Does frontal cortex hypometabolism in progressive supranuclear palsy result from subcortical dysfunction?

Progressive supranuclear palsy (PSP), a neurodegenerative disease with frontal lobe-like features, shows brain hypometabolism which predominates in frontal cortex, although the most severe histopathological lesions are subcortical. To test the hypothesis of the subcortical origin of the metabolic dysfunction in frontal cortex, we used previously obtained data measured using positron emission tomography (PET) in PSP patients and controls to examine the metabolic links between cortical and subcortical brain regions. We calculated interregional correlations of metabolic values in PSP patients and we compared these values to those obtained in controls. Compared to 20 age-matched controls, the 20 PSP patients studied showed an increase in positive metabolic coupling between frontal and non-frontal cortical regions. There was an abnormal linkage between frontal cortex and thalamus hypometabolism, the latter partly coupled to caudate nucleus hypometabolism. This study suggests a subcortical origin for frontal cortex hypometabolism in which thalamic activity appears to play a pivotal role.