TY - JOUR

T1 - Transcranial magnetic stimulation of the brain: What is stimulated? - A consensus and critical position paper

AU - Siebner, Hartwig Roman

AU - Funke, Klaus

AU - Aberra, Aman S

AU - Antal, Andrea

AU - Bestmann, Sven

AU - Chen, Robert

AU - Classen, Joseph

AU - Davare, Marco

AU - Di Lazzaro, Vincenzo

AU - Fox, Peter T

AU - Hallett, Mark

AU - Karabanov, Anke Ninija

AU - Kesselheim, Janine

AU - Beck, Mikkel Malling

AU - Koch, Giacomo

AU - Liebetanz, David

AU - Meunier, Sabine

AU - Miniussi, Carlo

AU - Paulus, Walter

AU - Peterchev, Angel V

AU - Popa, Traian

AU - Ridding, Michael C

AU - Thielscher, Axel

AU - Ziemann, Ulf

AU - Rothwell, John C

AU - Ugawa, Yoshikazu

N1 - Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

PY - 2022

Y1 - 2022

N2 - Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool.

AB - Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool.

KW - Faculty of Science

KW - Transcranial magnetic stimulation

KW - Motor cortex

KW - Mechanism of action

KW - Physiology

U2 - 10.1016/j.clinph.2022.04.022

DO - 10.1016/j.clinph.2022.04.022

M3 - Review

C2 - 35738037

VL - 140

SP - 59

EP - 97

JO - Electroencephalography and Clinical Neurophysiology - Electromyography and Motor Control

JF - Electroencephalography and Clinical Neurophysiology - Electromyography and Motor Control

SN - 1388-2457

ER -