Enhancing STDP After Spinal Cord Injury

VA Office of Research and Development62 enrolled

Overview

The overall goal is to develop new clinical approaches to restore limb function after spinal cord injury (SCI). Corticospinal tract (CST) axons are involved in controlling limb function. Paired pulse induced spike-timing dependent plasticity (STDP) enhances synaptic strength between residual CST axons and spinal motoneurons (SMNs) resulting in temporary improvements in limb function in humans with incomplete SCI. Motor training will be combined with paired-pulse STDP stimulation to further enhance plasticity and behavioral recovery.

To induce STDP with paired pulse, corticospinal volleys evoked by either transcranial magnetic stimulation over the primary motor cortex for upper extremities or electrical stimulation over the thoracic spine for lower extremities arrive at corticospinal-motor neuronal synapses of upper- or lower-limb muscles, 1-2 ms before antidromic potentials were elicited in motor neurons by electrical stimulation of corresponding peripheral nerves.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Spinal Cord Injury

Interventions

STDPOTHER

Paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined time.

TrainingBEHAVIORAL

The participant will be asked to perform exercises using their hands and arms.

Sham STDPOTHER

Sham or fake paired stimulation will be given to the brain and to a peripheral nerve so that the messages are received at the spinal cord at predetermined times.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Participants who are unimpaired healthy controls: * Male and females between ages 18-85 years * Right handed * Able to complete precision grips with both hands * Able to complete full wrist flexion-extension bilaterally * Able to walk unassisted * Able to complete full ankle flexion-extension bilaterally Participants who have had a spinal cord injury: * Male and females between ages 18-85 years * SCI ( 6 months of injury) * Spinal Cord injury at or above L5 * The ability to produce a visible precision grip force with one hand * Able to perform some small wrist flexion and extension * The ability to perform a small visible contraction with dorsiflexion and hip flexor muscles * No subjects will be excluded based on their race, religion, ethnicity, gender or HIV status. * ASIA A,B,C, or D Exclusion Criteria: Exclusion criteria for enrollment For SCI and Healthy Control Subjects (4-8 exclusion for non-invasive brain stimulation only): * Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease * Any debilitating disease prior to the SCI that caused exercise intolerance * Premorbid, ongoing major depression or psychosis, altered cognitive status * History of head injury or stroke * Metal plate in skull * History of seizures * Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold (see appendix 2) * Pregnant females * Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida, MS, or herniated disk * Individuals with scalp shrapnel, cochlear implants, or aneurysm clips.

Locations (1)

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, United States

Outcomes

Primary Outcomes

Functional Assessment

The Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) assessment is a standardized test of functional abilities of the hand. We measure time required to complete the GRASSP test for upper extremity functional assessment. 10-m walk test is used to measure walking speed for lower extremity functional assessment. The time to complete the task is assessed in seconds for both measurements and normalized as percentage of Baseline. Normalization to baseline allows comparison across two different tasks. For STDP, STDP+Training, and Sham-STDP+Training groups, either GRASSP or 10-m walk test was performed in each participant depending on the targeted muscle. For Multisite-STDP + Training group, both GRASSP and 10-m walk test were performed in each participant and the average of two tests were reported below.

Time frame: Measured at baseline, after 10-20 sessions, and follow up (after 6 months) for STDP, STDP+Training, and Sham-STDP+Training groups . Measured at baseline, after 20 and 40 sessions, and follow up (after 9 months) for Multisite-STDP + Training group.

Secondary Outcomes

Amplitude of Motor Evoked Potential (MEP)

We measure amplitude of a motor evoked potential evoked by transcranial magnetic stimulation (TMS) or thoracic spine stimulation. The amplitude of MEP is assessed in millivolts and normalized as percentage of Baseline. Normalization to baseline is necessary to allow comparison across different muscles because the targeted muscle is different for each individual depending on the level of injury.

Time frame: Measured at baseline, after 10-20 sessions, and follow up (after 6 months) for STDP, STDP+Training, and Sham-STDP+Training groups . Measured at baseline and after 20 and 40 sessions for Multisite-STDP + Training group.

Maximum Voluntary Contraction

We measure maximum voluntary contraction (MVC) of muscles recorded by electromyography (EMG) in the targeted muscle(s). Average of muscles was reported for Multisite-STDP + Training group. The maximum voluntary contraction is assessed in millivolts and normalized as percentage of Baseline. Normalization to baseline is needed to allow comparison across different muscles because the targeted muscle is different for each individual depending on the level of injury.

Data from ClinicalTrials.gov

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