Transcutaneous Spinal Direct Current Stimulation Research Articles

113. Spinal Direct Current Stimulation modulates short intracortical inhibition

Transcutaneous spinal Direct Current Stimulation (tsDCS) is a new and safe technique for modulating spinal cord excitability. We evaluated healthy subjects before (T0) and at different intervals (T1 and T2) after anodal, cathodal and sham tsDCS (20 ′ ,2.0 mA) applied over the thoracic spinal cord (T10–T12). We assessed changes in cortical Silent Period (cSP), paired-pulse short intracortical inhibition (SICI, interstimulus interval, ISI = 3 ms) and intracortical facilitation (ICF, ISI = 10 ms). Motor Evoked Potentials (MEPs) were recorded from first digital interosseus (FDI) and tibialis anterior (TA) muscles. Cathodal tsDCS increased MEP amplitudes at ISI of 3 ms, while anodal one elicited opposite effects (FDI: p = 0.0023; TA: p = 0.0004); conversely, tsDCS left MEP amplitudes unchanged at ISI of 10 ms (FDI: p = 0.39; TA: p = 0.45). No significant change in cSP duration was found from upper ( p = 0.81) and lower limb ( p = 0.33). tsDCS modulates inhibitory GABA(A) ergic drive, as assessed by SICI, without interfering with cSP and ICF. tsDCS may be helpful to modulate spinal drive through non spinal mechanisms. tsDCS could represent an early rehabilitation strategy in patients with acute brain lesions and in the treatment of spinal diseases or pain syndromes.

Noninvasive Spinal Cord Stimulation: Technical Aspects and Therapeutic Applications.

Electrical and magnetic trans-spinal stimulation can be used to increase the motor output of multiple spinal segments and modulate cortico-spinal excitability. The application of direct current through the scalp as well as repetitive transcranial magnetic stimulation are known to influence brain excitability, and hence can also modulate other central nervous system structures, including spinal cord. This study aimed to evaluate the effects and the therapeutic usefulness of these noninvasive neuromodulatory techniques in healthy subjects and in the neurorehabilitation of patients with spinal cord disorders, as well as to discuss the possible mechanisms of action. A comprehensive review that summarizes previous studies using noninvasive spinal cord stimulation is lacking. PubMed (MEDLINE) and EMBASE were systematically searched to identify the most relevant published studies. We performed here an extensive review in this field. By decreasing the spinal reflex excitability, electrical and magnetic trans-spinal stimulation could be helpful in normalizing reflex hyperexcitability and treating hypertonia in subjects with lesions to upper motor neurons. Transcutaneous spinal direct current stimulation, based on applying direct current through the skin, influences the ascending and descending spinal pathways as well as spinal reflex excitability, and there is increasing evidence that it also can induce prolonged functional neuroplastic changes. When delivered repetitively, magnetic stimulation could also modulate spinal cord functions; however, at present only a few studies have documented spastic-reducing effects induced by repetitive spinal magnetic stimulation. Moreover, paired peripheral and transcranial stimulation can be used to target the spinal cord and may have potential for neuromodulation in spinal cord-injured subjects. Noninvasive electrical and magnetic spinal stimulation may provide reliable means to characterize important neurophysiologic and pathophysiologic aspects of spinal cord function. Moreover, transcutaneous direct current stimulation and repetitive magnetic stimulation may hold therapeutic promise in patients with spinal cord disorders, although future well-controlled studies are needed to corroborate and extend the preliminary findings.

Combined effects of transcranial direct current stimulation (tDCS) and transcutaneous spinal direct current stimulation (tsDCS) on robot-assisted gait training in patients with chronic stroke: A pilot, double blind, randomized controlled trial.

