Abstract
Neurorehabilitation relies on core principles of neuroplasticity to activate and engage latent neural connections, promote detour circuits, and reverse impairments. Clinical interventions incorporating these principles have been shown to promote recovery and demote compensation. However, many clinicians struggle to find interventions centered on these principles in our nascent, rapidly growing body of literature. Not to mention the immense pressure from regulatory bodies and organizational balance sheets that further discourage time-intensive recovery-promoting interventions, incentivizing clinicians to prioritize practical constraints over sound clinical decision making. Modern neurorehabilitation practices that result from these pressures favor strategies that encourage compensation over those that promote recovery. To narrow the gap between the busy clinician and the cutting-edge motor recovery literature, we distilled 5 features found in early-phase clinical intervention studies—ones that value the more enduring biological recovery processes over the more immediate compensatory remedies. Filtering emerging literature through this lens and routinely integrating promising research into daily practice can break down practical barriers for effective clinical translation and ultimately promote durable long-term outcomes. This perspective is meant to serve a new generation of mechanistically minded and caring clinicians, students, activists, and research trainees, who are poised to not only advance rehabilitation science, but also erect evidence-based policy changes to accelerate recovery-based stroke care.
References
| 1. | Kitago, T, Krakauer, JW. Motor learning principles for neurorehabilitation. Handb Clin Neurol. 2013;110:93-103. Google Scholar | Crossref | Medline |
| 2. | Bernhardt, J, Hayward, KS, Kwakkel, G, et al. Agreed definitions and a shared vision for new standards in stroke recovery research: the Stroke Recovery and Rehabilitation Roundtable Taskforce. Neurorehabil Neural Repair. 2017;31:793-799. Google Scholar | SAGE Journals | ISI |
| 3. | Krakauer, JW, Carmichael, ST. Broken Movement: The Neurobiology of Motor Recovery After Stroke. MIT Press; 2017. Google Scholar | Crossref |
| 4. | Cirstea, MC, Levin, MF. Compensatory strategies for reaching in stroke. Brain. 2000;123(pt 5):940-953. doi:10.1093/brain/123.5.940 Google Scholar | Crossref | Medline |
| 5. | Dobkin, BH. Clinical practice: rehabilitation after stroke. N Engl J Med. 2005;352:1677-1684. Google Scholar | Crossref | Medline | ISI |
| 6. | Kalra, L. The influence of stroke unit rehabilitation on functional recovery from stroke. Stroke. 1994;25:821-825. Google Scholar | Crossref | Medline | ISI |
| 7. | Allred, RP, Jones, TA. Experience—a double edged sword for restorative neural plasticity after brain damage. Future Neurol. 2008;3:189-198. Google Scholar | Crossref | Medline |
| 8. | Hsu, JE, Jones, TA. Contralesional neural plasticity and functional changes in the less-affected forelimb after large and small cortical infarcts in rats. Exp Neurol. 2006;201:479-494. Google Scholar | Crossref | Medline | ISI |
| 9. | Allred, RP, Jones, TA. Maladaptive effects of learning with the less-affected forelimb after focal cortical infarcts in rats. Exp Neurol. 2008;210:172-181. Google Scholar | Crossref | Medline | ISI |
| 10. | Taub, E, Uswatte, G, Mark, VW, Morris, DMM. The learned nonuse phenomenon: implications for rehabilitation. Eura Medicophys. 2006;42:241-256. Google Scholar | Medline |
| 11. | Fisher, B, Woll, S. Considerations in the restoration of motor control. In: Montgomery, J , ed. Physical Therapy for Traumatic Brain Injury. Churchill Livingstone; 1995:55-78. Google Scholar |
