Open research questions in Olfactory and Sensory Function Studies

What the literature leaves open

• The study faced challenges in recruiting patients with severe long-term post-COVID-19 syndrome. The absence of a non-intervention control group limits the interpretation of the findings. Spontaneous recovery or regression to the mean cannot be excluded due to the lack of a control group.

  Limited observed efficacy of olfactory training in severe long-term post-COVID-19 syndrome: a prospective cohort study · 2026 · DOI

• Investigating the efficacy of olfactory training in patients with post-viral olfactory dysfunction, - Examining the impact of latency between infection and intervention on treatment outcomes, - Studying the effects of olfactory training on health-related quality of life

  Limited observed efficacy of olfactory training in severe long-term post-COVID-19 syndrome: a prospective cohort study · 2026 · DOI

• translating extra-nasal ORs structure-function into clinical applications, - high-throughput deorphanization and functional screening, - improving heterologous expression systems and functional screening technologies

  Extra-nasal odorant receptors: molecular mechanisms and therapeutic implications · 2026 · DOI

• The need for high selectivity and sensitivity in complicated matrices. The manual extraction process, which could bring about unpredictability during large-scale screenings. The clinical heterogeneity of olfactory dysfunction, which requires further investigation.

  Spectrofluorometric determination of nasal cGMP using a propidium iodide supramolecular probe for diagnosis and monitoring of chronic olfactory dysfunction · 2026 · DOI

• Investigating the directionality and underlying biological mechanisms of the association between cGMP and olfactory dysfunction, - Evaluating the method's performance in different causes of olfactory dysfunction, - Developing automated extraction processes, - Assessing the long-term stability of the PI-cGMP complex

  Spectrofluorometric determination of nasal cGMP using a propidium iodide supramolecular probe for diagnosis and monitoring of chronic olfactory dysfunction · 2026 · DOI

• further studies are needed to investigate the relationship between anosmia and pRBD, - longitudinal studies could provide more insight into the progression of PD

  Olfactory impairment and probable REM sleep behavior disorder in Parkinson’s disease: clinical relevance to the single- and dual-hit hypotheses · 2026 · DOI

• The implications of the coexistence of olfactory impairment and probable RBD in PD are uncertain. There is a need to examine whether probable RBD/anosmia-defined subgroups exhibit distinct clinical profiles. The study aims to address this gap by investigating the relationship between olfactory impairment and probable RBD in PD.

  Olfactory impairment and probable REM sleep behavior disorder in Parkinson’s disease: clinical relevance to the single- and dual-hit hypotheses · 2026 · DOI

• Further research should explore the effects of real and virtual urban green environments, - Further research should investigate the long-term effects of the virtual urban green environment, - Further research should explore the effects of the virtual urban green environment on different populations

  Effects of simulated multi-sensory stimulation integration on physiological and psychological restoration in virtual urban green space environment · 2024 · DOI

• The study requires the participants to maintain a state of stillness without any movement during EEG measurement. The study needs to control for potential confounding variables, such as excessive exercise, drinks containing alcohol, and caffeine. The study requires the use of specialized equipment, including EEG electrode caps and physiological measurement devices.

  Assessing the Anxiolytic and Relaxation Effects of Cinnamomum camphora Essential Oil in University Students: A Comparative Study of EEG, Physiological Measures, and Psychological Responses · 2024 · DOI

• Small sample size of 43 participants, - Limited to healthy university students, - No control group for comparison, - Study duration was approximately 50 minutes

  Assessing the Anxiolytic and Relaxation Effects of Cinnamomum camphora Essential Oil in University Students: A Comparative Study of EEG, Physiological Measures, and Psychological Responses · 2024 · DOI

• The main problem is that consciousness in other animals cannot be directly observed, only inferred. Determining whether it is possible to scientifically infer consciousness in nonhuman animals is not trivial.

  Neuroscience of animal consciousness: still agnostic after all · 2024 · DOI

• Olfaction is a key sense for many mammals, but its role in the social lives of anthropoid primates (monkeys, apes, humans) is poorly understood.

  Genetic and behavioural repertoires support olfactory communication in wild capuchin monkeys · 2026 · DOI

• Many species use microbiome-derived metabolites as chemosensory cues, yet the chemicals involved and the sensory pathways that detect and process them remain poorly understood.

  A microbiome-derived olfactory signal regulates inter-male aggression and social dominance in mice · 2026 · DOI

• Although contact-dependent mechanisms regulate the guidance of olfactory sensory neuron (OSN) axons, it remains unclear how the X-linked mosaic expression of cell adhesion molecules affects axon coalescence into target glomeruli.

  X-linked protocadherin-19 mosaicism induces abnormal sorting of the olfactory nerve · 2026 · DOI

• BACKGROUND: Olfactory-based cognitive stimulation is frequently proposed for memory-impaired patients (namely dementia patients), but little is known about the scientific rationale underlying odor choice.

  Investigating the Evolution of Odor-Evoked Memories Retrieval in Normal Aging: Theoretical and Clinical Implications · 2025 · DOI

• While often attributed to nasal mucosa inflammation, the underlying causes of the olfactory loss remain unknown.

