Assessment and modulation of cortical inhibition using transcranial magnetic stimulation

Abstract

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique, which is used for diagnostic, therapeutic and scientific purposes in the field of neurology and psychiatry. It is based on the physical principle of electromagnetic induction and allows for the local activation of cortical areas through the intact skull of conscious humans. When applied repeatedly (repetitive TMS; rTMS) sustained changes of cortical excitability can be observed. Hence, TMS resembles a promising approach for assessing and modulating neuronal networks in a non-invasive manner. However, despite its broad clinical application, the cellular and molecular mechanisms of rTMS-based therapies remain not well understood. Established therapeutic concepts assume that pathologically altered cortical excitability is normalised, which may involve 'long-term potentiation' or 'long-term depression' of excitatory synapses. Indeed, animal studies demonstrate that rTMS induces long-term changes of excitatory neurotransmission. However, it is unclear through which mechanisms synaptic changes, which are caused by external electromagnetic activation of the cortex and therefore are not specific for context or behaviour, could have a positive impact on complex brain function. More recent findings suggest that not only excitatory but also inhibitory neuronal networks are modulated by rTMS. It was shown for example that 10 Hz rTMS leads to a calcium-dependent long-term depression of inhibitory GABAergic synapses. Since the reduction of inhibitory neurotransmission (= disinhibition) is considered important for the expression of associative plasticity at excitatory synapses, it is conceivable that rTMS-induced disinhibition may promote context-and behaviour-specific synaptic changes. Hence, the model of rTMS-induced local disinhibition represents an attractive explanation for the observation that a seemingly unspecific (exogenous) magnetic stimulation could induce specific (endogenous) structural, functional and molecular changes of cortical synapses. Current research focuses on the effect of rTMSinduced disinhibition on synaptic plasticity in suitable animal models (both in vivo and in vitro). Thus, apart from its diagnostic and therapeutic potential TMS represents a promising method for conducting clinically-oriented translational plasticity studies.

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“…(A) Visualization of TMS of the motor cortex while recording motor evoked potentials (MEP) of the target muscle. The intensity of TMS is adjusted by recording the amplitude of MEPs elicited from the target muscle while stimulating its motor cortical representation (see Vlachos et al, 2017 ). (B) Schematic illustration of stimulation parameters of the 10 Hz and intermittent theta-burst stimulation (iTBS) repetitive TMS (rTMS) protocols.…”