Abnormal basal ganglia outflow in Parkinson's disease identified with PET. Implications for higher cortical functions.

In this study we examined the effects of striatal dopamine depletion on cortical and subcortical blood flow changes during two tasks known to involve frontostriatal circuitry. Regional cerebral blood flow was measured in six patients with moderate Parkinson's disease and in six age-matched control subjects while they performed easy and difficult versions of a modified Tower of London planning task and a mnemonic variant of this task that required short-term retention and reproduction of problem solutions, as well as a control condition that involved identical visual stimuli and motor responses. Relative to control conditions, the planning task was associated with an increase in cerebral blood flow centred on the internal segment of the right globus pallidus in the age-matched control subjects, and a decrease in the same region in the patients with Parkinson's disease. A similar inverse relationship between the task-specific blood flow change observed in the control group and that observed in the Parkinson's disease patients was not found in any other subcortical or cortical area examined, including regions of the dorsolateral frontal cortex known to be involved in this task. When blood flow in the spatial working memory task was examined, a similarly specific dissociation between the two groups of subjects was observed at similar coordinates in the right pallidum. We conclude that striatal dopamine depletion disrupts the normal pattern of basal ganglia outflow in Parkinson's disease and consequently, affects the expression of frontal-lobe functions by interrupting normal transmission of information through frontostriatal circuitry.