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Thalamic resting-state functional connectivity: disruption in patients with type 2 diabetes

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Abstract

To explore the disrupted thalamic functional connectivity and its relationships with cognitive dysfunction in type 2 diabetes mellitus (T2DM) by using resting-state functional magnetic resonance imaging (fMRI). A total of 38 T2DM patients and 39 well-matched healthy controls participated in the resting-state fMRI and T1-weighted imaging scans. The thalamic functional connectivity was characterized by using a seed-based whole-brain correlation method and compared T2DM patients with healthy controls. Pearson correlation analysis was performed between thalamic functional connectivity and clinical data. When compared with healthy controls, T2DM showed significantly decreased functional connectivity of the thalamus mainly in the right middle temporal gyrus (MTG), right precentral gyrus and bilateral occipital cortex; Increased functional connectivity of the thalamus was detected in the left cerebellum, bilateral middle frontal gyrus and middle cingulate gyrus (p < 0.05, corrected for AlphaSim). In T2DM patients, the decreased thalamic functional connectivity of the right MTG was positively associated with the Verbal Fluency Test score (r = 0.438, p = 0.006). Meanwhile, the decreased thalamic functional connectivity of the right cuneus was positively correlated with the Complex Figure Test-delayed score and negatively correlated with the Trail Making Test-B score, respectively (r = 0.492, p = 0.002; r = −0.504, p = 0.001). Moreover, there was no structural damage in the thalamus of T2DM patients. T2DM patients develop disrupted thalamocortical functional connectivity, which is associated with cognitive impairment in selected brain regions. Resting-state thalamocortical connectivity disturbance may play a central role in the underlying neuropathological process of T2DM-related cognitive dysfunction.

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References

  • Abbatecola AM, Lattanzio F, Molinari AM, Cioffi M, Mansi L, Rambaldi P, DiCioccio L, Cacciapuoti F, Canonico R, Paolisso G (2010) Rosiglitazone and cognitive stability in older individuals with type 2 diabetes and mild cognitive impairment. Diabetes Care 33:1706–1711

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Akisaki T, Sakurai T, Takata T, Umegaki H, Araki A, Mizuno S, Tanaka S, Ohashi Y, Iguchi A, Yokono K (2006) Cognitive dysfunction associates with white matter hyperintensities and subcortical atrophy on magnetic resonance imaging of the elderly diabetes mellitus Japanese elderly diabetes intervention trial (J-EDIT). Diabetes Metab Res Rev 22:376–384

    Article  PubMed  Google Scholar 

  • Alberti KGMM, Zimmet Pf (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med 15:539–553

    Article  CAS  PubMed  Google Scholar 

  • Andreasen NC, O’Leary DS, Cizadlo T, Arndt S, Rezai K, Ponto L, Watkins GL, Hichwa RD (1996) Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. Proc Natl Acad Sci 93:9985–9990

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA (2004) Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 61:661–666

    Article  PubMed  Google Scholar 

  • Arvanitakis Z, Wilson RS, Li Y, Aggarwal NT, Bennett DA (2006) Diabetes and function in different cognitive systems in older individuals without dementia. Diabetes Care 29:560–565

    Article  PubMed  Google Scholar 

  • Biessels GJ, Deary IJ, Ryan CM (2008) Cognition and diabetes: a lifespan perspective. The Lancet neurology 7:184–190

    Article  PubMed  Google Scholar 

  • Biessels GJ, Reijmer YD (2014) Brain changes underlying cognitive dysfunction in diabetes: what can we learn from MRI? Diabetes 63:2244–2252

    Article  PubMed  Google Scholar 

  • Cauda F, Sacco K, D’Agata F, Duca S, Cocito D, Geminiani G, Migliorati F, Isoardo G (2009) Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in diabetic neuropathic pain. BMC Neurosci 10:138

    Article  PubMed Central  PubMed  Google Scholar 

  • Chen Y-C, Jiao Y, Cui Y, Shang S-A, Ding J, Feng Y, Song W, Ju S-H, Teng G-J (2014) Aberrant brain functional connectivity related to insulin resistance in type 2 diabetes: a resting-state fMRI study. Diabetes Care 37:1689–1696

    Article  CAS  PubMed  Google Scholar 

  • Chen Z, Li L, Sun J, Ma L (2012) Mapping the brain in type II diabetes: voxel-based morphometry using DARTEL. Eur J Radiol 81:1870–1876

    Article  PubMed  Google Scholar 

  • Cui Y, Jiao Y, Chen Y-C, Wang K, Gao B, Wen S, Ju S, Teng G-J (2014) Altered spontaneous brain activity in type 2 diabetes: a resting-state functional MRI study. Diabetes 63:749–760

