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. 2022 Apr 6;42(14):2963-2972.
doi: 10.1523/JNEUROSCI.2123-21.2022. Epub 2022 Mar 1.

Thalamocortical Mechanisms for Nostalgia-Induced Analgesia

Ming Zhang  1   2 , Ziyan Yang  1   2 , Jiahui Zhong  3 , Yuqi Zhang  1   2 , Xiaomin Lin  1 , Huajian Cai  4   2 , Yazhuo Kong  4   2   5
Affiliations

Thalamocortical Mechanisms for Nostalgia-Induced Analgesia

Ming Zhang et al. J Neurosci. .

Abstract

As a predominately positive emotion, nostalgia serves various adaptive functions, including a recently revealed analgesic effect. The current fMRI study aimed to explore the neural mechanisms underlying the nostalgia-induced analgesic effect on noxious thermal stimuli of different intensities. Human participants' (males and females) behavior results showed that the nostalgia paradigm significantly reduced participants' perception of pain, particularly at low pain intensities. fMRI analysis revealed that analgesia was related to decreased brain activity in pain-related brain regions, including the lingual and parahippocampal gyrus. Notably, anterior thalamic activation during the nostalgia stage predicted posterior parietal thalamus activation during the pain stage, suggesting that the thalamus might play a key role as a central functional linkage in the analgesic effect. Moreover, while thalamus-PAG functional connectivity was found to be related to nostalgic strength, periaqueductal gray-dorsolateral prefrontal cortex (PAG-dlPFC) functional connectivity was found to be associated with pain perception, suggesting possible analgesic modulatory pathways. These findings demonstrate the analgesic effect of nostalgia and, more importantly, shed light on its neural mechanism.SIGNIFICANCE STATEMENT Nostalgia is known to reduce individuals' perception of physical pain. The underlying brain mechanisms, however, are unclear. Our study found that the thalamus plays a key role as a functional linkage between nostalgia and pain, suggesting a possible analgesic modulatory mechanism of nostalgia. These findings have implications for the underlying brain mechanisms of psychological analgesia.

Keywords: PAG; analgesia; nostalgia; pain; thalamus.

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Figures

Figure 1.
Figure 1.
A, The setup for each trial. In the current trial, participants viewed a nostalgic cue (i.e., a bicycle from childhood), while in the control trial, participants viewed a control cue (i.e., a bicycle from contemporary life). B, Manipulation check performed using a five-point Likert scale (error bars represent SD, ***p < 0.001). C, Mean of pain ratings in the four conditions (**p < 0.01). D, Correlation between the nostalgic effect and analgesic effect.
Figure 2.
Figure 2.
Pain-related activation in four conditions.
Figure 3.
Figure 3.
A, During the cue stage, brain activation of the lateral occipital cortex, the left supramarginal gyrus, and the right frontal orbital cortex was significantly increased in the nostalgia condition compared with the control condition. B, During the pain stage, brain activation of the thalamus, insular, lingual gyrus, and parahippocampal gyrus was significantly increased in the high-intensity condition compared with the low-intensity condition. C, Brain activation of the lingual gyrus and parahippocampal gyrus was significantly greater in the control condition compared with the nostalgia condition in the pain stage. D, Correlation between supramarginal gyrus activation (nostalgia > control) and the analgesic effect (control > nostalgia). E, ROI analysis revealed that brain activation of the lingual gyrus was significantly lower in the nostalgia condition compared with the control condition. F, ROI analysis revealed that brain activation of the parahippocampal gyrus was significantly lower in the nostalgia condition compared with the control condition. G, Correlation between lingual gyrus activation and pain rating in the nostalgia-low condition. H, Correlation between lingual gyrus activation and pain rating in the nostalgia-high condition (*p ≤ 0.05, ***p < 0.001).
Figure 4.
Figure 4.
Significant correlations between brain activation and behavioral scores in the cue and pain stages. Left, During nostalgia encoding, the prefrontal thalamus [–1, –14, –2] showed a positive correlation between the BOLD response magnitude and nostalgic strength. Middle, Brain activity in the prefrontal thalamus in the cue stage was positively correlated to brain activity in the posterior parietal thalamus in the pain stage. Right, During pain encoding, the posterior parietal thalamus [24, –29, 14] showed a positive correlation between the BOLD response and the analgesic effect.
Figure 5.
Figure 5.
Thalamus activation mediated how nostalgia affected the analgesic effect.
Figure 6.
Figure 6.
A, Functional connectivity between the BOLD time-series signals in the prefrontal thalamus (seed region) and PAG, as well as in the putamen, amygdala, and hippocampus. B, Correlation between the thalamus-PAG connectivity in the cue stage and nostalgic strength in the nostalgia condition. C, Functional connectivity between the BOLD time-series signals in the PAG (seed region), dlPFC, and the frontal pole in the pain stage. D, Correlation between the PAG-dlPFC connectivity in the pain stage and the pain rating in the nostalgia-low condition.
Figure 7.
Figure 7.
The model of thalamus-centered pathways affected by the analgesic effect associated with nostalgia.
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