Neuroplastic Alterations of the Motor Cortex by Caffeine

Study Overview
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Brief Summary
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Caffeine is a psychostimulant drug. It acts as a competitive antagonist at adenosine receptors, which modulate cortical excitability as well. In deep brain stimulation (DBS), the production of adenosine following the release of adenosine triphosphate (ATP) explains the reduction of tremor. Binding of adenosine to adenosine A1 receptors suppresses excitatory transmission in the thalamus and hereby reduces both tremor-and DBS-induced side effects. Also, the effect of adenosine was attenuated following the administration of the 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) adenosine A1 receptor antagonist. Therefore, the presence of a receptor antagonist such as caffeine was suggested to reduce the effectiveness of deep brain stimulation (DBS) in treating tremor and other movement disorders. Based on this finding, the investigators hypothesize that the antagonistic effect of caffeine can tentatively block the excitatory effects of transcranial alternating current stimulation (tACS). The plasticity effects might differ among caffeine users and non- caffeine users depending on the availability of receptor binding sites. Apart from that, a major issue in NIBS studies including those studying motor-evoked potentials is the response variability both within and between individuals. The trial to trial variability of motor evoked potentials (MEPs) may be affected by many factors. Inherent to caffeine is its effect on vigilance. In this study, the investigator shall monitor the participant's vigilance by pupillometry to (1) better understand the factors, which might cause variability in transcranial excitability induction studies and (2) to separate the direct pharmacological effect from the indirect attentional effect of caffeine.

Official Title
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Neuroplastic Alterations of the Motor Cortex by Caffeine: Differences Between Caffeine and Non-caffeine Users and Influence of Vigilance During Stimulation

Conditions
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Cortical Excitability, Brain Stimulation, Caffeine

Intervention / Treatment
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* Other: 200 mg caffeine tablet
* Other: Non-active tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female healthy participants between the ages of 18-45. Right-handed (Oldfield 1971). Free willing participation and written, informed consent of all subjects obtained prior to the start of the study. Participant's weight is above 60 kg Exclusion Criteria: Age < 18 or > 45 years old; Left hand dominant; Evidence of a chronic disease or history with a disorder of the nervous system History of epileptic seizures; Pacemaker or deep brain stimulation; Metal implants in the head region (metal used in the head region, for example, clips after the operation of an intracerebral aneurysm (vessel sacking in the region of the brain vessels), implantation of an artificial auditory canal); Cerebral trauma with loss of consciousness in prehistory; Existence of a serious internal (internal organs) or psychiatric (mental illness) Alcohol, medication or drug addiction; Receptive or global aphasia (disturbance of speech comprehension or additionally of speech); Participation in another scientific or clinical study within the last 4 weeks; Pregnancy Breastfeeding Intolerance to caffeine or coffee products Participant who has abnormal heart activity from an electrocardiography (ECG) finding Weight is less than 60 kg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 15 participants are assigned to caffeine group and another 15 are assigned to placebo group. Then, the participants who were initially in the caffeine group now be in placebo group and those who were in the placebo group were assigned to caffeine group. Finally, all participants received both placebo and caffeine
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Caffeine group<br>Participants will receive a caffeine tablet and all electrical stimulations in a random order (tACS 140 Hz at 1 mA and sham tACS). Participant's vigilance status will be monitor based on active vigilance condition or passive vigilance condition. | Other: 200 mg caffeine tablet<br>* Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and active vigilance condition Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and passive vigilance condition Transcranial alternating current stimulation (140 Hz tACS) sham and active vigilance condition Transcranial alternating current stimulation (140 Hz tACS) sham and passive vigilance condition<br>|
| Placebo Comparator: Placebo group<br>Participants will receive a placebo tablet and all electrical stimulations in a random order (tACS 140 Hz at 1 mA and sham tACS). Participant's vigilance status will be monitor based on active vigilance condition or passive vigilance condition. | Other: Non-active tablet<br>* Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and active vigilance condition Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and passive vigilance condition Transcranial alternating current stimulation (140 Hz tACS) sham and active vigilance condition Transcranial alternating current stimulation (140 Hz tACS) sham and passive vigilance condition<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuroplastic changes of the cortical areas | Motor cortex plasticity is measured from the changes in the amplitude of the motor evoked potentials (MEPs) at different time points. Transcranial magnetic stimulation (TMS) will be used to measure MEP amplitudes. | Baseline (pre-measurement), immediately after intervention, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes | 
| The influence of vigilance during stimulation | Participant's level of vigilance is monitored from pupil diameter and pupil unrest index (PUI) using pupillometer. This measurement is carried out during 10 minutes of transcranial alternating current stimulation (tACS) | 10 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic polymorphism | Brain-derived neurotrophic factor (BDNF) gene polymorphisms on cortical plasticity | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasticity, Variability, Non-invasive brain stimulation, Caffeine