Porcine Model of Cerebral Ischemic Stroke Utilizing Intracortical Recordings for the Continuous Monitoring of the Ischemic Area.

PURPOSE: Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time resolution in pigs. We employed electrophysiological measurements to obtain quick feedback on neural function, which might be useful for screening, e.g., for the optimal dosage and timing of agents prior to further pre-clinical evaluation. METHODS: Micro-electrode arrays containing 16 (animal 1) or 32 electrodes (animal 2-7) were implanted in the primary somatosensory cortex of seven female pigs, and continuous electrical stimulation was applied at 0.2 Hz to a cuff electrode implanted on the ulnar nerve. Ischemic stroke was induced after 30 min of baseline recording by injection of endothelin-1 onto the cortex adjacent to the micro-electrode array. Evoked responses were extracted over a moving window of 180 s and averaged across channels as a measure of cortical excitability. RESULTS: Across the animals, the cortical excitability was significantly reduced in all seven 30 min segments following endothelin-1 injection, as compared to the 30 min preceding this intervention. This difference was not explained by changes in the anesthesia, ventilation, end-tidal CO2, mean blood pressure, heart rate, blood oxygenation, or core temperature, which all remained stable throughout the experiment. CONCLUSIONS: The animal model may assist in maturing neuroprotective approaches by testing them in an accessible model of resemblance to human neural and cardiovascular physiology and body size. This would constitute an intermediate step for translating positive results from rodent studies into human application, by more efficiently enabling effective optimization prior to chronic pre-clinical studies in large animals.

Morphology and morphometry of the ulnar nerve in the forelimb of pigs.

The knowledge of the morphology and morphometry of peripheral nerves is essential for developing neural interfaces and understanding nerve regeneration in basic and applied research. Currently, the most adopted animal model is the rat, even though recent studies have suggested that the neuroanatomy of large animal models is more comparable to humans. The present knowledge of the morphological structure of large animal models is limited; therefore, the present study aims to describe the morphological characteristics of the Ulnar Nerve (UN) in pigs. UN cross-sections were taken from seven Danish landrace pigs at three distinct locations: distal UN, proximal UN and at the dorsal cutaneous branch of the UN (DCBUN). The nerve diameter, fascicle diameter and number, number of fibres and fibre size were quantified. The UN diameter was larger in the proximal section compared to the distal segment and the DCBUN. The proximal branch also had a more significant number of fascicles (median: 15) than the distal (median: 10) and the DCBUN (median: 11) segments. Additionally, the mean fascicle diameter was smaller at the DCBUN (mean: 165 µm) than at the distal (mean: 197 µm) and proximal (mean: 199 µm) segments of the UN. Detailed knowledge of the microscopical structure of the UN in pigs is critical for further studies investigating neural interface designs and computational models of the peripheral nervous system.

Referred Sensation Areas in Bilateral Upper Limb Amputee.

Phantom limb pain (PLP) following amputation considerably reduces the quality of life, given a difficult to treat pain of highly variate profile. The loss of sensory input induces a complex pattern of neuroplastic changes of the sensory neural pathways and their central projections. Referred sensation areas (RSAs) may occur on the stump as a consequence of amputation, providing a direct path towards the altered central sensory projections. Modulated electrical stimulation of RSAs was investigated in a long-term experiment in the case of a 62 years-old participant with bilateral upper limb amputation due to traumatic injury. RSAs were investigated using mechanical (vibration and pressure) and electrical stimuli over five sessions within a five weeks period. Further test of sensations induced by steady state and modulated electrical stimuli was performed during additional 4 sessions. Location and features of RSAs were highly dependent on the type of stimulus and time of delivery between sessions.Clinical Relevance- The case study presents a variety of types and locations of the sensation induced by electrical and mechanical stimuli that may eventually be used as artificially generated sensory input as individualized alternative form of therapy for PLP alleviation. Furthermore, possible multichannel stimulus delivery on RSAs on both arms and the cross-over effect of the bilateral amputation in perception of the induced sensation in the opposite phantom hand may be considered in dedicated design of an experimental setup that may possibly help investigation of mechanisms for PLP.

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.

On determining the mechanical nociceptive threshold in pigs: a reliability study.

