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BMC Neurology
Published in: BMC Neurology 1/2012

Open Access 01-12-2012 | Research article

Altered small-world properties of gray matter networks in breast cancer

Authors: S M Hadi Hosseini, Della Koovakkattu, Shelli R Kesler

Published in: BMC Neurology | Issue 1/2012

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Abstract

Background

Breast cancer survivors, particularly those treated with chemotherapy, are at significantly increased risk for long-term cognitive and neurobiologic impairments. These deficits tend to involve skills that are subserved by distributed brain networks. Additionally, neuroimaging studies have shown a diffuse pattern of brain structure changes in chemotherapy-treated breast cancer survivors that might impact large-scale brain networks.

Methods

We therefore applied graph theoretical analysis to compare the gray matter structural networks of female breast cancer survivors with a history of chemotherapy treatment and healthy age and education matched female controls.

Results

Results revealed reduced clustering coefficient and small-world index in the brain network of the breast cancer patients across a range of network densities. In addition, the network of the breast cancer group had less highly interactive nodes and reduced degree/centrality in the frontotemporal regions compared to controls, which may help explain the common impairments of memory and executive functioning among these patients.

Conclusions

These results suggest that breast cancer and chemotherapy may decrease regional connectivity as well as global network organization and integration, reducing efficiency of the network. To our knowledge, this is the first report of altered large-scale brain networks associated with breast cancer and chemotherapy.
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Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. 2011, a cancer journal for clinicians, CA
2.
Vardy J: Cognitive function in breast cancer survivors. Cancer Treat Res. 2009, 151: 387-419. 10.1007/978-0-387-75115-3_24.CrossRefPubMed
3.
Janelsins MC, Kohli S, Mohile SG, Usuki K, Ahles TA, Morrow GR: An update on cancer- and chemotherapy-related cognitive dysfunction: current status. Semin Oncol. 2011, 38: 431-438. 10.1053/j.seminoncol.2011.03.014.CrossRefPubMedPubMedCentral
4.
Kesler SR, Kent J, O'Hara R: Prefrontal cortex and executive function impairments in primary breast cancer. Arch Neurol. 2011, 68: 1447-1453. 10.1001/archneurol.2011.245.CrossRefPubMedPubMedCentral
5.
Ahles TA, Saykin AJ, McDonald BC, Li Y, Furstenberg CT, Hanscom BS, Mulrooney TJ, Schwartz GN, Kaufman PA: Longitudinal Assessment of Cognitive Changes Associated With Adjuvant Treatment for Breast Cancer: Impact of Age and Cognitive Reserve. J Clin Oncol. 2010, 28: 4434-4440. 10.1200/JCO.2009.27.0827.CrossRefPubMedPubMedCentral
6.
Quesnel C, Savard J, Ivers H: Cognitive impairments associated with breast cancer treatments: results from a longitudinal study. Breast Cancer Res Treat. 2009, 116: 113-123. 10.1007/s10549-008-0114-2.CrossRefPubMed
7.
Schagen SB, Muller MJ, Boogerd W, Mellenbergh GJ, van Dam FS: Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients. J Natl Cancer Inst. 2006, 98: 1742-1745. 10.1093/jnci/djj470.CrossRefPubMed
8.
Jansen CE, Cooper BA: Dodd MJ. 2010, A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients. Support Care Cancer, Miaskowski CA
9.
Wefel JS, Saleeba AK, Buzdar AU, Meyers CA: Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer. 2010, 116: 3348-3356. 10.1002/cncr.25098.CrossRefPubMed
10.
