Differential functional change in olfactory bulb and olfactory eloquent areas in Parkinson's disease.

Olfactory dysfunction, or hyposmia, frequently occurs as a prodromal symptom and ongoing sign of Parkinson's disease. Functional MRI is a powerful tool for studying functional changes in the olfactory brain regions in patients with Parkinson's disease. However, existing studies show inconsistent results and no study has measured olfactory functional MRI abnormalities in the human olfactory bulb directly. This is mainly due to the well-known susceptibility artefacts in conventional functional MRI images that affect several key olfactory-eloquent brain regions, and especially the olfactory bulb. In this study, olfactory functional MRI was performed using a recently developed functional MRI approach that can minimize susceptibility artefacts and measure robust functional MRI signals in the human olfactory bulb during olfactory stimulation. Experiments were performed on high magnetic field (7 T) in 24 early (<5 years of parkinsonian symptoms) Parkinson's disease patients and 31 matched healthy controls. Our data showed increased functional MRI signal changes (ΔS/S) in the olfactory bulb in patients with early Parkinson's disease, which correlated with behavioural olfactory measures. Temporally, functional MRI signals in the olfactory bulb returned to the pre-stimulus state earlier after reaching peak amplitude in patients with early Parkinson's disease, implicating a faster olfactory habituation effect. The piriform cortex showed reduced numbers of activated voxels in patients with early Parkinson's disease, which correlated with behavioural olfactory assessment. Several secondary olfactory regions including the orbitofrontal cortex, temporal pole and amygdala exhibited reduced numbers of activated voxels and increased functional MRI signal changes in patients with early Parkinson's disease. Our data also showed that functional MRI results are highly dependent on voxel selection in the functional analysis. In summary, we demonstrate differential spatial and temporal characteristics of olfactory functional MRI signals between the primary and secondary olfactory regions in patients with early Parkinson's disease. These results may assist the development of novel quantitative biomarkers (especially in the early stages of Parkinson's disease) to track and predict disease progression, as well as potential treatment targets for early intervention.