Preliminary evidence has shown no additional effects of transcranial direct current stimulation (tDCS) on robotic gait training in chronic stroke, probably due to the neural organization of locomotion involving cortical and spinal control. Our aim was to compare the combined effects of tDCS and transcutaneous spinal direct current stimulation (tsDCS) on robotic gait training in chronic stroke. Thirty chronic stroke patients received ten 20-minute robot-assisted gait training sessions, five days a week, for 2 consecutive weeks combined with anodal tDCS + sham tsDCS (group 1; n = 10) or sham tDCS + cathodal tsDCS (group 2; n = 10) or tDCS + cathodal tsDCS (group 3; n = 10). The primary outcome was the 6-minute walk test (6MWT) performed before, after, 2 weeks and 4 weeks post-treatment. Significant differences in the 6MWT distance were noted between group 3 and group 1 at the post-treatment and 2-week follow-up evaluations (post-treatment P = 0.015; 2-week follow-up P = 0.001) and between group 3 and group 2 (post-treatment P = 0.010; 2-week follow-up P = .015). No difference was found between group 2 and group 1. Our preliminary findings support the hypothesis that anodal tDCS combined with cathodal tsDCS may be useful to improve the effects of robotic gait training in chronic stroke.

Transcutaneous spinal direct current stimulation modulates human corticospinal system excitability.

This study aimed to assess the effects of thoracic anodal and cathodal transcutaneous spinal direct current stimulation (tsDCS) on upper and lower limb corticospinal excitability. Although there have been studies assessing how thoracic tsDCS influences the spinal ascending tract and reflexes, none has assessed the effects of this technique over upper and lower limb corticomotor neuronal connections. In 14 healthy subjects we recorded motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) from abductor hallucis (AH) and hand abductor digiti minimi (ADM) muscles before (baseline) and at different time points (0 and 30 min) after anodal or cathodal tsDCS (2.5 mA, 20 min, T9-T11 level). In 8 of the 14 subjects we also tested the soleus H reflex and the F waves from AH and ADM before and after tsDCS. Both anodal and cathodal tsDCS left the upper limb MEPs and F wave unchanged. Conversely, while leaving lower limb H reflex unchanged, they oppositely affected lower limb MEPs: whereas anodal tsDCS increased resting motor threshold [(mean ± SE) 107.33 ± 3.3% increase immediately after tsDCS and 108.37 ± 3.2% increase 30 min after tsDCS compared with baseline] and had no effects on MEP area and latency, cathodal tsDCS increased MEP area (139.71 ± 12.9% increase immediately after tsDCS and 132.74 ± 22.0% increase 30 min after tsDCS compared with baseline) without affecting resting motor threshold and MEP latency. Our results show that tsDCS induces polarity-specific changes in corticospinal excitability that last for >30 min after tsDCS offset and selectively affect responses in lower limb muscles innervated by lumbar and sacral motor neurons.

Spinal Direct Current Stimulation Modulates Short Intracortical Inhibition.

Transcutaneous spinal direct current stimulation (tsDCS) is a new and safe technique for modulating spinal cord excitability. We assessed changes in intracortical excitability following tsDCS by evaluating changes in cortical silent period (cSP), paired-pulse short intracortical inhibition (SICI), and intracortical facilitation (ICF). Healthy subjects were studied before (T0) and at different intervals (T1 and T2) after anodal, cathodal, and sham tsDCS (20', 2.0 mA) applied over the thoracic spinal cord (T10-T12). We assessed changes in cSP, SICI (interstimulus interval, ISI = 3 ms) and ICF (ISI = 10 ms). Motor-evoked potentials (MEPs) were recorded from first digital interosseus (FDI) and tibialis anterior (TA) muscles. Cathodal tsDCS increased MEP amplitudes at interstimulus interval of 3 ms, while anodal one elicited opposite effects (FDI: p = 0.0023; TA: p = 0.0004); conversely, tsDCS left MEP amplitudes unchanged at ISI of 10 ms (FDI: p = 0.39; TA: p = 0.45). No significant change in cSP duration was found from upper limb (p = 0.81) and lower limb (p = 0.33). tsDCS modulates inhibitory GABA(A)ergic drive, as assessed by SICI, without interfering with cSP and ICF. The possibility to interfere with cortical processing makes tsDCS a useful approach to modulate spinal drive through nonspinal mechanisms. tsDCS could also represent an early rehabilitation strategy in patients with acute brain lesions, when other noninvasive brain stimulation (NIBS) tools are not indicated due to safety concerns, as well as in the treatment of spinal diseases or pain syndromes.

