Paired Stimulation Plasticity for Motor Recovery

Cervical spinal cord injury (SCI) often impairs the reach and grasp movements which are so important to independent living. Targeted neural stimulation is a promising approach to enhance neural connections and improve function. This involves activating different parts of a neural circuit using paired stimuli. By changing the precise time between the two stimuli, it is possible to increase or decrease connection strength. Many studies have applied this concept to cortical circuits, but comparatively little attention has been paid to the potential for sub-cortical plasticity to aid recovery. We know that reaching and grasping movements involve coordinated control by corticospinal and reticulospinal descending tracts, originating in the cortex and brainstem respectively. Thus, exploiting plasticity in sub-cortical circuits could access new avenues to improve rehabilitation. This project investigates two promising methods to induce plasticity in subcortical motor circuits in humans, both with and without SCI: Spinal Paired Associative Stimulation (Spinal PAS) and the Startle protocol. Spinal PAS combines transcranial magnetic stimulation (TMS) of the motor cortex with supramaximal peripheral nerve stimulation, while the Startle protocol pairs TMS with a loud acoustic stimulus. We hypothesize that Spinal PAS primarily targets corticospinal synapses, whereas the Startle protocol engages the cortico-reticulospinal system. The first aim is to elucidate the mechanisms of these protocols by assessing transmission in cortico- and reticulospinal pathways to motoneurons in humans with and without SCI. Understanding these mechanisms will guide the rational combination of Spinal PAS and Startle to achieve synergistic and amplified plasticity. The second aim is to develop strategies to enhance these plastic changes by combining stimulation with targeted tasks that engage subcortical networks. We will use grasping behaviors including precision grip and power grip in humans with and without SCI as complementary strategies to further boost plasticity and optimize functional recovery. The outcome will be a mechanism-driven, optimized stimulation protocol designed to maximize recovery of motor function. This research will generate fundamental knowledge to support innovative therapies for individuals with SCI and other neurological disorders affecting corticospinal and reticulospinal connections.