Abstract
Respiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease. We hypothesized that a stimulation paradigm using temporal interference (TI) could restore breathing in such conditions. Following opioid overdose in rats, two high frequency (5000 Hz and 5001 Hz), low amplitude waveforms delivered via intramuscular wires in the neck immediately activated the diaphragm and restored ventilation in phase with waveform offset (1 Hz or 60 breaths/min). Following cervical spinal cord injury (SCI), TI stimulation via dorsally placed epidural electrodes uni- or bilaterally activated the diaphragm depending on current and electrode position. In silico modeling indicated that an interferential signal in the ventral spinal cord predicted the evoked response (left versus right diaphragm) and current-ratio-based steering. We conclude that TI stimulation can activate spinal motor neurons after SCI and prevent fatal apnea during drug overdose by restoring ventilation with minimally invasive electrodes.
Highlights
Respiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease
The temporal interference (TI) stimulation paradigm activated the diaphragm in all animals tested (Fig. 1d), and the magnitude of the TIevoked diaphragm burst was considerably greater than the spontaneously occurring EMG burst associated with inspiration
Breathing is fundamental to life and can be severely compromised in many neuromuscular diseases and injuries, as well as drug overdose
Summary
Respiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease. Simple and non-invasive electrical stimulation methods could provide health care professionals with an alternative or backup solution for restoring breathing if current approaches are ineffective, or could provide a user with no or limited medical training an option for restoring breathing efforts For these reasons, we aimed to determine if the principles of temporal interference (TI)[6] could be used to immediately restore diaphragm muscle activity sufficient to restore ventilation and sustain life following opioid overdose. Our second hypothesis was that TI electric fields could be steered to the ventral spinal cord to directly activate phrenic motor neurons, thereby restoring activity in the paralyzed diaphragm after cervical SCI To this end, in vivo neurophysiological and pharmacologic methods in rats were complimented with in silico computational modeling based on electromagnetic simulations and response functions obtained from the neurophysiological data. TI stimulation for targeted activation of neuronal populations at distance from the electrodes could revolutionize treatments for a range of neurologic disorders[21]
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