Paired Pulse Stimulation TMS and Cortical Excitability

Posted on: April 21, 2022

In a vast number of reports, scientists have shown that transcranial magnetic stimulation (TMS) is a safe technique to be applied in humans. The procedure consists of generating a strong electromagnetic field nearby target cortical neurons for a very short period of time, TMS is delivered in pulses that last for less than a second (ranges from 160 to 400 microseconds). The electromagnetic fields generated with this technology can bypass the resistance of bone without stimulating nociceptors, thus, the stimulation is noninvasive and painless.

TMS can be applied as a single-pulse, most experiments have been done using the motor cortex as a target, and many metrics of cortical function have been obtained using electromyography to obtain results, e.g. conduction time of the motor central pathway, neuronal motor threshold, silent-period duration, recruitment curves, and mapping of muscle representation in the motor cortex can be determined (Chen R., 2000). TMS can also be applied as paired pulses (pp-TMS), with short intervals in between pulses (e.g. 2, 5, 10, 100 milliseconds), several reports have shown these protocols a useful way to examine excitability of cortical neurons.

Pp-TMS has opened new possibilities to understand the cortical organization of neuronal networks, the pool of new information keeps growing larger every year, lots of new findings and more questions have driven the interest of scientists and clinicians. Some of the first protocols were reported in between 1992 and 1995 (Triggs et al. 1992; Kujirai et al. 1993; Hallett, 1995). Paired pulse stimulation has shown to have an effect within the stimulated cortex, where intracortical circuits are responsible for the inhibitory or excitatory responses to the stimulation; the interval time in between the stimuli has a crucial effect in the neuronal networks responding. Protocols using short pulse intervals 1–6 ms; have an inhibitory effect on the motor response, therefore called short interval intracortical inhibition (SICI); at long intervals 50–200 ms, a different type of inhibition occurs, thus named long interval intracortical inhibition, (LICI). The pulse intensities in the paired pulse configuration are different, suggesting that the neurons involved in the responses belong to different networks, which have different biological features (membrane threshold) and that influence the primary motor neurons at layer V, therefore having an effect on the total output of the motor cortex and exhibiting a regulatory behavior on the cortical system (Sanger, et, al. 2001). Studies combining pp-TMS and pharmacological agents have shown that the two forms of intracortical inhibition are most likely modulated by different neurotransmitters (Ziemann et al. 1996a; Werhahn et al. 1999). SICI being primarily mediated by GABA A receptors (Hanajima et al. 1998), and LICI by GABAB receptors (Roick et al. 1993; Siebner et al. 1998; Werhahn et al. 1999).

Pp-TMS has also shown excitatory effects by changing the intensities of the 2 pulses and inter stimulus intervals e.g. intervals in between 8 to 30 milliseconds, have an excitatory effect on the cortical output, so called intracortical facilitation (ICF). If the first pulse is followed, shortly (1-5 miliseconds); by a second pulse at threshold intensity yet another type of facilitation, known as: short interval intra-cortical facilitation (SICF), can be elicited (Tokimuraet al.1996; Ziemannet al.1998b; Rothwell, 1999).

More recent studies have looked into the value of SICI, LICI, and ICF as biomarkers to assess Alzheimer's disease and mild cognitive impairment (Mimura et. al, 2020), others have established the involvement of the motor cortex on Parkinson's disease and the potential value of pp-TMS as an evaluation tool on this condition (Saravanamuttu et. al, 2021).

R-TMS, another form of TMS that uses repetitive pulses, has proven useful to modulate cortical excitability with potential therapeutic in psychiatric and neurological disorders. (Lefaucheur, 2019).

At Jali Medical we offer innovative technology to further develop research. Our pp-TMS devices cover a wide range of options for clinicians and researchers.

About the author

Francisco Benavides, MD

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