Transcranial magnetic stimulation of primary motor cortex elicits an immediate transcranial evoked potential.

BACKGROUND: Transcranial evoked potentials (TEPs) measured via electroencephalography (EEG) are widely used to study the cortical responses to transcranial magnetic stimulation (TMS). Immediate transcranial evoked potentials (i-TEPs) have been obscured by pulse and muscular artifacts. Thus, the TEP peaks that are commonly reported have latencies that are too long to be caused by direct excitation of cortical neurons. METHODS: In 25 healthy individuals, we recorded i-TEPs evoked by a single biphasic TMS pulse targeting the primary motor hand area (M1HAND) or parietal or midline control sites. Sampling EEG at 50 kHz enabled us to reduce the duration of the TMS pulse artifact to a few milliseconds, while minor adjustments of the TMS coil tilt or position enabled us to avoid cranial muscular twitches during the experiment. RESULTS: We observed an early positive EEG deflection starting after approx. 2 ms followed by a series of superimposed peaks with an inter-peak interval of ∼1.1-1.4 ms in multiple electrodes surrounding the stimulated sensorimotor region. This multi-peak i-TEP response was only evoked by TMS of the M1HAND region and was modified by changes in stimulation intensity and current direction. DISCUSSION: Single-pulse TMS of the M1HAND evokes an immediate local multi-peak response at the cortical site of stimulation. Our results suggest that the observed i-TEP patterns are genuine cortical responses evoked by TMS caused by synchronized excitation of pyramidal neurons in the targeted precentral cortex. This notion needs to be corroborated in future studies, including further investigations into the potential contribution of instrumental or physiological artifacts.

From pulse width modulated TENS to cortical modulation: based on EEG functional connectivity analysis.

Modulation in the temporal pattern of transcutaneous electrical nerve stimulation (TENS), such as Pulse width modulated (PWM), has been considered a new dimension in pain and neurorehabilitation therapy. Recently, the potentials of PWM TENS have been studied on sensory profiles and corticospinal activity. However, the underlying mechanism of PWM TENS on cortical network which might lead to pain alleviation is not yet investigated. Therefore, we recorded cortical activity using electroencephalography (EEG) from 12 healthy subjects and assessed the alternation of the functional connectivity at the cortex level up to an hour following the PWM TENS and compared that with the effect of conventional TENS. The connectivity between eight brain regions involved in sensory and pain processing was calculated based on phase lag index and spearman correlation. The alteration in segregation and integration of information in the network were investigated using graph theory. The proposed analysis discovered several statistically significant network changes between PWM TENS and conventional TENS, such as increased local strength and efficiency of the network in high gamma-band in primary and secondary somatosensory sources one hour following stimulation. Our findings regarding the long-lasting desired effects of PWM TENS support its potential as a therapeutic intervention in clinical research.

Alteration in Cortical Activity and Perceived Sensation Following Modulated TENS.

Over the last decades, conventional transcutaneous electrical nerve stimulation (TENS) has been utilized as an efficient rehabilitation intervention for alleviation of chronic pain, including phantom limb pain (PLP). However, recently the literature has increasingly focused on alternative temporal stimulation patterns such as pulse width modulation (PWM). While the effect of non-modulated high frequency (NMHF) TENS on somatosensory (SI) cortex activity and sensory perception has been studied, the possible alteration following PWM TENS at the SI has not yet been explored. Therefore, we investigated the cortical modulation by PWM TENS for the first time and conducted a comparative analysis with the conventional TENS pattern. We recorded sensory evoked potentials (SEP) from 14 healthy subjects before, immediately, and 60 min after TENS interventions (PWM and NMHF). The results revealed suppression of SEP components, theta, and alpha band power simultaneously associated with the perceived intensity reduction when the single sensory pulses applied ipsilaterally to the TENS side. The reduction of N1 amplitude, theta, and alpha band activity occurred immediately after both patterns remained at least 60 min. However, the P2 wave was suppressed right after PWM TENS, while NMHF could not induce significant reduction immediately after the intervention phase. As such, since PLP relief has been shown to be correlated with inhibition at somatosensory cortex, we, therefore, believe that the result of this study provides further evidence that PWM TENS may also be potential therapeutic intervention for PLP reduction. Future studies on PLP patients with PWM TENS sessions is needed to validate our result.

Short-Term Suppression of Somatosensory Evoked Potentials and Perceived Sensations in Healthy Subjects Following TENS.

Transcutaneous electrical nerve stimulation (TENS) has been reported to alleviate pain in chronic pain patients. Currently, there is limited knowledge how TENS affects can cause cortical neuromodulation and lead to modulation of non-painful and painful sensations. Our aim was therefore to investigate the effect of conventional, high-frequency TENS on cortical activation and perceived sensations in healthy subjects. We recorded somatosensory evoked potentials (SEPs) and perceived sensations following high-frequency TENS (100 Hz) in 40 healthy subjects (sham and intervention group). The effect of TENS was examined up to an hour after the intervention phase, and results revealed significant cortical inhibition. We found that the magnitude of N100, P200 waves, and theta and alpha band power was significantly suppressed following the TENS intervention. These changes were associated with a simultaneous reduction in the perceived intensity and the size of the area where the sensation was felt. Although phantom limb pain relief previously has been associated with an inhibition of cortical activity, the efficacy of the present TENS intervention to induce such cortical inhibition and cause pain relief should be verified in a future clinical trial.

Modulation of Corticospinal Excitability by Two Different Somatosensory Stimulation Patterns; A Pilot Study.

Following amputation, almost two-thirds of amputees experience unpleasant to painful sensations in the area of the missing limb. Whereas the mechanism of phantom limb pain (PLP) remains unknown, it has been shown that maladaptive cortical plasticity plays a major role in PLP. Transcutaneous electrical nerve stimulation (TENS) generating sensory input is believed to be beneficial for PLP relief. TENS effect may be caused by possible reversing reorganization at the cortical level that can be evaluated by changes in the excitability of the corticospinal (CS) pathway. Excitability changes are dependent on the chosen stimulation patterns and parameters. The aim of this study was to investigate the effect of two TENS patterns on the excitability of the CS tract among healthy subjects. We compared a non-modulated TENS as a conventional pattern with pulse width modulated TENS pattern. Motor evoked potentials (MEPs) from APB muscles of stimulated arm (TENS-APB) and contralateral arm (Control-APB) were recorded. We applied single TMS pulses on two subjects for each TENS pattern. The results showed that both patterns increase the CS excitability, while the effects of the conventional TENS is stronger. However, the amplitude of MEPs from control-APB after TENS delivery remained almost the same.Clinical Relevance- The primary results revealed changes in the activity of CS pathway for both patterns. A future study on a larger population is needed to provide strong evidence on the changes in CS excitability. The evaluation part with more factors such as changes in intracortical inhibition (ICI) may be beneficial to find an optimal modulated TENS pattern to enhance pain alleviation process in PLP.