Anxiety-like States Enhance Beta-Band Functional Connectivity Between the Olfactory Bulb and Prefrontal Cortex

Document Type : Original Research

Author
A. Samii Moghaddam
School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Abstract
Introduction: Anxiety disorders involve altered brain circuit dynamics, but the neural mechanisms underlying olfactory-prefrontal interactions during anxiety remain unclear. Beta oscillations are implicated in long-range neural communication and emotional processing, but their specific role in anxiety remains underexplored.

Methods: I recorded simultaneous local field potentials (LFPs) from the olfactory bulb (OB) and prefrontal cortex (PFC) in male Wistar rats during anxiety-provoking behavioral tests, including the Elevated Plus Maze (EPM) and Open Field (OF). Functional connectivity was assessed through beta-band (13–30 Hz) synchronization using cross-correlation and power correlation analyses.

Results: Behavioral tests revealed a significant increase in beta-frequency synchronization between OB and PFC during anxiogenic conditions compared to resting states. Notably, enhanced functional coupling was observed specifically in anxiogenic zones—the open arms of the EPM and the center area of the OF. These effects suggest an intensity-dependent increase in OB-PFC interaction associated with anxiety states.

Conclusion: My findings identify beta-band OB-PFC synchronization as a novel electrophysiological marker of anxiety, providing insight into sensory-executive integration during threat processing. This enhanced connectivity may contribute to the neural circuitry underlying anxiety and represents a potential target for therapeutic intervention.

