Transcranial magnetic stimulation of the brain: What is stimulated? – A consensus and critical position paper. (August 2022)

• Record Type: Journal Article
• Authors: Siebner, Hartwig R.; Funke, Klaus; Aberra, Aman S.; Antal, Andrea; Bestmann, Sven; Chen, Robert; Classen, Joseph; Davare, Marco; Di Lazzaro, Vincenzo; Fox, Peter T.; Hallett, Mark; Karabanov, Anke N.; Kesselheim, Janine; Beck, Mikkel M.; Koch, Giacomo; Liebetanz, David; Meunier, Sabine; Miniussi, Carlo; Paulus, Walter; Peterchev, Angel V.; Popa, Traian; Ridding, Michael C.; Thielscher, Axel; Ziemann, Ulf; Rothwell, John C.; Ugawa, Yoshikazu
• Is Part Of: Clinical neurophysiology. Volume 140(2022)
• Page Start: 59
• Page End: 97
• Publication Date: 2022-08
• Subjects: Transcranial magnetic stimulation -- Motor cortex -- Mechanism of action -- Physiology; A-P Anterior-to-posterior -- BEM Boundary element method -- CBI Cerebellar-brain inhibition -- CSP Cortical silent period -- cTBS Continuous theta-burst stimulation -- D-wave Direct wave -- EEG Electroencephalography -- FEM Finite Element Methods -- fMRI Functional magnetic resonance imaging -- GABA γ-aminobutyric acid -- I-waves Indirect waves -- IPS Intraparietal sulcus -- ISI Interstimulus interval -- iTBS Intermittent theta-burst stimulation -- L-M Lateral-to-medial -- LAI Long-latency afferent inhibition -- LICI Long-interval intracortical inhibition -- M1 Primary motor cortex -- M1-HAND Hand representation of primary motor cortex -- MEP Motor evoked potential -- MT Motor threshold -- P-A Posterior-to-anterior -- PAS Paired associative stimulation -- PET Positron emission tomography -- PFC Prefrontal cortex -- PMd Dorsal premotor cortex -- PMv Ventral premotor cortex -- PT Phosphene threshold -- rCBF Regional cerebral blood flow -- rCMRglu Regional metabolic rate of glucose -- rTMS Repetitive transcranial magnetic stimulation -- S-D Strength–duration -- SAF Short-latency afferent facilitation -- SAI Short-latency afferent inhibition -- SICF Short-interval intracortical facilitation -- SICI Short-interval intracortical inhibition -- TEP TMS evoked EEG potential -- TES Transcranial electric stimulation -- TMS Transcranial magnetic stimulation -- VGSC Voltage-gated sodium channel Indices -- ANT anterior -- POST posterior; Neurophysiology -- Periodicals; Electroencephalography -- Periodicals; Electromyography -- Periodicals; Neurology -- Periodicals; 612.8
• DOI: 10.1016/j.clinph.2022.04.022
• Languages: English
• ISSNs: 1388-2457

Abstract

Highlights: TMS primarily targets the gyri at the hemispheric surface due to limited depth penetration. The direct response to TMS is complex, involving a mixture of neuronal populations. Myelinated axon terminals of pyramidal cells and inhibitory interneurons in the crown of the gyri constitute low-threshold targets for TMS. Neuronal excitation propagates along axons and across synapses from the primary stimulation site to connected regions in a state-dependent fashion. TMS always causes substantial peripheral somatosensory and auditory co-stimulation. Abstract: 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.