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Resting-sate functional reorganization of the rat limbic system following neuropathic injury.

Baliki MN, Chang PC, Baria AT, Centeno MV, Apkarian AV - Sci Rep (2014)

Bottom Line: Similar to the human, the rat brain topological properties exhibited small world features and did not differ between SNI and sham.Twenty-eight days after SNI, functional connection changes were localized mainly to within the limbic system, as well as between the limbic and nociceptive systems.Furthermore, these changes were lateralized and in proportion to the tactile allodynia exhibited by SNI animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

ABSTRACT
Human brain imaging studies from various clinical cohorts show that chronic pain is associated with large-scale brain functional and morphological reorganization. However, how the rat whole-brain network is topologically reorganized to support persistent pain-like behavior following neuropathic injury remains unknown. Here we compare resting state fMRI functional connectivity-based whole-brain network properties between rats receiving spared nerve injury (SNI) vs. sham injury, at 5 days (n = 11 SNI; n = 12 sham) and 28 days (n = 11 SNI; n = 12 sham) post-injury. Similar to the human, the rat brain topological properties exhibited small world features and did not differ between SNI and sham. Local neural networks in SNI animals showed minimal disruption at day 5, and more extensive reorganization at day 28 post-injury. Twenty-eight days after SNI, functional connection changes were localized mainly to within the limbic system, as well as between the limbic and nociceptive systems. No connectivity changes were observed within the nociceptive network. Furthermore, these changes were lateralized and in proportion to the tactile allodynia exhibited by SNI animals. The findings establish that SNI is primarily associated with altered information transfer of limbic regions and provides a novel translational framework for understanding brain functional reorganization in response to a persistent neuropathic injury.

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SNI is associated with late brain functional connectivity reorganization.Matrices show the connections with significantly (p<0.05, FDR corrected) stronger (red) and weaker (blue) functional connectivity strength in SNI compared to sham at day 5 (a) and day 28 (c). Connectivity differences between SNI and sham are displayed in the dorsal (top) and lateral views (Left and Right hemispheres separately), at day 5 (b) and day 28 (d). Each node represents the anatomical regions listed in Table 1. Overall, SNI showed robust connectivity changes compared to sham at day 28, but few changes at day 5. (A = anterior; P = posterior; L = left; R = right; V = ventral; D = dorsal).
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f2: SNI is associated with late brain functional connectivity reorganization.Matrices show the connections with significantly (p<0.05, FDR corrected) stronger (red) and weaker (blue) functional connectivity strength in SNI compared to sham at day 5 (a) and day 28 (c). Connectivity differences between SNI and sham are displayed in the dorsal (top) and lateral views (Left and Right hemispheres separately), at day 5 (b) and day 28 (d). Each node represents the anatomical regions listed in Table 1. Overall, SNI showed robust connectivity changes compared to sham at day 28, but few changes at day 5. (A = anterior; P = posterior; L = left; R = right; V = ventral; D = dorsal).

Mentions: It remains unknown whether the network organizational principles of the brain are preserved or changed in rodents displaying neuropathic pain-like behavior. Whole-brain resting-state networks were constructed from 96 anatomical ROIs (48 regions in each hemisphere) using a standard rat atlas32 (Fig. 1b, Table 1), following the methods described in5 (see methods for details). We compared five global network topological metrics between the SNI and sham animals. These include: 1) clustering, a topological measure of segregated information transfer, 2) global efficiency, a topological measure of integrative information transfer inversely related to characteristic path length, 3) maximum modularity, a global measure of the near-decomposability of the network into a community structure of sparsely interconnected modules, 4) betweenness centrality, which represents the number of shortest paths going through a given node, and 5) small-worldness, based on the tradeoff between clustering and efficiency. Strikingly, all metrics showed no statistically significant differences between the two groups (Fig. 2c–g, Table 2). Finally, the probability distribution of nodal degree (the number of links connecting each node to the network) was best fitted by an exponentially truncated power law. Both the SNI and sham groups exhibited similar degree distributions at day 05 and 28 following neuropathic injury. Thus despite the marked difference in mechanical allodynia between SNI and sham, the brain networks had conserved global properties of small-worldness that were maintained following SNI.