Background: A pressure algometer is a valuable tool for assessing the mechanical nociceptive threshold (MNT) in clinical pain studies. Recent research has turned to large animal models of pain because of the closer anatomy and physiology to humans. Although the reliability and usefulness of the MNT have been extensively validated in humans, similar data from large animals is still sparse. Objective: Therefore, the aim of the current study was to evaluate the reliability (within- and between-session) of MNT in the forelimb of pigs using a pressure algometer. Methods: Nine animals were used (23-40 kg), and MNTs were measured at both the right and left limbs at three different sessions, with three repetitions per session. The intraclass correlation coefficient (ICC) was used as a metric for relative reliability. The standard error of measurement (SEM) and coefficient of variation (CV) was used to assess absolute reliability. Systematic bias was also evaluated. Results: The average ICC was found to be 0.71 and 0.45 for the between-session and within-session, respectively. CV ranged from 17.9% to 20.5%, with a grand average of 19.1%. The grand average SEM was 249.5 kPa (16.6%). No systematic differences were found for the MNT between sessions, which suggests that there was no habituation to the stimulus. Conclusion: The reliability indices obtained in this study are comparable to results obtained in other species or anatomical regions and substantiate the use of the pressure algometer as a valuable tool to investigate the nociceptive system in pigs and translation to the human nociceptive withdrawal reflex.

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.

A Comparison of Delay-and-Add and Maximum Likelihood Estimation for Velocity-Selective Recording Using Multi-Electrode Cuffs.

Extracting information from the peripheral nervous system with implantable devices remains a significant challenge that limits the advancement of closed-loop neural prostheses. Linear electrode arrays can record neural signals with both temporal and spatial selectivity, and velocity selective recording using the delay-and-add algorithm can enable classification based on fibre type. The maximum likelihood estimation method also measures velocity and is frequently used in electromyography but has never been applied to electroneurography. Therefore, this study compares the two algorithms using in-vivo recordings of electrically evoked compound action potentials from the ulnar nerve of a pig. The performance of these algorithms was assessed using the velocity quality factor (Q-factor), computational time and the influence of the number of channels. The results show that the performance of both algorithms is significantly influenced by the number of channels in the recording array, with accuracies ranging from 77% with only two channels to 98% for 11 channels. Both algorithms were comparable in accuracy and Q-factor for all channels, with the delay-and-add having a slight advantage in the Q-factor.

Gamma-band enhancement of functional brain connectivity following transcutaneous electrical nerve stimulation.

Objective.Transcutaneous electrical nerve stimulation (TENS) has been suggested as a possible non-invasive pain treatment. However, the underlying mechanism of the analgesic effect of TENS and how brain network functional connectivity (FC) is affected following the use of TENS is not yet fully understood. The purpose of this study was to investigate the effect of high-frequency TENS on the alteration of functional brain network connectivity and the corresponding topographical changes, besides perceived sensations.Approach.Forty healthy subjects participated in this study. Electroencephalography (EEG) data and sensory profiles were recorded before and up to an hour following high-frequency TENS (100 Hz) in sham and intervention groups. Brain source activity from EEG data was estimated using the LORETA algorithm. In order to generate the functional brain connectivity network, the Phase Lag Index was calculated for all pair-wise connections of eight selected brain areas over six different frequency bands (i.e.δ, θ, α, ß, γ, and 0.5-90 Hz).Main results.The results suggested that the FC between the primary somatosensory cortex (SI) and the anterior cingulate cortex, in addition to FC between SI and the medial prefrontal cortex, were significantly increased in the gamma-band, following the TENS intervention. Additionally, using graph theory, several significant changes were observed in global and local characteristics of functional brain connectivity in gamma-band.Significance.Our observations in this paper open a neuropsychological window of understanding the underlying mechanism of TENS and the corresponding changes in functional brain connectivity, simultaneously with alteration in sensory perception.

Effect of Modulated TENS on Corticospinal Excitability in Healthy Subjects.

Conventional transcutaneous electrical nerve stimulation (TENS) has been reported to effectively alleviate chronic pain, including phantom limb pain (PLP). Recently, literature has focused on modulated TENS patterns, such as pulse width modulation (PWM) and burst modulation (BM), as alternatives to conventional, non-modulated (NM) sensory neurostimulation to increase the efficiency of rehabilitation. However, there is still limited knowledge of how these modulated TENS patterns affect corticospinal (CS) and motor cortex activity. Therefore, our aim was to first investigate the effect of modulated TENS patterns on CS activity and corticomotor map in healthy subjects. Motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) were recorded from three muscles before and after the application of TENS interventions. Four different TENS patterns (PWM, BM, NM 40 Hz, and NM 100 Hz) were applied. The results revealed significant facilitation of CS excitability following the PWM intervention. We also found an increase in the volume of the motor cortical map following the application of the PWM and NM (40 Hz). Although PLP alleviation has been reported to be associated with an enhancement of corticospinal excitability, the efficiency of the PWM intervention to induce pain alleviation should be validated in a future clinical study in amputees with PLP.

