Cervical Spinal Cord Associative Plasticity

Associative plasticity has been used to promote functional recovery in patient populations, such as adults with spinal cord injuries (SCI). Using non-invasive neuromodulation approaches, pairing of motor cortical stimulation and peripheral nerve stimulation has been shown to augment motor responses and promote plasticity, primarily through the convergence of sensory afferent stimuli and descending cortical stimuli in the motor cortex.

However, prior work from the Carmel laboratory has shown that paired associative stimulation timed to converge in the cervical spinal cord induces significantly larger upper limb motor responses than if timed to converge in the motor cortex. While paired associative stimulation has shown promise for strengthening motor responses, it is unclear if plasticity from convergence of non-invasive stimuli in the spinal cord (termed spinal cord associative plasticity or SCAP) instead of the motor cortex can produce greater motor effects, and potentially greater promotion of movement recovery.

The goal of this present study is to test the effects of pairing sub-threshold hand motor cortical and median nerve stimulation targeted to induce plasticity in the cervical spinal cord, rather than in the motor cortex. The investigators aim to fill a knowledge gap regarding the ideal target of non-invasive stimulation to maximize associative plasticity for upper limb movement recovery. The study hypothesis is that pairing low-intensity stimulation of the hand motor cortex with low-intensity median nerve stimulation will produce associative plasticity in the cervical spinal cord measured through augmentation of motor responses in upper limb muscles.

Based on preliminary data, the investigators are performing a confirmatory study to test the physiological and behavioral effects of the paired brain and peripheral nerve protocol, called the SCAP-Nerve protocol. This protocol uses a specific set of TMS (transcranial magnetic stimulation) and PNS (peripheral nerve stimulation) parameters: targeting hand motor cortex at 90% resting motor threshold and targeting median nerve sensory afferents (with a nerve stimulus pulse duration of 1000 microseconds) at 90% resting motor threshold, precisely timed to converge in the cervical spinal cord.

This study will first be conducted with a single session of 90 trials of pairing in typically developing adults to confirm the cervical spinal cord as the ideal target and verify the present stimulation parameters as sufficient to promote induction of associative plasticity of sensorimotor connections for manual dexterity. Prior work from the Carmel laboratory has shown that the magnitude and duration of lasting effects of paired motor cortex and afferent stimulation is similar in rodents with and without neural injury.

This then drives the premise for this study that the identification of the cervical spinal cord as an ideal target for associative plasticity involving cortical and sensory afferents would inform translation to people suffering from neurological injuries such as spinal cord injury and cerebral palsy. The outcomes from this study could be translated to efficacy studies in these patient populations to determine if this plasticity is present in those populations as well. This could then lead to the investigation of whether pairing brain and afferent-targeted nerve stimulation for convergence in the cervical spinal cord can lead to clinically meaningful improvements in manual dexterity.

Inclusion criteria

• Willingness to participate in up to 4 sessions
• Maintenance of caffeine and exercise levels at time of sessions
• Ability to provide informed consent
• No known central or peripheral neurological disease or injury
• No known musculoskeletal injury of the tested arm or hand

Exclusion criteria

• Personal or family history of seizures
• Use of medications that lower seizure threshold
• History of implanted equipment including stimulators/pacemakers