Evaluation of brain and neurophysiologic function in isolated congenital anosmia

Isolated congenital anosmia (ICA) is a relatively rare condition characterized by a complete lack of olfactory perception dating from birth or early childhood. Congenital deficits in sensory systems appear to have distinct effects on brain function and nervous system pathway, but little is known about ICA. The study aims to explore the neural basis of ICA through measuring brain activation in response to olfactory stimuli and cerebral processing in patients with ICA.

Retrospective review of medical records of 11 ICA patients from two smell and taste centers. All patients who were diagnosed ICA thorough interview and medical investigation. We used olfactory pathway magnetic resonance imaging (MRI) to evaluate the structural change of olfactory system, and functional MRI (fMRI) to observe the brain's response to pleasant and unpleasant olfactory stimuli (phenethyl alcohol and isovaleric acid) in 11 patients with ICA and 11 age- and sex-matched controls. Additionally, we measured EEG signals using olfactory and trigeminal event-related potentials (oERP and tERP) in response to phenethyl alcohol and CO₂ stimuli, respectively. The Sniffin' Sticks test was used to evaluate the participants' subjective olfactory function.

ICA patients showed the smaller olfactory bulb and shallower olfactory sulcus than controls. Healthy subjects showed brain activity in multiple regions associated with olfactory processing. Subjects with ICA exhibited reduced or no activation in the olfactory cortex, which is responsible for olfactory processing. Nevertheless, these subjects had activation outside the olfactory cortex, indicating functional compensation. In the case of ICA, oERP was missing in all patients while it was present in all control subjects. tERP was detected in 8 patients with anosmia, and these patients displayed higher amplitude signals in the N₁ and P₂ waves than the controls (p < 0.001, p < 0.05).

Congenital anosmia patients exhibit functional inactivation in the olfactory cortex and neurophysiologic deficits throughout the olfactory pathway. Our findings support the concept of distinct central nervous system abnormalities in ICA.