Introduction

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) was shown to be a potential complementary rehabilitation intervention for recovery after a spinal cord injury (SCI)¹. The safety and neuromodulatory outcomes of some promising HF-rTMS protocols tested in rodent models of SCI² needs to be further investigated in humans.

Materials / Methods

For this study, we investigated the effects of a HF-rTMS paradigm combined with 30 minutes of targeted hand motor training in individuals with chronic cervical SCI. The therapeutic stimulation protocol were previously published¹. We will present the data obtained from 3 participants with complete and incomplete SCI. The intensity of the HF-rTMS stimuli was adjusted to the session-specific individual resting motor threshold (RMT) measure and was set to induce visible hand twitches. We assessed changes in RMT and motor performance, as the percentage difference in the number of repetitions to perform a given motor task for 10 min, between 1^st (baseline) to the 8^th (mid) and mid to 15^th (last) training session. TMS / rTMS side-effects’ questionnaires were also administered at the end of each session. Brief EMG Burst (BEB)³ monitoring was constant.

Results

The proposed protocol repeated over 15 sessions was safely tested and well-tolerated in 3 SCI individuals. BEB was not detected. Mainly mild and transient headaches and tingling were reported by the participants after the HF-rTMS. Preliminary results reveal the neuromodulatory potential and the benefits on motor function of the therapeutic protocol; with increases in CSE (ΔRMT_KS1 = -5%MSO, ΔRMT_KS2 = -2%MSO) and motor performances (Δrepetition_KS2 = +31%, Δrepetition_KS3 = +5%) comparing between the baseline-to-mid and mid-to-last training sessions.

Discussion

Results suggest the potential of HF-rTMS as an intervention to combine with training for inducing neuroplasticity and boosting recovery after chronic complete and incomplete SCI. These few participants seem to respond differently to the treatment most likely because of the difference in the level and severity of the injury among them, suggesting injury severity-dependent neuroplasticity and function recovery as a result of the combined HF-rTMS and motor training protocol, without adverse effects.

Conclusions

The HF-rTMS combined with motor task training seems to be beneficial in improving corticospinal excitability and upper extremity motor function in individuals with SCI. However, they seem to respond differently to the treatment perhaps due to the level and severity of the injury, suggesting individualized underlying mechanisms.

Acknowledgments: This project has received a precious support from the New York State Department of Health (C34462GG, PI: J. Zhong), the Kessler Foundation and the Tim Reynolds Foundation.

References

1. Brihmat N, Bayram MB, Allexandre D, Saleh S, Yue GH, Guan X, Zhong J, Forrest GF. High-Frequency rTMS Combined with Task-Specific Hand Motor Training Modulates Corticospinal Plasticity in Motor Complete Spinal Cord Injury: A case report. In: 2022 44th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC). IEEE, p. 2385–2389.

2. Boato F, Guan X, Zhu Y, et al. Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration. Sci Transl Med. 2023;15(677):eabq6885. doi:10.1126/scitranslmed.abq6885

3. E. M. Wassermann, “Risk and safety of repetitive transcranial magnetic stimulation : report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation , June 5 – 7 , 1996,” Electroencephalogr. Clin. Neurophysiol., vol. 108, pp. 1–16, 1998

Learning Objectives

1. Demonstrate the HF-rTMS could be used as an adjunct intervention for SCI rehabilitation.

2. Confirm patient-specific underlying mechanisms based on injury level and severity.

3. Demonstrate a translational neuromodulatory protocol for SCI.