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A Snapshot of Parkinson's Disease

A Snapshot of Parkinson's Disease

Background: Parkinson’s disease (PD) is a neurological illness that has profound, disabling effects on motor control, speech, voice, and language. The mainstay of treatment since the 1960s has been administration of drugs that replace or mimic the neurotransmitter dopamine in the basal ganglia, which has been lost in the neurodegenerative process that characterizes this disorder. Antiparkinsonian drugs have well-recognized temporal effects, and often lose their effectiveness in alleviating the symptoms of Parkinson’s disease over time. Until recently, brain imaging studies have not attempted to map drug effects as they change over time in PD individuals.

Advance: NIDCD intramural scientists, traced the effects of the drug apormorphine, which mimics the action of dopamine in PD individuals with positron emission tomography (PET). They found that early changes in brain activity may support nonspecific effects on arousal, attention, and mood. On the other hand, later effects, more closely associated with reversal of Parkinsonian symptoms, were seen in those portions of the brain that involve movement. These effects were expected, but dramatic changes were also detected in other portions of the brain, usually not affected with movement. These findings were unexpected because, although changes in activity were strongly associated with clinical improvement, these latter brain regions (cerebellum and sensory cortices) are not part of the current model for PD, nor have they been thought to play a role in dopamine’s actions in the normal brain.

Implications: These results demonstrate that unexpectedly, antiparkinsonian drugs evoke changes in brain activity that occur well outside circuits traditionally thought to underlie symptom production in PD. The fact that these changes occur at the time of maximal clinical improvement suggests that the current model of PD may be over simplified, and needs to be modified. A greater role for the centers of the brain known to control movement in this disorder is consistent with state-of-the-art neuroimaging studies that have only very recently demonstrated a close (and similarly unexpected) interconnection between other sections of the brain.. The foregoing may precipitate a shift in our understanding of how dopamine regulates movement and speech in the normal brain and of the functional consequences of dopamine loss in PD. These studies should provide a baseline for the evaluation of newer drug treatments for PD and novel surgical interventions such as deep brain stimulation.

Citation: Hosey LA, Thompson JL, Metman LV, van den Munckhof P, Braun AR, Temporal dynamics of cortical and subcortical responses to apomorphine in Parkinson disease: an H2 15O PET study. Clin Neuropharmacol 28: 18-27, 2005.