Sex Differences in the Olfactory System: a Functional MRI Study Helena Melero 1 & Susana Borromeo 1 & Alexandra Cristobal-Huerta 1 & Eva Manzanedo 1 & Guillermo Luna 1 & Adolfo Toledano 2 & Juan Antonio Hernández-Tamames 1 Received: 7 February 2018 /Accepted: 7 September 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Introduction Olfactory dysfunction is an early marker of neurological disease and a common symptom in psychotic disorders. Previous anatomical and functional research suggests that sex effects may be crucial in the assessment of the olfactory system. Nonetheless, the neural mechanisms through which the factor sex impacts olfactory perception are still not well understood. In this context, we use fMRI to investigate sex differences in the passive processing of chemical stimuli, in order to obtain new neuroscientific data that may help improve the assessment of odor perception. Methods Thirty healthy subjects (17 women) were stimulated with mint and butanol (event-related design) in a 3.0-T MRI scanner. A one-sample t test analysis was performed in order to observe olfactory-related activations. Intergroup differences (women vs. men) and the influence of each aroma were analyzed using a 2 × 2 ANOVA and post hoc contrasts. Results Men and women showed differential activity (males > females) in right superior/middle temporal areas, the right inferior frontal cortex, and the hypothalamus. Both groups showed a predominance of the right hemisphere for the processing of odors. Conclusion Functional differences between women and men in olfaction are not restricted to specific sensory areas and reflect a more general sex-dependent effect in multisensory integration processes. Implications Considering sex differences is essential in order to develop more specific and efficient strategies for the assessment and rehabilitation of the olfactory system and for the interpretation of the olfactory loss as an early biomarker of neurological and psychiatric diseases. Keywords Olfaction . fMRI . Odors . Multisensory integration . Assessment . Neurodegenerative Introduction In recent years, the olfactory system has regained attention from the scientific community. The growth rate of scientific publications on this topic from 1997 to 2017 has increased more than three-fold (PubMed database). Specifically, the number of fMRI studies of the olfactory system has multiplied by 7 and the number of publications about the dysfunction of this system in neurodegenerative diseases has multiplied by 5. There are several reasons that justify this tendency. First, the neuroanatomical configuration of the human olfactory system is still being revisited and its investigation has recently pro- vided ground-breaking findings, such as the existence of ol- factory receptors in the central nervous system (Ansoleaga et al. 2013; Garcia-Esparcia et al. 2013). Second, several stud- ies have shown that a deficit in the sense of smell can be an early marker in several pathologies, such as Alzheimer’ s dis- ease (Bahar-Fuchs et al. 2010; Hawkes and Doty 2009), Parkinson’ s disease (Doty 2012; Hawkes and Doty 2009), or other neurodegenerative diseases (Albers et al. 2006). Additionally, a recent study evaluating olfaction in psychotic patients has pointed out that sex effects in this sensory system should be further analyzed to better understand the heteroge- neity of psychotic disorders (Good and Sullivan 2015). These findings reinforce the need to obtain additional empirical data on the neural basis of the olfactory function and the sex effects associated with it, both in clinical and healthy populations. The empirical data support the idea that women and men exhibit anatomical and functional differences in olfaction. For example, Garcia-Falgueras et al. ( 2006) have reported macroanatomical differences between women and men in Helena Melero and Susana Borromeo contributed equally to this work. * Helena Melero helena.melero@urjc.es 1 Laboratorio de Análisis de Imagen Médica y Biometría (LAIMBIO), Universidad Rey Juan Carlos, C/Tulipán s/n, Móstoles, 28933 Madrid, Spain 2 Departamento de Otorrinolaringología, Hospital Universitario Fundación Alcorcón, Madrid, Spain Chemosensory Perception https://doi.org/10.1007/s12078-018-9250-1