Functional imaging of the cerebral olfactory system in patients with Parkinson's disease

BACKGROUND: Olfactory dysfunction is a frequent non-motor symptom in Parkinson's disease (PD) and is considered to be an early manifestation of the disease. OBJECTIVE: To establish the cortical basis of olfactory function in patients with PD. METHOD: Functional magnetic resonance imaging (fMRI) was used to investigate brain activity related to olfactory processing in patients with hyposmic PD at mild to moderate stages of the disease (n = 12, median Hoehn and Yahr stage 2.0) and in healthy, age-matched controls (n = 16) while passively perceiving a positively valenced (rose-like) odorant. RESULTS: In both patients with PD and healthy controls, olfactory stimulation activated brain regions relevant for olfactory processing (ie the amygdaloid complex, lateral orbitofrontal cortex, striatum, thalamus, midbrain and the hippocampal formation). In controls, a bilateral activation of the amygdala and hippocampus was observed, whereas patients with PD involved these structures in the left hemisphere only. Group comparison showed that regions of higher activation in patients with PD were located bilaterally in the inferior frontal gyrus (BA 44/45) and anterior cingulate gyrus (BA 24/32), and the left dorsal and right ventral striatum. CONCLUSIONS: In patients with PD, results obtained under the specific conditions used suggest that neuronal activity in the amygdala and hippocampus is reduced. Assuming an impact on olfactory-related regions early in PD, our findings support the idea that selective impairment of these brain regions contributes to olfactory dysfunction. Furthermore, neuronal activity in components of the dopaminergic, cortico-striatal loops appears to be upregulated, indicating that compensatory processes are involved. This mechanism has not yet been demonstrated during olfactory processing in PD.