A systematic review of porcine models in translational pain research.

Translating basic pain research from rodents to humans has proven to be a challenging task. Efforts have been made to develop preclinical large animal models of pain, such as the pig. However, no consistent overview and comparison of pig models of pain are currently available. Therefore, in this review, our primary aim was to identify the available pig models in pain research and compare these models in terms of intensity and duration. First, we systematically searched Proquest, Scopus and Web of Science and compared the duration for which the pigs were significantly sensitized as well as the intensity of mechanical sensitization. We searched models within the specific field of pain and adjacent fields in which pain induction or assessment is relevant, such as pig production. Second, we compared assessment methodologies in surrogate pain models in humans and pigs to identify areas of overlap and possible improvement. Based on the literature search, 23 types of porcine pain models were identified; 13 of which could be compared quantitatively. The induced sensitization lasted from hours to months and intensities ranged from insignificant to the maximum attainable. We also found a near to complete overlap of assessment methodologies between human and pig models within the area of peripheral neurophysiology, which allows for direct comparison of results obtained in the two species. In spite of this overlap, further development of pain assessment methodologies is still needed. We suggest that central nervous system electrophysiology, such as electroencephalography, electrocorticography or intracortical recordings, may pave the way for future objective pain assessment.

The effect of peripheral high-frequency electrical stimulation on the primary somatosensory cortex in pigs.

This study implements the use of Danish Landrace pigs as subjects for the long-term potentiation (LTP)-like pain model. This is accomplished by analyzing changes in the primary somatosensory cortex (S1) in response to electrical stimulation on the ulnar nerve after applying high-frequency electrical stimulation (HFS) on the ulnar nerve. In this study, eight Danish Landrace pigs were electrically stimulated, through the ulnar nerve, to record the cortically evoked response in S1 by a 16-channel microelectrode array (MEA). Six of these pigs were subjected to HFS (four consecutive, 15 mA, 100 Hz, 1000 µs pulse duration) 45 min after the start of the experiment. Two pigs were used as control subjects to compare the cortical response to peripheral electrical stimulation without applying HFS. Low-frequency components of the intracortical signals (0.3-300 Hz) were analyzed using event-related potential (ERP) analysis, where the minimum peak during the first 30-50 ms (N1 component) in each channel was detected. The change in N1 was compared over time across the intervention and control groups. Spectral analysis was used to demonstrate the effect of the intervention on the evoked cortical oscillations computed between 75 ms and 200 ms after stimulus. ERP analysis showed an immediate increase in N1 amplitude that became statistically significant 45 mins after HFS (p < 0.01) for the intervention group. The normalized change in power in frequency oscillations showed a similar trend. The results show that the LTP-like pain model can be effectively implemented in pigs using HFS since the cortical responses are comparable to those described in humans.

Altered evoked low-frequency connectivity from SI to ACC following nerve injury in rats.

Objective. Despite decades of research on central processing of pain, there are still several unanswered questions, in particular regarding the brain regions that may contribute to this alerting sensation. Since it is generally accepted that more than one cortical area is responsible for pain processing, there is an increasing focus on the interaction between areas known to be involved.Approach. In this study, we aimed to investigate the bidirectional information flow from the primary somatosensory cortex (SI) to the anterior cingulate cortex (ACC) in an animal model of neuropathic pain.19 rats (nine controls and ten intervention) had an intracortical electrode implanted with six pins in SI and six pins in ACC, and a cuff stimulation electrode around the sciatic nerve. The intervention rats were subjected to the spared nerve injury (SNI) after baseline recordings. Electrical stimulation at three intensities of both noxious and non-noxious stimulation was used to record electrically evoked cortical potentials. To investigate information flow, two connectivity measures were used: phase lag index (PLI) and granger prediction (GP). The rats were anesthetized during the entire study.Main results. Immediately after the intervention (<5 min after intervention), the high frequency (γandγ+) PLI was significantly decreased compared to controls. In the last recording cycle (3-4 h after intervention), the GP increased consistently in the intervention group. Peripheral nerve injury, as a model of neuropathic pain, resulted in an immediate decrease in information flow between SI and ACC, possibly due to decreased sensory input from the injured nerve. Hours after injury, the connectivity between SI and ACC increased, likely indicating hypersensitivity of this pathway.Significance. We have shown that both a directed and non-directed connectivity between SI and ACC approach can be used to show the acute changes resulting from the SNI model.

