Individuals with cervical spinal cord injury (SCI) experience significant respiratory impairments that drive high rates of morbidity and mortality. Most cervical SCIs are incomplete, variably sparing spinal circuitry to drive respiratory motor neurons. However, these spared pathways do not allow sufficient recovery of respiratory muscles to support breathing to pre-injury levels. Transcutaneous spinal direct current stimulation (tsDCS) is a non-invasive neuromodulation approach that applies weak electrical current to the spinal cord via skin electrodes. Evidence indicates that tsDCS can modulate spared spinal circuit activity, thereby changing motor drive to muscles. In healthy humans, tsDCS has been shown to increase excitability of descending tracts to motor neurons innervating the diaphragm muscle. However, tsDCS has never been tested in the context of spinal injuries that have reduced motor output. In the present study, we hypothesized that tsDCS can augment respiratory output following cervical SCI. We also tested the efficacy of two DCS variables (polarity and current dose). Experimentally, adult male Sprague Dawley rats (n=17, 12 weeks) were implanted with bilateral EMG electrodes and received a C2 hemisection after pre-injury testing. EMG activity was recorded during spontaneous breathing under isoflurane anesthesia. Five stimulation protocols were evaluated, including cathodal and anodal tsDCS at 1 or 3 mA and a control leg stimulation, both before injury and during the acute phase (2 to 3 weeks post injury). Each session involved 20 mins of stimulation with at least two days between sessions. There was a treatment effect of stimulation on ipsilateral and contralateral peak diaphragm EMG amplitude in both pre-injury (p< 0.001; p< 0.001) and acute (p< 0.001; p< 0.001) phases. When comparing polarity, 3mA cathodal stimulation was most effective at increasing ipsilateral EMG activity in pre-injury (26.5±10.3% of baseline, p=0.01) and acute injury (11.4±2.4% of baseline, p=0.02) phases. In the acutely injured animals, this increase was sustained at the 20-minute timepoint during stimulation. 3mA stimulation showed a more robust increase in peak EMG amplitude compared to 1mA stimulation, demonstrating a dose-response relationship in both pre-injury (p=0.001) and acute injury (p=0.02) conditions. Interestingly, on the “intact” contralateral side, 3 mA anodal stimulation produced an inhibitory decrease in EMG amplitude in the injured animals following stimulation (p=0.02). Cathodal tsDCS did not affect contralateral diaphragm EMG activity at either pre-injury or acute time points. These findings indicate that electrode polarity and current intensity shape the effects of tsDCS on diaphragm motor output after cervical SCI. This work provides the first evidence that noninvasive spinal DCS can be used to augment respiratory motor drive in rodent models of cervical SCI. Future studies will evaluate whether pairing tsDCS with synergistic neuromodulatory interventions can support durable respiratory recovery after injury. Funding: 1K99NS133388-01A1 (SR), Parker B Francis Foundation Fellowship (SR) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Rease et al. (Fri,) studied this question.