Cardiorespiratory fitness: A predictor of cortical plasticity in multiple sclerosis Ruchika Shaurya Prakash, a Erin M. Snook, b Kirk I. Erickson, a Stanley J. Colcombe, a Michelle W. Voss, a Robert W. Motl, b and Arthur F. Kramer a, ⁎ a Beckman Institute and Department of Psychology, University of Illinois at Urbana–Champaign, IL 61801, USA b Department of Kinesiology and Community Health, University of Illinois at Urbana–Champaign, IL 61801, USA Received 11 August 2006; revised 26 September 2006; accepted 3 October 2006 Available online 28 November 2006 Deficits in cognitive abilities are commonly observed among individuals with multiple sclerosis (MS). Recent neuroimaging studies have provided evidence for the existence of cortical plasticity in MS, with cognitively impaired participants recruiting additional brain areas to perform challenging tasks. The existence of altered cerebral activations in MS provides hope for the utilization of neural resources to reduce cognitive deficits that challenge everyday living in MS by employing alternative interventions such as cognitive and fitness training. In this study, we examined whether higher physical fitness levels enhance cognitive and neural plasticity in MS patients. The present study is the first to investigate the impact of cardiorespiratory fitness on cerebrovascular functioning of MS patients. 24 participants with relapsing–remitting MS were recruited for the study. All participants went through a fitness assessment and were scanned in a 3 T MRI system during the Paced Visual Serial Addition Test (PVSAT). Higher fitness levels were associated with faster behavioral performance and greater recruitment of right IFG/MFG, a region of the cerebral cortex recruited by MS patients during performance of PVSAT to purport- edly compensate for the cognitive deterioration attributable to MS. In contrast, lower levels of fitness were associated with enhanced ACC activity, suggestive of the presence of greater interference and the potential for error in lower fit MS participants. These results are promising, suggesting the need for further investigation of the utility of aerobic fitness training as a possible method to support the development of additional cortical resources in an attempt to counter the cognitive decline resulting from MS. Published by Elsevier Inc. Keywords: Relapsing–remitting multiple sclerosis; Cardiorespiratory fitness; Cognition; fMRI; Cortical adaptability Introduction Multiple sclerosis (MS) is the most common neurological disease among young and middle-aged adults, affecting an estimated 1,000,000 individuals worldwide (Kantarci and Win- gerchuk, 2006). This autoimmune disease involves demyelination and axonal damage in the central nervous system. The demyelina- tion and axonal damage interfere with neuronal conduction and are associated with MS-related symptoms of which cognitive impair- ment is a prominent symptom that is reported in 45–65% of people with MS (Rao et al., 1991; Bobholz and Rao, 2003). Deficits are frequently seen in working memory (processing of information in temporary storage), executive control functions (planning, sche- duling, and task coordination), attention and concentration, and speed of information processing. The deficits in cognitive function coincide with declines in brain structure (reductions in white and grey matter volume) and function (Bobholz and Rao, 2003). The decrements in cognitive function influence the quality of an individual’ s life, leading to disease-related unemployment, reduc- tions in activities of daily living, and compromised social relationships. Consequently, development of strategies to maintain or enhance cognitive function in MS is an important public health goal. In addition to the necessity of developing training programs that target amelioration of cognitive deficits in the MS population, recent neuroimaging studies have provided evidence for the existence of cortical plasticity in those with MS (Staffen et al., 2002; Penner et al., 2003; Filippi et al., 2004; Audoin et al., 2005). These studies, using a wide variety of cognitive tasks, have examined and found altered patterns of brain activation in MS. Most of these studies have reported similar brain areas to be activated by healthy controls and MS patients, but also report that MS patients show a greater extent of overall activation, thereby arguing for a compensatory mechanism of the recruited brain areas. Despite the cortical adaptability evidenced by MS patients research on the management of cognitive impairment in this population has been limited (Bobholz and Rao, 2003; Heesen et al., 2006). Current symptomatic treatments are cognitive rehabilitation (e.g., cognitive exercises/drills) and pharmacological management (e.g., disease-modifying agents). To date, there is limited scientific evidence that those treatments are effective, the treatments are often costly and time intensive, and pharmacological management, www.elsevier.com/locate/ynimg NeuroImage 34 (2007) 1238 – 1244 ⁎ Corresponding author. Fax: +1 217 244 6534. E-mail address: a-kramer@uiuc.edu (A.F. Kramer). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter. Published by Elsevier Inc. doi:10.1016/j.neuroimage.2006.10.003