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Neuroplasticity in patients with post surgical olfactory dysfunction  after olfactory training, assessed with fMRI.
Francisco García-Huidobro1, Cristian Montalba2,3,4, Andrés Rosesbaum1, Mariana Zurita5, David Jofré1, Sergio Uribe2,3,4, Marcelo Andia2,3,4, Pablo Villanueva6, Claudio Callejas1, Claudia González1, and Cristian Montalba2

1Otorhinolaryngology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile, 2Biomedical Imaging Center, Pontificia Universidad Católica de Chile, Santiago, Chile, 3Radiology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile, 4Millennium Nucleus for Cardiovascular Magnetic Resonance, Santiago, Chile, 5Institute of Cognitive Neuroscience., University College London, London, UK., London, United Kingdom, 6Neurosurgery Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

Synopsis

We evaluated the effect of olfactory training in olfactory pathway brain areas in subjects with olfactory dysfunction after transsphenoidal surgery for pituitary tumors. For this purpose, we compare 2 groups of subjects, one with olfactory training, and a second without training. All of them underwent with an fMRI block designed with eucalyptus odor. An olfactory test were measured in all subjects. The subjects with olfactory training showed a clinical improvement and more activations of compensatory olfactory central brain areas, in comparison with subjects without olfactory training, that they did not show a clinical improvement and activated less compensatory olfactory areas.

Introduction

Olfactory dysfunction is a condition characterized by the decrease or absence of perceiving odors. Studies have shown that olfactory training improve the identification and discrimination of odors, assessed by olfactometry test before and after receiving the treatment (1-4). However, there is no evidence of the effect of the olfactory training at brain level. In this study, we evaluated the effect of olfactory training in patients with olfactory dysfunction, caused by surgery of pituitary tumor, using fMRI with odors stimulus.

Materials and Methods

Six female volunteers referred to have an olfactory dysfunction after transsphenoidal surgery for pituitary tumors were recruited. They were evaluated with olfactometry test “Sniffin stick test” and nasofibroscopy to evaluate the olfactory dysfunction. Subsequently, patients were randomized in two groups. The first group received olfactory training for 12 weeks and the second group did not undergo any intervention. Both groups were evaluated initially and 12 weeks later with fMRI (Figure 1). The MR room was equipped with a nebulization system, used to give compressed air with eucalyptus oil through a nasal cannula (Figure 1). A normosmic volunteer revised the system before each scan. The study was approved by the local ethics committee.

Images were acquired on a 1.5T MR scanner (Philips, Achieva, Best, Netherlands). T1W-3D images were acquired as anatomic reference. The olfactory stimulus was provided in blocks of 30 seconds of eucalyptus and 40 seconds of humidify medical air. This stimulus was repeated 4 times. The acquisition MR parameters were summarized in Table 1.

The data preprocessing was done using SPM12 (Wellcome Department of Imaging Neuroscience, London, UK). It consisted of slice timing correction, realignment, coregisteration, normalization and smoothing (8x8x8 mm3). A 1st-level analysis was made with GLM modeling and a 2nd-level pair T test between the same group of people between sessions.

Results

Clinical improvement was observed in all subjects that underwent with olfactory training, which was assessed with “Sniffin stick test” before and after treatment. The untreated patients did not show any clinical improvement. Figure 1 shows brain areas of the second level analysis of treated subjects. Significant differences were observed between sessions of subjects with olfactory training, presenting a greater recruitment of compensatory olfactory central areas, in comparison with the subjects without training that activated central olfactory brain areas (Figure 2).

Discussion and Conclusion

Our preliminary results suggest that the therapeutic effect of olfactory training has a significant effects at the brain level, that it is reflected in greater recruitment of compensatory areas of the olfactory pathway at the central level, possibly involving neuroplasticity correlated with a clinical improvement, in comparison with subjects that did not undergo with the olfactory training. Future work will include more volunteers and patients to corroborate our results.

Acknowledgements

This research was conducted with the support of Comisión Nacional de Investigación Científica y Tecnológica de Chile (CONICYT) through CONICYT-PIA Anillo ACT1416 and from Millennium Science Initiative of the Chilean Ministry of Economy, Development and Tourism, grant Nucleus for Cardiovascular Magnetic Resonance.

References

1. Damm M, et al. Olfactory Training is Helpful in Postinfectious Olfactory Loss : A Randomized , Controlled , Multicenter Study. 2014;(April):826-831.

2. Kollndorfer K, et al. Olfactory training induces changes in regional functional connectivity in patients with long-term smell loss. NeuroImage Clin. 2015;9:401-410.

3. Konstantinidis I, Tsakiropoulou E, Constantinidis J. Long term effects of olfactory training in patients with post-infectious olfactory loss. Rhinology. 2016;54(2):170-175.

4. Sorokowska A, Drechsler E, Karwowski M. Effects of olfactory training: a meta-analysis. Rhinology. 2016.5. Hudson L, Silva MC, Núñez JC, Gómez R, Venegas-Francke P. [Evaluation of olfaction in healthy subjects using the Sniffing Sticks battery]. Rev Med Chil. 2012;140(4):442-446.

Figures

Table 1. MR parameters.

Figure 2: A. Diagram of experimental procedures. B. Diagram of nebulization system.

Figure 3. Results of second level analysis between the first and second session of subjects with olfactory treatment. A. Activation of Brain areas. B. Table with activated brain areas.

Figure 4. Results of second level analysis between the first and second session of subjects with no olfactory treatment. A. Activation of Brain areas. B. Table with activated brain areas.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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