Trigeminal nerve stimulation modulates brainstem more than cortical excitability in healthy humans

Abstract

Multiple sites in the central nervous system (CNS) have been hypothesized to explain the beneficial effects of transcutaneous trigeminal nerve stimulation (TNS) on several disorders. This work investigated the acute effects of TNS on the excitability of brainstem and intracortical circuits, as well as on sensorimotor integration processes at cortical level in physiological conditions. Brainstem excitability was evaluated in seventeen healthy subjects measuring the R1 and R2 areas of the blink reflex (BR) and its recovery cycle, with cortical excitability and sensorimotor integration assessed by probing short-interval (SICI) and long-interval (LICI) intracortical inhibition, with short-interval (SICF), intracortical facilitation (ICF), short-latency (SAI) and long-latency (LAI) inhibition measuring motor potentials evoked in the first dorsal interosseous muscle by TMS of the contralateral motor cortex. Neurophysiological parameters were assessed, in seventeen healthy subjects, before and after cyclic 20-min TNS delivered bilaterally to the infraorbital nerve. After TNS, the area of the R2 was significantly reduced (p = 0.018). By contrast, R1 area and R2 recovery cycle were unaffected. Similarly, SICI, ICF, LICI, SICF, SAI and LAI appeared unaltered after TNS. These data suggest that, in normal subjects, TNS mainly acts on brainstem polysynaptic circuits mediating the R2 component of the BR and plays a minor role in modifying the activity of higher-level structures involved in the R2 recovery cycle and in modulation of cortical excitability. A further investigation of a chronic TNS-induced effect may disclose a higher potential for TNS in producing measurable after effects on its CNS targets.

Transcutaneous trigeminal nerve stimulation induces a long-term depression-like plasticity of the human blink reflex

“…In light of the similar effects induced by SON and infraorbital nerve (ION) stimulation (DeGiorgio et al 2006;Pop et al 2011) and of the effectiveness of ION stimulation on the R2 component of the BR (Mercante et al 2015), in the present study TNS was delivered to the ION through disposable, hypoallergenic, silver gel self-adhesive stimulating electrodes (30 mm diameter, SEI-EMG s.r.l. Cittadella, IT) with the cathode placed over the ION foramina and the anode 2 cm lateral, and connected to a Winner ® stimulator (Fisioline biomedical instrumentation, Verduno, CN, IT).…”

“…The aim of experiment 2 was to verify whether the prolonged inhibition of the R2 component of the BR, observed following TNS administration (Mercante et al 2015), could be due to a reflex habituation. Eleven participants (six females and five males; 26.1 ± 4.2 years old; range 20-33 years) underwent an ineffective 20-min bilateral TNS (sham-TNS).…”

“…A TNS protocol, which proved to be able to inhibit the area of the R2 component of the BR (Mercante et al 2015), was used. It consisted of asymmetric biphasic square-wave pulses (0.25-ms duration, 120 Hz) with an electrical mean equal to zero delivered in a cyclic modality (30-s ON and 30-s OFF) for 20 min, which was demonstrated to inhibit the R2 area (Mercante et al 2015).…”

“…It consisted of asymmetric biphasic square-wave pulses (0.25-ms duration, 120 Hz) with an electrical mean equal to zero delivered in a cyclic modality (30-s ON and 30-s OFF) for 20 min, which was demonstrated to inhibit the R2 area (Mercante et al 2015). In each subject, perceptual and pain thresholds were bilaterally calculated.…”

“…In fact, an LTP-or an LTD-like effect was observed when the burst coincided or preceded the reflex blink, respectively (Mao and Evinger 2001). Another method able to alter brain stem excitability is a cyclic 20-min TNS, which recently has been proved to depress significantly the area of the R2 component of the BR, without modifying its recovery cycle (Mercante et al 2015). Plastic mechanisms mediating this TNS-induced effect have been hypothesized, but evidence of this phenomenon is still lacking.…”