Transpinal and transcortical stimulation alter corticospinal excitability and increase spinal output

Abstract

The objective of this study was to assess changes in corticospinal excitability and spinal output following noninvasive transpinal and transcortical stimulation in humans. The size of the motor evoked potentials (MEPs), induced by transcranial magnetic stimulation (TMS) and recorded from the right plantar flexor and extensor muscles, was assessed following transcutaneous electric stimulation of the spine (tsESS) over the thoracolumbar region at conditioning-test (C-T) intervals that ranged from negative 50 to positive 50 ms. The size of the transpinal evoked potentials (TEPs), induced by tsESS and recorded from the right and left plantar flexor and extensor muscles, was assessed following TMS over the left primary motor cortex at 0.7 and at 1.1× MEP resting threshold at C-T intervals that ranged from negative 50 to positive 50 ms. The recruitment curves of MEPs and TEPs had a similar shape, and statistically significant differences between the sigmoid function parameters of MEPs and TEPs were not found. Anodal tsESS resulted in early MEP depression followed by long-latency MEP facilitation of both ankle plantar flexors and extensors. TEPs of ankle plantar flexors and extensors were increased regardless TMS intensity level. Subthreshold and suprathreshold TMS induced short-latency TEP facilitation that was larger in the TEPs ipsilateral to TMS. Noninvasive transpinal stimulation affected ipsilateral and contralateral actions of corticospinal neurons, while corticocortical and corticospinal descending volleys increased TEPs in both limbs. Transpinal and transcortical stimulation is a noninvasive neuromodulation method that alters corticospinal excitability and increases motor output of multiple spinal segments in humans.

Conflict of interest statement

Competing Interests: The author has declared that no competing interests exist.

Figures

Figure 1. Spatial spinal summation of MEPs and TEPs.

Rectified right tibialis anterior EMG following tsESS over the thoracolumbar region and TMS over the left primary motor cortex delivered at 1.3× tibialis anterior MEP resting threshold. In all paradigms TMS is the test stimuli and tsESS is the conditioning stimuli. At the conditioning-test intervals of 0 and 4 ms, the TEP following tsESS can be easily separated from the MEP based on latency and duration (A, B). However, at the negative C-T intervals of 8, 10, and 20 ms TEP and MEP do not occlude each other but are summated (C, D, E), and thus cannot be separated based on latency and duration. To counteract this neuronal phenomenon and establish the net effect of the conditioning stimulus, the control MEP values were subtracted from the conditioned TEP values and the control TEP values were subtracted from the conditioned MEP values in experiments that the conditioning stimulus was delivered at suprathreshold intensities. tsESS: transcutaneous electric stimulation of the spine. TMS: transcranial magnetic stimulation. MEP: motor evoked potential. TEP: transpinal evoked potential.

Figure 2. Recruitment curves of MEPs and TEPs.

(A) MEPs recorded from 14 subjects from the right (R) TA, SOL, MG, and PL muscles while seated are plotted against the maximum stimulator output, which was normalized to the associated MEP resting threshold. (B) TEPs recorded from 7 subjects from the right and left TA, SOL, MG, and PL muscles while seated are plotted against the stimulation intensities, which were normalized to TEP resting threshold. TA: tibialis anterior. SOL: soleus. MG: medialis gastrocnemius. MEPs: motor evoked potentials. TEPs: transpinal evoked potentials.

Figure 3. Effects of transcutaneous electric stimulation of the spine (tsESS) on TA MEPs.

(Aa, Ba) Waveform averages of the right TA MEPs from two representative subjects under control conditions (green lines) and following tsESS (black lines) for all conditioning-test (C-T) intervals tested. The action potential within the dotted circle identifies the right TA TEP induced by the conditioning tsESS stimuli. All EMGs are shown as captured and subtraction to counteract summation of MEPs and TEPs was not applied. (Ab, Bb) Overall mean amplitude of the conditioned right TA MEPs for the same subjects (subjects 4 and 10), in which the net conditioning stimulus effect (i.e., the TEPs induced by the conditioning tsESS were subtracted) is indicated. Asterisks indicate statistically significant differences of conditioned MEPs from control values (P<0.05; one-way ANOVA). Error bars denote the SEM. TA: tibialis anterior. MEPs: motor evoked potentials. TEPs: transpinal evoked potentials. tsESS: transcutaneous electric stimulation of the spine.

Figure 4. Effects of noninvasive transpinal stimulation on MEPs.

Amplitude of MEPs recorded from the right (R) soleus (SOL), medialis gastrocnemius (MG), tibialis anterior (TA), and peroneus longus (PL) muscles following transcutaneous electric stimulation of the spine over the thoracolumbar region from 14 subjects. On the abscissa the conditioning-test interval (ms) tested is indicated. A negative C-T interval denotes that transcutaneous electric stimulation of the spine was delivered before TMS. Asterisks indicate statistically significant differences of conditioned MEPs from control values (P<0.05; one-way ANOVA). Error bars denote the SEM.

Figure 5. Effects of subthreshold TMS on TEPs.

(A) Waveform averages of the right (R) and left (L) soleus (SOL), medialis gastrocnemius (MG), tibialis anterior (TA), and peroneus longus (PL) TEPs from one subject under control conditions (green lines) and following subthreshold TMS (black lines) for all conditioning-test (C-T) intervals tested. (B) Overall mean amplitude of the conditioned TEPs for the same subject. Asterisks indicate statistically significant differences of conditioned TEPs from control values (P<0.05; one-way ANOVA). Error bars denote the SEM. TEPs: transpinal evoked potentials. tsESS: transcutaneous electric stimulation of the spine. TMS: transcranial magnetic stimulation.

Figure 6. Effects of subthreshold TMS on right and left TA TEPs.

(A) Waveform averages of the right (R) and left (L) TA TEPs in two additional subjects (subject 6 and subject 14) under control conditions (green dotted lines) and following subthreshold TMS (solid black lines) for all conditioning-test (C-T) intervals tested. (B) Overall mean amplitude of the conditioned TEPs for the same subjects. Asterisks indicate statistically significant differences of conditioned TEPs from control values (P<0.05; one-way ANOVA). Error bars denote the SEM.

Figure 7. Modulation of TEPs by subthreshold TMS.

Overall mean amplitude of TEPs recorded from the right (R) and left (L) soleus (SOL), medialis gastrocnemius (MG), tibialis anterior (TA), and peroneus longus (PL) muscles following transcranial magnetic stimulation (TMS) delivered at intensities that motor evoked potentials were not evoked. On the abscissa the conditioning-test (C-T) interval (ms) is indicated. A negative C-T interval denotes that TMS was delivered after transcutaneous electric stimulation of the spine. Symbols “*” and “§” denote statistically significant differences of conditioned TEPs from control values for the right or left side TEPs, respectively. Error bars denote the SEM.

Figure 8. Modulation of TEPs by suprathreshold TMS.

Overall mean amplitude of TEPs recorded from the right (R) and left (L) soleus (SOL), medialis gastrocnemius (MG), tibialis anterior (TA), and peroneus longus (PL) muscles following transcranial magnetic stimulation (TMS) delivered above TA MEP resting threshold. On the abscissa the conditioning-test (C-T) interval (ms) is indicated. A negative C-T interval denotes that TMS was delivered after transcutaneous electric stimulation of the spine. Symbols “*” and “§” denote statistically significant differences of conditioned TEPs from control values for the right or left side TEPs, respectively. Error bars denote the SEM.