| 12. | van Kordelaar, J, van Wegen, EEH, Nijland, RHM, et al. Assessing longitudinal change in coordination of the paretic upper limb using on-site 3-dimensional kinematic measurements. Phys Ther. 2012;92:142-151. Google Scholar | Crossref | Medline | ISI |
| 13. | Stinear, CM, Lang, CE, Zeiler, S, Byblow, WD. Advances and challenges in stroke rehabilitation. Lancet Neurol. 2020;19:348-360. Google Scholar | Crossref | Medline |
| 14. | Dobkin, BH. Progressive staging of pilot studies to improve phase III trials for motor interventions. Neurorehabil Neural Repair. 2009;23:197-206. Google Scholar | SAGE Journals | ISI |
| 15. | NIH Clinical Trials and You . The basics. Published May 14, 2015. Accessed September 11, 2020. https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics Google Scholar |
| 16. | Hubbard, KE, Dunbar, SD. Perceptions of scientific research literature and strategies for reading papers depend on academic career stage. PLoS One. 2017;12:e0189753. Google Scholar | Crossref | Medline |
| 17. | Hachinski, V, Donnan, GA, Gorelick, PB, et al. Stroke: working toward a prioritized world agenda. Int J Stroke. 2010;5:238-256. Google Scholar | SAGE Journals | ISI |
| 18. | Zeiler, SR, Hubbard, R, Gibson, EM, et al. Paradoxical motor recovery from a first stroke after induction of a second stroke: reopening a postischemic sensitive period. Neurorehabil Neural Repair. 2016;30:794-800. Google Scholar | SAGE Journals | ISI |
| 19. | Nudo, RJ, Jenkins, WM, Merzenich, MM, Prejean, T, Grenda, R. Neurophysiological correlates of hand preference in primary motor cortex of adult squirrel monkeys. J Neurosci. 1992;12:2918-2947. Google Scholar | Crossref | Medline | ISI |
| 20. | Pons, T, Garraghty, P, Ommaya, A, Kaas, J, Taub, E, Mishkin, M. Massive cortical reorganization after sensory deafferentation in adult macaques. Science. 1991;252:1857-1860. doi:10.1126/science.1843843 Google Scholar | Crossref | Medline | ISI |
| 21. | Krakauer, JW, Pine, ZM, Ghilardi, MF, Ghez, C. Learning of visuomotor transformations for vectorial planning of reaching trajectories. J Neurosci. 2000;20:8916-8924. Google Scholar | Crossref | Medline | ISI |
| 22. | Taylor, JA, Ivry, RB. Implicit and explicit processes in motor learning. In: Prinz, W, Beisert, M, Herwig, A, eds. Action Science. MIT Press; 2013:63-87. Google Scholar | Crossref |
| 23. | O’Shea, J, Revol, P, Cousijn, H, et al. Induced sensorimotor cortex plasticity remediates chronic treatment-resistant visual neglect. Elife. 2017;6:e26602. doi:10.7554/eLife.26602 Google Scholar | Crossref | Medline |
| 24. | Ganguly, K, Poo, MM. Activity-dependent neural plasticity from bench to bedside. Neuron. 2013;80:729-741. Google Scholar | Crossref | Medline | ISI |
| 25. | Roemmich, RT, Bastian, AJ. Closing the loop: from motor neuroscience to neurorehabilitation. Annu Rev Neurosci. 2018;41:415-429. Google Scholar | Crossref | Medline |
| 26. | Reisman, DS, Wityk, R, Silver, K, Bastian, AJ. Locomotor adaptation on a split-belt treadmill can improve walking symmetry post-stroke. Brain. 2007;130(pt 7):1861-1872. Google Scholar | Crossref | Medline |
| 27. | Taub, E, Uswatte, G, Elbert, T. New treatments in neurorehabilitation founded on basic research. Nat Rev Neurosci. 2002;3:228-236. Google Scholar | Crossref | Medline | ISI |
| 28. | Corbett, D, Carmichael, ST, Murphy, TH, et al. Enhancing the alignment of the preclinical and clinical stroke recovery research pipeline: consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable translational working group. Neurorehabil Neural Repair. 2017;31:699-707. Google Scholar | SAGE Journals | ISI |
