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After ischemic stroke dynamic behavioral changes take place associated with different levels of recovery. Understanding the biological mechanisms that drive post-stroke recovery is of paramount clinical importance, since such knowledge could provide a basis for effective therapies. Functional magnetic resonance imaging (fMRI) studies have shown that the behavioral dynamics or recovery is paralleled by complex reorganization of neural networks. However, large-scale neuroimaging techniques such as fMRI and resting state CBF offer only an incomplete view on cortical plasticity, which is known to be sustained by both metabolic and the associated electrophysiological phenomena that shape neuronal synapses at a microscopic scale.
There is a growing body of evidence that motor recovery after stroke can be facilitated by selective serotonin reuptake inhibitors (SSRI’s). This is particularly interesting because serotonin enhances efficacy of glutaminergic synaptic transmission and through this mechanism also enhances long term potentiation (LTP), which is an important factor of motor learning and probably also cortical reorganization after stroke. With recent technical advances the electrophysiological correlate of LTP can be estimated by repetitive transcranial magnetic stimulation (rTMS) and the increase of the underlying cortical glutamate transmission can be quantified by MR-Spectroscopy (MRS).
In a first step, with a placebo controlled, blinded pilot study in healthy volunteers, we will investigate the effect size of a single dose of an SSRI (escitalopram) on transient cortical plasticity measured by rTMS and fMRI, and on glutamate concentrations in several cortical and subcortical regions of interest (ROIs) measured by MRS. 10 (5/5) healthy subjects will be investigated either with rTMS or with MRS and fMRI before and 3 hours after placebo or 20mg escitalopram. These results will then allow a more detailed power calculation for a rehabilitation study investigating the clinical, molecular and electrophysiological effect of escitalopram in poststroke patients.