title: Predictors and brain connectivity changes associated with arm motor function improvement from intensive practice in chronic stroke.
abstract: Background and Purpose:The brain changes that underlie 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.Results:Motor evoked potential (MEP) presence was associated 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 primary motor cortex (M1) activity became more correlated with other frontal motor regions after treatment. Resting state connectivity between affected hemisphere M1 and dorsal premotor area (PMAd) predicted recovery.Conclusions:Presence of motor evoked potentials in the affected motor cortex and its functional connectivity with PMAd may be useful in predicting recovery. Functional connectivity in the motor network shows a trends towards increasing after intensive robotic or non-robotic arm therapy. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00372411 \& NCT00333983.
authors.affiliation: 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.
authors.forename: George F
authors.initials: GF
authors.lastname: Wittenberg
authors.affiliation: North Florida/South Georgia Veterans Health System, Gainesville, FL, 32611, USA; University of Florida, Gainesville, FL, 32608, USA.
authors.forename: Lorie G
authors.initials: LG
authors.lastname: Richards
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, University of Maryland, Baltimore, MD, 21201, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Jones-Lush
authors.affiliation: Department of Radiology, University of Maryland, Baltimore, MD, 21201, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Roys
authors.affiliation: Department of Radiology, University of Maryland, Baltimore, MD, 21201, USA.
authors.forename: Rao P
authors.initials: RP
authors.lastname: Gullapalli
authors.affiliation: VA Cooperative Studies Program Coordinating Center, West Haven, CT, 06516, USA.
authors.forename: Suzy
authors.initials: S
authors.lastname: Yang
authors.affiliation: VA Cooperative Studies Program Coordinating Center, West Haven, CT, 06516, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Guarino
authors.affiliation: Providence VA Medical Center and VA Research and Development Center of Excellence, Center for Restorative and Regenerative Medicine, Brown University, Providence, RI, 02908, USA.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Lo
keywords: Predictors; brain connectivity; motor function; robotic