    Article  CAS  PubMed  Google Scholar 

  • De Bresser J, Tiehuis AM, Van Den Berg E, Reijmer YD, Jongen C, Kappelle LJ, Mali WP, Viergever MA, Biessels GJ (2010) Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes. Diabetes Care 33:1309–1314

    Article  PubMed Central  PubMed  Google Scholar 

  • de Haan W, Mott K, van Straaten EC, Scheltens P, Stam CJ (2012) Activity dependent degeneration explains hub vulnerability in Alzheimer’s disease. PLoS Comput Biol 8:e1002582

    Article  PubMed Central  PubMed  Google Scholar 

  • Den Heijer T, Vermeer S, Van Dijk E, Prins N, Koudstaal P, Hofman A, Breteler M (2003) Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI. Diabetologia 46:1604–1610

    Article  Google Scholar 

  • Espeland MA, Bryan RN, Goveas JS, Robinson JG, Siddiqui MS, Liu S, Hogan PE, Casanova R, Coker LH, Yaffe K (2013) Influence of type 2 diabetes on brain volumes and changes in brain volumes results from the women’s health initiative magnetic resonance imaging studies. Diabetes Care 36:90–97

    Article  PubMed Central  PubMed  Google Scholar 

  • Gold S, Dziobek I, Sweat V, Tirsi A, Rogers K, Bruehl H, Tsui W, Richardson S, Javier E, Convit A (2007) Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes. Diabetologia 50:711–719

    Article  CAS  PubMed  Google Scholar 

  • Greicius M (2008) Resting-state functional connectivity in neuropsychiatric disorders. Curr Opin Neurol 21:424–430

    Article  PubMed  Google Scholar 

  • Haldane M, Cunningham G, Androutsos C, Frangou S (2008) Structural brain correlates of response inhibition in bipolar disorder I. J Psychopharmacol 22(2):138–143

  • Klein R, Klein B, Magli YL, Brothers RJ, Meuer SM, Moss SE, Davis MD (1986) An alternative method of grading diabetic retinopathy. Ophthalmology 93:1183–1187

    Article  CAS  PubMed  Google Scholar 

  • Lowe M, Mock B, Sorenson J (1998) Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations. NeuroImage 7:119–132

    Article  CAS  PubMed  Google Scholar 

  • Manschot SM, Brands AM, van der Grond J, Kessels RP, Algra A, Kappelle LJ, Biessels GJ (2006) Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes. Diabetes 55:1106–1113

    Article  CAS  PubMed  Google Scholar 

  • Mantini D, Perrucci MG, Del Gratta C, Romani GL, Corbetta M (2007) Electrophysiological signatures of resting state networks in the human brain. Proc Natl Acad Sci 104:13170–13175

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Moore EM, Mander AG, Ames D, Kotowicz MA, Carne RP, Brodaty H, Woodward M, Boundy K, Ellis KA, Bush AI (2013) Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care 36:2981–2987

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Moran C, Phan TG, Chen J, Blizzard L, Beare R, Venn A, Münch G, Wood AG, Forbes J, Greenaway TM (2013) Brain atrophy in type 2 diabetes regional distribution and influence on cognition. Diabetes Care 36:4036–4042

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Musen G, Jacobson AM, Bolo NR, Simonson DC, Shenton ME, McCartney RL, Flores VL, Hoogenboom WS (2012) Resting-state brain functional connectivity is altered in type 2 diabetes. Diabetes 61:2375–2379

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Petersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256:183–194

    Article  CAS  PubMed  Google Scholar 

  • Pihlajamaki M, Tanila H, Hanninen T, Kononen M, Laakso MP, Partanen K, Soininen H, Aronen HJ (2000) Verbal fluency activates the left medial temporal lobe: a functional magnetic resonance imaging study. Neurobiol Aging 21:106

    Article  Google Scholar 

  • Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL (2001) A default mode of brain function. Proc Natl Acad Sci 98:676–682

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sahin I, Alkan A, Keskin L, Cikim A, Karakas HM, Firat AK, Sigirci A (2008) Evaluation of in vivo cerebral metabolism on proton magnetic resonance spectroscopy in patients with impaired glucose tolerance and type 2 diabetes mellitus. J Diabetes Complicat 22:254–260

    Article  PubMed  Google Scholar 

  • Schmahmann JD, Caplan D (2006) Cognition, emotion and the cerebellum. Brain 129:290–292

