Enhancing Corticospinal Excitability to Improve Functional Recovery

Restoration of upper extremity function is often the top rehabilitation goal for persons who have sustained a cervical spinal cord injury (SCI). Following SCI, beyond the disruption caused by the injury itself, maladaptive cortical reorganization further limits descending corticospinal drive. Therefore, therapies aimed at increasing the descending drive provided by corticospinal and other descending supraspinal tracts could be beneficial adjuncts to commonly used rehabilitation therapies. While many rehabilitation research strategies for improving function following SCI target the spinal circuitry, relatively few rehabilitative approaches are directed toward promoting supraspinal neuroplasticity to reduce impairment by increasing volitional control. Spectacular high-tech interventions and elegant high-tech outcome measures generate a great deal of excitement in the scientific world. However, the technological investment and training required for these approaches and the questionable clinical meaningfulness of the outcomes is a major limitation to their real-world value. Transcranial direct current stimulation (tDCS) is a clinically accessible form of non-invasive brain stimulation (NIBS) that has been shown to improve upper extremity function in persons with SCI. Clinical accessibility and the potential for prolonged modulation of cortical excitability make tDCS is an attractive tool for non-invasive modulation of corticospinal excitability. Beyond traditional tDCS, intriguing recent studies in non-disabled individuals suggest a novel form of NIBS, transcranial pulsed current stimulation (tPCS), may be more effective for inducing changes in corticospinal excitability. tPCS utilizes unidirectional, positive pulses of current separated by brief interpulse intervals rather than continuous direct current. Some evidence from our lab and others indicates that patterned stimulation has a larger influence on neural excitability than uniform stimulation. Importantly, the efficacy of NIBS is dependent upon stimulation site. Since persons with tetraplegia have bimanual impairments, it has been suggested that bihemispheric anodal (excitatory) tDCS may be of value. Bihemispheric anodal tDCS has been studied in non-disabled individuals; this approach was found to be safe and was associated with improved bimanual control. However, the value of this approach has not previously been assessed in persons with tetraplegia. The investigators propose a randomized, sham-controlled crossover study in which two forms of NIBS (tDCS and tPCS) will be compared with a sham-control intervention to determine their relative efficacy for improving upper extremity strength and motor control (Aim 1) and corticospinal excitability (Aim 2) in individuals with chronic (≥ 6 months) tetraplegia. The efficacy of two different stimulation montages, uni- and bihemispheric, will also be compared (Aim 3). Subjects will receive a single session of each NIBS condition (unihemispheric tDCS, bihemispheric tDCS, unihemispheric tPCS, bihemispheric tPCS) and a sham-control condition.