  Cystic fibrosis alters the structure of the olfactory epithelium and the expression of olfactory receptors affecting odor perception · 2025 · DOI

• 4 , 5 , 6 Although enlightening, this focus on adaptation has left aspects of evolution in high-altitude locations understudied—including the role of gene loss and pseudogenization, maladaptation and trait loss, and physiological aspects outside of respiration and gas exchange.

  Convergent reduction of olfactory genes and olfactory bulb size in mammalian species at altitude · 2025 · DOI

• Due to their poor functional expression in vitro, reproducible receptor-ligand pairs are known for only a minority of them, and the pharmacology of human olfaction is still poorly understood.

  Decoding human olfaction by high heterologous expression of odorant receptors detecting signature odorants · 2025 · DOI

• Yet, evidence for this framework in humans is lacking due to spatiotemporal limitations of neuroimaging methods.

  Spatiotemporal dissociation of physical salience and stimulus evaluation in the human midbrain · 2025 · DOI

• While certain ORs, such as Olfr2, have been linked to inflammation and atherosclerosis modulation in mice, the roles of many other ORs remain unexplored.

  Olfactory Receptors in Immunity: Macrophage-Expressed Olfr519 Regulates Inflammation and Drives Atherosclerosis Progression 3634 · 2025 · DOI

• Moreover, the relationship between various olfactory receptors (ORs) and the composition of multiple aromatic compounds remains to be understood.

  Aroma Formation, Release, and Perception in Aquatic Products Processing: A Review · 2025 · DOI

• Fundamental principles of its physico-mechanical function, including basic aspects of stimulus sampling, remain poorly explored.

  A revised conceptual framework for mouse vomeronasal pumping and stimulus sampling · 2024 · DOI

• Despite its crucial role as a sensor for pheromones and other behaviorally instructive chemical cues, the vomeronasal organ (VNO) remains a poorly characterized mammalian sensory structure.

  A revised conceptual framework for mouse vomeronasal pumping and stimulus sampling · 2024 · DOI

• Future research should focus on large-scale studies to elucidate the underlying mechanisms of bidirectional interaction between diet and migraine and develop evidence-based clinical guidelines.

  The Brain, the Eating Plate, and the Gut Microbiome: Partners in Migraine Pathogenesis · 2024 · DOI

• The scarcity of evidence on the functional properties of the olfactory amygdala. The lack of understanding of the developmental regulation of synaptic plasticity in the olfactory amygdala.

  Experience-dependent critical period for synaptic plasticity in the rat olfactory amygdala · 2026 · DOI

Most-cited papers in Olfactory and Sensory Function Studies

• SARS-CoV-2 is associated with changes in brain structure in UK Biobank · Nature · 2022 · 1,338 citations
• Prevalence of Olfactory Impairment in Older Adults · JAMA · 2002 · 917 citations
• Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors · Science Translational Medicine · 2022 · 469 citations
• Stimuli–organism-response framework: A meta-analytic review in the store environment · Journal of Business Research · 2012 · 367 citations
• Changes in Spatial Patterns of Rabbit Olfactory EEG with Conditioning to Odors · Psychophysiology · 1982 · 355 citations
• An Odor is Not Worth a Thousand Words: From Multidimensional Odors to Unidimensional Odor Objects · Annual Review of Psychology · 2009 · 354 citations
• There's Something in the Air: Effects of Congruent or Incongruent Ambient Odor on Consumer Decision Making · Journal of Consumer Research · 1995 · 277 citations
• Odors are expressible in language, as long as you speak the right language · Cognition · 2014 · 274 citations
• Hippocampal system dysfunction and odor discrimination learning in rats: Impairment of facilitation depending on representational demands. · Behavioral Neuroscience · 1988 · 253 citations
• The role of congruency and pleasantness in odor-induced taste enhancement · Acta Psychologica · 1996 · 240 citations

Most recent work

• Spatial organization and detection of social odors in mouse primary olfactory system · Cell · 2026
• Identification of Or5v1/Olfr110 as an oxylipin receptor and anti-obesity target · Cell · 2026
• Structural decoding of reversible covalent linkage of odorants in human olfactory receptor OR6A2 · Cell · 2026
• A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain · Cell · 2026
• Mechanistic insights into fatty acid odor detection mediated by class II olfactory receptors · Cell · 2026
• Mice navigate scent trails using predictive policies · bioRxiv · 2026
• Positive early-life olfactory memory is rooted in the olfactory bulb and triggers large-scale changes beyond the olfactory system · PLoS Biology · 2026
• Aromatherapy with essential oils to reduce anxiety, pain, and discomfort during in-office dental procedures: A scoping review · Journal of Dentistry · 2026
• The posteroventral part of the medial amygdala nucleus glutamatergic neurons encodes conspecifics’ individual identity in rodents · Science Advances · 2026
• Odor preference maps to cohesive transcriptional domains in the olfactory bulb · bioRxiv · 2026

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