Open Peer Review RESEARCH ARTICLE Predictors and brain connectivity changes associated with arm motor function improvement from intensive practice in chronic stroke [version 2; peer review: 1 approved, 2 approved with reservations] Previously titled: Predictors and brain connectivity changes associated with arm motor function improvement from intensive robotic practice in chronic stroke George F. Wittenberg , Lorie G. Richards , Lauren M. Jones-Lush , Steven R. Roys , Rao P. Gullapalli , Suzy Yang , Peter D. Guarino , Albert C. Lo 8 Department of Veterans Affairs (VA) Maryland Health Care System, Geriatrics Research, Education and Clinical Center, and Maryland Exercise & Robotics Center of Excellence, Baltimore, MD, 21201, USA Departments of Neurology, Physical Therapy and Rehabilitation Science, Internal Medicine, Older Americans Independence Center, University of Maryland, Baltimore, MD, 21201, USA North Florida/South Georgia Veterans Health System, Gainesville, FL, 32611, USA University of Florida, Gainesville, FL, 32608, USA Department of Physical Therapy and Rehabilitation Science, University of Maryland, Baltimore, MD, 21201, USA Department of Radiology, University of Maryland, Baltimore, MD, 21201, USA VA Cooperative Studies Program Coordinating Center, West Haven, CT, 06516, USA Providence VA Medical Center and VA Research and Development Center of Excellence, Center for Restorative and Regenerative Medicine, Brown University, Providence, RI, 02908, USA Abstract The brain changes that underlie Background and Purpose: therapy-induced improvement in motor function after stroke remain obscure. This study sought to demonstrate the feasibility and utility of measuring motor system physiology in a clinical trial of intensive upper extremity rehabilitation in chronic stroke-related hemiparesis. Methods: This was a substudy of two multi-center clinical trials of intensive robotic and intensive conventional therapy arm therapy in chronic, significantly hemiparetic, stroke patients. Transcranial magnetic stimulation was used to measure motor cortical output to the biceps and extensor digitorum communus muscles. Magnetic resonance imaging (MRI) was used to determine the cortical anatomy, as well as to measure fractional anisotropy, and blood oxygenation (BOLD) during an eyes-closed rest state. Region-of-interest time-series correlation analysis was performed on the BOLD signal to determine interregional connectivity. Functional status was measured with the upper extremity Fugl-Meyer and Wolf Motor Function Test. Motor evoked potential (MEP) presence was associated Results: with better functional outcomes, but the effect was not significant when considering baseline impairment. Affected side internal capsule fractional anisotropy was associated with better function at baseline. Affected side 1,2 3,4 5 6 6 7 7 8 1 2 3 4 5 6 7 8 Reviewer Status Invited Reviewers version 2 (revision) 28 Feb 2017 version 1 31 Aug 2016 1 2 3 report report report report , John Hopkins School of Argye E. Hillis Medicine, Baltimore, USA 1 , Heinrich Heine University Rudiger Seitz Düsseldorf, Düsseldorf, Germany 2 31 Aug 2016, :2119 ( First published: 5 ) https://doi.org/10.12688/f1000research.8603.1 28 Feb 2017, :2119 ( Latest published: 5 ) https://doi.org/10.12688/f1000research.8603.2 v2 Page 1 of 17 F1000Research 2017, 5:2119 Last updated: 03 APR 2020