Brain-immune interaction accompanying odor-evoked autobiographic memory

Abstract

The phenomenon in which a certain smell evokes a specific memory is known as the Proust phenomenon. Odor-evoked autobiographic memories are more emotional than those elicited by other sensory stimuli. The results of our previous study indicated that odor-evoked autobiographic memory accompanied by positive emotions has remarkable effects on various psychological and physiological activities, including the secretion of cytokines, which are immune-signaling molecules that modulate systemic inflammation. In this study, we aimed to clarify the neural substrates associated with the interaction between odor-evoked autobiographic memory and peripheral circulating cytokines. We recruited healthy male and female volunteers and investigated the association between brain responses and the concentration of several cytokines in the plasma by using positron emission tomography (PET) recordings when an autographic memory was evoked in participants by asking them to smell an odor that was nostalgic to them. Participants experienced positive emotions and autobiographic memories when nostalgic odors were presented to them. The levels of peripheral proinflammatory cytokines, such as the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), were significantly reduced after experiencing odor-evoked autobiographic memory. Subtraction analysis of PET images indicated that the medial orbitofrontal cortex (mOFC) and precuneus/posterior cingulate cortex (PCC) were significantly activated during experiences of odor-evoked autobiographic memory. Furthermore, a correlation analysis indicated that activities of the mOFC and precuneus/PCC were negatively correlated with IFN-γ concentration. These results indicate that the neural networks including the precuneus/PCC and mOFC might regulate the secretion of peripheral proinflammatory cytokines during the experience of odor-evoked autobiographic memories accompanied with positive emotions.

Figure 1. Psychological and plasma cytokine data.

(A) Differences in the rating scores for the characteristics of control and nostalgic odors. **p < 0.01 and *p < 0.05 vs. control, paired t test. (B) Differences in the plasma concentration of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) between control and nostalgic odors. **p < 0.01 and *p < 0.05 vs. control, paired t test.

Figure 2. Neuroimaging analysis.

Statistical parametric map showing a cluster that was activated significantly in the Proust condition compared with the control and LLC conditions. The statistical thresholds for the analysis were set at an uncorrected p < 0.001 at the voxel level, and at an uncorrected p < 0.05 at the cluster level.

Figure 3. Correlation between peripheral cytokine levels and neuroimaging findings.

(A) Scatter plot showing the correlation between the beta value of the mOFC cluster in the Proust condition and the beta value of the precuneus/PCC cluster in the Proust condition. (B) Scatter plot showing the correlation between the beta value of the precuneus/PCC cluster in the Proust condition and IFN-γ concentration after smelling a nostalgic odor that evoked an autobiographic memory. (C) Scatter plot showing the correlation between the beta value of the mOFC cluster in the Proust condition and IFN-γ concentration after smelling a nostalgic odor that evoked an autobiographic memory.