Modulation of cortical excitability induced by repetitive transcranial magnetic stimulation: influence of timing and geometrical parameters and underlying mechanisms |
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| Authors: | Pell Gaby S Roth Yiftach Zangen Abraham |
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| Affiliation: | Department of Neurobiology, Weizmann Institute, Rechovot 76100, Israel. |
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| Abstract: | Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that activates neurons via generation of brief pulses of high-intensity magnetic field. If these pulses are applied in a repetitive fashion (rTMS), persistent modulation of neural excitability can be achieved. The technique has proved beneficial in the treatment of a number of neurological and psychiatric conditions. However, the effect of rTMS on excitability and the other performance indicators shows a considerable degree of variability across different sessions and subjects. The frequency of stimulation has always been considered as the main determinant of the direction of excitability modulation. However, interactions exist between frequency and several other stimulation parameters that also influence the degree of modulation. In addition, the spatial interaction of the transient electric field induced by the TMS pulse with the cortical neurons is another contributor to variability. Consideration of all of these factors is necessary in order to improve the consistency of the conditioning effect and to better understand the outcomes of investigations with rTMS. These user-controlled sources of variability are discussed against the background of the mechanisms that are believed to drive the excitability changes. The mechanism behind synaptic plasticity is commonly accepted as the driver of sustained excitability modulation for rTMS and indeed, plasticity and rTMS share many characteristics, but definitive evidence is lacking for this. It is more likely that there is a multiplicity of mechanisms behind the action of rTMS. The different mechanisms interact with each other and this will contribute to the variability of rTMS-induced excitability changes. This review investigates the links between rTMS and synaptic plasticity, describes their similarities and differences, and highlights a neglected contribution of the membrane potential. In summary, the principal aims of this review are (i) to discuss the different experimental and subject-related factors that contribute to the variability of excitability modulation induced by rTMS, and (ii) to discuss a generalized underlying mechanism for the excitability modulation. |
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| Keywords: | AMPA, amino-3-hydroxyl-5-methyl-4-isoxazole-propionate AMT, active motor threshold AP, anterior–posterior BiPA, biphasic pulse with initial phase of induced current anteriorly directed (second phase posteriorly directed) BiAP, biphasic pulse with initial phase of induced current posteriorly directed (second phase anteriorly directed) BDNF, brain derived neurotrophic factor cAMP, cyclic adenosine monophosphate CMAP, compound muscle action potential cMEP, contralateral MEP cSP, cortical silent period CSF, cerebrospinal fluid cTBS, continuous TBS D–H, depolarization–hyperpolarization biphasic pulse DTI, diffusion tensor imaging EMG, electromyogram EP, evoked potential EPSP, excitatory postsynaptic potential FDG, fluorodeoxyglucose fMRI, functional magnetic resonance imaging GABA, gamma-aminobutyric acid GABA-R, GABA receptor GFAB, glial fibrillary acidic protein H–D, hyperpolarization–depolarization biphasic pulse HF, high frequency ICF, intracortical facilitation IHI, inter-hemispheric inhibition INB, ischemic nerve block IPSP, inhibitory post-synaptic potential ISI, inter-stimulus interval iMEP, ipsilateral MEP iTBS, intermittent TBS iTMS, TMS at I-wave periodicity LF, low frequency LFP, local field potential LM, lateral-medial LTD, long term depression LTP, long term potentiation M1, primary motor cortex MEP, motor evoked potential ML, medial–lateral MonoAP, monophasic pulse with induced current posteriorly directed MonoPA, monophasic pulse with induced current anteriorly directed MRI, magnetic resonance imaging N/A, non-applicable NMDA, N-methyl-d-aspartate NMDA-R, NMDA receptor N/S, information not supplied qTMS, quadripulse TMS PA, posterior–anterior PAS, paired associative stimulation PBS, primed burst stimulation PMC, premotor cortex RDP, rate dependent plasticity RMT, resting motor threshold rTMS, repetitive transcranial magnetic stimulation SICF, short interval cortical facilitation SICI, short interval cortical inhibition STDP, spike-timing dependent plasticity tDCS, transcranial direct current stimulation TBS, theta burst stimulation TMS, transcranial magnetic stimulation Vm, transmembrane potential |
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