Online Closed-Loop Control Using Tactile Feedback Delivered Through Surface and Subdermal Electrotactile Stimulation.

AIM: Limb loss is a dramatic event with a devastating impact on a person's quality of life. Prostheses have been used to restore lost motor abilities and cosmetic appearance. Closing the loop between the prosthesis and the amputee by providing somatosensory feedback to the user might improve the performance, confidence of the amputee, and embodiment of the prosthesis. Recently, a minimally invasive method, in which the electrodes are placed subdermally, was presented and psychometrically evaluated. The present study aimed to assess the quality of online control with subdermal stimulation and compare it to that achieved using surface stimulation (common benchmark) as well as to investigate the impact of training on the two modalities. METHODS: Ten able-bodied subjects performed a PC-based compensatory tracking task. The subjects employed a joystick to track a predefined pseudorandom trajectory using feedback on the momentary tracking error, which was conveyed via surface and subdermal electrotactile stimulation. The tracking performance was evaluated using the correlation coefficient (CORR), root mean square error (RMSE), and time delay between reference and generated trajectories. RESULTS: Both stimulation modalities resulted in good closed-loop control, and surface stimulation outperformed the subdermal approach. There was significant difference in CORR (86 vs 77%) and RMSE (0.23 vs 0.31) between surface and subdermal stimulation (all p < 0.05). The RMSE of the subdermal stimulation decreased significantly in the first few trials. CONCLUSION: Subdermal stimulation is a viable method to provide tactile feedback. The quality of online control is, however, somewhat worse compared to that achieved using surface stimulation. Nevertheless, due to minimal invasiveness, compactness, and power efficiency, the subdermal interface could be an attractive solution for the functional application in sensate prostheses.

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.

The Use of the Velocity Selective Recording Technique to Reveal the Excitation Properties of the Ulnar Nerve in Pigs.

Decoding information from the peripheral nervous system via implantable neural interfaces remains a significant challenge, considerably limiting the advancement of neuromodulation and neuroprosthetic devices. The velocity selective recording (VSR) technique has been proposed to improve the classification of neural traffic by combining temporal and spatial information through a multi-electrode cuff (MEC). Therefore, this study investigates the feasibility of using the VSR technique to characterise fibre type based on the electrically evoked compound action potentials (eCAP) propagating along the ulnar nerve of pigs in vivo. A range of electrical stimulation parameters (amplitudes of 50 µA-10 mA and pulse durations of 100 µs, 500 µs, 1000 µs, and 5000 µs) was applied on a cutaneous and a motor branch of the ulnar nerve in nine Danish landrace pigs. Recordings were made with a 14 ring MEC and a delay-and-add algorithm was used to convert the eCAPs into the velocity domain. The results revealed two fibre populations propagating along the cutaneous branch of the ulnar nerve, with mean velocities of 55 m/s and 21 m/s, while only one dominant fibre population was found for the motor branch, with a mean velocity of 63 m/s. Because of its simplicity to provide information on the fibre selectivity and direction of propagation of nerve fibres, VSR can be implemented to advance the performance of the bidirectional control of neural prostheses and bioelectronic medicine applications.

Modulation of SI and ACC response to noxious and non-noxious electrical stimuli after the spared nerve injury model of neuropathic pain.

