Combining Optogenetic Stimulation and Motor Training Improves Functional Recovery and Perilesional Cortical Activity
Year: 2022
Authors: Conti E., Scaglione A., de Vito G., Calugi F., Pasquini M., Pizzorusso T., Micera S., Mascaro ALA., Pavone FS.
Autors Affiliation: CNR, Neurosci Inst, Via Moruzzi 1, I-56124 Pisa, Italy; Univ Florence, European Lab Nonlinear Spect, Florence, Italy; Univ Florence, Dept Phys & Astron, Florence, Italy; Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, Florence, Italy; Scuola Super Sant Anna, BioRobot Inst, Pisa, Italy; Scuola Super Sant Anna, Dept Excellence Robot & AI, Pisa, Italy; Ecole Polytech Fed Lausanne EPFL, Ctr Neuroprosthet, Bertarelli Fdn Chair Translat NeuroEngn, Lausanne, Switzerland; Ecole Polytech Fed Lausanne EPFL, Inst Bioengn, Bertarelli Fdn Chair Translat NeuroEngn, Lausanne, Switzerland; CNR, Natl Inst Opt, Florence, Italy.
Abstract: Background. An ischemic stroke is followed by the remapping of motor representation and extensive changes in cortical excitability involving both hemispheres. Although stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the remapping of motor representation of the single and combined treatments is largely unexplored. Objective. We investigated if spatio-temporal features of motor-related cortical activity and the new motor representations are related to the rehabilitative treatment or if they can be specifically associated to functional recovery. Methods. We designed a novel rehabilitative treatment that combines neuro-plasticizing intervention with motor training. In detail, optogenetic stimulation of peri-infarct excitatory neurons expressing Channelrhodopsin 2 was associated with daily motor training on a robotic device. The effectiveness of the combined therapy was compared with spontaneous recovery and with the single treatments (ie optogenetic stimulation or motor training). Results. We found that the extension and localization of the new motor representations are specific to the treatment, where most treatments promote segregation of the motor representation to the peri-infarct region. Interestingly, only the combined therapy promotes both the recovery of forelimb functionality and the rescue of spatio-temporal features of motor-related activity. Functional recovery results from a new excitatory/inhibitory balance between hemispheres as revealed by the augmented motor response flanked by the increased expression of parvalbumin positive neurons in the peri-infarct area. Conclusions. Our findings highlight that functional recovery and restoration of motor-related neuronal activity are not necessarily coupled during post-stroke recovery. Indeed the reestablishment of cortical activation features of calcium transient is distinctive of the most effective therapeutic approach, the combined therapy.
Journal/Review: NEUROREHABILITATION AND NEURAL REPAIR
Volume: 36 (2) Pages from: 1.5459683211056 to: 1.5459683211056
More Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project has received funding from the H2020 EXCELLENT SCIENCE -European Research Council (ERC) under grant agreement 692943 BrainBIT. In addition, it was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreements 785907 (HBP SGA2), and 654148 (Laserlab-Europe).KeyWords: photothrombotic stroke; optogenetic stimulation; motor training; calcium imaging; rehabilitationDOI: 10.1177/15459683211056656Citations: 13data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2024-10-20References taken from IsiWeb of Knowledge: (subscribers only)Connecting to view paper tab on IsiWeb: Click hereConnecting to view citations from IsiWeb: Click here