Precise Modulation Strategies for Transcranial Magnetic Stimulation: Advances and Future Directions

Abstract

Transcranial magnetic stimulation (TMS) is a popular modulatory technique for the noninvasive diagnosis and therapy of neurological and psychiatric diseases. Unfortunately, current modulation strategies are only modestly effective. The literature provides strong evidence that the modulatory effects of TMS vary depending on device components and stimulation protocols. These differential effects are important when designing precise modulatory strategies for clinical or research applications. Developments in TMS have been accompanied by advances in combining TMS with neuroimaging techniques, including electroencephalography, functional near-infrared spectroscopy, functional magnetic resonance imaging, and positron emission tomography. Such studies appear particularly promising as they may not only allow us to probe affected brain areas during TMS but also seem to predict underlying research directions that may enable us to precisely target and remodel impaired cortices or circuits. However, few precise modulation strategies are available, and the long-term safety and efficacy of these strategies need to be confirmed. Here, we review the literature on possible technologies for precise modulation to highlight progress along with limitations with the goal of suggesting future directions for this field.

Keywords: Coil location; Individual treatment paradigm; Modulation strategies; Precise stimulation target; Transcranial magnetic stimulation.

Fig. 1

The modulatory effects of circular and figure-of-eight coils in TMS. A The modulation effect of a circular coil has high penetration power, but the activated brain area is not focal. B The modulation effect of a figure-of-eight coil is more focal but has limited penetration. C TMS effects may result from active initiation of action potentials in stimulated neurons or alterations in brain networks.

Fig. 2

Stimulation protocols for TMS. A The initial current through TMS coils can be delivered as a single pulse, paired pulses, or a train of pulses (modified from ref. [164]). B A diphasic current pulse. C In ppTMS, the interstimulus intervals (ISIs) between the test stimulus (TS) and the conditioning stimulus (CS) can be changed to allow different stimulation effects. D The TBS pattern consists of a burst of three 50-Hz pulses in trains repeated every 200 ms. E QPS consists of repeated trains of four monophasic TMS pulses, and the ISIs can be changed. F PAS consists of repetitive low-frequency pairings of electrical stimulation of a peripheral nerve with TMS over the contralateral M1.

Fig. 3

Temporal and spatial resolution for modulatory effects of TMS patterns and neuroimaging techniques, which are helpful for evaluating the online and offline responses to TMS modulation.

Fig. 4

Flow diagram for identifying potential precise TMS strategies.