BACKGROUND: The current knowledge on the role of SI and ACC in acute pain processing and how these contribute to the development of chronic pain is limited. Our objective was to investigate differences in and modulation of intracortical responses from SI and ACC in response to different intensities of peripheral presumed noxious and non-noxious stimuli in the acute time frame of a peripheral nerve injury in rats. METHODS: We applied non-noxious and noxious electrical stimulation pulses through a cuff electrode placed around the sciatic nerve and measured the cortical responses (six electrodes in each cortical area) before and after the spared nerve injury model. RESULTS: We found that the peak response correlated with the stimulation intensity and that SI and ACC differed in both amplitude and latency of cortical response. The cortical response to both noxious and non-noxious stimulation showed a trend towards faster processing of non-noxious stimuli in ACC and increased cortical processing of non-noxious stimuli in SI after SNI. CONCLUSIONS: We found different responses in SI and ACC to different intensity electrical stimulations based on two features and changes in these features following peripheral nerve injury. We believe that these features may be able to assist to track cortical changes during the chronification of pain in future animal studies. SIGNIFICANCE: This study showed distinct cortical processing of noxious and non-noxious peripheral stimuli in SI and ACC. The processing latency in ACC and accumulated spiking activity in SI appeared to be modulated by peripheral nerve injury, which elaborated on the function of these two areas in the processing of nociception.

Nerve Injury Decreases Hyperacute Resting-State Connectivity Between the Anterior Cingulate and Primary Somatosensory Cortex in Anesthetized Rats.

A better understanding of neural pain processing and of the development of pain over time, is critical to identify objective measures of pain and to evaluate the effect of pain alleviation therapies. One issue is, that the brain areas known to be related to pain processing are not exclusively responding to painful stimuli, and the neuronal activity is also influenced by other brain areas. Functional connectivity reflects synchrony or covariation of activation between groups of neurons. Previous studies found changes in connectivity days or weeks after pain induction. However, less in known on the temporal development of pain. Our objective was therefore to investigate the interaction between the anterior cingulate cortex (ACC) and primary somatosensory cortex (SI) in the hyperacute (minute) and sustained (hours) response in an animal model of neuropathic pain. Intra-cortical local field potentials (LFP) were recorded in 18 rats. In 10 rats the spared nerve injury model was used as an intervention. The intra-cortical activity was recorded before, immediately after, and three hours after the intervention. The interaction was quantified as the calculated correlation and coherence. The results from the intervention group showed a decrease in correlation between ACC and SI activity, which was most pronounced in the hyperacute phase but a longer time frame may be required for plastic changes to occur. This indicated that both SI and ACC are involved in hyperacute pain processing.

Referred Sensation Areas in a Bilateral Toes Amputee.

Various mechanisms in generating phantom limb pain (PLP) have been hypothesized in the literature. However, there still is no clear understanding of how PLP develops and why it presents. Amputation leads to permanent anatomical and physiological changes of the neural path previously supplying the brain with sensory input, as well as to formation of referred sensation areas (RSAs) on the stump or its vicinity. Sensations may be evoked in the lost body part upon stimulation of RSAs that may be exploited as artificial sensory input. In this work, we present the analysis of RSA maps from a 45-year-old female with bilateral toes amputation. Maps of the RSAs were identified in eight sessions over 107 days, characterized by dynamics in both location and type of associated evoked sensation. The evoked sensations were reported to be felt like current through and brushing of the phantom toes at low intensities close to the sensation threshold. Sensations evoked by electrical stimuli delivered through electrodes covering one or more RSAs approximated the sensation of summation of sensations evoked by mechanical stimuli (light brushing). No painful evoked sensations were observed.Clinical Relevance- The technique presented may be further improved by using various profiles for stimulation over a longer period of time for possible efficient PLP treatment with artificially generated sensory input.

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.

Transcutaneous Electrical Stimulation Influences the Time-Frequency Map of Cortical Activity - A Pilot Study.

Phantom limb pain (PLP) is pain felt in the missing limb in amputees. Somatosensory input delivered as high-frequency surface electrical stimulation may provoke a significant temporary decrease in PLP. Also, transcutaneous electrical nerve stimulation (TENS) is a somatosensory input that may activate descending inhibitory systems and thereby relieve pain. Our aim was to investigate changes in cortical activity following long-time sensory TENS. Time-frequency features were extracted from EEG signals of Cz and C4 channels (contralateral to the stimulation site) with or without TENS (2 subjects). We found that the TENS caused inhibition of the spectral activity of the somatosensory cortex following TENS, whereas no change was found when no stimulation was applied.Clinical Relevance- Although our preliminary results show a depression of the cortical activity following TENS, a future study with a larger population is needed to provide strong evidence to evaluate the effectiveness of sensory TENS on cortical activity. Our results may be useful for the design of TENS protocols for relief of PLP.