Transspinal Stimulation Plus Locomotor Training for SCI

Priming With High-Frequency Trans-spinal Stimulation to Augment Locomotor Benefits in Spinal Cord Injury

Locomotor training is often used with the aim to improve corticospinal function and walking ability in individuals with Spinal Cord Injury. Excitingly, the benefits of locomotor training may be augmented by noninvasive electrical stimulation of the spinal cord and enhance motor recovery at SCI. This study will compare the effects of priming locomotor training with high-frequency noninvasive thoracolumbar spinal stimulation. In people with motor-incomplete SCI, a series of clinical and electrical tests of brain and spinal cord function will be performed before and after 40 sessions of locomotor training where spinal stimulation is delivered immediately before either lying down or during standing.

Spinal cord injury (SCI) greatly impairs standing and walking ability, which severely compromises daily living activities. While these deficits are partially improved by locomotor training, even after multiple training sessions, abnormal muscle activity and coordination still persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits. As such, treatment interventions that effectively promote neuromodulation of spinal locomotor networks and strengthen neural connectivity of the injured human spinal cord in combination with physical rehabilitation are greatly needed. It is proposed that transcutaneous spinal cord (transspinal) stimulation as a method to synergistically 'prime' the nervous system to better respond to locomotor training. Transspinal stimulation alters motoneuron excitability over multiple spinal segments, a pre-requisite for functioning descending and local inputs. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after SCI is unknown. The goal of this clinical trial is to use high frequency (30 Hz) transspinal stimulation to prime locomotor training and ultimately improve standing, walking, and overall function in individuals with chronic incomplete SCI (iSCI). Forty-five individuals with iSCI will undergo 40 sessions of body weight-supported step training primed with high-frequency transspinal stimulation. Participants will be randomized to receive transspinal stimulation during standing (real or sham) or while supine (real). Aim 1 evaluates how priming locomotor training with high-frequency transspinal stimulation in SCI alters corticomotoneuronal connectivity strength, as indicated by motor evoked potentials recorded from the legs. Aim 2 evaluates how priming locomotor training with high-frequency transspinal stimulation in iSCI affects reorganization and appropriate engagement of spinal neuronal circuits. Finally, Aim 3 evaluates activity-based motor function, ability to stand and walk, and quality of life. These results will support the notion that tonic high-frequency transspinal stimulation strengthens corticomotoneuronal connectivity and improves spinal circuit organization through posture-dependent corticospinal neuroplasticity. It is anticipated that the information gained from this mechanistic clinical trial will greatly impact clinical practice. This is because in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation.

Locomotor Training, Transcutaneous Spinal Cord Stimulation, Lokomat, Peripheral Nerve Stimulation, H-Reflex, Spinal Neural Circuits, Neuroplasticity, Recovery

This is a mechanistic randomized clinical trial. We will enroll 45 individuals with SCI. We will use blocked randomization into three groups with a block size of nine, with stratification according to severity of SCI (ambulatory with assistive device, or not ambulatory).1 We will check after completion of intervention by all subjects in each group whether the groups are balanced or not regarding baseline motor function and perform tests of association accordingly.

Transspinal tonic stimulation of the thoracolumbar region will be delivered at a frequency of 30 Hz during standing with as needed body weight support (BWS) in a standing frame or in the Lokomat to ensure safety.

One sham group will be receiving transspinal stimulation during standing at an intensity where sensation is absent.

Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of non-invasive high frequency (e.g. 30 Hz) transcutaneous transspinal stimulation during standing followed by 30 minutes of assisted stepping robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.

Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of non-invasive high frequency (e.g. 30 Hz) transcutaneous transspinal stimulation while lying supine on a therapy table followed by 30 minutes of assisted stepping robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.

Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of sham transspinal stimulation during standing at an intensity where sensation is absent followed by 30 minutes of robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.

Neurophysiological assessments probing changes in excitatory and inhibitory spinal reflex excitability from interventions by recording amplitude modulation of the soleus H-reflex following posterior tibial and common peroneal nerves stimulation both at rest and during robotic-assisted stepping.

Neurophysiological measurements assessing changes in corticospinal excitability from the interventions by recording responses to single-pulse transcranial magnetic stimulation (TMS) at rest and during robotic-assisted stepping.

Inclusion Criteria: Willingness to comply with all study procedures and availability for the duration of the study. Ability to understand the consent form, and sign the consent form. Male or female, age 18-70 years old. In good general health as evidenced by medical history. Diagnosed with motor incomplete SCI (AIS C-D). Bone mineral density of the hip (proximal femur) T-score <3.5 SD from age- and gender-matched normative data. Lesion above thoracic (T) 10 to ensure absent lower motoneuron lesion. Presence of tendon reflexes to be able to elicit the soleus H-reflex. Absent permanent ankle joint contractures that prevent passive or active ankle movement because corticospinal and spinal excitability is based on the ankle angle. The ankle straps of the Lokomat require also flexible ankle joints. A diagnosis of first time SCI due to trauma, vascular, or orthopedic pathology. Time after SCI of more than 6 months. Stable medical condition without cardiopulmonary disease or cognitive impairment. Exclusion Criteria: Supraspinal lesions. Significant neuropathies of the peripheral nervous system. Significant degenerative neurological disorders of the spine or spinal cord. AIS A or B. Presence of pressure sores. Advanced urinary tract infection. Neoplastic or vascular disorders of the spine or spinal cord. Participation in an ongoing research study or new rehabilitation program. Pregnant women or women who suspect they may be, or may become pregnant will be excluded from participation because the risks of thoracolumbar stimulation to the fetus are unknown. People with cochlear implants, pacemaker, implanted infusion device, and/or implanted stimulators of any type and purpose will be excluded to avoid their malfunction due to stimulation. People with history of seizures. Medical conditions that increase the possibility of seizures. Medications that may change the seizure threshold.

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