The olfactory nerve as a channel for electrical stimulation of the salience network

Introduction: Seven million people in Germany suffer from depression. The data emphasizes the need for finding a therapeutic alternative for individuals who do not respond to the standard options. As the salience network is a key component in the pathology of the disease and also closely related to the olfactory system, it serves as a potential target. Hence, we wanted to investigate whether the activity in salience structures in the brain can be influenced by electrical stimulation of the olfactory mucosa in the nose.

Methods: A total of 45 healthy subjects were included in the study. On the first appointment the individual stimulation threshold was determined and normosmia was tested. On the second and third appointment the olfactory/respiratory mucosa was stimulated for 12 minutes followed by an fMRI scan of the brain. Sequence of stimulation site was randomized across participants. During each session a resting-state and a task-based fMRI scan was performed.

Results: The task-based data showed an increase in the BOLD-signal of the right insula when the olfactory stimulation is weighted against the trigeminal stimulation. Also, the activity in the left and right precuneus was significantly reduced. When performing a small volume correction, especially the right anterior insula and the left insula showed a higher BOLD-signal. The resting-state data revealed an increased connectivity between the right and left anterior insula, as well as between the right anterior insula and the ACC. The ACC also has an increased functional connectivity to the left piriform cortex.

Conclusion: The results suggest that an intranasal electrical stimulation of the olfactory nerve can affect deep brain areas of the salience network and influence its neural activity.

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