The Differential Effects of Transcutaneous Spinal Cord Stimulation (TSS) on Neural Structure Activation

Background Introduction

Transcutaneous Spinal Cord Stimulation (TSS) is a non-invasive neurostimulation technique that applies electrical currents through electrodes on the skin surface to activate neural structures in the spinal cord, thereby eliciting muscle responses. TSS has shown potential in the rehabilitation of spinal cord injuries (SCI), enhancing patients’ motor functions. However, the exact mechanisms of TSS remain incompletely understood, especially how different stimulation waveforms and intensities affect the activation of neural structures. This issue has yet to be thoroughly investigated.

To better understand the mechanisms of TSS, researchers explored the effects of different stimulation waveforms (conventional and high-frequency burst waveforms) and intensities (threshold and suprathreshold) on muscle responses evoked by lumbar TSS. Specifically, this study aimed to answer the following question: Do the neural structures activated by TSS vary with changes in stimulation waveform and intensity? The answer to this question is crucial for optimizing the therapeutic effects of TSS, particularly in restoring motor functions in different muscles.

Research Source

This study was conducted by a research team from Neuroscience Research Australia, the University of New South Wales, Edith Cowan University, and Prince of Wales Hospital. The main authors include Harrison T. Finn, Marel Parono, Elizabeth A. Bye, and others. The research was published in the Journal of Neurophysiology in 2025.

Research Process

1. Research Subjects and Experimental Design

The study recruited 15 healthy adults (9 females, 6 males), all over the age of 18 and with no history of neurological conditions. Participants remained seated during the experiment, with their hip joints flexed at 120 degrees, knee joints flexed at 20 degrees, and ankle joints plantarflexed at 130 degrees. All muscles were at rest.

2. Stimulation Parameters

TSS stimulation was delivered through electrodes placed on the surface of the L1-L3 vertebrae, using two waveforms: - Conventional waveform: A single 400-microsecond biphasic pulse. - High-frequency burst waveform: Ten 40-microsecond biphasic pulses at a frequency of 10 kHz.

Stimulation intensities were divided into threshold and suprathreshold levels. The threshold was defined as the minimum intensity required to elicit a visible muscle response, while the suprathreshold intensity was set to evoke muscle responses with a peak-to-peak amplitude of 5% of the maximal M wave (Mmax).

3. Experimental Procedures

The experiment consisted of the following steps: - Single TSS stimulation: The spinally evoked motor response (SEMR) in the vastus medialis (VM), tibialis anterior (TA), and medial gastrocnemius (MG) was recorded. - Double TSS stimulation: Double stimulations were delivered with an interval of 80 milliseconds to assess the suppression of the second SEMR (postactivation depression). - Paired TMS and TSS stimulation: Transcranial magnetic stimulation (TMS) was paired with TSS to study their interaction on motor neurons. The TMS intensity was set to evoke motor evoked potentials (MEPs) in the VM that were larger than the suprathreshold SEMR.

4. Data Analysis

The effects of stimulation waveform and intensity on the activation of neural structures were analyzed by comparing the latencies and areas of SEMRs, MEPs, and Mmax under different stimulation conditions. Data were processed using Python scripts, and statistical analysis was performed using generalized linear mixed models (GLMM).

Main Results

1. Responses in the Vastus Medialis (VM)

• SEMR latency: The SEMR latency for the VM was short, averaging 8-9 milliseconds, similar to the latency of M waves evoked by femoral nerve stimulation, indicating that TSS primarily activated motor axons.
• Double TSS stimulation: The area of the second SEMR was 20-30% smaller than the first, suggesting minimal activation of sensory axons by TSS.
• Paired TMS and TSS stimulation: No significant facilitation of responses was observed when TMS and TSS reached the motor neuron simultaneously or slightly earlier, further supporting the conclusion that TSS mainly activated motor axons.

2. Responses in the Tibialis Anterior (TA) and Medial Gastrocnemius (MG)

• SEMR latency: The SEMR latencies for the TA and MG were also short, indicating that TSS may have activated both motor and sensory axons.
• Double TSS stimulation: Greater suppression of the second SEMR was observed with suprathreshold stimulation using the conventional waveform, suggesting that the conventional waveform activated more sensory axons.
• Paired TMS and TSS stimulation: Under suprathreshold stimulation, the combined responses for the TA and MG were significantly facilitated when TMS arrived slightly earlier or simultaneously with TSS, further supporting the conclusion that TSS activated sensory axons.

Conclusions and Significance

This study demonstrated that the neural structures activated by transcutaneous spinal cord stimulation (TSS) differ depending on the stimulation waveform and intensity. For the vastus medialis (VM), TSS primarily activated motor axons, while for the tibialis anterior (TA) and medial gastrocnemius (MG), TSS activated both sensory and motor axons. Suprathreshold stimulation and the conventional waveform more effectively activated sensory axons, while the high-frequency burst waveform may have activated more motor axons.

These findings are significant for optimizing the application of TSS in rehabilitation therapy. By adjusting stimulation parameters, target neural structures can be more precisely activated, thereby improving therapeutic outcomes. Additionally, this study provides new insights into the mechanisms of TSS, laying the groundwork for future research.

Research Highlights

1. Cross-muscle differences: The study found that the neural structures activated by TSS varied across different muscles, a finding with important implications for personalized rehabilitation therapy.
2. Impact of stimulation parameters: Suprathreshold stimulation and the conventional waveform more effectively activated sensory axons, providing a basis for optimizing TSS parameters.
3. Innovative experimental design: By combining TMS and TSS paired stimulation, the research team gained deeper insights into the mechanisms of TSS activation of motor neurons.
4. Application of statistical models: The use of generalized linear mixed models (GLMM) ensured the accuracy and reliability of data analysis.

Additional Valuable Information

The limitations of this study include certain assumptions in calculating central conduction times and the lack of control over the SEMR sizes for the TA and MG. Future research could validate these findings by optimizing experimental designs.