Abstract
Paired associative stimulation (PAS) combines transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) to induce plastic changes in the corticospinal tract. PAS employing single 0.2-Hz TMS pulses synchronized with the first pulse of 50–100 Hz PNS trains potentiates motor-evoked potentials (MEPs) in a stable manner in healthy participants and enhances voluntary motor output in spinal cord injury (SCI) patients. We further investigated the impact of settings of this PAS variant on MEP potentiation in healthy subjects. In experiment 1, we compared 0.2-Hz vs 0.4-Hz PAS. In experiment 2, PNS frequencies of 100 Hz, 200 Hz, and 400 Hz were compared. In experiment 3, we added a second TMS pulse. When compared with 0.4-Hz PAS, 0.2-Hz PAS was significantly more effective after 30 minutes (p = 0.05) and 60 minutes (p = 0.014). MEP potentiation by PAS with 100-Hz and 200-Hz PNS did not differ. PAS with 400-Hz PNS was less effective than 100-Hz (p = 0.023) and 200-Hz (p = 0.013) PNS. Adding an extra TMS pulse rendered PAS strongly inhibitory. These negative findings demonstrate that the 0.2-Hz PAS with 100-Hz PNS previously used in clinical studies is optimal and the modifications employed here do not enhance its efficacy.
Highlights
Several studies have recently demonstrated the potential therapeutic applications of non-invasive brain stimulation, including transcranial magnetic stimulation (TMS) [1, 2]
We further investigated the impact of settings of this Paired associative stimulation (PAS) variant on motor-evoked potentials (MEPs) potentiation in healthy subjects
We have shown in several case reports and series that PAS with a high-frequency peripheral component (0.2-Hz TMS paired with 100-Hz peripheral nerve stimulation (PNS)) enhances motor output of paretic or paralytic muscles in patients with chronic incomplete spinal cord injury (SCI) [16,17,18,19]
Summary
Several studies have recently demonstrated the potential therapeutic applications of non-invasive brain stimulation, including transcranial magnetic stimulation (TMS) [1, 2]. Non-invasive depolarization of neuronal membranes by TMS initiates action potentials and enables targeting and modulation of activity of cortical neuronal ensembles. Activation or suppression of neuronal activity provides therapeutic opportunities for numerous neurological conditions [1]. Paired associative stimulation (PAS) combines TMS of the primary motor cortex (M1). With electrical peripheral nerve stimulation (PNS) of the contralateral extremities.
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