Posted on: July 14, 2022
Monophasic pseudo square pulses have been used in transcranial magnetic stimulation (TMS) since the first devices were created for this purpose, most likely because monophasic electric pulses were used already as a tool to electrically stimulate peripheral nerves and brain cortex. Many reports have used monophasic devices to study cortical physiological effects of the magnetic fields and to describe the behavior of neuronal networks, in contrast very few have studied the effect of biphasic pulses on cortical neuronal networks. In the latest years rTMS (which is composed mainly by biphasic pulses) have gained more attention due to its effect on neuronal plasticity and especially after FDA’s approval for the clinical use of rTMS on Major Depressive Disorder, Obsessive Compulsive Disorder and its potential use other cognitive and neurological pathologies. Biphasic stimulation using relatively high frequencies (>5 Hz) had been reported to increase cortical excitability, whereas low frequencies rTMS (<1 Hz) have shown a decrease of cortical excitability for an extended period of time (Chen et al., 1997; Chen, 2000)
Few studies have been designed to compare the cortical effects of monophasic vs. biphasic stimulation, some technical limitations used to include the frequency at which the monophasic stimulation could be delivered. In 2006, Sommer et al., reported a comparison of single pulses, monophasic, biphasic and half sine wave forms, on well understood measures of cortico-spinal excitability. Their results showed that biphasic single pulses evoked lower motor thresholds, shortened MEP latencies and evoked the longer silent period cortical effects, their conclusions were that the latest portions of the sinus waves in the biphasic pulse were responsible for the extra effect seen in the cortical measures.
In 2008 Hosono et al., reported a comparison of rTMS monophasic vs biphasic at rather low frequencies (0.2, 0.8 Hz, and 0.2, 1Hz respectively) over the premotor cortex, the authors explored the effects of the stimulation on somatosensory evoked potentials and cerebral blood flow, and concluded that monophasic stimulation was more effective than biphasic rTMS to evoke cortical changes, while the 0.2 vs 0.8 Hz frequency did show no statistically significant difference. The authors discussed the potential interneuronal cancellation effects of the biphasic stimuli, while others had previously reported frequency dependent effects using biphasic stimulation at 1-5 Hz. (Siebner et al., 2001). By that time it was not possible to test short intracortical inhibition, (SICI), long intracortical inhibition (LICI) or other intracortical measures of neuronal function, that require short interval paired pulses, because of technical limitations to the monophasic pulse repetition rate.
Other groups have investigated the effects of higher frequencies, Arai applied a total of a thousand pulses, in a train of 10 Hz, 100 pulses delivered every minute (ten trains for 10min). Simulating the motor cortex and recording the effects on muscles of the hand, both at rest and while executing a mild level of contraction. This group studied the effects of the intervention during 30 minutes after the pulses were delivered. Their results suggest that enhancement after rTMS occurs at the motor cortex. Monophasic rTMS has a stronger after-effect on motor cortical excitability than biphasic rTMS. “This is probably because monophasic pulses preferentially activate a relatively uniform population of neurons oriented in the same direction and their effects summate more readily than biphasic rTMS activating differently oriented neurons at slightly different timings altogether” Arai et al., 2007.
Ulterior studies, have focused more in the shape of the biphasic wave, In a very elegant study Sommer et al., 2018, focused on a more quadratic biphasic pulse, they used a controllable TMS device (cTMS) to eliminate the difficulty of studying the interaction between the two phases with a cosine waveform, (that most rTMS machines present). To understand their results we should bring back the concept of the complex organization of neuronal networks in the motor cortex, multiple layers of neurons interact with each other, some to inhibit and some to facilitate the function of primary motor neuron pools (which are the final cortical effectors), this networks seem to be anatomically aligned and seem to respond differently to the direction of the electromagnetic fields generated by the TMS coils. When the electromagnetic field moves backwards, over the motor cortex, it would excite one type of neurons and a different set of neurons respond to currents that run frontwards, since the biphasic most asymmetric pulses used in this study would have acted as monophasic pulses running in opposite directions, the authors concluded that: “At threshold, the reverse phase of an initially posterior-anterior pulse increases threshold compared with monophasic stimulation. At higher intensities, the reverse phase on the biphasic wave begins to activate anterior posterior-sensitive neurons and increase the effectiveness of stimulation above that of a "monophasic" posterior-anterior pulse. Biphasic stimulation with initially anterior-posterior pulses is dominated at threshold by activation produced by the lower threshold reverse (posterior-anterior) phase”.
While the neuroscience field keeps exploring the advantages of rTMS, and our understanding of its impact is expanding, technology is also offering more and more alternatives providing researchers with better tools to approach complex disorders. Soon devices capable of strong monophasic pulses with high frequencies would be available to be synced with special brain function recording techniques (EEG, fMRI, etc.), allowing comparison among other variables like high frequency stimulation and its effects on cortical excitability and plasticity in multiple areas of the cortex and the impact of these changes at deeper structures of the brain and their pathways.
At Jali Medical, we offer innovative technology to further support research. Also, noting the pp-TMS devices we have on our product line cover a wide range of options for clinicians and researchers. We are happy to share our insights, please let us know the convenient time to setup a conference call. Contact Us
Francisco Benavides, MD
Neuroscientist
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