Shared functional organization between pulvinar-cortical and cortico-cortical connectivity and its structural and molecular imaging correlates
- Brain Mapping Lab, Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Italy
- IRCCS Centro Neurolesi 'Bonino Pulejo', Italy
- Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), Italy
- S. Anna Institute, Italy
- Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health Science and Nutrition, University of Calabria, Italy
- Nuclear Medicine Unit, Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Italy
- Radiology Unit, Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Italy
- Section of Cytomorphology, Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, Italy
- Department of Radiology, University of Massachusetts Chan Medical School, United States
- Department of Biomedical Sciences, Humanitas University, Italy
- IRCCS Humanitas Research Hospital, Italy
Figures
Figure 1
Schematic overview of the gradient mapping protocol.
For each different imaging modality (DWI, BOLD, PET), a feature matrix was built by extracting voxel-wise features in the left and right pulvinar separately. Structural and functional connectivity to 400 cortical areas, as well as the expression profiles of 19 receptors and transporters, were extracted for each pulvinar voxel. Symmetric, affinity matrices comparing the feature profile similarity of each voxel against each other were estimated using cosine similarity and fed into the diffusion embedding algorithm. Additional details can be found in the main text. PET, positron emission tomography.
Figure 2 with 3 supplements
Functional connectivity (A), structural connectivity (B), and receptor coexpression (C) pulvinar gradients.
For each panel, the top row shows the scree plots of explained variance for each gradient. The gradients that have been considered for subsequent analyses are marked with red circles. The bottom row shows 3D reconstruction of the normalized gradient images overlaid on the thalamic outline (gray-shaded area). The thalamic volume has been obtained from the AAL3 atlas. Gradients are shown in posterior (left), superior (center), and anterior (right) views. A: anterior; P: posterior; L: left; R: right.
Figure 2—figure supplement 1
Replication of functional (A), structural (B), and receptor coexpression (C) gradients on a thalamic-specific atlas (Su et al., 2019).
For each panel, the top row shows the scree plots of explained variance for each gradient. The gradients that have been considered for the following analysis are marked with red circles. The bottom row shows 3D volume renderings of the normalized gradient images overlaid on the thalamic outline (gray-shaded area). The thalamic volume has been obtained from the THOMAS atlas (Su et al., 2019). Gradients are shown in posterior (left), superior (center), and anterior (right) view. A: anterior; P: posterior; L: left; R: right.
Figure 2—figure supplement 2
K-means clustering of pulvinar gradients and their correspondence with histological pulvinar nuclei.
Panels to the left show the silhouette plots for left and right pulvinar clustering solutions; error bars are standard errors calculated across 50 resamples. Panels to the right show matrix plots of Dice similarity coefficients of pulvinar clusters against histological nuclei (AAL atlas). INF: inferior; ANT: anterior; LAT: lateral; MED: medial.
Figure 2—figure supplement 3
Reliability and reproducibility of diffusion embedding of pulvinar-cortical connectivity data.
(A) Split-half stability analysis. Violin plots show the distribution of correlation values across 100 split-half resamples (bars on the median and extreme values). (B) Test-retest repeatability. (C) Reproducibility on the supplementary dataset (Leipzig Study for Mind-Body-Emotion Interactions [LEMON]). (D) Spatial correlation between gradient values and averaged voxel-wise estimates of signal-to-noise ratio (SNR).
Figure 3 with 2 supplements
Gradient-weighted connectivirty and cortico-cortical gradients.
(A) The relationship between pulvinar-cortical and cortico-cortical functional gradients. The left panels show gradient-weighted connectivity values for the first three cortico-pulvinar functional connectivity gradients, each paired with the most correlated cortico-cortical functional connectivity gradient. Normalized values of each cortical region of interest (ROI) (Schaefer atlas, 400 parcels) are plotted on the cortical surface. The right panels show matrix plots of Pearson’s correlation values between cortico-cortical gradients (y-axis) and pulvinar-cortical gradient-weighted connectivity maps. Only values showing statistical significance (spatial autocorrelation [SA]-corrected, false discovery rate [FDR]-adjusted p<0.01) are shown. (B) The relationship between pulvinar-cortical functional gradients and cortical connectivity networks. Violin plots of normalized gradient-weighted connectivity values grouped by seven intrinsic connectivity networks (as in Thomas Yeo et al., 2011); VN: visual network; SMN: sensorimotor network; DAN: dorsal attention network; VAN: ventral attention network; LN: limbic network; FPN: frontoparietal network, DMN: default-mode network.
Figure 3—figure supplement 1
Cortico-cortical functional connectivity gradients.