Keywords

Subjects

1. Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues in clinical neuroscience. 2015;17(3):327-35.
2. Lieb R, Becker E, Altamura C. The epidemiology of generalized anxiety disorder in Europe. European Neuropsychopharmacology. 2005;15(4):445-52.
3. Connelly T, Yu Y, Grosmaitre X, Wang J, Santarelli LC, Savigner A, et al. G protein-coupled odorant receptors underlie mechanosensitivity in mammalian olfactory sensory neurons. Proceedings of the National Academy of Sciences. 2015;112(2):590-5.
4. Grosmaitre X, Santarelli LC, Tan J, Luo M, Ma M. Dual functions of mammalian olfactory sensory neurons as odor detectors and mechanical sensors. Nature neuroscience. 2007;10(3):348-54.
5. Ueki S, NURIMOTO S, OGAWA N. Characteristics in emotional behavior of the rat with bilateral olfactory bulb ablations. Psychiatry and Clinical Neurosciences. 1972;26(3):227-37.
6. Cain DP. The role of the olfactory bulb in limbic mechanisms. Psychological Bulletin. 1974;81(10):654.
7. Mollenauer S, Plotnik R, Snyder E. Effects of olfactory bulb removal on fear responses and passive avoidance in the rat. Physiology & Behavior. 1974;12(1):141-4.
8. Rottstaedt F, Weidner K, Strauß T, Schellong J, Kitzler H, Wolff-Stephan S, et al. Size matters–The olfactory bulb as a marker for depression. Journal of affective disorders. 2018;229:193-8.
9. Salimi M, Ghazvineh S, Zare M, Parsazadegan T, Dehdar K, Nazari M, et al. Distraction of olfactory bulb-medial prefrontal cortex circuit may induce anxiety-like behavior in allergic rhinitis. PloS one. 2019;14(9):e0221978.
10. Cinelli A, Ferreyra-Moyano H, Barragan E. Reciprocal functional connections of the olfactory bulbs and other olfactory related areas with the prefrontal cortex. Brain research bulletin. 1987;19(6):651-61.
11. Stenwall A, Uggla A-L, Weibust D, Fahlström M, Ryttlefors M, Latini F. The Bulb, the Brain and the Being: New Insights into Olfactory System Anatomy, Organization and Connectivity. Brain Sciences. 2025;15(4):368.
12. Price JL, Carmichael ST, Carnes K, Clugnet M, Kuroda M, Ray J. Olfactory input to the prefrontal cortex. Olfaction: A model system for computational neuroscience. 1991:101-20.
13. Euston DR, Gruber AJ, McNaughton BL. The role of medial prefrontal cortex in memory and decision making. Neuron. 2012;76(6):1057-70.
14. Price JL. Prefrontal cortical networks related to visceral function and mood. Annals of the new York Academy of Sciences. 1999;877(1):383-96.
15. Alexander WH, Brown JW. Medial prefrontal cortex as an action-outcome predictor. Nature neuroscience. 2011;14(10):1338-44.
16. Akirav I, Maroun M. Ventromedial prefrontal cortex is obligatory for consolidation and reconsolidation of object recognition memory. Cerebral cortex. 2006;16(12):1759-65.
17. Gilmartin MR, Balderston NL, Helmstetter FJ. Prefrontal cortical regulation of fear learning. Trends in neurosciences. 2014;37(8):455-64.
18. Giustino TF, Maren S. The role of the medial prefrontal cortex in the conditioning and extinction of fear. Frontiers in behavioral neuroscience. 2015;9:298.
19. Kenwood MM, Kalin NH, Barbas H. The prefrontal cortex, pathological anxiety, and anxiety disorders. Neuropsychopharmacology. 2022;47(1):260-75.
20. Vidal-Gonzalez I, Vidal-Gonzalez B, Rauch SL, Quirk GJ. Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learning & memory. 2006;13(6):728-33.
21. Kim MJ, Gee DG, Loucks RA, Davis FC, Whalen PJ. Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest. Cerebral cortex. 2011;21(7):1667-73.
22. Baeg EH, Kim YB, Jang J, Kim HT, Mook-Jung I, Jung MW. Fast spiking and regular spiking neural correlates of fear conditioning in the medial prefrontal cortex of the rat. Cerebral cortex. 2001;11(5):441-51.
23. Gallego-Carracedo C, Perich MG, Chowdhury RH, Miller LE, Gallego JÁ. Local field potentials reflect cortical population dynamics in a region-specific and frequency-dependent manner. Elife. 2022;11:e73155.
24. Buschman TJ, Denovellis EL, Diogo C, Bullock D, Miller EK. Synchronous oscillatory neural ensembles for rules in the prefrontal cortex. Neuron. 2012;76(4):838-46.
25. Gervais R, Buonviso N, Martin C, Ravel N. What do electrophysiological studies tell us about processing at the olfactory bulb level? Journal of Physiology-Paris. 2007;101(1-3):40-5.
26. Martin C, Beshel J, Kay LM. An olfacto-hippocampal network is dynamically involved in odor-discrimination learning. Journal of neurophysiology. 2007;98(4):2196-205.
27. Schneider TR, Hipp JF, Domnick C, Carl C, Büchel C, Engel AK. Modulation of neuronal oscillatory activity in the beta-and gamma-band is associated with current individual anxiety levels. NeuroImage. 2018;178:423-34.
28. Sporn S, Hein T, Herrojo Ruiz M. Alterations in the amplitude and burst rate of beta oscillations impair reward-dependent motor learning in anxiety. Elife. 2020;9:e50654.
29. Mooziri M, Samii Moghaddam A, Mirshekar MA, Raoufy MR. Olfactory bulb-medial prefrontal cortex theta synchronization is associated with anxiety. Scientific Reports. 2024;14(1):12101.
30. Salimi M, Tabasi F, Nazari M, Ghazvineh S, Raoufy MR. The olfactory bulb coordinates the ventral hippocampus–medial prefrontal cortex circuit during spatial working memory performance. The Journal of Physiological Sciences. 2022;72(1):9.
31. Pavlidou A, Schnitzler A, Lange J. Beta oscillations and their functional role in movement perception. Translational Neuroscience. 2014;5:286-92.
32. Kopell N, Ermentrout G, Whittington MA, Traub RD. Gamma rhythms and beta rhythms have different synchronization properties. Proceedings of the National Academy of Sciences. 2000;97(4):1867-72.
33. Kühn AA, Doyle L, Pogosyan A, Yarrow K, Kupsch A, Schneider G-H, et al. Modulation of beta oscillations in the subthalamic area during motor imagery in Parkinson's disease. Brain. 2006;129(3):695-706.
34. van Elswijk G, Maij F, Schoffelen J-M, Overeem S, Stegeman DF, Fries P. Corticospinal beta-band synchronization entails rhythmic gain modulation. Journal of Neuroscience. 2010;30(12):4481-8.
Pathobiology Reserach
Volume 28, Issue 2
March 2025
Pages 95-103