Transspinal stimulation increases motoneuron output of multiple segments in human spinal cord injury

Lynda M Murray, Maria Knikou, Lynda M Murray, Maria Knikou

Abstract

Targeted neuromodulation strategies that strengthen neuronal activity are in great need for restoring sensorimotor function after chronic spinal cord injury (SCI). In this study, we established changes in the motoneuron output of individuals with and without SCI after repeated noninvasive transspinal stimulation at rest over the thoracolumbar enlargement, the spinal location of leg motor circuits. Cases of motor incomplete and complete SCI were included to delineate potential differences when corticospinal motor drive is minimal. All 10 SCI and 10 healthy control subjects received daily monophasic transspinal stimuli of 1-ms duration at 0.2 Hz at right soleus transspinal evoked potential (TEP) subthreshold and suprathreshold intensities at rest. Before and two days after cessation of transspinal stimulation, we determined changes in TEP recruitment input-output curves, TEP amplitude at stimulation frequencies of 0.1, 0.125, 0.2, 0.33 and 1.0 Hz, and TEP postactivation depression upon transspinal paired stimuli at interstimulus intervals of 60, 100, 300, and 500 ms. TEPs were recorded at rest from bilateral ankle and knee flexor/extensor muscles. Repeated transspinal stimulation increased the motoneuron output over multiple segments. In control and complete SCI subjects, motoneuron output increased for knee muscles, while in motor incomplete SCI subjects motoneuron output increased for both ankle and knee muscles. In control subjects, TEPs homosynaptic and postactivation depression were present at baseline, and were potentiated for the distal ankle or knee flexor muscles. TEPs homosynaptic and postactivation depression at baseline depended on the completeness of the SCI, with minimal changes observed after transspinal stimulation. These results indicate that repeated transspinal stimulation increases spinal motoneuron responsiveness of ankle and knee muscles in the injured human spinal cord, and thus can promote motor recovery. This noninvasive neuromodulation method is a promising modality for promoting functional neuroplasticity after SCI.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Transspinal evoked potentials (TEPs) in…
Fig 1. Transspinal evoked potentials (TEPs) in individuals with and without spinal cord injury (SCI).
Non-rectified TEP waveform averages recorded (N = 15, elicited at 0.2 Hz) bilaterally from ankle and knee muscles (solid black lines) in a healthy control participant (N-005) and two individuals with SCI presenting with American Spinal Injury Association Impairment Scale (AIS) D (R-003) and AIS A (R-010), respectively. Latencies of the soleus (SOL) maximal M-wave and H-reflex (dashed lines) along with all TEPs across individuals are also presented. MG: medial gastrocnemius; PL: peroneus longus; TA: tibialis anterior; MH: medial hamstring; LH: lateral hamstring; RF: rectus femoris; GRC: gracilis.
Fig 2. Transspinal evoked potential (TEP) recruitment…
Fig 2. Transspinal evoked potential (TEP) recruitment curves before and after transspinal stimulation in AIS C-D.
(A) TEPs normalized to the homonymous maximal TEP and plotted against normalized stimulation intensities to the S50-TEPmax obtained before transspinal stimulation training along with the sigmoid function fitted to the data. (B) Schematic representation of changes observed in the TEP recruitment input-output curves where red represents an increase and blue represents a decrease in the corresponding muscle from which the TEP was recorded. SOL: soleus; MG: medial gastrocnemius; TA: tibialis anterior; PL: peroneus longus; MH: medial hamstring; LH: lateral hamstring; RF: rectus femoris; GRC: gracilis. An asterisk indicates a significant difference before and after transspinal stimulation.
Fig 3. Transspinal evoked potential (TEP) recruitment…
Fig 3. Transspinal evoked potential (TEP) recruitment curves before and after transspinal stimulation in AIS A-B.
