A functional MRI study of cortical activations associated with object manipulation in patients with MS

Abstract

Previous functional magnetic resonance imaging (fMRI) studies of simple motor tasks have shown that in patients with multiple sclerosis (MS), there is an increased recruitment of several regions part of a complex sensorimotor network. These studies have suggested that this might be the case because patients tend to activate, when performing a simple motor task, regions that are usually activated in healthy subjects during the performance of more complex tasks due to the presence of subcortical structural damage. In this study, we tested this hypothesis by comparing the patterns of cortical activations during the performance of two tasks with different levels of complexity from 16 MS patients and 16 age- and sex-matched controls. The first task (simple) consisted of flexion–extension of the last four fingers of the right hand, and the second task (complex) consisted of object manipulation. During the simple task, MS patients had, when compared to controls, more significant activations of the supplementary motor area (SMA), secondary sensorimotor area, posterior lobe of the cerebellum, superior parietal gyrus (SPG), and inferior frontal gyrus (IFG). These three latter regions are part of a fronto-parietal circuit, whose activation occurs typically in the contralateral hemisphere of healthy subjects during object manipulation, as shown also by the present study. During the performance of the complex task, MS patients showed an increased bilateral recruitment of several areas of the fronto-parietal circuit associated with object manipulation, as well of several other areas, which were mainly in the frontal lobes. This study confirms that some of the regions that are activated by MS patients during the performance of simple motor tasks are part of more complex pathways, recruited by healthy subjects when more complex and difficult tasks have to be performed.

Introduction

Although the last few years have witnessed a dramatically increased application of modern structural magnetic resonance (MR) techniques, capable to provide accurate estimates of the extent and severity of tissue damage, to the in vivo assessment of patients with multiple sclerosis (MS) (Filippi et al., 2002c), the strength of the correlation between clinical and MR imaging (MRI) findings remains moderate (Filippi et al., 2002c). One of the potential factors that has been considered to explain this discrepancy between clinical and MRI findings is the presence of functional cortical changes, which might contribute to the maintenance of a normal level of function, despite the presence of widespread tissue damage Filippi et al., 2002a, Lee et al., 2000, Reddy et al., 2000a, Reddy et al., 2002, Rocca et al., 2002a. Conversely, the inefficiency of the adaptive properties of the cortex might be an additional factor responsible for the accumulation of MS irreversible disability Filippi et al., 2002b, Rocca et al., 2002b.

Against this background, functional magnetic resonance imaging (fMRI) studies of MS have been performed, mainly using simple motor tasks with the dominant hand. These studies have shown, in patients with MS, an increased recruitment of several brain regions, which are considered to be part of a complex sensorimotor network, which includes the primary and secondary sensorimotor cortices, as well as regions in the frontal and parietal lobes Filippi et al., 2002a, Filippi et al., 2002b, Lee et al., 2000, Pantano et al., 2002a, Pantano et al., 2002b, Reddy et al., 2000a, Reddy et al., 2002, Rocca et al., 2002a, Rocca et al., 2002b. Many of these studies also showed a strong correlation between the extent of functional cortical changes and several MRI metrics of structural tissue damage Filippi et al., 2002b, Lee et al., 2000, Pantano et al., 2002b, Reddy et al., 2000a, Reddy et al., 2002, Rocca et al., 2002a, Rocca et al., 2002b. This finding has been interpreted as evidence that cortical functional reorganization might yet be an additional factor with the potential to limit the clinical impact of MS-related subcortical injury. In other words, it has been suggested that MS patients, when performing a simple motor task, might tend to activate regions that are activated in normal individuals when performing complex tasks as a result of the presence of structural disease-related damage to the white matter. This hypothesis has never been tested directly.

This study was planned to gain additional insight into the mechanisms of cortical functional reorganization in MS. To this aim, we analyzed and compared the patterns of movement-associated cortical activations following two tasks with different levels of complexity, using fMRI and a general search method.