Neurorehabilitation in the 21st Century: New Science, New Strategies, New Expectations.

Background: Neurorehabilitation is among the most vibrant areas of biomedical research. Its main strategy has been skill-specific practice, which often fails to produce adequate recovery. Now, new recognition of central nervous system (CNS) plasticity, new understanding of skills, and new technologies provide new strategies that enhance the efficacy of practice. Objectives: The substrate of a skill is a network of neurons and synapses that extends from cortex to spinal cord and is now called a heksor. A heksor changes continually to maintain the key features of its skill, the attributes that make the skill satisfactory. Muscle activity and kinematics may change; key features are maintained. Heksors share neurons and synapses. Through their concurrent changes, they keep the CNS in a negotiated equilibrium that enables each to maintain its skill. When CNS damage occurs, the goal is to enable damaged heksors to repair themselves. Results: Two new strategies enhance the efficacy of skill-specific practice. One increases plasticity. A damaged heksor shapes the additional plasticity through practice. The other targets beneficial plasticity to a critical site in a damaged heksor. This improves practice, enabling the heksor to achieve wider beneficial plasticity. In animals and humans, protocols that combine these strategies with practice enhance lasting recovery. Conclusions: The challenge is to develop, optimize, and validate these combined protocols. Computational modeling can accelerate the process. Controlled trials and comprehensive outcome assessments are essential. Pre-morbid factors and physiological measures may identify biomarkers that can predict efficacy or guide patient-specific protocol design. Many combined protocols will be noninvasive and suitable for home use.