Fig. 1.

NiBS techniques. (a) Transcranial Magnetic Stimulation (TMS) can be applied as a single stimulation pulse (single pulse TMS, spTMS), pairs of stimuli separated by variable intervals (paired pulse TMS, ppTMS) delivered to the same or different brain areas, or as trains of repetitive stimuli at various frequencies (repetitive TMS, rTMS) to respectively measure cortical excitability, excitation/inhibition balance and induce long-lasting neuromodulation effects and changes in plasticity. Outside the motor cortex, accurate targeting is guaranteed by a neuronavigation system that provides, on the basis of individual MRI data, the spatial coordinates of a target area allowing the coil to be held in the correct position during a stimulation session, as well as in subsequent ones. Long Term Depression (LTD) and Long Term Potentiation (LTP)-like effects are mediated by multiple mechanisms, such as actions on GABA and NMDA receptors, gene induction and modulation of numerous neurotransmitters. When spTMS is applied to the motor cortex, TMS elicits motor evoked potentials (MEPs) recorded via surface electromyography, whose amplitude reflects the excitability and integrity of the corticospinal system, the conduction properties along peripheral motor pathways, and the degree of excitability of the motor cortex itself [27]. When ppTMS is delivered, depending on the specific stimulation parameters, intracortical Inhibition and Facilitation can be assessed, respectively measuring the activity of GABAergic and glutamatergic (inter)neurons as well as excitation/inhibition balance (E/I). (b) Transcranial electrical stimulation (tES) can be applied using 2 electrode or adopting multifocal montages that allow for finer customisation of stimulation protocol and targeting accuracy over the region(s) of interest. tDCS: Direct Current Stimulation causes a subthreshold depolarisation of neurons under the anode (increased excitability) and hyperpolarization of neurons under the cathode (decreased excitability). Transcranial alternating current stimulation (tACS) is capable of modulating cortical rhythms, i.e. to entrain neuronal firing at a specific frequency and causing enhancement of related brain functions [28,29]. tACS depolarised and hyperepolarised neurons at a specific frequency (e.g., 10Hz), increasing the probability of neuronal spiking in response to other inputs during their depolarised phase via stochastic resonance mechanism [23]. As per the STDP law, synapses of neuronal network that have a resonance frequency matching that of repetitive inputs are strengthened. Transcranial random noise stimulation (tRNS) delivers electrical noise in a wide frequency band (1–640 Hz) to modulate cortical excitability. The injection of noise is thought to promote the excitability of pyramidal cells via stochastic resonance mechanism, but activation of voltage-gated sodium channels has been documented as well [23]. tRNS after-effects seems to be mediated by GABA receptors and voltage-gated sodium channels [23]