What's that smell? A pictorial review of the olfactory pathways and imaging assessment of the myriad pathologies that can affect them

The olfactory pathway is composed of peripheral sinonasal and central sensorineural components. The wide variety of different pathologies that can affect the olfactory pathway reflect this complex anatomical relationship. Localising olfactory pathology can present a challenge to the reporting radiologist. This imaging review will illustrate the normal anatomy of the olfactory system and describe a systematic approach to considering olfactory dysfunction. Key concepts in image interpretation will be demonstrated using examples of olfactory pathway pathologies.

Circuits for integrating learnt and innate valences in the fly brain

Animal behavior is shaped both by evolution and by individual experience. In many species parallel brain pathways are thought to encode innate and learnt behavior drives and as a result may link the same sensory cue to different actions if innate and learnt drives are in opposition. How these opposing drives are integrated into a single coherent action is not well understood. In insects, the Mushroom Body Output Neurons (MBONs) and the Lateral Horn Neurons (LHNs) are thought to provide the learnt and innate drives, respectively. However their patterns of convergence and the mechanisms by which their outputs are used to select actions are not well understood. We used electron microscopy reconstruction to comprehensively map the downstream targets of all MBONs in Drosophila larva and characterise their patterns of convergence with LHNs. We discovered convergence neurons that receive direct input from MBONs and LHNs and compare opposite behaviour drives. Functional imaging and optogenetic manipulation suggest these convergence neurons compute the overall predicted value of approaching or avoiding an odor and mediate action selection. Our study describes the circuit mechanisms allowing integration of opposing drives from parallel olfactory pathways.

The Neural Response of Deep Brain Structures to Odorant Stimulations: A Manganese-Enhanced MRI Study

An increased understanding of how odors are processed in the central nervous system may provide comprehensive information about the neural basis of odor-related behavior and learning. In this study, we investigated how different odors are processed from the olfactory bulb to the deep cerebral structures through various olfactory pathways. To do this, we employed a novel manganese-enhanced magnetic resonance imaging (MEMRI) method to map the activity-dependent functional connectivity of the olfactory and non-olfactory pathways associated with various odorants. Our MEMRI data revealed odor-specific neural pathways that correspond to different odorant stimulations, suggesting that different neural circuits may process different odorants. Among the odorants tested, formic acid, an alarm pheromone, stimulated not only the primary and secondary olfactory pathways but also the mesolimbic neural circuit, which overlaps with the dopaminergic neural pathway. Linalool, which is a major component of aroma oils, showed high Mn2+ uptake in the hypothalamus, which plays a role in the stress response through the secretion of corticotropin-releasing hormone (CRH), and consequently, the stimulation of corticotropin secretion. Acetone mainly activated the primary olfactory pathway, whereas saline acted as a non-odorous trigeminal stimulus. Taken together, our functional MEMRI using anatomic standardization and statistical analyses could be a promising in vivo imaging method to map neural connectivity, enabling further understanding of the neural processing of different odorants.

Olfactory function as an independent prognostic factor in glioblastoma

ObjectiveTo determine the role of olfactory function in patients with glioblastoma multiforme (GBM) as a prognostic clinical measure.MethodsIn a prospective case-control study, olfactory testing was performed in 73 patients with primary GBM at baseline during first-line treatment and at later follow-ups. An age-matched control cohort consisted of 49 patients with neurologic diseases, excluding those known to affect olfactory function per se. Depending on the olfactory testing score, patients were allotted to a hyposmia group (HG) or normosmia group (NG). MRI analysis was performed to assess whether tumor location affects olfactory pathways.ResultsPatients with GBM had olfactory dysfunction significantly more often compared to the control cohort (p = 0.003). Tumor location could not explain this finding since no relevant difference in MRI-based olfactory pathway involvement was found between HG and NG (p = 0.131). Patients with olfactory dysfunction had significantly worse overall survival (OS) and progression-free survival (PFS) compared to those without dysfunction (median OS 20.9 vs 40.6 months, p = 0.035; median PFS, 9 vs 19 months, p = 0.022). Multivariate analysis in patients without MRI-based involvement of olfactory pathways confirmed olfaction is an independent prognostic factor for OS (hazard ratio [HR] 0.43; p = 0.042) and PFS (HR 0.51; p = 0.049).ConclusionThis pilot study provides the first indication that olfactory dysfunction is frequently observed in GBM and may be associated with worse survival outcome in GBM. However, validation of these results in an independent cohort is needed.

Congenital anosmia: a case report

Congenital anosmia, isolated or as a symptom of Kallmann or Klinefelter syndrome, is a rare condition found in young patients and children. Anosmia is detected during childhood, being reported by the patient or by his/her family. Besides the clinical examination and olfactometric evaluation, imaging is mandatory for the olfactory pathways investigation. Multidisciplinary approach is needed for these patients in order to determine the etiology of the smell loss. In the current paper, we are presenting the case of an 11-year-old child diagnosed in our ENT Department with congenital anosmia.