(A) TEPs normalized to the homonymous maximal TEP and plotted against normalized stimulation intensities to the S50-TEPmax obtained before transspinal stimulation training along with the sigmoid function fitted to the data. (B) Schematic representation of changes observed in the TEP recruitment input-output curves where red represents an increase and blue represents a decrease in the corresponding muscle from which the TEP was recorded. SOL: soleus; MG: medial gastrocnemius; TA: tibialis anterior; PL: peroneus longus; MH: medial hamstring; LH: lateral hamstring; RF: rectus femoris; GRC: gracilis. An asterisk indicates a significant difference before and after transspinal stimulation.
Fig 4. Transspinal evoked potential (TEP) recruitment…
Fig 4. Transspinal evoked potential (TEP) recruitment curves before and after transspinal stimulation in healthy control subjects.
(A) TEPs normalized to the homonymous maximal TEP and plotted against normalized stimulation intensities to the S50-TEPmax obtained before transspinal stimulation training along with the sigmoid function fitted to the data. (B) Schematic representation of changes observed in the TEP recruitment input-output curves where red represents an increase and blue represents a decrease in the corresponding muscle from which the TEP was recorded. SOL: soleus; MG: medial gastrocnemius; TA: tibialis anterior; PL: peroneus longus; MH: medial hamstring; LH: lateral hamstring; RF: rectus femoris; GRC: gracilis. An asterisk indicates a significant difference before and after transspinal stimulation.
Fig 5. Homosynaptic transspinal evoked potential (TEP)…
Fig 5. Homosynaptic transspinal evoked potential (TEP) depression before and after transspinal stimulation in spinal cord injury (SCI).
Overall percent change of TEPs recorded at 0.125, 0.2, 0.33 and 1.0 Hz from the associated TEP recorded at 0.1 Hz before (black lines) and after (green lines) transspinal stimulation training in individuals with (A) AIS C-D and (B) AIS A-B. SOL: soleus; MG: medial gastrocnemius; TA: tibialis anterior; PL: peroneus longus; MH: medial hamstring; LH: lateral hamstring; RF: rectus femoris; GRC: gracilis. Error bars indicate SE. An asterisk indicates a significant difference before and after transspinal stimulation.
Fig 6. Postactivation transspinal evoked potential (TEP)…
Fig 6. Postactivation transspinal evoked potential (TEP) depression upon paired transspinal stimuli before and after transspinal stimulation in spinal cord injury (SCI).
Overall amplitude of the second TEP (TEP2) as a percentage of the first mean homonymous TEP amplitude (TEP1) evoked at interstimulus intervals of 500, 300, 100 and 60 ms at a constant stimulation frequency of 0.2 Hz for participants with (A) AIS C-D and (B) AIS A-B. SOL: soleus; MG: medial gastrocnemius; TA: tibialis anterior; PL: peroneus longus; MH: medial hamstring; LH: lateral hamstring; RF: rectus femoris; GRC: gracilis. Error bars indicate SE. An asterisk indicates a significant difference before and after the transspinal stimulation.
Fig 7. Homosynaptic and postactivation transspinal evoked…
Fig 7. Homosynaptic and postactivation transspinal evoked potential (TEP) depression before and after transspinal stimulation in healthy control subjects.
(A) Overall percent change of TEPs recorded at 0.125, 0.2, 0.33 and 1.0 Hz from the associated TEP recorded at 0.1 Hz before (black lines) and after (green lines) transspinal stimulation training. (B) Overall amplitude of the second TEP (TEP2) as a percentage of the first homonymous mean TEP (TEP1) evoked at interstimulus intervals of 500, 300, 100 and 60 ms at a constant stimulation frequency of 0.2 Hz. SOL: soleus; MG: medial gastrocnemius; TA: tibialis anterior; PL: peroneus longus; MH: medial hamstring; LH: lateral hamstring; RF: rectus femoris; GRC: gracilis. Error bars indicate SE. An asterisk indicates a significant difference before and after transspinal stimulation.

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