Cerebral Cortex Advance Access originally published online on September 30, 2004
Cerebral Cortex 2005 15(6):846-853; doi:10.1093/cercor/bhh185
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Cerebral Cortex V 15 N 6 © Oxford University Press 2004; all rights reserved
Thalamic Atrophy in Huntington's Disease Co-varies with Cognitive Performance: A Morphometric MRI Analysis
1 Department of Neurology, University of Ulm, Germany and 2 Department of Nuclear Medicine, University of Bern, Switzerland
Address correspondence to Jan Kassubek, Department of Neurology, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. Email: jan.kassubek{at}medizin.uni-ulm.de.
The pattern of motor, behavioral and cognitive symptoms in Huntington's disease (HD) implicates dysfunction of basal-ganglia-thalamo-cortical circuits. This study explored if cognitive performance in HD is correlated with localized cerebral changes. Psychomotor functions were investigated by verbal fluency, Stroop color word and Digit Symbol tests in 44 HD patients and 22 controls. Three-dimensional magnetic resonance imaging (MRI) data were analyzed with regard to regional gray matter changes by use of the observer-independent whole-brain-based approach of voxel-based morphometry (VBM). Using statistical parametric mapping, the MRI data of the HD patients were analyzed in an ANCOVA including the individual results of the neuropsychological tests. Besides striatal areas, symmetrical regional atrophy of the thalamus was found to co-vary significantly with cognitive performance (P < 0.001, corrected for multiple comparisons). In particular, thalamic subnuclei projecting to prefrontal areas (dorsomedial subnucleus) and connected to the striatum (centromedian/parafascicular and ventrolateral nuclear complex) displayed volume loss, in agreement with neuropathological studies. These results suggest that thalamic degeneration contributes in an important way to the impairment of executive function in early HD. Patients who are impaired in executive tests display structural double lesions of the basal-ganglia-thalamo-cortical circuitry both at the striatal and at the thalamic level.
Key Words: basal ganglia • executive functions • neurodegenerative disease • thalamus • voxel-based morphometry
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