Figures and data
Neural representation of associative threat learning in pulvinar divisions, MD and LGN.
a. Human fear conditioning paradigm in the fMRI. b-d. Means ± SE of activation in response to CS+ vs. CS- at both block-wise and trial-wise levels within the pulvinar divisions (b), MD (c), and LGN (d). e. ROI-to-ROI connectivity. Right: the red line represents significant positive connectivity to CS+ vs. CS- (PFDR < 0.05), while the gray lines indicate non-significant connectivity. Thalamic nuclei that showed no significant connectivity with other regions (i.e., amygdala, hippocampus, etc.) were omitted from the visualization. Left: boxplots and kernel density estimates illustrate the distribution of connectivity values in response to CS+ and CS-. SE: Standard error. MD: Mediodorsal thalamus. LGN: Lateral geniculate nucleus. CS+ vs. CS-: Conditioned stimulus predicting shock vs. no shock. ROI: Region of interest. *p<0.05, **p<0.01, ***p<0.001 Display items in panel a were created using BioRender (BioRender.com/t54zvyf).
Quantifying the relationships between the anterior pulvinar and MD during conditioning.
a. Hierarchical regression models of trial-wise relationships between the anterior pulvinar and MD activations while controlling for a potential effect of anatomical proximity. The effect of anatomical proximity was controlled by progressively adding other pulvinar divisions as controls. b. Results of a hierarchical model that included the LGN as an alternative control, distinct from the pulvinar. c. Comparison of activation levels in the anterior pulvinar and MD at both block-wise and trial-wise levels (means ± SE). *p<0.05, **p<0.01, ***p<0.001 MD: Mediodorsal thalamus. LGN: Lateral geniculate nucleus. SE: Standard error.
A data-driven approach to understanding the functional relationships between pulvinar divisions during conditioning
a. Means ± SE of activation differences between pulvinar divisions. b. Network analysis reveals that the medial pulvinar serves as a central hub, mediating interactions among pulvinar divisions and exhibiting increased centrality measures. c. Schematic visualization of activation patterns we observed in pulvinar divisions. d. Previous studies suggest that the inferior and lateral pulvinar are involved in processing basic visual information, while the medial pulvinar is associated with higher-level functions, including working memory. e. Based on b-d, we hypothesize that the medial pulvinar mediates the relationships with other divisions. f. Mediation analysis supports our hypothesis (panel e). g. Validation of the mediation model on an additional independent sample. Dashed paths in panels f and g represent statistically unstable paths, while the continuous paths indicate stable paths. SE: Standard error. SC: Superior colliculus. *p<0.05, **p<0.01, ***p<0.001 Display items in panels d and e were created using BioRender (BioRender.com/1m4j5bz).
Neural representation of extinction learning in pulvinar divisions, MD and LGN.
a. Human extinction learning paradigm in the fMRI. b-d. Means ± SE of activation in response to extinguished CS+ vs. CS- at both block-wise and trial-wise levels within the pulvinar divisions (b), MD (c), and LGN (d). e. ROI-to-ROI connectivity. Right: the red line represents significant positive connectivity to extinguished CS+ vs. CS- (PFDR < 0.05), while the gray lines indicate no significant connectivity. Thalamic nuclei that showed non-significant connectivity with other regions (i.e., amygdala, hippocampus, etc.) were omitted from the visualization. Left: boxplots and kernel density estimates illustrate the distribution of connectivity values in response to extinguished CS+ and CS-. SE: Standard error. MD: Mediodorsal thalamus. LGN: Lateral geniculate nucleus. Extinguished CS+ vs. CS-: A conditioned stimulus that no longer predicts shock vs. a stimulus that was never paired with shock. ROI: Region of interest. *p<0.05, **p<0.01, ***p<0.001 Display items in panel a were created using BioRender (BioRender.com/iori2z1).
Neural representation of extinction recall in pulvinar divisions, MD and LGN.
a. Human extinction recall paradigm in the fMRI conducted within safe contextual cues. b-d. Means ± SE of activation in response to extinguished CS+ vs. CS-at both block-wise and trial-wise levels within the pulvinar divisions (b), MD (c), and LGN (d). e. ROI-to-ROI connectivity. Right: the red line represents significant positive connectivity to extinguished CS+ vs. CS-(PFDR < 0.05), while the gray lines indicate non-significant connectivity. Thalamic nuclei that showed no significant connectivity with other regions (i.e., amygdala, hippocampus, etc.) were omitted from the visualization. Left: boxplots and kernel density estimates illustrate the distribution of connectivity values in response to extinguished CS+ and CS-. SE: Standard error. MD: Mediodorsal thalamus. LGN: Lateral geniculate nucleus. Extinguished CS+ vs. CS-: A conditioned stimulus that no longer predicts shock vs. a stimulus that was never paired with shock. ROI: Region of interest. *p<0.05, **p<0.01, ***p<0.001 Display items in panel a were created using BioRender (BioRender.com/imzbkmn).
Neural representation of threat renewal in pulvinar divisions, MD and LGN.
a. Human threat renewal paradigm in the fMRI conducted within threat contextual cues in the original context where fear conditioning occurred. b-d. Means ± SE of activation in response to extinguished CS+ vs. CS-at both block-wise and trial-wise levels within the pulvinar divisions (b), MD (c), and LGN (d). e. ROI-to-ROI connectivity. Right: the red line represents significant positive connectivity to extinguished CS+ vs. CS- (PFDR < 0.05), while the gray lines indicate non-significant connectivity. Thalamic nuclei that showed no significant connectivity with other regions (i.e., amygdala, hippocampus, etc.) were omitted from the visualization. Left: boxplots and kernel density estimates illustrate the distribution of connectivity values in response to extinguished CS+ and CS-. SE: Standard error. MD: Mediodorsal thalamus. LGN: Lateral geniculate nucleus. Extinguished CS+ vs. CS-: A conditioned stimulus that no longer predicts shock vs. a stimulus that was never paired with shock. ROI: Region of interest. *p<0.05, **p<0.01, ***p<0.001 Display items in panel a were created using BioRender (BioRender.com/r9bhqjs).
Neurobehavioral models of thalamic involvement in associative threat learning and memory.
a. Schematic illustration of thalamic circuitry during the acquisition of associative threat learning, highlighting interactions between pulvinar divisions, MD, and LGN with key brain regions involved in fear expression. b. A thalamic-dependent “toggle switch” regulates the retrieval of safety vs. threat-related memory. The MD-dACC connectivity modulates the interaction between dACC and vmPFC, promoting vmPFC dominance during extinction recall. In contrast, the anterior pulvinar-vmPFC connectivity promotes dACC dominance, enhancing the expression of threat memory during threat renewal. MD: Mediodorsal thalamus. LGN: Lateral geniculate nucleus. vmPFC = Ventromedial prefrontal cortex. dACC = Dorsal anterior cingulate cortex. V1, V2, and V4: Primary, secondary, and fourth visual areas. TEO, TE: Temporal cortex regions. Hypo.: Hypothalamus. Hippo.: Hippocampus. Created using BioRender (BioRender.com/5pdf54t).