| 29. | Winstein, C, Lewthwaite, R, Blanton, SR, Wolf, LB, Wishart, L. Infusing motor learning research into neurorehabilitation practice: a historical perspective with case exemplar from the accelerated skill acquisition program. J Neurol Phys Ther. 2014;38:190-200. Google Scholar | Crossref | Medline |
| 30. | Biernaskie, J, Corbett, D. Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury. J Neurosci. 2001;21:5272-5280. Google Scholar | Crossref | Medline | ISI |
| 31. | Nithianantharajah, J, Hannan, AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci. 2006;7:697-709. Google Scholar | Crossref | Medline | ISI |
| 32. | Rosbergen, ICM, Grimley, RS, Hayward, KS, et al. Embedding an enriched environment in an acute stroke unit increases activity in people with stroke: a controlled before-after pilot study. Clin Rehabil. 2017;31:1516-1528. doi:10.1177/0269215517705181 Google Scholar | SAGE Journals | ISI |
| 33. | Whyte, J, Dijkers, MP, Hart, T, et al. Development of a theory-driven rehabilitation treatment taxonomy: conceptual issues. Arch Phys Med Rehabil. 2014;95(1, suppl):S24-S32.e2. Google Scholar | Crossref |
| 34. | Kleim, JA, Jones, TA. Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage. J Speech Lang Hear Res. 2008;51:S225-S239. Google Scholar | Crossref | Medline |
| 35. | Kleim, JA, Hogg, TM, VandenBerg, PM, Cooper, NR, Bruneau, R, Remple, M. Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning. J Neurosci. 2004;24:628-633. Google Scholar | Crossref | Medline | ISI |
| 36. | Xu, T, Yu, X, Perlik, AJ, et al. Rapid formation and selective stabilization of synapses for enduring motor memories. Nature. 2009;462:915-919. Google Scholar | Crossref | Medline | ISI |
| 37. | Rioult-Pedotti, MS, Friedman, D, Donoghue, JP. Learning-induced LTP in neocortex. Science. 2000;290:533-536. Google Scholar | Crossref | Medline | ISI |
| 38. | Harms, KJ, Rioult-Pedotti, MS, Carter, DR, Dunaevsky, A. Transient spine expansion and learning-induced plasticity in layer 1 primary motor cortex. J Neurosci. 2008;28:5686-5690. Google Scholar | Crossref | Medline |
| 39. | Sanes, JN, Donoghue, JP. Plasticity and primary motor cortex. Annu Rev Neurosci. 2000;23:393-415. Google Scholar | Crossref | Medline | ISI |
| 40. | Krakauer, JW, Carmichael, ST, Corbett, D, Wittenberg, GF. Getting neurorehabilitation right: what can be learned from animal models? Neurorehabil Neural Repair. 2012;26:923-931. Google Scholar | SAGE Journals | ISI |
| 41. | Zeiler, SR, Krakauer, JW. The interaction between training and plasticity in the poststroke brain. Curr Opin Neurol. 2013;26:609-616. Google Scholar | Crossref | Medline | ISI |
| 42. | Guadagnoli, MA, Lee, TD. Challenge point: a framework for conceptualizing the effects of various practice conditions in motor learning. J Mot Behav. 2004;36:212-224. Google Scholar | Crossref | Medline | ISI |
| 43. | Onla-or, S, Winstein, CJ. Determining the optimal challenge point for motor skill learning in adults with moderately severe Parkinson’s disease. Neurorehabil Neural Repair. 2008;22:385-395. Google Scholar | SAGE Journals | ISI |
| 44. | Pollock, CL, Boyd, LA, Hunt, MA, Garland, SJ. Use of the challenge point framework to guide motor learning of stepping reactions for improved balance control in people with stroke: a case series. Phys Ther. 2014;94:562-570. Google Scholar | Crossref | Medline | ISI |
| 45. | Lotay, R, Mace, M, Rinne, P, Burdet, E, Bentley, P. Optimizing self-exercise scheduling in motor stroke using Challenge Point Framework theory. IEEE Int Conf Rehabil Robot. 2019;2019:435-440. Google Scholar | Medline |
| 46. | Kleim, JA, Barbay, S, Nudo, RJ. Functional reorganization of the rat motor cortex following motor skill learning. J Neurophysiol. 1998;80:3321-3325. Google Scholar | Crossref | Medline | ISI |