Does spinal direct current stimulation enhance synaptic inputs to phrenic motoneurons in humans? A double-blind, sham controlled, randomized crossover study

Background Pilot studies have evidenced the possibility of altering corticospinal projections to phrenic motoneurons (PMNs) and modifying respiratory behavior using repetitive transcranial magnetic stimulation (rTMS). Similar evidence lacks regarding induced neuroplasticity at the spinal level. Objective This study was designed to investigate the immediate and long-lasting effects of a single session of transcutaneous spinal direct current stimulation (tsDCS), a non-invasive way of modulating spinal cord functions, on corticophrenic excitability in healthy humans. Methods Using a double-blind, controlled, randomized crossover approach, we examined the effects of anodal, cathodal, and sham tsDCS delivered to C3–C5 on: – diaphragm motor-evoked potentials (DiMEP) elicited by transcranial magnetic stimulation (TMS); – resting motor threshold (rMT) of the diaphragm and short interval intracortical inhibition (sICI) thought to reflect GABAergic inhibition in the motor cortex; – spontaneous ventilation, as measured by respiratory inductance plethysmography and a measure of ventilatory mathematical complexity (noise limit). Results and conclusions Both anodal and cathodal tsDCS induced a progressive increase of DiMEP amplitude during stimulation that persisted for at least 20 min after current offset. They also lowered rMT. sICI and noise limit were unchanged, suggesting that enhanced excitability was spinal rather than cortical or medullary. Cathodal tsDCS induced a persistent increase in tidal volume. tsDCS can therefore result in polarity-dependent breathing pattern changes, which opens the perspective of harnessing respiratory plasticity as a therapeutic tool in disorders altering the central ventilatory command or its spinal transmission.

Modulation of temporal summation threshold of the nociceptive withdrawal reflex by transcutaneous spinal direct current stimulation in humans

ObjectiveTranscutaneous spinal direct current stimulation (tsDCS) modulates spinal cord pain pathways. The study is aimed to clarify the neurophysiology of the tsDCS-induced modulation of the spinal cord pain processing by evaluating the effect of the tsDCS on temporal summation threshold (TST) of the nociceptive withdrawal reflex (NWR). MethodsIn a randomized, double-blind, crossover study the effects of anodal, cathodal and sham tsDCS (2mA, 15min) applied on the skin overlying the thoracic spinal cord were investigated in 10 healthy subjects. ResultsAnodal tsDCS induced a long-lasting (up to 60min) increase in TST of the NWR as well as a parallel decrease in related psychophysical temporal summation of pain, while cathodal and sham tsDCS resulted ineffective. ConclusionsAnodal tsDCS represents a non-invasive tool able to induce an early and long-lasting depression of the transitory facilitation of the wide dynamic range neurons activity at the basis of both the temporal summation of the NWR and the related temporal summation of pain sensation. SignificanceThe modulation of the temporal processing of nociceptive stimuli could be effective in treating clinical pain conditions in which pain is generated by spinal cord structures.

