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Neural Plasticity
Volume 2012, Article ID 473538, 13 pages
Review Article

Widespread Structural and Functional Connectivity Changes in Amyotrophic Lateral Sclerosis: Insights from Advanced Neuroimaging Research

1Department of Neurological Sciences, Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy
2Neurological Institute for Diagnosis and Care “Hermitage Capodimonte”, Via Cupa delle Tozzole 2, 80131 Naples, Italy
3Magnetic Resonance Imaging Center, Italian Foundation for Multiple Sclerosis (FISM), Via Cupa delle Tozzole 2, 80131 Naples, Italy
4Department of Neuroscience, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy

Received 22 February 2012; Revised 20 April 2012; Accepted 23 April 2012

Academic Editor: Hansen Wang

Copyright © 2012 Francesca Trojsi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease principally affecting motor neurons. Besides motor symptoms, a subset of patients develop cognitive disturbances or even frontotemporal dementia (FTD), indicating that ALS may also involve extramotor brain regions. Both neuropathological and neuroimaging findings have provided further insight on the widespread effect of the neurodegeneration on brain connectivity and the underlying neurobiology of motor neurons degeneration. However, associated effects on motor and extramotor brain networks are largely unknown. Particularly, neuropathological findings suggest that ALS not only affects the frontotemporal network but rather is part of a wide clinicopathological spectrum of brain disorders known as TAR-DNA binding protein 43 (TDP-43) proteinopathies. This paper reviews the current state of knowledge concerning the neuropsychological and neuropathological sequelae of TDP-43 proteinopathies, with special focus on the neuroimaging findings associated with cognitive change in ALS.