Stage I Cross-Over Award Winner: Ela B. Plow


Summary:

Improving Spinal Cord Injury Rehabilitation Interventions by Retraining the Brain with Stimulation: Applying Concepts from Stroke

Summary: In line with the mission of Conquer Paralysis Now (CPN), we aim to achieve functional recovery in spinal cord injury (SCI) by addressing a neglected issue– challenges imposed by the brain in rehabilitation of patients with SCI. To this end, we will apply concepts evidenced in stroke to help counter brain’s maladaptation and maximize recovery in individuals living with SCI. Injury to the spinal cord remains one of the most common and debilitating causes of long-term disability among young adults. To affect its burden, we focus on recovery of the upper limbs in quadriplegia resulting from an injury to the cervical spinal cord because it is the most common and debilitating form of SCI and it imposes the greatest burden on healthcare. In addition, 75% of quadriplegic patients would prefer to have their upper limb function restored than any other deficit. Our proposal is based on the premise that restoring upper limb function is challenging in chronic quadriplegia due to maladaptive processes of plasticity occurring in the brain. Following an injury, as patients increasingly rely on using their stronger muscles above the lesion at the cost of paralyzed muscles below the lesion, motor cortices in the brain lose memory of the paralyzed muscles, while memory of the stronger muscles magnifies into territories occupied by paralyzed muscles. This maladaptation hinders rehabilitative efforts. Though rehabilitation help restore memory of the paralyzed muscles, the process is arduous, inconsistent and weakly effective. 

Our solution to maximize rehabilitative outcomes in SCI derives from concepts evidenced to be most critical for upper limb recovery in stroke. Similar to SCI, over-use of the intact upper limb in stroke weakens brain’s memory of the paralytic upper limb. To help restore memories, several hundred groups in stroke, including our own, electrically stimulate regions of the motor cortex in the brain that are dedicated to the paralytic upper limb. The approach facilitates adaptive plasticity, where memory of the paralyzed limb is restored, and as such individuals become increasingly responsive to rehabilitation. In line with these concepts, here, we aim to harness the brain’s extraordinary capacity for fast-paced redistribution of memories using brain stimulation in SCI. We hypothesize that stimulating the brain would help re-train its memory of weaker muscles below the lesion in SCI and potentiate greater recovery in rehabilitation. Our efforts to translate would be even more successful in SCI than in stroke because unlike stroke, an injury to the spinal cord often spares the brain and its pathways to the weak muscles. Although seemingly counter-intuitive at first given that pathways are damaged at the spinal cord, signals from the brain to the weaker muscles can still be transmitted because a vast majority of patients have spared pathways due to >65% of injuries being incomplete. In short, stimulating cortical regions that represent weak muscles in SCI, based on concepts derived from stroke, is a novel, disruptive ‘out-of-box’ concept because it aims to recruit the most consistently spared neuronal resources in SCI, an approach that inevitably carries high-risk yet holds high-potential to maximize rehabilitative outcomes.

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