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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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Functional connectivity changes 28 days after SNI are mainly within limbic, and between limbic and nociceptive regions.(a) Bar graph show the number of significantly decreased (blue) and increased (red) connections for all ROIs in SNI compare to sham 28 days following injury. Black and gray circles denote limbic and nociceptive ROIs respectively. Significantly (b) increased and (c) decreased functional connectivity are shown relative to sham. Limbic (gray labels) and nociceptive (black labels) ROIs were grouped into two separate functional–anatomical modules, labeled at the approximate brain location. Normalized weighted edges and nodes indicate extent of reorganization between and within the seven regions. Pie charts show the percentages of significantly changed limbic and nociceptive connections relative to the total number of changed connections. There were no connectivity differences between nociceptive regions (i.e. nociceptive-nociceptive = 0). See Table 3 for the list of regions and the corresponding ROIs. (A = Anterior; P = posterior; V = ventral; D = dorsal).
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f3: Functional connectivity changes 28 days after SNI are mainly within limbic, and between limbic and nociceptive regions.(a) Bar graph show the number of significantly decreased (blue) and increased (red) connections for all ROIs in SNI compare to sham 28 days following injury. Black and gray circles denote limbic and nociceptive ROIs respectively. Significantly (b) increased and (c) decreased functional connectivity are shown relative to sham. Limbic (gray labels) and nociceptive (black labels) ROIs were grouped into two separate functional–anatomical modules, labeled at the approximate brain location. Normalized weighted edges and nodes indicate extent of reorganization between and within the seven regions. Pie charts show the percentages of significantly changed limbic and nociceptive connections relative to the total number of changed connections. There were no connectivity differences between nociceptive regions (i.e. nociceptive-nociceptive = 0). See Table 3 for the list of regions and the corresponding ROIs. (A = Anterior; P = posterior; V = ventral; D = dorsal).

Mentions: Compared to nociceptive regions, ROIs (nodes) within the limbic systems exhibited larger numbers of connectivity changes (both positive and negative) in SNI compared to sham 28 days following injury (Fig 1a). To better conceptualize the complex pattern of altered functional connectivity, we calculated information flow within and across the seven regions comprising the limbic and nociceptive systems (Table 3). The weight of the edge between two regions was normalized as a percentage of the total number of significantly changed connections between the ROIs (nodes) within two regions (p < 0.05 with FDR correction), relative to the total number of all possible connections. Similarly, the node size was normalized relative to the all possible connections within the region (based on the number of possible connection for all ROIs within the region)5. The results show that SNI was associated with increased connectivity within the striatum, hippocampus, and amygdala. The striatum showed increased connectivity to thalamus, amygdala, and parts of the hippocampus, as well as to itself. Furthermore, the amygdala showed increased connectivity to sensorimotor areas (Fig 3b). These increases in functional connectivity were coupled with decreases in hippocampal connectivity to thalamic and sensorimotor regions (Fig 3c). Collectively, these results indicate that most functional changes (both increases and decreases) in 28-day SNI animals were either limbic-limbic or limbic-nociceptive in nature (Fig. 3 pie charts). In fact, limbic-limbic connections constituted 72.2% of all significantly increased connections and 39.5% of all decreased functional connections in SNI animals, whereas limbic-nociceptive connections constituted 19.7% and 41.7% of increased and decreased connections, respectively. There were no changes in functional connectivity within the nociceptive system (i.e., nociceptive-nociceptive connections = 0%).


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)

Functional connectivity changes 28 days after SNI are mainly within limbic, and between limbic and nociceptive regions.(a) Bar graph show the number of significantly decreased (blue) and increased (red) connections for all ROIs in SNI compare to sham 28 days following injury. Black and gray circles denote limbic and nociceptive ROIs respectively. Significantly (b) increased and (c) decreased functional connectivity are shown relative to sham. Limbic (gray labels) and nociceptive (black labels) ROIs were grouped into two separate functional–anatomical modules, labeled at the approximate brain location. Normalized weighted edges and nodes indicate extent of reorganization between and within the seven regions. Pie charts show the percentages of significantly changed limbic and nociceptive connections relative to the total number of changed connections. There were no connectivity differences between nociceptive regions (i.e. nociceptive-nociceptive = 0). See Table 3 for the list of regions and the corresponding ROIs. (A = Anterior; P = posterior; V = ventral; D = dorsal).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Functional connectivity changes 28 days after SNI are mainly within limbic, and between limbic and nociceptive regions.(a) Bar graph show the number of significantly decreased (blue) and increased (red) connections for all ROIs in SNI compare to sham 28 days following injury. Black and gray circles denote limbic and nociceptive ROIs respectively. Significantly (b) increased and (c) decreased functional connectivity are shown relative to sham. Limbic (gray labels) and nociceptive (black labels) ROIs were grouped into two separate functional–anatomical modules, labeled at the approximate brain location. Normalized weighted edges and nodes indicate extent of reorganization between and within the seven regions. Pie charts show the percentages of significantly changed limbic and nociceptive connections relative to the total number of changed connections. There were no connectivity differences between nociceptive regions (i.e. nociceptive-nociceptive = 0). See Table 3 for the list of regions and the corresponding ROIs. (A = Anterior; P = posterior; V = ventral; D = dorsal).
Mentions: Compared to nociceptive regions, ROIs (nodes) within the limbic systems exhibited larger numbers of connectivity changes (both positive and negative) in SNI compared to sham 28 days following injury (Fig 1a). To better conceptualize the complex pattern of altered functional connectivity, we calculated information flow within and across the seven regions comprising the limbic and nociceptive systems (Table 3). The weight of the edge between two regions was normalized as a percentage of the total number of significantly changed connections between the ROIs (nodes) within two regions (p < 0.05 with FDR correction), relative to the total number of all possible connections. Similarly, the node size was normalized relative to the all possible connections within the region (based on the number of possible connection for all ROIs within the region)5. The results show that SNI was associated with increased connectivity within the striatum, hippocampus, and amygdala. The striatum showed increased connectivity to thalamus, amygdala, and parts of the hippocampus, as well as to itself. Furthermore, the amygdala showed increased connectivity to sensorimotor areas (Fig 3b). These increases in functional connectivity were coupled with decreases in hippocampal connectivity to thalamic and sensorimotor regions (Fig 3c). Collectively, these results indicate that most functional changes (both increases and decreases) in 28-day SNI animals were either limbic-limbic or limbic-nociceptive in nature (Fig. 3 pie charts). In fact, limbic-limbic connections constituted 72.2% of all significantly increased connections and 39.5% of all decreased functional connections in SNI animals, whereas limbic-nociceptive connections constituted 19.7% and 41.7% of increased and decreased connections, respectively. There were no changes in functional connectivity within the nociceptive system (i.e., nociceptive-nociceptive connections = 0%).

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