Brain reorganization during attention and memory tasks in multiple sclerosis: Insights from functional MRI studies Caterina Mainero a,b, * , Patrizia Pantano c , Francesca Caramia c , Carlo Pozzilli b a Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA b Section of Neurology, Department of Neurological Sciences, University ‘‘La Sapienza’’, Rome, Italy c Section of Neuroradiology, Department of Neurological Sciences, University ‘‘La Sapienza’’, Rome, Italy Received 30 May 2005; received in revised form 12 July 2005; accepted 10 August 2005 Available online 19 April 2006 Abstract Deficits in memory and attention frequently occur during the course of multiple sclerosis (MS). In patients with MS the severity of cognitive manifestations is not closely related to indices of structural brain damage on both conventional and non conventional magnetic resonance imaging (MRI). It is conceivable that the ability of the brain to compensate for tissue impairment or loss may contribute to the maintenance of normal performance despite scattered brain lesions. Accordingly, using functional MRI (fMRI), patients with multiple sclerosis showed a greater extent of brain activation during motors tasks than controls. Changes in functional organization of the cerebral cortex have also been reported by fMRI studies comparing the activation patterns during cognitive tasks in patients with MS and in healthy subjects. Differences in patients’ selection, activation paradigm, experimental design and MR acquisition parameters make, however, the results obtained from fMRI studies difficult to be compared and may explain, at least partially, some discrepant findings. Nevertheless, fMRI studies provide a new interesting way of understanding how the brain can change its functional organization in response to MS pathology, and might be useful in the study of the effects of either rehabilitation or pharmacological agents on brain plasticity. D 2006 Elsevier B.V. All rights reserved. Keywords: Functional MRI; Neuroplasticity; Multiple sclerosis; Cognitive impairment; Memory; Attention 1. Introduction Cognitive dysfunction is a frequent finding in patients with MS [1–3]. Deficits in memory, attention, and speed of information processing are typical, and about 30% to 70% of patients experience impairment in these cognitive domains during the course of the disease [2,4]. Cognitive impairment may be present in the earliest stages of MS, even in the absence of clinical disability [5,6]. Several studies have shown that the extent and severity of the macroscopic and microscopic brain changes seen on conventional and non-conventional MRI are related to neuropsychologic measures of cognitive performance in MS [7–11]. The correlation, however, is far from perfect, and the pathological mechanisms underlying cognitive dysfunction in MS are still largely unexplained. One explanation for the weak relationship between neuropsy- chological deficits and conventional measures of disease burden in MS is that neuroplasticity, the ability of the brain to respond to various insults, allows adaptive reorganization of cognitive functions to limit impairment, despite wide- spread tissue damage. Blood oxygenation level dependent (BOLD) fMRI is a technique with relatively high spatial and temporal resolution that allows noninvasive mapping of brain activity related to specific cognitive tasks. fMRI has made possible the identification of large-scale activation patterns associated with higher-order cognitive processes in healthy subjects [12], as well as the monitoring of functional 0022-510X/$ - see front matter D 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2005.08.024 * Corresponding author. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Bldg 149, 13th Street, Charlestown, MA 02129, USA. Tel.: +1 617 724 7746; fax: +1 617 726 7422. E-mail addresses: caterina@nmr.mgh.harvard.edu, caterina.mainero@uniroma1.it (C. Mainero). Journal of the Neurological Sciences 245 (2006) 93 – 98 www.elsevier.com/locate/jns