Transspinal Focused Ultrasound Suppresses Spinal Reflexes in Healthy Rats

Abstract

Objectives Low-intensity, focused ultrasound (FUS) is an emerging noninvasive neuromodulation approach, with improved spatial and temporal resolution and penetration depth compared to other noninvasive electrical stimulation strategies. FUS has been used to modulate circuits in the brain and the peripheral nervous system, however, its potential to modulate spinal circuits is unclear. In this study, we assessed the effect of trans-spinal FUS (tsFUS) on spinal reflexes in healthy rats. Materials and methods tsFUS targeting different spinal segments was delivered for 1 minute, under anesthesia. Monosynaptic H-reflex of the sciatic nerve, polysynaptic flexor reflex of the sural nerve, and withdrawal reflex tested with a hot plate were measured before, during, and after tsFUS. Results tsFUS reversibly suppresses the H-reflex in a spinal segment-, acoustic pressure- and pulse-repetition frequency (PRF)-dependent manner. tsFUS with high PRF augments the degree of homosynaptic depression of the H-reflex observed with paired stimuli. It suppresses the windup of components of the flexor reflex associated with slower, C-afferent, but not faster, A- afferent fibers. Finally, it increases the latency of the withdrawal reflex. tsFUS does not elicit neuronal loss in the spinal cord. Conclusions Our study provides evidence that tsFUS reversibly suppresses spinal reflexes and suggests that tsFUS could be a safe and effective strategy for spinal cord neuromodulation in disorders associated with hyperreflexia, including spasticity after spinal cord injury and painful syndromes.

Abstract via europepmc.

Flags from extraction

• exposures[0].unspecified_domain.pressure_kpa — 1.48 MPa given for all subsequent experiments; voltage-to-pressure calibration was in degassed water, but the paper does not say 1.48 MPa is a free-field value.
• exposures[1].free_field.pressure_kpa — Earlier experiments used 'different pressure levels' not stated per condition; pressure not reported for DRG, T10 and Sa exposures.
• exposures[0].timing.pulse_duration_ms — Pulse duration (200 us burst) is from the Fig. 1 legend, stated for burst mode 'at different interburst intervals'; with PRF 100 Hz and 40% duty cycle 200 us would not give 40%, so it may not apply to the 100 Hz condition.
• exposures[0].timing.pulse_repetition_frequency_hz — PRF 2 kHz and 100 Hz both used; PRF 100 kHz also appears once in the text (likely a typo for 100 Hz).
• n_subjects — 35 rats in total; some rats had several sessions with different parameters, and group sizes vary across experiments.
• sham_type — Sham stimulation is mentioned for the hot plate test and histology (sham-treated animals) but how it was produced is not described.
• exposures[0].target.terms — Spinal levels mapped by the authors to vertebrae (MN segment T13, DRG L5, T10 at T9, Sa at S2); term choice is an interpretation.