title: Functional MRI of congenital hyposmia: brain activation to odors and imagination of odors and tastes.
abstract: OBJECTIVE
  Our goal was to use functional MRI (fMRI) to define brain activation in response to odors and imagination ("memory") of odors and tastes in patients who never recognized odors (congenital hyposmia).
  
  
  METHODS
  Functional MR brain scans were obtained in nine patients with congenital hyposmia using multislice echo planar imaging (EPI) in response to odors of amyl acetate, menthone, and pyridine and to imagination ("memory") of banana and peppermint odors and to salt and sweet tastes. Functional MR brain scans were compared with those in normal subjects and patients with acquired hyposmia. Activation images were derived using correlation analysis, and ratios of areas of brain activated to total and hemispheric brain areas were calculated. Total and hemispheric activated pixel counts were used to quantitate regional brain activation.
  
  
  RESULTS
  Brain activation in response to odors was present in patients with congenital hyposmia. Activation was significantly lower than in normal subjects and patients with acquired hyposmia and did not demonstrate differential vapor pressure-dependent detection responsiveness or odor response lateralization. Regional activation localization was in anterior frontal and temporal cortex similar to that in normal subjects and patients with acquired hyposmia. Activation in response to presented odors was diverse, with a larger group exhibiting little or no activation with localization only in anterior frontal and temporal cortex and a smaller group exhibiting greater activation with localization extending to more complex olfactory integration sites. "Memory" of odors and tastes elicited activation in the same central nervous system (CNS) regions in which activation in response to presented odors occurred, but responses were significantly lower than in normal subjects and patients with acquired hyposmia and did not lateralize.
  
  
  CONCLUSIONS
  Odors induced CNS activation in patients with congenital hyposmia, which distinguishes olfaction from vision and audition since neither light nor acoustic stimuli induce CNS activation. Odor activation localized to anterior frontal and temporal cortex, consistent with the hypothesis that olfactory pathways are hard-wired into the CNS and that further pathways are undeveloped with primary olfactory system CNS connections but lack of secondary connections. However, some patients exhibited greater odor activation with response localization extending to cingulate and opercular cortex, indicating some olfactory signals impinge on and maintain secondary connections consistent with similar functions in vision and audition. Activation localization of taste "memory" to anterior frontal and temporal cortex is consistent with CNS plasticity and cross-modal CNS reorganization as described for vision and audition. Thus, there are differences and similarities between olfaction, vision, and audition, the differences dependent on unique qualities of olfaction, perhaps due to its diffuse, primitive, fundamental role in survival. Response heterogeneity to odors may reflect heterogeneous genetic abnormalities, independent of anatomic or hormonal changes but dependent on molecular abnormalities in growth factor function interfering with growth factor/stem cell interactions. Patients with congenital hyposmia offer an unique model system not previously explored in which congenital smell lack as measured by fMRI is reflective of congenital dysfunction of a major sensory system.
authors.affiliation: Taste and Smell Clinic, Washington, DC 20016, USA. doc@tasteandsmell.com
authors.forename: Robert I
authors.initials: RI
authors.lastname: Henkin
authors.forename: Lucien M
authors.initials: LM
authors.lastname: Levy
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D017352:Echo-Planar Imaging; D005260:Female; D006801:Humans; D007092:Imagination; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D009812:Odorants; D000857:Olfaction Disorders / Q000151:congenital / Q000175:diagnosis / Q000503:physiopathology*; D009833:Olfactory Pathways / Q000502:physiology; D012903:Smell; D013649:Taste