de Ruiter MB, Reneman L, Boogerd W, Veltman DJ, van Dam FS, Nederveen AJ, Boven E, Schagen SB: Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer. Hum Brain Mapp. 2011, 32: 1206-1219. 10.1002/hbm.21102.CrossRefPubMed
11.
Wefel JS, Witgert ME, Meyers CA: Neuropsychological sequelae of non-central nervous system cancer and cancer therapy. Neuropsychol Rev. 2008, 18: 121-131. 10.1007/s11065-008-9058-x.CrossRefPubMed
12.
13.
Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD: Neurodegenerative diseases target large-scale human brain networks. Neuron. 2009, 62: 42-52. 10.1016/j.neuron.2009.03.024.CrossRefPubMedPubMedCentral
14.
Deprez S, Amant F, Yigit R, Porke K, Verhoeven J, Van den Stock J, Smeets A, Christiaens MR, Leemans A, Van Hecke W, et al: Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients. Hum Brain Mapp. 2011, 32: 480-493. 10.1002/hbm.21033.CrossRefPubMed
15.
McDonald BC, Conroy SK, Ahles TA, West JD, Saykin AJ: Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat. 2010, 123: 819-828. 10.1007/s10549-010-1088-4.CrossRefPubMedPubMedCentral
16.
Inagaki M, Yoshikawa E, Matsuoka Y, Sugawara Y, Nakano T, Akechi T, Wada N, Imoto S, Murakami K, Uchitomi Y: Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy. Cancer. 2007, 109: 146-156. 10.1002/cncr.22368.CrossRefPubMed
17.
Abraham J, Haut M, Moran M, Filburn S, Lemiuex S, Kuwabara H: Adjuvant chemotherapy for breast cancer: effects on cerebral white matter seen in diffusion tensor imaging. Clin Breast Cancer. 2008, 8: 88-91. 10.3816/CBC.2008.n.007.CrossRefPubMed
18.
Leh SE, Petrides M, Strafella AP: The Neural Circuitry of Executive Functions in Healthy Subjects and Parkinson's Disease. Neuropsychopharmacology. 2010, 35: 70-85. 10.1038/npp.2009.88.CrossRefPubMed
19.
Bakkum-Gamez JN, Laughlin SK, Jensen JR, Akogyeram CO, Pruthi S: Challenges in the Gynecologic Care of Premenopausal Women With Breast Cancer. Mayo Clin Proc. 2011, 86: 229-240. 10.4065/mcp.2010.0794.CrossRefPubMedPubMedCentral
20.
Bassett DS, Bullmore E: Small-world brain networks. Neuroscientist. 2006, 12: 512-523. 10.1177/1073858406293182.CrossRefPubMed
21.
Simard D, Nadeau L: Fastest learning in small-world neural networks. Physics Letters A. 2005, 336: 8-15. 10.1016/j.physleta.2004.12.078.CrossRef
22.
Fan Y, Shi F, Smith JK, Lin W, Gilmore JH, Shen D: Brain anatomical networks in early human brain development. NeuroImage. 2011, 54: 1862-1871. 10.1016/j.neuroimage.2010.07.025.CrossRefPubMed
23.
Chen ZJ, He Y, Rosa-Neto P, Germann J, Evans AC: Revealing modular architecture of human brain structural networks by using cortical thickness from MRI. Cerebral cortex. 2008, 18: 2374-2381. 10.1093/cercor/bhn003.CrossRefPubMedPubMedCentral
24.
Petrella JR: Use of graph theory to evaluate brain networks: a clinical tool for a small world?. Radiology. 2011, 259: 317-320. 10.1148/radiol.11110380.CrossRefPubMed
25.
Sporns O, Chialvo DR, Kaiser M, Hilgetag CC: Organization, development and function of complex brain networks. Trends Cogn Sci. 2004, 8: 418-425. 10.1016/j.tics.2004.07.008.CrossRefPubMed
26.
Bassett DS, Bullmore E, Verchinski BA, Mattay VS, Weinberger DR, Meyer-Lindenberg A: Hierarchical organization of human cortical networks in health and schizophrenia. J Neurosci. 2008, 28: 9239-9248. 10.1523/JNEUROSCI.1929-08.2008.CrossRefPubMedPubMedCentral
27.
Bernhardt BC, Chen Z, He Y, Evans AC, Bernasconi N: Graph-Theoretical Analysis Reveals Disrupted Small-World Organization of Cortical Thickness Correlation Networks in Temporal Lobe Epilepsy. Cerebral Cortex. 2011, 21 (9): 2147-2157. 10.1093/cercor/bhq291.CrossRefPubMed
28.
