Identification of critical areas for motor function recovery in chronic stroke subjects using voxel-based lesion symptom mapping Ryan Lo a,b , Darren Gitelman a,b,c , Robert Levy a,d , Justin Hulvershorn e , Todd Parrish a,b, ⁎ a Feinberg School of Medicine, Northwestern University, Chicago, IL, USA b Department of Radiology, Northstar Neuroscience, Seattle, WA, USA c Department of Neurology, Northstar Neuroscience, Seattle, WA, USA d Department of Neurological Surgery, Northstar Neuroscience, Seattle, WA, USA e Northstar Neuroscience, Seattle, WA, USA abstract article info Article history: Received 15 February 2009 Revised 30 June 2009 Accepted 19 August 2009 Available online 27 August 2009 Introduction: Previous stroke studies using fMRI or lesion characterization methods to study the preservation of motor performance have been limited in defining anatomical structure critical for functional performance. This study attempts to overcome this limitation by using voxel-based lesion symptom mapping (VLSM) to identify specific anatomical regions required for preservation of motor function. Methods: Forty-one moderate to moderately severe stroke subjects (upper extremity Fugl-Meyer between 28 and 50, Arm Motor Ability Test N 35) were imaged with a 1 mm isotropic T1-weighted volumetric sequence, and their motor performance was assessed. The T1 volume images were normalized to a symmetric template using SPM5 and oriented so the lesion appeared in the left hemisphere. The lesioned areas were manually segmented on the normalized T1 image. All 3D lesion maps were entered into the VLSM analysis. Areas showing significant correlations with functional performance measures were identified using the false discovery rate corrected at p ≤ 0.05. Results: The areas most correlated with a decrease in motor performance were at the junction of the corona radiata leading into the corticospinal tract. The Arm Motor Ability Test scores produced the most significant results, while the other measures showed similar anatomical patterns. Conclusion: The use of lesion symptom mapping in conjunction with behavioral measures produced anatomically specific results demonstrating that the area leading from the corticospinal tract to cortical motor areas is critical for maintaining hand motor performance after a stroke. This area may represent the joining of parallel redundant tracts that, when damaged, limit recovery potential. © 2009 Elsevier Inc. All rights reserved. Introduction Stroke remains the third leading cause of death in the United States and the leading cause of long-term disability worldwide. Recovery from stroke is varied and often results in deficits that can affect daily living. Because of this incomplete recovery, it is extremely important to have a comprehensive prognosis for patients so they understand the level of recovery to expect and which treatments may be applicable for their condition. However, an informed prognosis would require a complete understanding of the anatomical regions affected by the stroke, the brain's response to the stroke, and the subsequent effects on behavioral performance. The most debilitating factors associated with stroke are often the cognitive and motor deficits which affect daily living. There have been many recent functional magnetic resonance imaging (fMRI) studies investigating the effects of a stroke on the motor processing network and its associated areas in the brain (Johansen-Berg et al., 2002; Calautti and Jean-Claude, 2003; Ward et al., 2004). The hemiparesis in the current study resulted from the interruption of motor control signals that travel from the primary motor cortex (M1) through the corticospinal tract to the spinal cord. While the corticospinal tract is mainly comprised of white matter tracts from M1, there are additional fibers from the premotor cortex (PMC), primary sensory cortex (S1), and other secondary motor regions such as the supplemental motor area (SMA). These motor and sensory signals are integrated to allow for the performance of complex movements and to provide feedback about these movements. The integration of the multi-modal signals as well as coordination with the unaffected hemisphere is key for full recovery from stroke. Functional magnetic resonance imaging studies show that after a stroke, the motor cortex compensates for deficits in brain function by undergoing functional reorganization of the remaining healthy brain (Cao et al., 1998; Zemke et al., 2003; Ward et al., 2004; Hanlon et al., 2005; Cramer and Crafton, 2006; Stinear et al., 2007). Typically the reorganization results in increased activation in the contralesional NeuroImage 49 (2010) 9–18 ⁎ Corresponding author. 737 N. Michigan Ave, 16th floor, Chicago, IL 60611, USA. Fax: +1 312 926 5991. E-mail address: toddp@northwestern.edu (T. Parrish). 1053-8119/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2009.08.044 Contents lists available at ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/ynimg