The effect of TMS is entirely due to electric current driven by the induced E-field. This current accumulates charge at cell membranes and neurons in the path of an E-field depolarize. Depolarization initiates synchronous action potentials, and the neurons will “fire”. These TMS-initiated action potentials propagate along axons in precisely the same manner as naturally occurring ones. Once a stimulation session has finished, any resulting longer-term effects in the brain are 100% endogenous. In other words, TMS as a therapy can be considered to be completely natural.
It is important to realize that neurons are excited at lower thresholds when applied voltages induce currents oriented along, rather than across, an axon. Since the trajectories of pyramidal tract axons are one of the main activation mechanisms, the cortical response is very sensitive to the orientation of the coil. Any induced E-field (via the coil) can be moved in the three dimensions (x, y, z) of space, but also rotated and tilted up or sideways (aviators use the terms yaw, pitch and roll).
Repeating a TMS mapping or therapy session with precision requires replicating the positioning of the coil in ALL six dimensions with a high degree of accuracy. Needless to say, repeating the positioning of a coil is very challenging to perform without the software-based guidance provided in the Nexstim systems. Without feedback, such as a specific muscle MEP, replicating with precision the position of a hand-held TMS coil is nigh impossible without navigation.*
Stimulating the motor cortex
When a single TMS pulse of TMS is applied to the scalp over the primary motor cortex, a motor evoked potential (MEP) can be generated in a contralateral muscle. This MEP can be observed as a twitch of the muscle and measured by EMG using surface electrodes.
The use of repeated TMS stimuli to the same target in the brain is called repetitive TMS (rTMS). An rTMS E-field can have either excitatory or inhibitory effects, depending on the frequency and duration of the pulses. High frequency rTMS, for example at 10 Hz, excites the cortical volume in focus and is the basis of the effects seen in the treatment of major depressive disorder (MDD) when TMS is targeted to the left DLPFC as well as in chronic pain therapy, when TMS is targeted to the motor cortex. The transient inhibitory effect of short-duration bursts of TMS is the basis of speech mapping – localization of cortical areas that do not contain essential speech function. Low frequency TMS, for example 1Hz, has an inhibitory effect on the underlying cortex in focus. The longer-term inhibitory effects of low-frequency TMS targeted to the motor cortex are being studied for stoke rehabilitation.
* Conforto AB et al. Impact of coil position and electrophysiological monitoring on determination of motor thresholds to transcranial magnetic stimulation. Clin Neurophysiol. 2004 Apr;115(4):812-9.