| 47. | Ellis, MD, Sukal-Moulton, T, Dewald, JPA. Progressive shoulder abduction loading is a crucial element of arm rehabilitation in chronic stroke. Neurorehabil Neural Repair. 2009;23:862-869. Google Scholar | SAGE Journals | ISI |
| 48. | Xu, J, Branscheidt, M, Schambra, H, et al. Rethinking interhemispheric imbalance as a target for stroke neurorehabilitation. Ann Neurol. 2019;85:502-513. Google Scholar | Crossref | Medline |
| 49. | Dromerick, AW, Lang, CE, Birkenmeier, RL, et al. Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS): a single-center RCT. Neurology. 2009;73:195-201. Google Scholar | Crossref | Medline | ISI |
| 50. | Winstein, CJ, Wolf, SL, Dromerick, AW, et al. Effect of a task-oriented rehabilitation program on upper extremity recovery following motor stroke: the ICARE randomized clinical trial. JAMA. 2016;315:571-581. Google Scholar | Crossref | Medline | ISI |
| 51. | Ward, NS, Brander, F, Kelly, K. Intensive upper limb neurorehabilitation in chronic stroke: outcomes from the Queen Square programme. J Neurol Neurosurg Psychiatry. 2019;90:498-506. Google Scholar | Crossref | Medline |
| 52. | Kwakkel, G, Van Wegen, EEH, Burridge, JH, et al. Standardized measurement of quality of upper limb movement after stroke: consensus-based core recommendations from the Second Stroke Recovery and Rehabilitation Roundtable. Neurorehabil Neural Repair. 2019;33:951-958. Google Scholar | SAGE Journals | ISI |
| 53. | Duncan, PW, Goldstein, LB, Matchar, D, Divine, GW, Feussner, J. Measurement of motor recovery after stroke: outcome assessment and sample size requirements. Stroke. 1992;23:1084-1089. doi:10.1161/01.str.23.8.1084 Google Scholar | Crossref | Medline | ISI |
| 54. | Nakayama, H, Jørgensen, HS, Raaschou, HO, Olsen, TS. Recovery of upper extremity function in stroke patients: the Copenhagen Stroke Study. Arch Phys Med Rehabil. 1994;75:394-398. Google Scholar | Crossref | Medline | ISI |
| 55. | Forkan, R, Pumper, B, Smyth, N, Wirkkala, H, Ciol, MA, Shumway-Cook, A. Exercise adherence following physical therapy intervention in older adults with impaired balance. Phys Ther. 2006;86:401-410. Google Scholar | Crossref | Medline | ISI |
| 56. | Grönstedt, H, Frändin, K, Bergland, A, et al. Effects of individually tailored physical and daily activities in nursing home residents on activities of daily living, physical performance and physical activity level: a randomized controlled trial. Gerontology. 2013;59:220-229. Google Scholar | Crossref | Medline | ISI |
| 57. | Morley, JE, Philpot, CD, Gill, D, Berg-Weger, M. Meaningful activities in the nursing home. J Am Med Dir Assoc. 2014;15:79-81. Google Scholar | Crossref | Medline |
| 58. | Wolf, SL, Winstein, CJ, Miller, JP, et al. Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. JAMA. 2006;296:2095-2104. Google Scholar | Crossref | Medline | ISI |
| 59. | Taub, E, Morris, DM. Constraint-induced movement therapy to enhance recovery after stroke. Curr Atheroscler Rep. 2001;3:279-286. Google Scholar | Crossref | Medline |
| 60. | Page, SJ, Sisto, S, Johnston, MV, Levine, P. Modified constraint-induced therapy after subacute stroke: a preliminary study. Neurorehabil Neural Repair. 2002;16:290-295. Google Scholar | SAGE Journals | ISI |
| 61. | Ostendorf, CG, Wolf, SL. Effect of forced use of the upper extremity of a hemiplegic patient on changes in function: a single-case design. Phys Ther. 1981;61:1022-1028. Google Scholar | Crossref | Medline | ISI |
| 62. | Kitago, T, Liang, J, Huang, VS, et al. Improvement after constraint-induced movement therapy: recovery of normal motor control or task-specific compensation? Neurorehabil Neural Repair. 2013;27:99-109. Google Scholar | SAGE Journals | ISI |
| 63. | Gauthier, LV, Taub, E, Perkins, C, Ortmann, M, Mark, VW, Uswatte, G. Remodeling the brain. Stroke. 2008;39:1520-1525. doi:10.1161/strokeaha.107.502229 Google Scholar | Crossref | Medline | ISI |