Resting-sate functional reorganization of the rat limbic system following neuropathic injury.

Baliki MN, Chang PC, Baria AT, Centeno MV, Apkarian AV - Sci Rep (2014)

SNI is associated with late brain functional connectivity reorganization.Matrices show the connections with significantly (p<0.05, FDR corrected) stronger (red) and weaker (blue) functional connectivity strength in SNI compared to sham at day 5 (a) and day 28 (c). Connectivity differences between SNI and sham are displayed in the dorsal (top) and lateral views (Left and Right hemispheres separately), at day 5 (b) and day 28 (d). Each node represents the anatomical regions listed in Table 1. Overall, SNI showed robust connectivity changes compared to sham at day 28, but few changes at day 5. (A = anterior; P = posterior; L = left; R = right; V = ventral; D = dorsal).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151103&req=5

f2: SNI is associated with late brain functional connectivity reorganization.Matrices show the connections with significantly (p<0.05, FDR corrected) stronger (red) and weaker (blue) functional connectivity strength in SNI compared to sham at day 5 (a) and day 28 (c). Connectivity differences between SNI and sham are displayed in the dorsal (top) and lateral views (Left and Right hemispheres separately), at day 5 (b) and day 28 (d). Each node represents the anatomical regions listed in Table 1. Overall, SNI showed robust connectivity changes compared to sham at day 28, but few changes at day 5. (A = anterior; P = posterior; L = left; R = right; V = ventral; D = dorsal).
Mentions: It remains unknown whether the network organizational principles of the brain are preserved or changed in rodents displaying neuropathic pain-like behavior. Whole-brain resting-state networks were constructed from 96 anatomical ROIs (48 regions in each hemisphere) using a standard rat atlas32 (Fig. 1b, Table 1), following the methods described in5 (see methods for details). We compared five global network topological metrics between the SNI and sham animals. These include: 1) clustering, a topological measure of segregated information transfer, 2) global efficiency, a topological measure of integrative information transfer inversely related to characteristic path length, 3) maximum modularity, a global measure of the near-decomposability of the network into a community structure of sparsely interconnected modules, 4) betweenness centrality, which represents the number of shortest paths going through a given node, and 5) small-worldness, based on the tradeoff between clustering and efficiency. Strikingly, all metrics showed no statistically significant differences between the two groups (Fig. 2c–g, Table 2). Finally, the probability distribution of nodal degree (the number of links connecting each node to the network) was best fitted by an exponentially truncated power law. Both the SNI and sham groups exhibited similar degree distributions at day 05 and 28 following neuropathic injury. Thus despite the marked difference in mechanical allodynia between SNI and sham, the brain networks had conserved global properties of small-worldness that were maintained following SNI.

Bottom Line: Similar to the human, the rat brain topological properties exhibited small world features and did not differ between SNI and sham.Twenty-eight days after SNI, functional connection changes were localized mainly to within the limbic system, as well as between the limbic and nociceptive systems.Furthermore, these changes were lateralized and in proportion to the tactile allodynia exhibited by SNI animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

ABSTRACT
Human brain imaging studies from various clinical cohorts show that chronic pain is associated with large-scale brain functional and morphological reorganization. However, how the rat whole-brain network is topologically reorganized to support persistent pain-like behavior following neuropathic injury remains unknown. Here we compare resting state fMRI functional connectivity-based whole-brain network properties between rats receiving spared nerve injury (SNI) vs. sham injury, at 5 days (n = 11 SNI; n = 12 sham) and 28 days (n = 11 SNI; n = 12 sham) post-injury. Similar to the human, the rat brain topological properties exhibited small world features and did not differ between SNI and sham. Local neural networks in SNI animals showed minimal disruption at day 5, and more extensive reorganization at day 28 post-injury. Twenty-eight days after SNI, functional connection changes were localized mainly to within the limbic system, as well as between the limbic and nociceptive systems. No connectivity changes were observed within the nociceptive network. Furthermore, these changes were lateralized and in proportion to the tactile allodynia exhibited by SNI animals. The findings establish that SNI is primarily associated with altered information transfer of limbic regions and provides a novel translational framework for understanding brain functional reorganization in response to a persistent neuropathic injury.

Show MeSH
Related in: MedlinePlus