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

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.

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Key information

Conditions

Cortical Excitability Brain Stimulation

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Prof. Dr. Walter Paulus

Goettigen, Lower Saxony, 37075, Germany

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Caffeine_TMS

Combination Product

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)]

Primary outcomes

Cortical excitabiliy changes induced by caffeine consumption

Time frame: Baseline (pre-measurement), immediately after intervention, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 60 minutes

Amplitude of motor evoked potential change (MEP)

Secondary outcomes

Brain-derived neurotrophic factor (BDNF) gene polymorphisms on cortical plasticity

Time frame: 3-6 months

Valine (Val) and Methionine (Met) alleles (i.e. Val66Met; Val66Val; Met66Met; Met66Val)

Sponsors and collaborators

Lead sponsor

University Medical Center Goettingen

Other

Registry information

Important dates

Study start: 2018
Primary completion: 2019
Study completion: 2019
First posted: Oct 25, 2018
Registry last updated: Nov 29, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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