| 64. | Pedlow, K, Lennon, S, Wilson, C. Application of constraint-induced movement therapy in clinical practice: an online survey. Arch Phys Med Rehabil. 2014;95:276-282. Google Scholar | Crossref | Medline |
| 65. | Page, SJ, Levine, P, Sisto, S, Bond, Q, Johnston, MV. Stroke patients’ and therapists’ opinions of constraint-induced movement therapy. Clin Rehabil. 2002;16:55-60. Google Scholar | SAGE Journals | ISI |
| 66. | Wolf, SL. Revisiting constraint-induced movement therapy: are we too smitten with the mitten? Is all nonuse “learned?” and other quandaries. Phys Ther. 2007;87:1212-1223. Google Scholar | Crossref | Medline | ISI |
| 67. | Winstein, C, Wolf, SL, Schweighofer, N. Task-oriented training to promote upper extremity recovery. In: Stein, J, Harvey, R, Winstein, C, Zorowit, R, Wittenberg, G eds. Stroke Recovery and Rehabilitation. 2nd ed. Demos Medical; 2014; 597-636. Google Scholar | Crossref |
| 68. | Winstein, C, Varghese, R. Been there, done that, so what’s next for arm and hand rehabilitation in stroke? NeuroRehabilitation. 2018;43:3-18. Google Scholar | Crossref | Medline |
| 69. | Wang, C, Winstein, C, D’Argenio, DZ, Schweighofer, N. The efficiency, efficacy, and retention of task practice in chronic stroke. Neurorehabil Neural Repair. 2020;34:881-890. Google Scholar | SAGE Journals | ISI |
| 70. | Barker, RN, Gill, TJ, Brauer, SG. Factors contributing to upper limb recovery after stroke: a survey of stroke survivors in Queensland Australia. Disabil Rehabil. 2007;29:981-989. Google Scholar | Crossref | Medline | ISI |
| 71. | van Vliet, PM, Wulf, G. Extrinsic feedback for motor learning after stroke: what is the evidence? Disabil Rehabil. 2006;28:831-840. Google Scholar | Crossref | Medline | ISI |
| 72. | Wulf, G, Lewthwaite, R. Optimizing performance through intrinsic motivation and attention for learning: the OPTIMAL theory of motor learning. Psychon Bull Rev. 2016;23:1382-1414. Google Scholar | Crossref | Medline | ISI |
| 73. | Kapral, MK, Wang, H, Mamdani, M, Tu, JV. Effect of socioeconomic status on treatment and mortality after stroke. Stroke. 2002;33:268-273. Google Scholar | Crossref | Medline | ISI |
| 74. | Cox, AM, McKevitt, C, Rudd, AG, Wolfe, CDA. Socioeconomic status and stroke. Lancet Neurol. 2006;5:181-188. Google Scholar | Crossref | Medline | ISI |
| 75. | Lewthwaite, R, Winstein, CJ, Lane, CJ, et al. Accelerating stroke recovery: body structures and functions, activities, participation, and quality of life outcomes from a large rehabilitation trial. Neurorehabil Neural Repair. 2018;32:150-165. Google Scholar | SAGE Journals | ISI |
| 76. | Krakauer, JW, Kitago, T, Goldsmith, J, et al. Comparing a novel neuroanimation experience to conventional therapy for high-dose, intensive upper-limb training in subacute stroke: the SMARTS2 randomized trial. bioRxiv. Published online August 7, 2020. doi:10.1101/2020.08.04.20152538 Google Scholar | Crossref |
| 77. | Committee on Quality of Health Care in America, Institute of Medicine . Crossing the Quality Chasm: A New Health System for the 21st Century. National Academies Press; 2001. Google Scholar |
| 78. | Winstein, C. Thoughts about the negative results of clinical trials in rehabilitation medicine. Kinesiol Rev (Champaign). 2018;7:58-63. Google Scholar | Crossref |
| 79. | Mead, N, Bower, P. Patient-centredness: a conceptual framework and review of the empirical literature. Soc Sci Med. 2000;51:1087-1110. Google Scholar | Crossref | Medline | ISI |
| 80. | Rosenbaum, L. The whole ball game—overcoming the blind spots in health care reform. N Engl J Med. 2013;368:959-962. Google Scholar | Crossref | Medline | ISI |


