Olfactory nerve as channel for Electrical Stimulation of the Salience Network

• Applicants: Professorin Dr. Ilona Croy; Professor Dr. Thomas Hummel
• Subject Area: Otolaryngology, Phoniatrics and Audiology ; Biological Psychiatry ; Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 468395727

Depression is a severe mental disorder, affecting about 7,000,000 people in Germany. Besides leading to significant impairments of quality of life, depression has a high case fatality. Hence, an effective anti-depressive treatment is warranted. For very severe or medication-resistant cases, electro-convulsive therapy is the state of the art option leading to alterations of the genesis of synapses, neurons and glia cells in the region of the amygdala, hippocampus, the anterior cingulate Cortex (ACC) and medial and inferior temporal cortex. This treatment has however side effects, which is why a broader variety of treatment options is desirable. Because depression is specifically related to impaired salience network processing, a focussed approach may target relevant brain regions, such as the ACC, the anterior insula and the amygdala. We are confident that stimulation via the olfactory nerve is a promising pathway. Major depressive disorder presents a close anatomical and functional overlap with olfaction - vulnerability to depression is enhanced by a factor of three in patients with smell disorders and major depression is often accompanied by reduced olfactory function. This relation originates from the close connection between central olfactory structures and structures involved in salience processing and is based on a co-evolution of functions. Chemosensation is the oldest form of communication between species, emerging 500 million years ago and the central structures, originally dedicated to olfactory processing, are now pivotal for emotion processing. Our previous and preliminary work suggests that stimulation of the olfactory tract can alter the reactivity of central salience structures to emotional stimuli. A recent publication from another group showed, that brain connectivity within olfactory regions can be altered by electrical stimulation of the olfactory epithelium. It has not been examined yet, whether electrical stimulation of the olfactory nerve impacts the neural functioning in terms of connectivity or activation of salience relevant structures, such as the amygdala, the anterior insula and the ACC. We aim to examine this possibility in healthy participants by examining how intranasal electrical stimulation alters behavioural emotion responses and neural activity and connectivity in the salience network. Our research group has both the knowledge and the equipment for successful stimulation of the olfactory epithelium, for brain network analysis and for studying emotion behavior. The interdisciplinary of our team furthermore allows us to continuously include a clinical perspective in this basic research proposal. This project has the potential to pave the way for a focused and only mildly invasive stimulation of the salience network in patients with severe depression.

• DFG Programme: Research Grants
• International Connection: Israel
• Cooperation Partner: Professor Dr. Noam Sobel