Cortical Excitability Changes on the Sensorimotor Cortex Induced by Caffeine Consumption: A TMS Study

Study Overview
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Brief Summary
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Caffeine is a widely used psychostimulant drug and acts as a competitive antagonist at adenosine receptors. Its effect is on neurons and glial cells of all brain areas. Chronic consumption of caffeine leads to tolerance which might be associated with an increased number of binding sites in the brain. In deep brain stimulation (DBS), the production of adenosine following the release of adenosine triphosphate (ATP) explains the reduction of in tremor. Binding of adenosine to adenosine A1 receptor suppresses excitatory transmission in the thalamus and thus 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. In light with this finding, we anticipate that the antagonistic effect of caffeine is a culprit to the reduction of effectiveness of any stimulation protocol in non-invasive stimulation (NIBS). In particular the excitatory effects of a NIBS protocol can tentatively be blocked in the presence of caffeine. In this study, the effects of caffeine consumption on cortical excitability at the sensorimotor cortex shall be examined on focal and non-focal plasticity. Focal plasticity will be induced by paired associated stimulation (PAS) and global cortical plasticity from transcranial alternating current (tACS) stimulation. In case of tACS stimulation, 1) an excitatory protocol (tACS, 140 Hz, 1 mA) and 2) an inhibitory protocol (tACS, 140 Hz, 0.4 mA) with the active electrode over M1 and the return electrode over the orbitofrontal cortex will be used. Changes in cortical excitability are assessed using transcranial magnetic stimulation (TMS) recordings. Research goals are to examine the effects of caffeine consumption on sensorimotor cortical excitability and stimulation induced plasticity. In addition, this study explores further factors which usually contribute to variability in cortical excitability studies. The results are expected to give a useful recommendation for researchers to reduce confounding factors and hereby improves repeatability.

Official Title
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Cortical Excitability Changes on the Sensorimotor Cortex Induced by Caffeine Consumption: A TMS Study

Conditions
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Cortical Excitability, Brain Stimulation

Intervention / Treatment
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* Combination Product: Caffeine_TMS


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 who willingly stop consuming caffeinated drinks at least three days before the experiment is performed Participant's weight is above 60 kg Exclusion Criteria: Age < 18 or > 45 years old; Left hand dominant; Evidence of a chronic disease or residuals of a disorder of the nervous system in the history, in particular stroke 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 Still period Participant who is unable to tolerate with 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>200mg caffeine tablet transcranial alternating current stimulation (140 Hz tACS) at 1 mA transcranial alternating current stimulation (140 Hz tACS) at 0.4 mA transcranial alternating current stimulation (140 Hz tACS) sham paired associative stimulation (PAS 25) | Combination Product: Caffeine_TMS<br>* Caffeine group: participants will receive a caffeine tablet and all electrical stimulations in a random order [transcranial electrical stimulation (tACS 140 Hz at 1 mA, 0.4 mA, sham) and paired associative stimulation (PAS 25)] Placebo tablet: participants will receive a placebo tablet and all electrical stimulations in a random order [transcranial electrical stimulation (tACS 140 Hz at 1 mA, 0.4 mA, sham) and paired associative stimulation (PAS 25)]<br>|
| Placebo Comparator: Placebo group<br>Non-active tablet transcranial alternating current stimulation (140 Hz tACS) at 1 mA transcranial alternating current stimulation (140 Hz tACS) at 0.4 mA transcranial alternating current stimulation (140 Hz tACS) sham paired associative stimulation (PAS 25) | Combination Product: Caffeine_TMS<br>* Caffeine group: participants will receive a caffeine tablet and all electrical stimulations in a random order [transcranial electrical stimulation (tACS 140 Hz at 1 mA, 0.4 mA, sham) and paired associative stimulation (PAS 25)] Placebo tablet: participants will receive a placebo tablet and all electrical stimulations in a random order [transcranial electrical stimulation (tACS 140 Hz at 1 mA, 0.4 mA, sham) and paired associative stimulation (PAS 25)]<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortical excitabiliy changes induced by caffeine consumption | Amplitude of motor evoked potential change (MEP) | Baseline (pre-measurement), immediately after intervention, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain-derived neurotrophic factor (BDNF) gene polymorphisms on cortical plasticity | Valine (Val) and Methionine (Met) alleles (i.e. Val66Met; Val66Val; Met66Met; Met66Val) | 3-6 months |