Transcutaneous spinal DC stimulation reduces pain sensitivity in humans

Non-invasive approaches to pain management are needed to manage patient pain escalation and to providing sufficient pain relief. Here, we evaluate the potential of transcutaneous spinal direct current stimulation (tsDCS) to modulate pain sensitivity to electrical stimuli and mechanical pinpricks in 24 healthy subjects in a sham-controlled, single-blind study. Pain ratings to mechanical pinpricks and electrical stimuli were recorded prior to and at three time points (0, 30, and 60min) following 15min of anodal tsDCS (2.5mA, “active” electrode centered over the T11 spinous process, return electrode on the left posterior shoulder). Pain ratings to the pinpricks of the highest forces tested (128, 256, 512mN) were reduced at 30min and 60min following anodal tsDCS. These findings demonstrate that pain sensitivity in healthy subjects can be suppressed by anodal tsDCS and suggest that tsDCS may provide a non-invasive tool to manage mechanically-induced pain.

Does trans-spinal direct current stimulation alter phrenic motoneurons and respiratory neuromechanical outputs in humans? A double-blind, sham-controlled, randomized, crossover study.

Although compelling evidence has demonstrated considerable neuroplasticity in the respiratory control system, few studies have explored the possibility of altering descending projections to phrenic motoneurons (PMNs) using noninvasive stimulation protocols. The present study was designed to investigate the immediate and long-lasting effects of a single session of transcutaneous spinal direct current stimulation (tsDCS), a promising technique for modulating spinal cord functions, on descending ventilatory commands in healthy humans. Using a double-blind, controlled, randomized, crossover approach, we examined the effects of anodal, cathodal, and sham tsDCS delivered to the C3-C5 level on (1) diaphragm motor-evoked potentials (DiMEPs) elicited by transcranial magnetic stimulation and (2) spontaneous ventilation, as measured by respiratory inductance plethysmography. Both anodal and cathodal tsDCS induced a progressive increase in DiMEP amplitude during stimulation that persisted for at least 15 min after current offset. Interestingly, cathodal, but not anodal, tsDCS induced a persistent increase in tidal volume. In addition, (1) short-interval intracortical inhibition, (2) nonlinear complexity of the tidal volume signal (related to medullary ventilatory command), (3) autonomic function, and (4) compound muscle action potentials evoked by cervical magnetic stimulation were unaffected by tsDCS. This suggests that tsDCS-induced aftereffects did not occur at brainstem or cortical levels and were likely not attributable to direct polarization of cranial nerves or ventral roots. Instead, we argue that tsDCS could induce sustained changes in PMN output. Increased tidal volume after cathodal tsDCS opens up the perspective of harnessing respiratory neuroplasticity as a therapeutic tool for the management of several respiratory disorders.

Effects of transcutaneous spinal direct current stimulation in idiopathic restless legs patients.

Transcutaneous spinal direct current stimulation (tsDCS) is a new non-invasive technique to modulate spinal cord activity. The pathophysiological concept of primary RLS proposes increased spinal excitability. This pilot study used tsDCS to reduce pathologically enhanced spinal excitability in RLS patients and to thereby ameliorate clinical symptoms. 20 patients with idiopathic RLS and 14 healthy subjects participated in this double-blinded, placebo-controlled study. All participants received one session of cathodal, anodal and sham stimulation of the thoracic spinal cord for 15min (2.5mA) each, in randomized order during their symptomatic phase in the evening. The soleus Hoffmann-reflex with Hmax/Mmax-ratio and seven different H2/H1-ratios (of two H-reflex responses to double stimuli) were measured. The RLS symptoms were assessed by a visual analogue scale (VAS). All parameters were measured before and twice after tsDCS. RLS patients showed increased H2/H1-ratios during their symptomatic phase in the evening. Application of anodal stimulation led to a decreased H2/H1-ratio for 0.2 and 0.3s interstimulus intervals in patients. Furthermore, application of anodal and cathodal stimulation led to a reduction in restless legs symptoms on the VAS, whereas application of sham stimulation had no effects on either the VAS or on the H2/H1-ratio in patients. VAS changes did not correlate with changes of H2/H1-ratios. This is the first tsDCS study in idiopathic RLS, which resulted in short-lasting clinical improvement. Furthermore, our results support the pathophysiological concept of spinal cord hyperexcitability in primary RLS and provide the basis for a new non-pharmacological treatment tool.

