Gamma Band Functional Connectivity in Olfactory-Prefrontal Pathways During Anxious States

Document Type : Original Research

Author
School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Abstract
Introduction: Anxiety disorders affect nearly 30% of adults worldwide and involve dysfunctional threat processing, yet the neural mechanisms remain partially understood. This study investigates the role of gamma-band oscillations in olfactory bulb (OB) and prefrontal cortex (PFC) interactions during anxiety-like behavior.

Methods: Chronic local field potentials were recorded simultaneously from OB and PFC in male Wistar rats (n = 12) during Elevated Plus Maze (EPM) and Open Field (OF) tasks. Directional functional connectivity was assessed using Granger causality analysis across low (30–50 Hz) and high (50–100 Hz) gamma frequency bands.

Results: Results showed significant feedforward (OB→PFC) connectivity in both gamma bands during behavioral tasks. The directional influence from OB to PFC was significantly greater than the reverse pathway across conditions. These findings indicate robust bottom-up communication between OB and PFC.

Conclusion: Gamma oscillations appear to mediate sensory-to-prefrontal information transfer during threat evaluation, with low gamma supporting interregional coordination and high gamma facilitating localized processing within the PFC. This frequency-dependent coupling highlights potential neural mechanisms underlying anxiety.

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. 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.
3. 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.
4. 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.
5. 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.
6. Euston DR, Gruber AJ, McNaughton BL. The role of medial prefrontal cortex in memory and decision making. Neuron. 2012;76(6):1057-70.
7. Price JL. Prefrontal cortical networks related to visceral function and mood. Annals of the new York Academy of Sciences. 1999;877(1):383-96.
8. Gilmartin MR, Balderston NL, Helmstetter FJ. Prefrontal cortical regulation of fear learning. Trends in neurosciences. 2014;37(8):455-64.
9. 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.
10. Kenwood MM, Kalin NH, Barbas H. The prefrontal cortex, pathological anxiety, and anxiety disorders. Neuropsychopharmacology. 2022;47(1):260-75.
11. 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.
12. 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.
13. Strüber D, Herrmann CS. Gamma activity in sensory and cognitive processing. The Oxford Handbook of EEG Frequency. 2022:145-C8.
14. Crone NE, Korzeniewska A, Franaszczuk PJ. Cortical gamma responses: searching high and low. International Journal of Psychophysiology. 2011;79(1):9-15.