Background: Loss of the sense of smell can seriously affect a person's quality of life. The ability to smell can be damaged by many factors, including illnesses, injuries, and exposure to toxic chemicals. The effects can vary, including complete loss of smell, partial loss, and parosomia, which is when things smell differently than they should. Objective: To study how brain function changes in people with different types of smell disorders. Also, to look at how smell loss affects quality of life over time. Eligibility: People aged 18 years or older with a disorder that affects their sense of smell. Healthy volunteers are also needed. Design: Participants will have 5 study visits over 1 year. They will have various tests and procedures: Smell tests. They will have several tests that involve smelling different items and answering questions. Questionnaires. They will answer questions about their health, mood, sense of smell, and daily habits. Magnetic resonance imaging (MRI) scans. They will lie on a bed that slides into a tube. Padding will hold their head still. They will smell different odors while in the scanner. Electrobulbogram (EBG). They will wear a soft cap with sensors that measure brain activity. They will smell different odors while wearing the cap. Nasal endoscopy. A flexible tube will be inserted into a nostril to view the inside of the nose. Biopsy. A numbing substance will be sprayed into the nose. Then a scissor-like tool will be used to collect a sample of tissue from one or both nasal passages. Samples of blood, urine, and nasal fluid will be taken.
Study Description: This pilot study investigates the mechanisms of parosmia, a qualitative olfactory dysfunction increasingly seen after COVID-19, by examining functional and structural brain changes and peripheral inflammation. Using neuroimaging and biochemical analysis, it aims to distinguish parosmia from other olfactory disorders and provide a foundation for future diagnostic and therapeutic approaches. Objectives: Primary objective: * Evaluate the feasibility, validity, and methodological framework for deep phenotyping of acquired chemosensory disorders. * Examine task-based functional connectivity patterns from the olfactory bulb to higher-order central processing regions across groups with varying olfactory symptoms. * Associate central findings with peripheral inflammatory patterns at the olfactory mucosa. Secondary Objective: -Investigate the differences and longitudinal changes in white matter microstructural integrity associated with the progression and recovery of olfactory dysfunctions across the recruited patient population. Tertiary objective: -Investigate the psychophysiological impacts of altered smell perception, with an emphasis on its negative effects on dietary habits, oral health, and cognitive functions. Endpoints: Co-Primary Endpoints: To identify functional connectivity differences across subgroups, with focus on parosmia. The study hypothesizes that parosmia patients exhibit neuroinflammation at the olfactory bulb or in the amygdala and hippocampus, leading to distorted valence perception. Altered connectivity between primary and secondary olfactory cortices is expected, differing significantly from hyposmia and, to a lesser extent, anosmia. These connectivity changes are expected to correlate with variations in smell function to uncover disrupted neural pathways underlying parosmia. To identify local inflammatory signatures at the olfactory mucosa that are associated with chemosensory dysfunction and altered functional connectivity. Secondary Endpoints: To evaluate whether changes in functional connectivity are associated with structural alterations, specifically reduced axonal myelination between primary and secondary olfactory cortices (amygdala and hippocampus), in parosmia patients (along with their symptoms graph) compared to healthy controls and, to a lesser extent, anosmia patients. Longitudinal analysis will determine if these structural changes lead to higher-order neural degeneration or other significant brain alterations. Tertiary endpoints: To investigate whether regions with structural and functional differences correlate with the duration and severity of smell loss, and to assess the impact of prolonged smell dysfunction on psychological health, eating behaviors, oral health, and quality of life.
Study Type
OBSERVATIONAL
Enrollment
80
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Functional Connectivity Differences in Olfactory Dysfunction
differences in functional brain connectivity between parosmia, anosmia and hyposmia groups, assessed longitudinally.
Time frame: baseline, 3, 6, 9 and 12 months
Structural Brain Changes in Olfactory Dysfunction
Structural brain architecture differences in olfactory-related regions, measured with neuroimaging.
Time frame: baseline, 3, 6, 9 and 12 months
Cognitive, Mood and Dietary Impact of Olfactory Dysfunction
Associations between olfactory function and changes in cognition, depressive symptoms and dietary habits, evaluated through surveys and behavioral measures.
Time frame: baseline, 3, 6, 9 and 12 months
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