Abstract

To determine whether the range of normal variation of human olfactory functional magnetic resonance imaging (fMRI) activations in healthy single subjects is compatible with the detection of atypical patterns. In an event-related olfactory experiment, the variability of fMRI activation in six bilateral olfactory areas known to be affected in neurodegenerative diseases was measured in a region of interest (ROI) analysis in terms of intensity, localization, and overlap on 51 subjects. fMRI measurements were compared against measurements from a visual experiment performed on 25 subjects. Olfaction induced activations with low intensity, high variability, and a 4-fold lower contrast-to-noise ratio (CNR) than vision. Even in the best case (piriform cortex), mean pairwise activation overlap was still less than 40%. None of the olfactory ROIs showed significant activation for all subjects at the permissive threshold of P < 0.001. A gender-dependent significantly stronger activation was found in the bilateral piriform cortex of male subjects. Linking t-statistics and CNR showed that for all olfactory ROIs, CNR is either near or below the estimated threshold of 0.73 found to be necessary to obtain significant activations. In our experimental conditions the low reliability of olfactory activations should prompt major reservations over using fMRI of human olfaction as a diagnostic tool in single subjects.

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