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Selective vulnerability of Rich Club brain regions is an organizational principle of structural connectivity loss in Huntington's disease.

McColgan P, Seunarine KK, Razi A, Cole JH, Gregory S, Durr A, Roos RA, Stout JC, Landwehrmeyer B, Scahill RI, Clark CA, Rees G, Tabrizi SJ, Track-HD Investigato - Brain (2015)

Bottom Line: By understanding such principles we can gain insight into the link between the cellular pathology caused by mutant huntingtin and its downstream effect at the macroscopic level.We also observed greater reductions in the connectivity of brain regions that have higher network traffic and lower clustering of neighbouring regions.This provides a potential mechanism that results in a characteristic pattern of structural connectivity loss targeting highly connected brain regions with high network traffic and low clustering of neighbouring regions.

View Article: PubMed Central - PubMed

Affiliation: 1 Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG, UK s.tabrizi@ucl.ac.uk g.rees@ucl.ac.uk.

No MeSH data available.


Related in: MedlinePlus

Summary of findings. There is selective loss of basal ganglia rich club connectivity due to high higher connection to the basal ganglia, higher network traffic and reduced clustering coefficients of rich club regions. This results in increased network segregation leading to the subtle motor and cognitive symptoms seen in premanifest Huntington’s disease. Further loss of cortical rich club connectivity results in reduced network integration resulting in the overt cognitive and motor symptoms seen in manifest Huntington’s disease. HD = Huntington’s disease.
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awv259-F8: Summary of findings. There is selective loss of basal ganglia rich club connectivity due to high higher connection to the basal ganglia, higher network traffic and reduced clustering coefficients of rich club regions. This results in increased network segregation leading to the subtle motor and cognitive symptoms seen in premanifest Huntington’s disease. Further loss of cortical rich club connectivity results in reduced network integration resulting in the overt cognitive and motor symptoms seen in manifest Huntington’s disease. HD = Huntington’s disease.

Mentions: We performed a graph theory analysis, complemented by network-based statistics, corticobasal ganglia connectivity and VCP analyses to focus on structural connectivity loss of rich club regions in Huntington’s disease. We found altered brain network connectivity specifically affecting rich club regions, predominantly in the basal ganglia (caudate) in premanifest Huntington’s disease, but extending to cortical rich club regions (superior frontal, superior parietal, precuneus and insula) in manifest disease. By using network-based statistics, corticobasal ganglia connectivity and VCP analyses, we were also able to demonstrate selective loss of connections and altered patterns of connectivity between the basal ganglia and cortical rich club regions. In conjunction with these regional group differences we identified altered whole brain network topology with isolated increase of network segregation in the premanifest Huntington’s disease participants when compared to controls; this extended to an increase in segregation and loss of integration when comparing manifest against both premanifest Huntington’s disease and controls. This suggests that increases of whole brain network segregation occur in the earliest stages of the neurodegenerative disease process, before symptom onset, and subsequently progress to loss of network integration in the manifest stages. We postulate that conversion from premanifest to manifest Huntington’s disease, in addition to the emergence of chorea through an imbalance in the indirect and direct pathways of the basal ganglia (Andre et al., 2011), may reflect a breakdown of such network integration (Fig. 8).Figure 8


Selective vulnerability of Rich Club brain regions is an organizational principle of structural connectivity loss in Huntington's disease.

McColgan P, Seunarine KK, Razi A, Cole JH, Gregory S, Durr A, Roos RA, Stout JC, Landwehrmeyer B, Scahill RI, Clark CA, Rees G, Tabrizi SJ, Track-HD Investigato - Brain (2015)

Summary of findings. There is selective loss of basal ganglia rich club connectivity due to high higher connection to the basal ganglia, higher network traffic and reduced clustering coefficients of rich club regions. This results in increased network segregation leading to the subtle motor and cognitive symptoms seen in premanifest Huntington’s disease. Further loss of cortical rich club connectivity results in reduced network integration resulting in the overt cognitive and motor symptoms seen in manifest Huntington’s disease. HD = Huntington’s disease.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4620513&req=5

awv259-F8: Summary of findings. There is selective loss of basal ganglia rich club connectivity due to high higher connection to the basal ganglia, higher network traffic and reduced clustering coefficients of rich club regions. This results in increased network segregation leading to the subtle motor and cognitive symptoms seen in premanifest Huntington’s disease. Further loss of cortical rich club connectivity results in reduced network integration resulting in the overt cognitive and motor symptoms seen in manifest Huntington’s disease. HD = Huntington’s disease.
Mentions: We performed a graph theory analysis, complemented by network-based statistics, corticobasal ganglia connectivity and VCP analyses to focus on structural connectivity loss of rich club regions in Huntington’s disease. We found altered brain network connectivity specifically affecting rich club regions, predominantly in the basal ganglia (caudate) in premanifest Huntington’s disease, but extending to cortical rich club regions (superior frontal, superior parietal, precuneus and insula) in manifest disease. By using network-based statistics, corticobasal ganglia connectivity and VCP analyses, we were also able to demonstrate selective loss of connections and altered patterns of connectivity between the basal ganglia and cortical rich club regions. In conjunction with these regional group differences we identified altered whole brain network topology with isolated increase of network segregation in the premanifest Huntington’s disease participants when compared to controls; this extended to an increase in segregation and loss of integration when comparing manifest against both premanifest Huntington’s disease and controls. This suggests that increases of whole brain network segregation occur in the earliest stages of the neurodegenerative disease process, before symptom onset, and subsequently progress to loss of network integration in the manifest stages. We postulate that conversion from premanifest to manifest Huntington’s disease, in addition to the emergence of chorea through an imbalance in the indirect and direct pathways of the basal ganglia (Andre et al., 2011), may reflect a breakdown of such network integration (Fig. 8).Figure 8

Bottom Line: By understanding such principles we can gain insight into the link between the cellular pathology caused by mutant huntingtin and its downstream effect at the macroscopic level.We also observed greater reductions in the connectivity of brain regions that have higher network traffic and lower clustering of neighbouring regions.This provides a potential mechanism that results in a characteristic pattern of structural connectivity loss targeting highly connected brain regions with high network traffic and low clustering of neighbouring regions.

View Article: PubMed Central - PubMed

Affiliation: 1 Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG, UK s.tabrizi@ucl.ac.uk g.rees@ucl.ac.uk.

No MeSH data available.


Related in: MedlinePlus