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The process of olfaction, also known as the sense of smell, is a sophisticated chemical response system. The specialized sensory neurons that facilitate this process, known as olfactory receptor neurons, are situated in an upper segment of the nasal cavity, known as the olfactory epithelium. Olfactory sensory neurons are bipolar, with their dendrites extending from the epithelium's apex into the mucus that lines the nasal cavity. Airborne molecules, when inhaled, traverse the olfactory...
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Updated: Aug 1, 2025

A Free-breathing fMRI Method to Study Human Olfactory Function
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Cognitive and functional connectivity impairment in post-COVID-19 olfactory dysfunction.

Lorenzo Muccioli1, Giovanni Sighinolfi1, Micaela Mitolo2

  • 1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Neuroimage. Clinical
|April 27, 2023
PubMed
Summary

Persistent olfactory dysfunction following COVID-19 is linked to altered olfactory network connectivity. This brain network change correlates with smell severity and cognitive deficits in patients.

Keywords:
HyposmiaLong Covidfunctional MRI (fMRI)post acute COVID syndrome (PACS)

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Area of Science:

  • Neuroscience
  • Medical Imaging
  • Olfactory Research

Background:

  • Persistent olfactory dysfunction (OD) is a common sequela of COVID-19.
  • The underlying neural mechanisms and cognitive impact of prolonged COVID-19-related OD require further investigation.

Purpose of the Study:

  • To investigate the neuropsychological profile of patients with persistent COVID-19-related OD.
  • To assess the integrity and functional connectivity of the olfactory network in these patients using advanced neuroimaging techniques.

Main Methods:

  • Olfactory and neuropsychological assessments were performed on patients with persistent COVID-19-related OD.
  • Brain MRI, including T1-weighted and resting-state functional MRI (rs-fMRI), was conducted on patients and healthy controls.
  • Graph theory analysis was applied to rs-fMRI data to evaluate olfactory network properties and their correlation with clinical scores.

Main Results:

  • Patients exhibited impaired visuospatial memory and executive functions.
  • No significant gross morphological abnormalities were detected; however, trends for reduced volumes in the lateral orbital cortex, hippocampus, and amygdala were observed.
  • Functional olfactory network analysis revealed altered global and local connectivity in patients, with specific correlations between network properties, smell severity, and verbal memory.

Conclusions:

  • Persistent COVID-19-related OD is associated with altered functional connectivity within the olfactory network.
  • These network alterations correlate with the severity of smell impairment and specific neuropsychological deficits.
  • While gross brain structure remains largely intact, functional network changes may underlie persistent olfactory and cognitive dysfunction post-COVID-19.