Understanding fear responses and their attenuation is crucial in addressing anxiety disorders and PTSD. A recent study, published in Biological Psychiatry: Global Open Science, investigates the role of carbon dioxide reactivity in predicting fear expression after extinction and retrieval-extinction in rats. The research, led by Professor Marie Monfils, delves into how individual differences in carbon dioxide reactivity can inform the effectiveness of extinction-based therapies.
The study involved male rats undergoing a carbon dioxide challenge, fear conditioning, and then either standard extinction or retrieval-extinction protocols. Standard extinction involves repeated exposure to a conditioned stimulus without the aversive unconditioned stimulus, leading to a gradual reduction in fear responses. Retrieval-extinction, on the other hand, involves a brief re-exposure to the conditioned stimulus to destabilize the fear memory, followed by extinction training. This method aims to overwrite the original fear memory more effectively.
Professor Monfils’ team found that retrieval-extinction resulted in significantly lower fear responses compared to standard extinction. This was evident during extinction training, long-term memory tests, and reinstatement tests. Additionally, carbon dioxide reactivity, measured by behaviors such as ambulation, grooming, rearing, and labored breathing during a carbon dioxide challenge, was a strong predictor of fear memory retention. Specifically, high carbon dioxide reactivity was associated with better extinction outcomes, indicating that rats with higher carbon dioxide reactivity retained less fear memory, though this association was stronger in rats that underwent extinction than those that underwent retrieval-extinction.
Marissa Raskin, the first author of the study, emphasized the significance of these findings. “Our most important conclusion is that carbon dioxide reactivity could serve as a screening tool to identify individuals who may benefit most from extinction-based therapies,” she said. This insight is particularly valuable, as it suggests that carbon dioxide reactivity could help tailor treatments to individual needs, potentially improving therapeutic outcomes for anxiety and PTSD patients.
The study also highlighted the differential effectiveness of extinction and retrieval-extinction. While both methods reduced fear responses, retrieval-extinction was more robust in preventing the return of fear, as originally discovered by Monfils et al in 2009. This also aligns with previous findings that retrieval-extinction engages both extinction and reconsolidation mechanisms, leading to more persistent fear attenuation.
The implications of this research extend to clinical settings. Carbon dioxide reactivity tests could be integrated into diagnostic procedures to identify patients who are likely to respond well to extinction-based therapies. Moreover, retrieval-extinction could be adopted as a more effective method for long-term fear reduction in therapeutic practices.
Future research will aim to extend these studies to include female subjects and diverse cue modalities to examine the generalizability of the results. The research group has also teamed up with clinician collaborators to begin testing the application of carbon dioxide reactivity as a predictive tool in human clinical trials.
In summary Professor Monfils and colleagues’ study provides compelling evidence that carbon dioxide reactivity can predict fear memory retention and highlights the superior effectiveness of retrieval-extinction over standard extinction. These findings pave the way for more personalized and effective treatments for anxiety and PTSD, potentially improving the quality of life for many patients.
Journal Reference
Raskin, M., Keller, N. E., Agee, L. A., Shumake, J., Smits, J. A. J., Telch, M. J., Otto, M. W., Lee, H. J., & Monfils, M.-H. (2024). Carbon Dioxide Reactivity Differentially Predicts Fear Expression After Extinction and Retrieval-Extinction in Rats. Biological Psychiatry: Global Open Science. https://doi.org/10.1016/j.bpsgos.2024.100310
About the Author
Prof. Marie Monfils received her Ph.D. in behavioral neuroscience from the Canadian Centre for Behavioural Neuroscience, and conducted a postdoctoral fellowship at New York University. She is currently a professor at the University of Texas at Austin where she and her team are currently pursuing 3 research streams:
- investigating post-consolidation manipulations that can persistently attenuate fear memories,
- isolating the factors that underlie affiliative kinship and the social transmission of information,
- assessing individual differences and their impact on fear attenuation.
