Neuromodulation to Improve Grasping Function After SCI

The investigators will use paired corticospinal-motoneuronal stimulation (PCMS) in combination with intermittent theta burst stimulation (iTBS). During PCMS, the investigators will use paired stimulation of the primary motor cortex by transcranial magnetic stimulation to elicit late corticospinal descending volleys and the peripheral nerve by electrical stimulation to improve corticospinal transmission and functional recovery in humans with cervical incomplete SCI. In addition, the investigators will investigate how priming iTBS affects neuroplasticity of late corticospinal descending volleys. The investigators will apply iTBS on primary motor cortex prior to paired stimulation with PCMS to facilitate late corticospinal volleys and potentiate the effect of PCMS. In Aim 2, the investigators propose to combine our neuromodulation in Aim 1 with long-term motor training focused on hand grasping to strengthen spared connections and promote functional improvement in humans with cervical incomplete SCI.

• iTBS (Other): Intermittent theta burst stimulation (iTBS) will be utilized since they have been reported to have a cortical neuromodulatory effect. The iTBS protocol will be applied over primary motor cortex to investigate its effect on corticospinal excitability and functional outcome. Theta burst stimulation (TBS) consists of bursts of pulses containing 3 pulses at 50 Hz (3 pulses per second) repeated at 200 ms intervals (5 Hz). During iTBS, a 2 second train of TBS is repeated every 10 seconds (600 pulses in 190 seconds).
• Sham iTBS (Other): Sham iTBS protocols will be applied with the same parameters as in iTBS protocol. However, sham coil will be used.
• PCMS (Other): During PCMS, paired stimulation of the primary motor cortex by transcranial magnetic stimulation to elicit late corticospinal descending volleys and the peripheral nerve by electrical stimulation will be used to improve corticospinal transmission.
• Sham PCMS (Other): During PCMS, the same parameters will be used as in real PCMS but sham TMS coil will be used with minimum PNS intensity.
• Exercise (Behavioral): The motor training will be focused on participant's hand motor function such as grasping function.

Primary outcomes

• Motor evoked potential (MEP) [For the first study, the time frame will be one day. For the second study, the time frame will be 4 weeks.]: Transcranial magnetic stimuli (TMS) will be delivered through a figure-of-eight coil over primary motor cortex to the optimal scalp position for activation of hand muscles. The optimal scalp position will be determined by moving the coil in small steps along the hand representations of the primary motor cortex to find the region where the largest MEP can be evoked with the minimum intensity in the targeted muscle. Twenty MEPs will be collected and the peak-to-peak amplitude of MEP will be averaged across trials.

Secondary outcomes

• Maximum voluntary contraction (MVC) [For the first study, the time frame will be one day. For the second study, the time frame will be 4 weeks.]: Individuals will perform a MVC of the targeted hand muscle (first dorsal interosseous) through surface EMG electrodes. The investigators will collect two MVC trials and use the average of the two.
• Grip force [For the first study, the time frame will be one day. For the second study, the time frame will be 4 weeks.]: Grip force will be assessed with hand grip dynamometer. The highest value of the three trials will be used.
• Toronto Rehabilitation Institute-Hand Function Test (TRI-HFT) [For the first study, the time frame will be one day. For the second study, the time frame will be 4 weeks.]: TRI-HFT is clinical assessment tool to measure specifically unilateral pinch and grasp hand function.

Sex: All, ages: 18 Years to 75 Years, accepts healthy volunteers

Inclusion Criteria:

For individuals with SCI:

* Ages 18-75 years
* Chronic SCI (≥1 year of injury)
* Cervical injury at C8 or above
* Individuals who have MEP responses in at least one FDI muscle

Exclusion Criteria:

* Uncontrolled medical problems including pulmonary or cardiovascular disease
* 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 such as antipsychotic drugs
* Pregnant females
* Individuals who suffer from a spinal cord disease such as spinal stenosis, spinal bifida or herniated cervical