Cathodal transcutaneous spinal direct current stimulation (tsDCS) improves motor unit recruitment in healthy subjects

Transcutaneous spinal direct current stimulation (tsDCS) is a new promising technique for modulating spinal cord function in humans. However, its effects on corticospinal pathways and lower motorneuron excitability are poorly understood. We studied the effects of tsDCS on motor unit recruitment by evaluating changes in motor unit number (MUNE) and peripheral silent period (PSP) after sham (s-tsDCS), anodal (a-tsDCS) and cathodal (c-tsDCS) tsDCS applied either over the cervical or the lower thoracic spinal cord in healthy subjects. For the calculation of MUNE we used the multipoint incremental technique recording from either the ulnar nerve innervated abductor digiti minimi (ADM) or the median nerve innervated abductor pollicis brevis (APB) muscle. c-tsDCS dramatically increases MUNE values following cervical polarization, while sham and anodal polarization have no significant effect (APB: F(4,99)=26.4, p<0.001, two-way repeated measures ANOVA with “time” and “stimulation” as factors; ADM: F(4,99)=22.1, p<0.0001). At the same time, c-tsDCS dampened PSP respect to sham and anodal conditions (p<0.0001). Interestingly, also thoracic c-tsDCS significantly improved motor unit recruitment compared with both s-tsDCS and a-tsDCS (APB: F(4,99)=20.1, p<0.0001; ADM: F(4,99)=16.6, p<0.0001). Our data in healthy subjects suggest that tsDCS, possibly also through supraspinal effects, could provide a novel therapeutic tool in managing several pathological conditions characterized by reduced motor unit recruitment, such as stroke and spinal cord injuries.

P651: Dorsal transcutaneous spinal direct current stimulation (tsDCS) induces remote effects on the Ia-motoneuron connections in the cervical spinal segments

P651: Dorsal transcutaneous spinal direct current stimulation (tsDCS) induces remote effects on the Ia-motoneuron connections in the cervical spinal segments

Modeling the current density generated by transcutaneous spinal direct current stimulation (tsDCS)

ObjectiveNon-invasive transcutaneous spinal direct current stimulation (tsDCS) induces changes in spinal cord function in humans. Nonetheless, the current density (J) spatial distributions generated by tsDCS are unknown. This work aimed to estimate the J distributions in the spinal cord during tsDCS. MethodsComputational electromagnetics techniques were applied to realistic human models, based on high-resolution MRI of healthy volunteers (a 26-years-old female adult model “Ella”; a 14years-old male adolescent model “Louis”; an 11years old female adolescent model “Billie”). Three electrode montages were modeled. In all cases, the anode was always over the spinal process of the tenth thoracic vertebra and the cathode was placed: (A) above the right arm; (B) over the umbilicus; (C) over Cz. The injected current was 3mA. The electrodes were conductors within rectangular sponges. ResultsDespite inter-individual differences, the J tends to be primarily directed longitudinally along the spinal cord and cauda equina with the region of higher amplitude influenced by the reference electrode position; on transversal sections, the J amplitude distributions were quite uniform. ConclusionsOur modeling approach reveals that the J generated by tsDCS reaches the spinal cord, with a current spread also to the muscle on the back and the spinal nerve. SignificanceThis study is a first step in better understanding the mechanisms underlying tsDCS.