He Y, Chen Z, Evans A: Structural insights into aberrant topological patterns of large-scale cortical networks in Alzheimer's disease. J Neurosci. 2008, 28: 4756-4766. 10.1523/JNEUROSCI.0141-08.2008.CrossRefPubMed
29.
Wu K, Taki Y, Sato K, Kinomura S, Goto R, Okada K, Kawashima R, He Y, Evans AC, Fukuda H: Age-related changes in topological organization of structural brain networks in healthy individuals. Hum Brain Mapp. 2011, 33 (3): 552-568.CrossRefPubMed
30.
He Y, Dagher A, Chen Z, Charil A, Zijdenbos A, Worsley K, Evans A: Impaired small-world efficiency in structural cortical networks in multiple sclerosis associated with white matter lesion load. Brain. 2009, 132: 3366-3379. 10.1093/brain/awp089.CrossRefPubMedPubMedCentral
31.
32.
Wilke M, Holland S, Altaye M, Gaser C: Template-O-Matic: A toolbox for creating customized pediatric templates. NeuroImage. 2008, 41: 903-913. 10.1016/j.neuroimage.2008.02.056.CrossRefPubMed
33.
Ashburner J, Friston KJ: Unified segmentation. NeuroImage. 2005, 26: 839-851. 10.1016/j.neuroimage.2005.02.018.CrossRefPubMed
34.
Zalesky A, Fornito A, Harding IH, Cocchi L, Yucel M, Pantelis C, Bullmore ET: Whole-brain anatomical networks: does the choice of nodes matter?. NeuroImage. 2010, 50: 970-983. 10.1016/j.neuroimage.2009.12.027.CrossRefPubMed
35.
Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M: Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage. 2002, 15: 273-289. 10.1006/nimg.2001.0978.CrossRefPubMed
36.
He Y, Chen ZJ, Evans AC: Small-world anatomical networks in the human brain revealed by cortical thickness from MRI. Cerebral cortex. 2007, 17: 2407-2419.CrossRefPubMed
37.
van Wijk BC, Stam CJ, Daffertshofer A: Comparing brain networks of different size and connectivity density using graph theory. PLoS One. 2010, 5: e13701-10.1371/journal.pone.0013701.CrossRefPubMedPubMedCentral
38.
Rubinov M, Sporns O: Complex network measures of brain connectivity: uses and interpretations. NeuroImage. 2010, 52: 1059-1069. 10.1016/j.neuroimage.2009.10.003.CrossRefPubMed
39.
Maslov S, Sneppen K: Specificity and stability in topology of protein networks. Science. 2002, 296: 910-913. 10.1126/science.1065103.CrossRefPubMed
40.
Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U: Network motifs: simple building blocks of complex networks. Science. 2002, 298: 824-827. 10.1126/science.298.5594.824.CrossRefPubMed
41.
Supekar K, Menon V, Rubin D, Musen M, Greicius MD: Network analysis of intrinsic functional brain connectivity in Alzheimer's disease. PLoS Comput Biol. 2008, 4: e1000100-10.1371/journal.pcbi.1000100.CrossRefPubMedPubMedCentral
42.
Sailer M, Fischl B, Salat D, Tempelmann C, Schoenfeld MA, Busa E, Bodammer N, Heinze HJ, Dale A: Focal thinning of the cerebral cortex in multiple sclerosis. Brain. 2003, 126: 1734-1744. 10.1093/brain/awg175.CrossRefPubMed
43.
Sepulcre J, Goni J, Masdeu JC, Bejarano B, Velez N, Toledo JB, Villoslada P: Contribution of white matter lesions to gray matter atrophy in multiple sclerosis. Arch Neurol. 2009, 66: 173-179. 10.1001/archneurol.2008.562.CrossRefPubMed
44.
Dietrich J, Han R, Yang Y, Mayer-Proschel M, Noble M: CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. J Biol. 2006, 5: 22-10.1186/jbiol50.CrossRefPubMedPubMedCentral
45.
Seigers R, Schagen SB, Beerling W, Boogerd W, van Tellingen O, van Dam FS, Koolhaas JM, Buwalda B: Long-lasting suppression of hippocampal cell proliferation and impaired cognitive performance by methotrexate in the rat. Behav Brain Res. 2008, 186: 168-175. 10.1016/j.bbr.2007.08.004.CrossRefPubMed
46.
