Transspinal constant-current long-lasting stimulation: a new method to induce cortical and corticospinal plasticity

Abstract

Functional neuroplasticity in response to stimulation and motor training is a well-established phenomenon. Transcutaneous stimulation of the spine is used mostly to alleviate pain, but it may also induce functional neuroplasticity, because the spinal cord serves as an integration center for descending and ascending neuronal signals. In this work, we examined whether long-lasting noninvasive cathodal (c-tsCCS) and anodal (a-tsCCS) transspinal constant-current stimulation over the thoracolumbar enlargement can induce cortical, corticospinal, and spinal neuroplasticity. Twelve healthy human subjects, blind to the stimulation protocol, were randomly assigned to 40 min of c-tsCCS or a-tsCCS. Before and after transspinal stimulation, we established the afferent-mediated motor evoked potential (MEP) facilitation and the subthreshold transcranial magnetic stimulation (TMS)-mediated flexor reflex facilitation. Recruitment input-output curves of MEPs and transspinal evoked potentials (TEPs) and postactivation depression of the soleus H reflex and TEPs was also established. We demonstrate that both c-tsCCS and a-tsCCS decrease the afferent-mediated MEP facilitation and alter the subthreshold TMS-mediated flexor reflex facilitation in a polarity-dependent manner. Both c-tsCCS and a-tsCCS increased the tibialis anterior MEPs recorded at 1.2 MEP resting threshold, intermediate, and maximal intensities and altered the recruitment input-output curve of TEPs in a muscle- and polarity-dependent manner. Soleus H-reflex postactivation depression was reduced after a-tsCCS and remained unaltered after c-tsCCS. No changes were found in the postactivation depression of TEPs after c-tsCCS or a-tsCCS. Our findings reveal that c-tsCCS and a-tsCCS have distinct effects on cortical and corticospinal excitability. This method can be utilized to induce targeted neuroplasticity in humans.

Keywords: brain stimulation; motor evoked potential; neuroplasticity; spinal cord stimulation; transcranial magnetic stimulation; transspinal evoked potential.

Copyright © 2015 the American Physiological Society.

Figures

Fig. 1.

Schematic diagrams of the neuronal pathways/circuits undergoing neuroplastic changes after long-lasting transspinal stimulation. A: afferent-mediated tibialis anterior (TA) motor evoked potential (MEP) facilitation and subthreshold transcranial magnetic stimulation (TMS)-mediated flexor reflex facilitation were established to assess cortical plasticity. B: changes in the TA MEP recorded at 1.2 TA MEP resting threshold and TA recruitment input-output curves were established to assess corticospinal plasticity. C: postactivation depression of the soleus H reflex and transspinal evoked potentials (TEPs) was established to assess spinal plasticity. MN, motoneuron. Gray filled triangles indicate the site for each neurophysiological test conducted to probe neuroplasticity.

Fig. 2.

Cortical plasticity after transspinal stimulation: afferent-mediated MEP facilitation. A and C: nonrectified waveform averages of TA MEPs conditioned by sensory stimulation from a representative subject [subject (S#)12] before and after 40 min of cathodal (c-tsCCS) and anodal (a-tsCCS) transspinal constant-current stimulation. C-T interval, conditioning-test interval. B and D: overall amplitude of TA MEPs conditioned by sensory stimulation from all subjects. x-Axis shows the C-T interval between the conditioning sensory stimulation and the test TMS. y-Axis shows the TA MEP as % of the control MEP size. Error bars indicate SE.

Fig. 3.

Cortical plasticity after transspinal stimulation: subthreshold TMS-mediated flexor reflex facilitation. A and C: nonrectified waveform averages of TA flexor reflexes conditioned by subthreshold TMS in 2 representative subjects (subjects 7 and 10) before and after 40 min of c-tsCCS and a-tsCCS. B and D: overall amplitude of TA flexor reflexes conditioned by subthreshold TMS from all subjects. x-Axis shows the C-T interval between the conditioning subthreshold TMS and medial arch test stimulation. y-Axis shows TA flexor reflex size as % of control reflex values. Error bars indicate SE.

Fig. 4.

Corticospinal plasticity after transspinal stimulation. A and D: nonrectified waveform averages of TA MEPs recorded at 1.2 MEP resting threshold before and after 40 min of transspinal stimulation. B and E: % of change of TA MEPs at 1.2 MEP resting threshold and % of change of maximal MEP sizes from all subjects of each group before and after c-tsCCS and a-tsCCS. C and F: TA MEP recruitment curves from all subjects of each group before and after transspinal stimulation. x-Axis shows multiples of TA MEP resting threshold. y-Axis shows TA MEP sizes as % of the associated maximal MEP size obtained before transspinal stimulation.

Fig. 5.

Spinal plasticity after c-tsCCS. TEP recruitment curves: recruitment input-output curves of TEPs recorded bilaterally from the TA, medial gastrocnemius (MG), soleus (SOL), gracilis (GRC), medial hamstrings (MH), rectus femoris (RF), and vastus medialis (VM) muscles from all subjects. x-Axis shows multiples of TEP resting threshold. y-Axis shows TEP sizes as % of the associated maximal TEP size obtained before transspinal stimulation.

Fig. 6.

Spinal plasticity after a-tsCCS. TEP recruitment curves: recruitment input-output curves of TEPs recorded bilaterally from the TA, MG, SOL, GRC, MH, RF, and VM muscles from all subjects. x-Axis shows multiples of TEP resting threshold. y-Axis shows the TEP sizes as % of the associated maximal TEP size obtained before transspinal stimulation.

Fig. 7.

Spinal plasticity after 40 min of a-tsCCS and c-tsCCS: TEPs recorded at 0.2 Hz. A: nonrectified waveform averages of TEPs from 1 representative subject before and after 40 min of c-tsCCS and a-tsCCS. TEPs were recorded at an intensity equivalent to 1.2 TEP resting threshold at 0.2 Hz. B and C: overall % change for each TEP recorded at 0.2 Hz after transspinal stimulation from the associated TEP recorded before transspinal stimulation. x-Axis shows the muscle from which TEPs were recorded. Error bars indicate SE.

Fig. 8.

Spinal plasticity after 40 min of c-tsCCS and a-tsCCS: postactivation depression. A and B: % of change for each TEP evoked at an interstimulus interval of 1 s from the associated TEP recorded at an interstimulus interval of 5 s before and after transspinal stimulation from all subjects. x-Axis shows the muscle from which TEPs were recorded. C and D: amplitude of soleus H reflexes from all subjects before and after c-tsCCS and a-tsCCS at interstimulus intervals of 5 s and 1 s and following paired pulses at an interstimulus interval of 50 ms at a constant stimulation frequency (0.2 Hz). Soleus H reflexes were normalized to the maximal M wave. Error bars indicate SE.