147. Dorsal transcutaneous spinal direct current stimulation (tsDCS) modulates human corticospinal system excitability

Despite studies investigating how dorsal transcutaneous spinal direct current stimulation (tsDCS) influences the spinal ascending tract and reflexes, no data show whether and how it modulates function in the human corticospinal system. In 11 healthy subjects we recorded soleus H-reflex, F-waves and motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) from abductor hallucis (AH) and abductor digiti minimi (ADM) muscles before and at a different time-points (T0, T30) after anodal or cathodal tsDCS applied at 2.5 mA for 20 min over the thoracic spinal cord (T10–T12 level). Whereas cathodal tsDCS decreased MEP thresholds, after anodal tsDCS MEP thresholds from the lower limb muscles increased significantly ( F (2,20) = 5.01, p = 0.017). Similarly, after cathodal tsDCS, lower-limb MEP areas increased, whereas after anodal tsDCS they decreased significantly ( F (2,20) = 10.2, p = 0.0009). tsDCS left the lower-limb H/reflex and upperlimb F wave unchanged from baseline. Dorsal tsDCS modulates human corticospinal pathway function. The tsDCS-induced functional changes last for almost 20′ after DC offset and selectively affect muscle innervated by lumbosacral motorneurons caudal to the tsDCS stimulation site. These findings suggest that tsDCS acts on the corticospinal system leaving motoneuronal and neuromuscolar excitability unchanged.

P 225. Computational models of current densities in transcutaneous spinal direct current stimulation (tsDCS)

Introduction Non-invasive transcutaneous spinal direct current stimulation (tsDCS) induces changes in spinal cord function in humans (Cogiamanian et al., 2012). The physiological mechanisms underlying these changes however remain speculative. A relevant issue to better understand this innovative non-invasive neuromodulation technique is the estimation of the spatial distribution of the current density in the spinal cord during tsDCS. Objective To evaluate the current density ( J ) induced by dorsal tsDCS in the spinal cord using electromagnetics computational techniques applied to realistic human models of different age and gender. Materials and methods The computation was conducted using the simulation platform SEMCAD X (Schmid & Partner Engineering AG, Zurich, Switzerland) solving the Laplace equation. Three realistic human models of the Virtual Family (Christ et al., 2010) were used. The models are based on high resolution magnetic resonance images of healthy volunteers (a 26-years-old female adult model Ella; a 34years-old male adult model Duke; an 11years old female adolescent model Billie). The models consist of up to 77 different tissues, the dielectric properties of which were assigned on the basis of the data at low frequency (Gabriel et al., 1996). In this preliminary study three electrode montages were modeled in which the anode was always over the spinal process of the tenth thoracic vertebra and the cathode was placed: (i) above the right deltoid (ii) over the umbilicus; (iii) over Cz. The injected current was 3mA. The electrodes were conductors within rectangular sponges. Results Preliminary data indicates that in the dorsal spinal cord below the stimulating electrode the peaks of J across the models are of 0.02 A/m 2 , 0.03 A/m 2 and 0.06 A/m 2 for the three electrode montages, respectively. Conclusion The electric field generated by tsDCS reaches the spinal cord at physiologically effective strength.

P 7. Effects of transcutaneous spinal direct current stimulation (tsDCS) on long-term potentiation (LTP)-like central sensitization of pain sensation