Winocur G, Vardy J, Binns MA, Kerr L, Tannock I: The effects of the anti-cancer drugs, methotrexate and 5-fluorouracil, on cognitive function in mice. Pharmacol Biochem Behav. 2006, 85: 66-75. 10.1016/j.pbb.2006.07.010.CrossRefPubMed
47.
Han R, Yang YM, Dietrich J, Luebke A: Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system. J Biol. 2008, 7 (4): 12-10.1186/jbiol69.CrossRefPubMedPubMedCentral
48.
Seigers R, Schagen SB, Coppens CM, van der Most PJ, van Dam FS, Koolhaas JM, Buwalda B: Methotrexate decreases hippocampal cell proliferation and induces memory deficits in rats. Behav Brain Res. 2009, 201: 279-284. 10.1016/j.bbr.2009.02.025.CrossRefPubMed
49.
Sporns O: The human connectome: a complex network. Annals NewYork Academy Sci. 2011, 1224: 109-25. 10.1111/j.1749-6632.2010.05888.x.CrossRef
50.
Kesler SR, Bennett FC, Mahaffey ML, Spiegel D: Regional brain activation during verbal declarative memory in metastatic breast cancer. Clin Cancer Res. 2009, 15: 6665-6673. 10.1158/1078-0432.CCR-09-1227.CrossRefPubMedPubMedCentral
51.
Silverman DH, Dy CJ, Castellon SA, Lai J, Pio BS, Abraham L, Waddell K, Petersen L, Phelps ME, Ganz PA: Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5-10 years after chemotherapy. Breast Cancer Res Treat. 2007, 103: 303-311. 10.1007/s10549-006-9380-z.CrossRefPubMed
52.
Samatovicz RA: Genetics and brain injury: apolipoprotein E. J head trauma rehab. 2000, 15: 869-874. 10.1097/00001199-200006000-00002.CrossRef
53.
Ahles TA, Saykin AJ, Noll WW, Furstenberg CT, Guerin S, Cole B, Mott LA: The relationship of APOE genotype to neuropsychological performance in long-term cancer survivors treated with standard dose chemotherapy. Psycho-Oncology. 2003, 12: 612-619. 10.1002/pon.742.CrossRefPubMed
54.
Krabbe KS, Reichenberg A, Yirmiya R, Smed A, Pedersen BK, Bruunsgaard H: Low-dose endotoxemia and human neuropsychological functions. Brain Behav Immun. 2005, 19: 453-460. 10.1016/j.bbi.2005.04.010.CrossRefPubMed
55.
Wilson CJ, Finch CE, Cohen HJ: Cytokines and cognition–the case for a head-to-toe inflammatory paradigm. J Am Geriatr Soc. 2002, 50: 2041-2056. 10.1046/j.1532-5415.2002.50619.x.CrossRefPubMed
56.
Aalto S, Bruck A, Laine M, Nagren K, Rinne JO: Frontal and temporal dopamine release during working memory and attention tasks in healthy humans: a positron emission tomography study using the high-affinity dopamine D2 receptor ligand [11 C]FLB 457. J neurosci official j Soc Neurosci. 2005, 25: 2471-2477. 10.1523/JNEUROSCI.2097-04.2005.CrossRef
57.
Vehmanen L, Elomaa I, Blomqvist C, Saarto T: Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status. J Clin Oncol. 2006, 24: 675-680. 10.1200/JCO.2005.02.3515.CrossRefPubMed
58.
Boulware MI, Kent BA, Frick KM: The Impact of Age-Related Ovarian Hormone Loss on Cognitive and Neural Function. Curr Top Behav Neurosci. 2012, 10: 165-184.CrossRefPubMed
59.
Castellon SA, Ganz PA, Bower JE, Petersen L, Abraham L, Greendale GA: Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol. 2004, 26: 955-969. 10.1080/13803390490510905.CrossRefPubMed
60.
Eberling JL, Wu C, Tong-Turnbeaugh R, Jagust WJ: Estrogen- and tamoxifen-associated effects on brain structure and function. NeuroImage. 2004, 21: 364-371. 10.1016/j.neuroimage.2003.08.037.CrossRefPubMed
61.
Poreh A: The Quantified Process Approach to Neuropsychological Assessment. 2006, Taylor and Francis, New York, NY
Metadata
Title
Altered small-world properties of gray matter networks in breast cancer
Authors
S M Hadi Hosseini
Della Koovakkattu
Shelli R Kesler
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2012
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-12-28

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