| Résumé: | <p>Motor learning is extremely important in everyday life: from learning how to reach and
grab objects to learning complex movements, like driving a car or playing the piano, most daily activities and hobbies rely on previously acquired motor skills. Increasing evidence indicates that inhibition mediated by GABA, the most common inhibitory neurotransmitter, plays a key role in learning new motor skills. Modulating GABAergic inhibition may therefore influence motor learning.</p>
<p>In this thesis, I investigated the role of inhibition in human motor learning by conducting
two within-subject, randomised, placebo-controlled pharmacological studies, targeting
distinct GABA-receptors, in young, healthy volunteers. In each study, I used a GABA receptor agonist, hypothesising that increasing GABAergic inhibition would lead to
impairments in motor learning.</p>
<p>Firstly, I used baclofen, a GABAB-receptor agonist, in a pharmaco-neuroimaging study. I evaluated the participants’ motor learning behaviour and their patterns of brain activity
during task performance and at rest. Using a novel technique, Magnetic Resonance
Spectroscopic Imaging (MRSI), I measured [GABA] in motor areas before and after task
performance. I found that baclofen significantly impaired motor sequence learning and
changed the pattern of learning-related [GABA] dynamics during learning. Baclofen was associated with the recruitment of additional brain areas during task performance, likely as a compensatory mechanism, and with decreased functional connectivity in resting-state networks. </p>
<p>In the second study, I used zolpidem, a GABAA-receptor agonist. I measured participants’ motor learning behaviour and their cortical excitability using transcranial magnetic stimulation (TMS). Zolpidem significantly slowed down response times and impaired the retention of visuomotor adaptation skills. I found no significant effects of zolpidem on TMS metrics.</p>
<p>Taken together, these results enhance our understanding of the neurophysiological
mechanisms underlying human motor learning. They are also clinically relevant: both
baclofen and zolpidem are commonly administered medications and they might be
detrimental to the motor rehabilitation of clinical populations.</p>
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