Optimal peripheral nerve stimulation intensity for paired associative stimulation with high-frequency peripheral component in healthy subjects

Abstract

Paired associative stimulation (PAS) with high-frequency peripheral nerve stimulation (PNS), called “high-PAS”, induces motor-evoked potential (MEP) potentiation in healthy subjects and improves muscle activity and independence in incomplete spinal cord injury patients. Data on optimal PNS intensity in PAS are scarce. In a high-PAS protocol, PNS intensity is defined as “minimal intensity required to produce F-responses”. We sought to further refine this definition and to investigate how PNS intensity affects PAS outcome. Two experiments were performed on 10 healthy subjects where MEP amplitude change was measured 0, 30, and 60 min after PAS. In the first experiment, the intensity required to achieve 7/10 persistence of F-responses was used to define PNS intensity level. In the second experiment, we used the intensity required to achieve 1/10 persistence (“baseline”). In addition, we applied this intensity at + 25%, − 25%, and − 50% levels. In the first experiment, PAS did not produce significant MEP potentiation. In the second experiment, PAS produced statistically significant MEP potentiation, with PNS intensity of “baseline” and “baseline − 25%” levels but not at + 25% or − 50% levels. In conclusion, for PAS utilizing high-frequency PNS, the intensity required to achieve 1/10 F-response persistence or the intensity 25% lower produces significant MEP potentiation in healthy subjects.

Repetitive sensorimotor mu-alpha phase-targeted afferent stimulation produces no phase-dependent plasticity related changes in somatosensory evoked potentials or sensory thresholds

“…Second, on the other hand, using PES triplets instead of single pulses may have also led to a reduction of temporal precision and prevented the proposed mechanisms of phase-dependent plasticity to take effect. However, given the effective induction of LTP-like plasticity using mu-alpha trough targeted 100 Hz TMS triplets [ 6 ] as well as the successful use of high-frequency bursts in a novel paired associative stimulation (PAS) protocol [ 40 , 41 ], this choice is unlikely responsible for the complete lack of phase-specific after-effects observable in this study. Nonetheless, it should be noted in that previous work using 100 Hz TMS triplets, the first of the three pulses pulse was applied at the target phase angle while the following two pulses already fell into the beginning of the rising phase of the mu-alpha cycle, a phase that was later shown to be even more excitable than the very trough [ 42 ].…”

The effect of paired associative stimulation with a high-intensity cortical component and a high-frequency peripheral component on heart rate and heart rate variability in healthy subjects

“…Stimulation (Dantec Keypoint® Natus Medical Incorporated, California, USA) was applied to the tibial nerve, which is behind the left medial malleolus. Stimulation intensity was individually determined during the same session with TMS parameters: the lowest intensity where F-responses were detectable was used for stimulation ( 39 ). Local anesthesia using 5% lidocaine/prilocaine (EMLA) ointment was offered to the participants to reduce the effect of the sensation of the pricking skin associated with PNS stimulation ( 40 ).…”

The effects of music combined to paired associative stimulation on motor-evoked potentials and alertness in spinal cord injury patients and healthy subjects

“…Stimulation was applied to the tibial nerve behind the left malleolus in healthy subjects and to the median nerve in the middle of the palmar side of the wrist in SCI patients. Stimulation intensity was set individually to the lowest intensity where F-responses were detectable when recorded with 1-ms pulses, as previously described 52 . For F-latency determination required for ISI calculation, 0.2-ms pulses at supramaximal intensity were applied and F-responses recorded from the AH for healthy subjects or APB for patients, and minimum latency was determined.…”

“…During PAS, navigated TMS (eXimia magnetic stimulator, Nexstim Ltd, Helsinki, Finland) was delivered using single pulses at 100% of the maximum stimulator output, corresponding to 172 V/m ± 2 measured 25 mm below the figure-of-eight coil (Nexstim NBS manual) to AH or APB hotspot determined as described above. ISI between TMS pulse and the first train of the PNS pulse was calculated individually by the formula [F latency-MEP latency] to make the stimuli coincide at the spinal cord level as described previously 52 . F latency and MEP latency determination is described above.…”