What is the mechanism of action of transcranial magnetic stimulation (TMS)?

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Mechanism of Action of Transcranial Magnetic Stimulation (TMS)

TMS works by electromagnetic induction, where brief focal magnetic pulses penetrate the skull to directly induce neuronal firing in targeted brain regions, with the magnetic field being strong enough to cause action potentials in neurons beneath the coil positioned over the scalp. 1

Primary Physical Mechanism

  • TMS is based on the electromagnetic induction principle where a time-varying magnetic field generates an electric field in brain tissue 1
  • The induced electric field is strongest in the superficial parts of targeted cortical gyri and underlying white matter 2
  • The magnetic field strength is sufficient to induce firing of neurons directly beneath the area where the coil is positioned 1

Neuronal Targets and Excitation Pathways

  • TMS primarily targets axonal terminals in the crown top and lip regions of cortical gyri, with secondary excitation of bends of myelinated axons in the juxtacortical white matter below the gyral crown 2
  • TMS likely targets axons of both excitatory and inhibitory neurons 2
  • The propensity of individual axons to fire depends on their geometry, myelination, spatial relation to the imposed electric field, and the physiological state of the neuron 2

Direct vs. Transsynaptic Activation

  • TMS excites pyramidal neurons transsynaptically, giving rise to I (indirect) waves, distinguishing it from transcranial electrical stimulation which produces D (direct) waves 3
  • Neuronal excitation spreads both orthodromically and antidromically along stimulated axons, causing secondary excitation of connected neuronal populations within local intracortical microcircuits 2
  • Axonal and transsynaptic spread of excitation occurs along cortico-cortical and cortico-subcortical connections, impacting neuronal activity in the targeted network 2

Frequency-Dependent Effects on Cortical Excitability

Acute Effects During Stimulation

  • High-frequency rTMS (>5 Hz) facilitates motor cortical excitability, while low-frequency rTMS (<1 Hz) inhibits it 1
  • Intermittent theta-burst stimulation (iTBS) facilitates cortical excitability, whereas continuous theta-burst stimulation (cTBS) reduces it, both with shorter stimulation duration compared to standard rTMS 1

Underlying Plasticity Mechanisms

  • The primary hypothesized mechanism underlying neuromodulatory effects is long-term potentiation (LTP)- or long-term depression (LTD)-like changes in synaptic coupling of neurons 1
  • A rapid post-synaptic increase in calcium ions induces LTP with high frequency (10 Hz) rTMS or iTBS, whereas a slower and sustained flux of calcium ions induces LTD after 1 Hz rTMS or cTBS 1
  • The directionality of LTP or LTD depends on the frequency, intensity, and duration of stimulation 1

Critical Parameters Affecting Stimulation

The mechanism and effectiveness of TMS depend on several crucial parameters 1:

  • Stimulation frequency (single pulses, paired-pulses, or repetitive trains)
  • Pattern of stimulation (continuous at specific frequency or patterned with specific inter-train intervals)
  • Intensity of stimulation
  • Coil geometry and positioning relative to target brain regions

Important Caveats

  • TMS causes substantial direct co-stimulation of the peripheral nervous system, with peripheral co-excitation propagating centrally in auditory and somatosensory networks and producing brain responses in networks subserving multisensory integration, orienting, or arousal 2
  • Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network 2
  • The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioral consequences 2

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Research

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

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2022

3
Research

Basic mechanisms of TMS.

Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society, 2002

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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