Brain Advance Access published online on September 16, 2009
Brain, doi:10.1093/brain/awp233
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Language networks in semantic dementia
1 Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA 2 Neuroimaging Research Unit, Institute of Experimental Neurology, Scientific Institute and University Hospital San Raffaele, Milan, Italy 3 Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA 4 Department of Neurological Sciences, II University of Naples, Naples, Italy 5 Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA 6 Center for Aphasia and Related Disorders, VA Northern California Health Care System, Martinez, CA, USA 7 Department of Neurology, University of California, Davis, CA, USA 8 Centre de recherche, Institut Universitaire de Gériatrie de Montréal, Montréal, Québec, Canada 9 Center for Mind/Brain Sciences (CIMeC), University of Trento, Trento, Italy
Correspondence to:
Maria Luisa Gorno-Tempini, Memory and Aging Center, Department of Neurology, University of California, San Francisco, 350 Parnassus Avenue, Suite 905, San Francisco, CA 94143-1207, USA E-mail: marilu{at}memory.ucsf.edu
Cognitive deficits in semantic dementia have been attributed to anterior temporal lobe grey matter damage; however, key aspects of the syndrome could be due to altered anatomical connectivity between language pathways involving the temporal lobe. The aim of this study was to investigate the left language-related cerebral pathways in semantic dementia using diffusion tensor imaging-based tractography and to combine the findings with cortical anatomical and functional magnetic resonance imaging data obtained during a reading activation task. The left inferior longitudinal fasciculus, arcuate fasciculus and fronto-parietal superior longitudinal fasciculus were tracked in five semantic dementia patients and eight healthy controls. The left uncinate fasciculus and the genu and splenium of the corpus callosum were also obtained for comparison with previous studies. From each tract, mean diffusivity, fractional anisotropy, as well as parallel and transverse diffusivities were obtained. Diffusion tensor imaging results were related to grey and white matter atrophy volume assessed by voxel-based morphometry and functional magnetic resonance imaging activations during a reading task. Semantic dementia patients had significantly higher mean diffusivity, parallel and transverse in the inferior longitudinal fasciculus. The arcuate and uncinate fasciculi demonstrated significantly higher mean diffusivity, parallel and transverse and significantly lower fractional anisotropy. The fronto-parietal superior longitudinal fasciculus was relatively spared, with a significant difference observed for transverse diffusivity and fractional anisotropy, only. In the corpus callosum, the genu showed lower fractional anisotropy compared with controls, while no difference was found in the splenium. The left parietal cortex did not show significant volume changes on voxel-based morphometry and demonstrated normal functional magnetic resonance imaging activation in response to reading items that stress sublexical phonological processing. This study shows that semantic dementia is associated with anatomical damage to the major superior and inferior temporal white matter connections of the left hemisphere likely involved in semantic and lexical processes, with relative sparing of the fronto-parietal superior longitudinal fasciculus. Fronto-parietal regions connected by this tract were activated normally in the same patients during sublexical reading. These findings contribute to our understanding of the anatomical changes that occur in semantic dementia, and may further help to explain the dissociation between marked single-word and object knowledge deficits, but sparing of phonology and fluency in semantic dementia.
Key Words: semantic dementia; semantic knowledge; diffusion tensor-based tractography; functional MRI; voxel-based morphometry
Abbreviations:
ATL, anterior temporal lobe; BA, Brodmann area; DTI, diffusion tensor imaging; FA, fractional anisotropy; FACT, fibre-assignment-by-continuous-tracking; fMRI, functional magnetic resonance imaging; ILF, inferior longitudinal fasciculus; 
//, parallel diffusivity; 
, transverse diffusivity; MD, mean diffusivity; ROI, region of interest; SLF, superior longitudinal fasciculus
Received July 20, 2009. Accepted July 26, 2009.