Functional MRI in Malformations of Cortical Development: Activation of Dysplastic Tissue and Functional Reorganization Paolo Vitali, MD, Ludovico Minati, MSc, Ludovico D’Incerti, MD, Elio Maccagnano, MD, Nicola Mavilio, MD, Dario Capello, MD, Suela Dylgjeri, MD, Guido Rodriguez, MD, Silvana Franceschetti, MD, Roberto Spreafico, MD, Flavio Villani, MD From the Department of Clinical Neurophysiology, Di.M.I., University of Genova, Genova, Italy (PV, NM, DC, GR); Department of Neuroradiology (PV, LM,LD, EM), Scientific Direction (LM), and Department of Clinical Neurophysiology (SD, SF, RS, FV), Istituto Nazionale Neurologico “Carlo Besta,” Milan, Italy. Keywords: Malformations of cortical development, functional MRI, functional reorganization. Acceptance: Received January 6, 2007, and in revised form March 10, 2007. Accepted for publication April 29, 2007. Correspondence: Address correspon- dence to Paolo Vitali, MD, Department of Neuroradiology, Istituto Nazionale Neurologico “Carlo Besta,” Via Celo- ria 11, 20133 Milan, Italy. E-mail: pvitali@istituto-besta.it. J Neuroimaging 2008;18:296-305. DOI: 10.1111/j.1552-6569.2007.00164.x ABSTRACT BACKGROUND AND PURPOSE Functional neuroimaging and electrophysiological studies suggest that dysplastic neural tissue in malformations of cortical development may participate in task performance, and that functional organization can be altered beyond visible lesion boundaries. The aim of this work was to investigate cortical function in a heterogeneous group of patients with malformations of cortical development. METHODS Twelve patients participated in the study, 2 for each of the following categories: sub- cortical, periventricular, and band heterotopia, unilateral and bilateral polymicrogyria, and focal cortical dysplasia. Functional magnetic resonance imaging was performed with finger tapping, somatosensory and visual stimulation, and language-related tasks. RESULTS We found activations within the dysplastic tissue in subcortical heterotopia, band het- erotopia, and polymicrogyria, but not in periventricular heterotopic nodules. In one of the patients with focal cortical dysplasia, language-related activation involved part of the lesion. Functional reorganization beyond visible lesion boundaries was seen, with different patterns, in 4 patients. CONCLUSIONS In accordance with previous reports, our findings indicate that dysplastic neural tissue can be activated during task performance, and that in some patients, extensive functional re- organization occurs, highlighting the importance of functional magnetic resonance imag- ing in presurgical planning in those patients for whom epilepsy surgery is considered as an option. Introduction Malformations of cortical development (MCD) encompass a broad spectrum of structural abnormalities of the brain, and are recognized to be a leading cause of epilepsy and developmen- tal delay. As a result of rapid improvement in the resolution of magnetic resonance imaging (MRI), they are detected in an in- creasing number of patients with “cryptogenic” drug-refractory focal epilepsy. They have been estimated to account for about 15-25% of surgical cases. 1,2 MCD have been classified on the basis of the stage of brain development which is altered: abnormal neuronal and glial pro- liferation, neuronal migration, and cortical organization; focal and multifocal forms are found in each group. 3,4 In the clinical practice, MCD are classified on the basis of their morphological and histological features and genetics. 3, 5 In cortical heterotopia, a relatively common type, an abnor- mal arrest of the migration of immature neurons toward the cortex causes the formation of periventricular or subcortical nodules, or of a smooth subcortical layer of gray matter, some- times referred to as “double cortex.” These lesions are always isointense to the normal cortex on T 1 - and T 2 -weighted images. In polymicrogyria, it is hypothesized that migrating neurons reach the cortex but distribute abnormally, giving rise to multi- ple small gyri. Although it can sometimes appear hyperintense on T 2 -weighted images, polymicrogyric cortex is always isoin- tense to the normal cortex on T 1 -weighted images. Abnormal proliferation and differentiation of glial and neuronal precur- sors are the causative factors of focal cortical dysplasia, whose MRI correlates include mild thickening of the cortex, anoma- lous gyration, and mild blurred T 2 -hyperintensity extending to the white matter. 3,4 Measurements of diffusivity and diffusional anisotropy by means of diffusion-tensor imaging revealed that in a wide range of malformations, including nodular and band heterotopia and polymicrogyria, hidden structural abnormalities may extend beyond the anatomical boundaries visible on MRI. 6,7 Invasive electroencephalogram (EEG) recordings have shown that heterotopia, polymicrogyria, and focal cortical dys- plasia are all characterized by an intrinsic epileptogenicity, with the generation of isolated or rhythmic epileptiform dis- charges. 8-10 Connectivity with normal brain regions has been con- firmed by pathological examination in nodular heterotopia, and visualized by means of diffusion tractography in band 296 Copyright ◦ C 2008 by the American Society of Neuroimaging