title: Combining Dopaminergic Facilitation with Robot-Assisted Upper Limb Therapy in Stroke Survivors: A Focused Review.
abstract: Despite aggressive conventional therapy, lasting hemiplegia persists in a large percentage of stroke survivors. The aim of this article is to critically review the rationale behind targeting multiple sites along the motor learning network by combining robotic therapy with pharmacotherapy and virtual reality-based reward learning to alleviate upper extremity impairment in stroke survivors. Methods for personalizing pharmacologic facilitation to each individual's unique biology are also reviewed. At the molecular level, treatment with levodopa was shown to induce long-term potentiation-like and practice-dependent plasticity. Clinically, trials combining conventional therapy with levodopa in stroke survivors yielded statistically significant but clinically unconvincing outcomes because of limited personalization, standardization, and reproducibility. Robotic therapy can induce neuroplasticity by delivering intensive, reproducible, and functionally meaningful interventions that are objective enough for the rigors of research. Robotic therapy also provides an apt platform for virtual reality, which boosts learning by engaging reward circuits. The future of stroke rehabilitation should target distinct molecular, synaptic, and cortical sites through personalized multimodal treatments to maximize motor recovery.
authors.affiliation: From the Department of Physical Medicine and Rehabilitation, Harvard Medical School, Charlestown, Massachusetts (DAT, J-FD, FF, PB, RZ); University Hospital Virgen del Rocío, Seville, Spain (MP-B); Washington Hospital Center, Washington, DC (JGG); and Cajal Institute, Spanish National Research Council, Madrid, Spain (JP).
authors.forename: Duc A
authors.initials: DA
authors.lastname: Tran
authors.forename: Marta
authors.initials: M
authors.lastname: Pajaro-Blazquez
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Daneault
authors.forename: Jaime G
authors.initials: JG
authors.lastname: Gallegos
authors.forename: Jose
authors.initials: J
authors.lastname: Pons
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonato
authors.forename: Ross
authors.initials: R
authors.lastname: Zafonte
mesh_terms: D003131:Combined Modality Therapy; D015259:Dopamine Agents / Q000627:therapeutic use*; D005081:Exercise Therapy / Q000379:methods*; D006429:Hemiplegia / Q000188:drug therapy / Q000503:physiopathology / Q000534:rehabilitation*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D009473:Neuronal Plasticity / Q000187:drug effects; D012371:Robotics / Q000379:methods*; D020521:Stroke / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D000071939:Stroke Rehabilitation / Q000379:methods*; D017741:Survivors; D034941:Upper Extremity / Q000503:physiopathology
chemical_list: D015259:Dopamine Agents; D007980:Levodopa
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