Abstract
Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation technique which modulates cortical excitability beyond the stimulation period. However, despite its clinical use rTMS-based therapies which prevent or reduce disabilities in a functionally significant and sustained manner are scarce. It remains unclear how rTMS-mediated changes in cortical excitability, which are not task- or input-specific, exert beneficial effects in some healthy subjects and patients. While experimental evidence exists that repetitive magnetic stimulation (rMS) is linked to the induction of long-term potentiation (LTP) of excitatory neurotransmission, less attention has been dedicated to rTMS-induced structural, functional and molecular adaptations at inhibitory synapses. In this review article we provide a concise overview on basic neuroscience research, which reveals an important role of local disinhibitory networks in promoting associative learning and memory. These studies suggest that a reduction in inhibitory neurotransmission facilitates the expression of associative plasticity in cortical networks under physiological conditions. Hence, it is interesting to speculate that rTMS may act by decreasing GABAergic neurotransmission onto cortical principal neurons. Indeed, evidence has been provided that rTMS is capable of modulating inhibitory networks. Consistent with this suggestion recent basic science work discloses that a 10 Hz rTMS protocol reduces GABAergic synaptic strength on principal neurons. These findings support a model in which rTMS-induced long-term depression (LTD) of GABAergic synaptic strength mediates changes in excitation/inhibition-balance of cortical networks, which may in turn facilitate (or restore) the ability of stimulated networks to express input- and task-specific associative synaptic plasticity.
Highlights
A remarkable property of the central nervous system is its ability to respond to specific stimuli with lasting structural, functional and molecular adaptations
Evidence for human cortical plasticity came from studies employing Transcranial Magnetic Stimulation (TMS; Barker et al, 1985; reviewed in Ziemann et al, 2008)
Even though a considerable degree of inter- and intra-individual variability has been reported (e.g., Müller-Dahlhaus et al, 2008; Hamada et al, 2013; Goldsworthy et al, 2014; López-Alonso et al, 2014; Nettekoven et al, 2015), pharmacological approaches and analogies to basic research findings have indicated that repetitive TMS modulates cortical excitability via ‘‘long-term potentiation (LTP)-like’’ or ‘‘long-term depression (LTD)-like’’ excitatory synaptic mechanisms (Ziemann et al, 2008)
Summary
In this review article we provide a concise overview on basic neuroscience research, which reveals an important role of local disinhibitory networks in promoting associative learning and memory These studies suggest that a reduction in inhibitory neurotransmission facilitates the expression of associative plasticity in cortical networks under physiological conditions. Evidence has been provided that rTMS is capable of modulating inhibitory networks Consistent with this suggestion recent basic science work discloses that a 10 Hz rTMS protocol reduces GABAergic synaptic strength on principal neurons. These findings support a model in which rTMS-induced long-term depression (LTD) of GABAergic synaptic strength mediates changes in excitation/inhibition-balance of cortical networks, which may in turn facilitate (or restore) the ability of stimulated networks to express inputand task-specific associative synaptic plasticity
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