# Heart rate variability in patients with incomplete spinal cord injury during a single session of paired associative stimulation

## TL;DR

This study examines heart rate variability in spinal cord injury patients during a single session of paired associative stimulation to assess cardiovascular effects and pain responses.

## Contribution

The study is the first to investigate cardiovascular effects of high-PAS in patients with incomplete spinal cord injury using HRV.

## Key findings

- No signs of sympathetic nervous system activation were detected during high-PAS.
- Moderate parasympathetic activation was observed during high-PAS, similar to findings in healthy participants.

## Abstract

Heart-rate variability (HRV) reflects the balance between sympathetic and parasympathetic nervous systems and is commonly used as a biomarker for the state of the autonomous nervous system (ANS). Acute pain can also be detected by HRV. We applied a single session of paired-associative stimulation (high-PAS) combining high-intensity transcranial magnetic stimulation (TMS) and high-frequency peripheral-nerve stimulation (PNS) on patients with incomplete cervical spinal-cord injury (SCI). High-PAS has shown promising results in improving motor function after incomplete SCI. The cardiovascular effects of high-PAS have not been studied in patients with SCI. We used HRV to record any pain or stress-related reactions in patients with SCI and as an indicator for cardiovascular effects of high-PAS. Twelve patients with cervical SCI received a 20-min single session of high-PAS. HRV was recorded continuously from the 15-min rest period before the stimulation until the end of the 60-min follow-up period after the stimulation. Five-minute sections at the timepoints of PRE, STIM, POST, POST30, and POST60 min after the stimulation were analyzed. Although two patients reported uncomfortable sensations and one reported slight pain during the stimulation, no signs of increase in sympathetic nervous system activation were detected. Instead, we observed moderate parasympathetic activation occurring during the high-PAS, similar to our previous findings in healthy participants.

The online version contains supplementary material available at 10.1038/s41598-025-25802-x.