Recording (Behavioral)
Placebo Session
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.
干预措施: Placebo (Drug)
Intake Session
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.
干预措施: Barratt Impulsiveness Scale (Behavioral)
Drug Session
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.
干预措施: Rest Recording (Behavioral)
Drug Session
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.
干预措施: Go/No-Go Task (Behavioral)
Placebo Session
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.
干预措施: Language Task (Behavioral)
Placebo Session
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.
干预措施: Processing Speed (Behavioral)
Intake Session
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.
干预措施: Operation Span (Behavioral)
Intake Session
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.
干预措施: Reading Span (Behavioral)
Drug Session
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.
干预措施: Methylphenidate 20 Mg Oral Tablet (Drug)
结局指标
主要结局
Language Task Alpha Power Placebo Session
时间窗: 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.
Language Task ERP Drug Session
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Default Mode Alpha Power Placebo Session(First or second testing session depending on which session corresponds to the session where the placebo was administered.)
- 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.)
- 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.)
- Default Mode Alpha Power Drug Session(First or second testing session depending on which session corresponds to the session where the placebo was administered.)