The left panel shows the scree plot of explained variance for each gradient, where gradients that have been considered for subsequent analyses (1–5) are marked with red circles. The right panel shows normalized gradient values for gradients 4–5 plotted on the cortical surface. Gradients 1–3 are shown in Figure 3A.
Figure 3—figure supplement 2
Cortico-cortical structural connectivity gradients and their relationship to pulvinar-cortical structural gradients.
The left panel shows cortico-cortical structural gradients; normalized gradient values are plotted on the cortical surface (Schaefer atlas, 400 parcels). The right panel shows scree plots of explained variance, where gradients that have been considered for subsequent analyses (1–4) are marked with red circles. Bottom right: heatmaps of Pearson’s correlation values between pulvinar-cortical gradient-weighted connectivity (x-axis) and the corresponding four cortico-cortical structural connectivity gradients (y-axis).
Figure 4
Pulvinar correlates of the unimodal-transmodal cortical gradient.
(A) Scatter plots illustrate the relationship between the first pulvinar-cortical connectivity gradient, corresponding to the unimodal-transmodal hierarchy of cortico-cortical connectivity, and its most correlated gradient values across other modalities. Due to the intrinsic sign indeterminacy of gradient values, absolute correlation values are considered. (B) The relationship between correlated pulvinar gradients and discrete histological nuclei. Violin plots illustrating normalized gradient values grouped by histological nuclei (AAL atlas). MED: medial pulvinar; LAT: lateral pulvinar; ANT: anterior pulvinar; INF: inferior pulvinar. (C) Structural connectivity and receptor coexpression patterns correlating with the unimodal-transmodal hierarchy. Left panels: gradient-weighted structural connectivity. Normalized values for each cortical region of interest (ROI) (Schaefer atlas, 400 parcels) are plotted on the cortical surface. Violin plots show values grouped by seven intrinsic connectivity networks (as in Thomas Yeo et al., 2011). VN: visual network; SMN: sensorimotor network; DAN: dorsal attention network; VAN: ventral attention network; LN: limbic network; FPN: frontoparietal network; DMN: default-mode network. Right panels: gradient-correlated receptor density values for the top 5 most correlated receptors. Details can be found in the main text.
Figure 5
Pulvinar correlates of the visual-to-sensorimotor cortical gradient.
(A) Scatter plots illustrate the relationship between the third pulvinar-cortical connectivity gradient, corresponding to the visual-to-sensorimotor hierarchy of cortico-cortical connectivity, and its most correlated gradient values across other modalities. Due to the intrinsic sign indeterminacy of gradient values, absolute correlation values are considered. (B) The relationship between correlated pulvinar gradients and discrete histological nuclei. Violin plots illustrating normalized gradient values grouped by histological nuclei (AAL atlas). MED: medial pulvinar; LAT: lateral pulvinar; ANT: anterior pulvinar; INF: inferior pulvinar. (C) Structural connectivity and receptor coexpression patterns correlating with the visual-to-sensorimotor hierarchy. Left panels: gradient-weighted structural connectivity. Normalized values for each cortical region of interest (ROI) (Schaefer atlas, 400 parcels) are plotted on the cortical surface. Violin plots show values grouped by seven intrinsic connectivity networks (as in Thomas Yeo et al., 2011). VN: visual network; SMN: sensorimotor network; DAN: dorsal attention network; VAN: ventral attention network; LN: limbic network; FPN: frontoparietal network, DMN: default-mode network. Right panels: gradient-correlated receptor density values for the top 5 most correlated receptors. Details can be found in the main text.
Author response image 1
Group-level structural connectivity of the pulvinar complex.
Track-density images have been normalized and overlaid on the MNI152 standard template.
Author response image 2
K-means clustering of pulvinar gradients on the secondary dataset (LEMON) and their correspondence with histological pulvinar nuclei.
Panels on the left show the silhouette plots for left and right pulvinar clustering solutions; error bars are standard error calculated across 50 resamples. Panels on the right show matrix plots of Dice similarity coefficients for pulvinar clusters against histological nuclei (AAL3 atlas). INF: inferior; ANT: anterior; LAT: lateral; MED: medial.
Additional files
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Supplementary file 1
Information on the neurotransmitter, tracers, and number of subjects for each study.
- https://cdn.elifesciences.org/articles/100937/elife-100937-supp1-v1.xlsx
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MDAR checklist
- https://cdn.elifesciences.org/articles/100937/elife-100937-mdarchecklist1-v1.pdf
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Shared functional organization between pulvinar-cortical and cortico-cortical connectivity and its structural and molecular imaging correlates
eLife 13:RP100937.
https://doi.org/10.7554/eLife.100937.3