Strong stimulation of nociceptive afferents results in hyperalgesia based on facilitation of spinal nociceptive pathways, which plays a role in pathological pain conditions. This central sensitization can be experimentally induced via nociceptive high frequency stimulation (HFS) at high intensities in animals (nociceptive LTP) and humans (pain-LTP), and has many mechanistic and molecular similarities with LTP described in the hippocampus. Since LTP in the hippocampus can be inhibited by post-synaptic hyperpolarization, altering the resting membrane potential (RMP) of neurons in the spinal cord could also modulate pain sensitivity and experimentally-induced hyperalgesia. Transcranial direct current stimulation over M1 is thought to enhance or reduce motor neuron excitability via an NMDA-dependent mechanism in a polarity-specific manner. When applied over the spine (tsDCS) this technique may have a similar effect on the spinal circuitry and has in fact already been shown to affect motor and nociceptive reflex responses. We therefore postulated that tsDCS could alter the hyperalgesia induced by nociceptive HFS in a polarity-specific manner. In a double-blind, randomized study 14 healthy right-handed male volunteers each took part in three sessions separated by at least 2 weeks. Painful electrical trains of HFS (5 trains of 100 Hz for 1 s, 9 s onset interval) were given to the right distal thigh. TsDCS was applied directly following HFS via two 7 × 5 cm saline-soaked sponges over T12 vertebral process and the left shoulder. Anodal, cathodal (2.5 mA, 15 min) and sham (1.5 mA, 45 s) stimulation polarities referred to the electrode over T12. Sensory perception was tested on both sides using electrical and mechanical stimuli before (baseline) and at three time points (0, 30, 60 min) post-tsDCS. Subjects gave pain ratings from 0 (non pain) to 100 (worst pain imaginable), resulting in electrical detection threshold (EDT), mechanical pain threshold (MPT), and electrical and mechanical pain sensitivity (EPS and MPS) scores. Baseline and post-stimulation scores were compared using repeated measures ANOVA and Tukey HSD post hoc tests to identify time and stimulation effects. HFS induced significant hyperalgesia after not only sham tsDCS but also following anodal and cathodal polarities. MPS and EPS pain ratings were significantly elevated for all three post-stimulationtime points in all sessions ( p < 0.001–0.03). EDT was significantly reduced at T0 in all sessions ( p < 0.03) whereas MPT decreased marginally, which never reached significance at any time point in any session. None of the responses differed significantly between tsDCS and sham condition. This study confirmed that LTP-like central sensitization induced by HFS is a robust effect and for the first time showed that tsDCS applied immediately following HFS does not influence the resulting hyperalgesia seen within the first hour. Whether sensitized neurons are more resistant to the applied current or whether RMP changes from tsDCS occur in neurons insignificant to the development of hyperalgesia is unknown. To test this first hypothesis we plan to repeat this study, this time applying tsDCS before HFS.

P 31. Effects of transcutaneous spinal Direct Current Stimulation (tsDCS) on the conduction along the human corticospinal system

Objective There are to date few studies investigating the effects of spinal direct current stimulation (tsDCS) on spinal ascending tract and reflexes. Whether tsDCS interferes with conduction along pyramidal tract at a spinal level is unknown. Methods Eleven healthy subjects underwent anodal and cathodal tsDCS of the thoracic spinal cord, at the T10–T12 level (2.5 mA, 20 min). The two conditions were tested in random order and at least 1 week elapsed between sessions. The subjects were blinded about the polarity of conditioning stimulation. MEPs elicited by transcranial magnetic stimulation (TMS) were recorded from abductor hallucis (AH) and abductor digiti minimi (ADM) before tsDCS and after the current offset. We also evaluated AH and ADM F-waves and soleus H-reflex. Results Baseline neurophysiological variables (MEPs threshold, area and latency; H-reflex threshold, latency, amplitude and Hmax/Mmax ratio; F-wave mean latency, minimal latency, amplitude and chronodispersion) from upper and lower limb were comparable in anodal and cathodal sessions. After tsDCS, whereas cathodal tsDCS left MEP threshold unchanged ( p > 0.1), anodal tsDCS increased significantly MEP threshold (two-way ANOVA as “time” and “stimulation” as factors: F (2,20) = 5.01, p = 0.017). Similarly, lower limb MEPs area significantly decreased after anodal tsDCS, increasing however after cathodal stimulation (two-way ANOVA as “time” and “stimulation” as factors: F (2,20) = 10.2, p = 0.0009). Both anodal and cathodal tsDCS failed to affect lower limb MEP latency, upper limb MEPs threshold, area and latency, H-reflex and F-wave. Discussion tsDCS modulates the function of human corticospinal pathways. The effects occur selectively in muscles controlled by corticospinal axons running below the tsDCS electrode over the lower thoracic spinal cord without concomitant effect on both upper limb muscles and motorneuronal excitability. Overall these findings suggest a direct effect of tsDCS on the corticospinal system below the stimulating electrode: among the possible explanations, anodal tsDCS could block impulse conduction along corticospinal axons. A further possibility is that changes of corticospinal function in the brain after tsDCS could be indirectly elicited by its effect on tonic resting activity of ascending spinal pathways-an important input to motor areas–ultimately influencing the excitability of corticospinal neurons at cortical level. Conclusions tsDCS over the dorsal spinal cord can modulate the corticospinal input to sacral motoneurons. The possibility of modulating corticospinal input to motorneurons has potential clinical implications.

BDNF Val66Met polymorphism alters spinal DC stimulation-induced plasticity in humans

The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence neuronal survival, synaptic plasticity, and neurogenesis. A common single nucleotide polymorphism (SNP) of the BDNF gene due to valine-to-methionine substitution at codon 66 (BDNF Val66Met) in the normal population has been associated with complex neuronal phenotype, including differences in brain morphology, episodic memory, or cortical plasticity following brain stimulation and is believed to influence synaptic changes following motor learning task. However, the effect of this polymorphism on spinal plasticity remains largely unknown. Here, we used anodal transcutaneous spinal direct current stimulation (tsDCS), a novel noninvasive technique that induces plasticity of spinal neuronal circuits in healthy subjects. To investigate whether the susceptibility of tsDCS probes of spinal plasticity is significantly influenced by BDNF polymorphism, we collected stimulus-response curves of the soleus (Sol) H reflex before, during, at current offset, and 15 min after anodal tsDCS delivered at Th11 (2.5 mA, 15 min, 0.071 mA/cm(2), and 64 mC/cm(2)) in 17 healthy, Met allele carriers and 17 Val homozygotes who were matched for age and sex. Anodal tsDCS induced a progressive leftward shift of recruitment curve of the H reflex during the stimulation that persisted for at least 15 min after current offset in Val/Val individuals. In contrast, this shift was not observed in Met allele carriers. Our findings demonstrate for the first time that the BDNF Val66Met genotype impacts spinal plasticity in humans, as assessed by tsDCS, and may be one factor influencing the natural response of the spinal cord to injury or disease.

Modulation of spinal neuronal excitability by spinal direct currents and locomotion after spinal cord injury

ObjectiveSpinal neuronal function is impaired after a severe spinal cord injury (SCI) and can be assessed by the analysis of spinal reflex (SR) behavior. We applied transcutaneous spinal direct current stimulation (tsDCS) and locomotor activity, to determine whether the excitability of spinal neuronal circuitries underlying locomotion can be modulated after motor complete SCI. MethodSRs were evoked by non-noxious electrical stimulation of the tibial nerve. SR behavior was assessed before, immediately after, and 20min after four different interventions (anodal, cathodal, sham tsDCS, or locomotion) in subjects with motor complete SCI and healthy subjects. ResultsSR amplitudes in SCI subjects were increased after anodal tsDCS by 84% (p<0.05). Cathodal, sham tsDCS and locomotion had no influence on SR amplitudes. In addition, reflex threshold was lower after anodal tsDCS and locomotion in SCI subjects (p<0.05). ConclusionAnodal tsDCS is able to modulate spinal neuronal circuitries after SCI. SignificanceThis novel, noninvasive approach might be used as a tool to excite spinal neuronal circuitries. If applied repetitively within a training approach, anodal tsDCS might prevent adverse alterations in spinal reflex function in severely affected SCI subjects, i.e., a manifestation of a spinal neuronal dysfunction taking part below the level of a spinal lesion.

Is Transcutaneous Spinal Direct Current Stimulation Efficient in Symptomatic Treatment of Patients with Idiopathic Restless Legs Syndrome? (P02.060)

Is Transcutaneous Spinal Direct Current Stimulation Efficient in Symptomatic Treatment of Patients with Idiopathic Restless Legs Syndrome? (P02.060)