    Article  PubMed  Google Scholar 

  • Schrijvers E, Witteman J, Sijbrands E, Hofman A, Koudstaal P, Breteler M (2010) Insulin metabolism and the risk of Alzheimer disease the Rotterdam study. Neurology 75:1982–1987

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Seeley WW (2011) Divergent network connectivity changes in healthy APOE ε4 carriers: disinhibition or compensation? Arch Neurol 68:1107–1108

    Article  PubMed  Google Scholar 

  • Starr J, Wardlaw J, Ferguson K, MacLullich A, Deary I, Marshall I (2003) Increased blood–brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging. J Neurol Neurosurg Psychiatry 74:70–76

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stolk RP, Pols HA, Lamberts SW, de Jong PT, Hofman A, Grobbee DE (1997) Diabetes mellitus, impaired glucose tolerance, and hyperinsulinemia in an elderly population the Rotterdam study. Am J Epidemiol 145:24–32

    Article  CAS  PubMed  Google Scholar 

  • Van den Berg E, Reijmer Y, De Bresser J, Kessels R, Kappelle L, Biessels G (2010) A 4 year follow-up study of cognitive functioning in patients with type 2 diabetes mellitus. Diabetologia 53:58–65

    Article  PubMed Central  PubMed  Google Scholar 

  • Van der Werf YD, Witter MP, Uylings H, Jolles J (2000) Neuropsychology of infarctions in the thalamus: a review. Neuropsychologia 38:613–627

    Article  PubMed  Google Scholar 

  • Wahlund L, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjögren M, Wallin A, Ader H, Leys D, Pantoni L (2001) A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32:1318–1322

    Article  CAS  PubMed  Google Scholar 

  • Walther S, Federspiel A, Horn H, Razavi N, Wiest R, Dierks T, Strik W, Müller TJ (2011) Resting state cerebral blood flow and objective motor activity reveal basal ganglia dysfunction in schizophrenia. Psychiatry Res Neuroimaging 192:117–124

    Article  PubMed  Google Scholar 

  • Xia W, Wang S, Sun Z, Bai F, Zhou Y, Yang Y, Wang P, Huang Y, Yuan Y (2013) Altered baseline brain activity in type 2 diabetes: a resting-state fMRI study. Psychoneuroendocrinology 38:2493–2501

    Article  PubMed  Google Scholar 

  • Yan C, Zang Y (2010) DPARSF: a MATLAB toolbox for “pipeline” data analysis of resting-state fMRI. Frontiers in systems neuroscience 4:13

  • Yang S, Ajilore O, Wu M, Lamar M, Kumar A (2014) Impaired Macromolecular Protein Pools in Fronto-Striato-Thalamic Circuits in Type 2 Diabetes Revealed by Magnetization Transfer Imaging. Diabetes 64(1):183–192

  • Zhang D, Snyder AZ, Fox MD, Sansbury MW, Shimony JS, Raichle ME (2008) Intrinsic functional relations between human cerebral cortex and thalamus. J Neurophysiol 100:1740–1748

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhang J, Wang Y, Wang J, Zhou X, Shu N, Wang Y, Zhang Z (2014) White matter integrity disruptions associated with cognitive impairments in type 2 diabetic patients. Diabetes 63:3596–3605

    Article  CAS  PubMed  Google Scholar 

  • Zhou H, Lu W, Shi Y, Bai F, Chang J, Yuan Y, Teng G, Zhang Z (2010) Impairments in cognition and resting-state connectivity of the hippocampus in elderly subjects with type 2 diabetes. Neurosci Lett 473:5–10

    Article  CAS  PubMed  Google Scholar 

  • Zou Q, Long X, Zuo X, Yan C, Zhu C, Yang Y, Liu D, He Y, Zang Y (2009) Functional connectivity between the thalamus and visual cortex under eyes closed and eyes open conditions: a resting-state fMRI study. Hum Brain Mapp 30:3066–3078

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The authors thank the contribution of Yu-Feng Zang, Center for Cognition and Brain Disorders and the affiliated hospital, Hangzhou Normal University, Hangzhou, China. This work was supported by the Major State Basic Research Development Program of China (973 Program) (NOs.2013CB733800, 2013CB733803), National Natural Science Foundation of China (NOs.81230034, 81271739), Jiangsu Provincial Special Program of Medical Science (NO.BL2013029), Key Project of Jiangsu Province Natural Science Foundation of China (NO. BK20130057), Fundamental Research Funds for the Central Universities and Jiangsu Graduate Student Innovation Grant (NO.KYZZ_0076, KYZZ_0073). Y.C.C acknowledges the financial support from the China Scholarship Council for his joint PhD scholarship (NO. 201406090139). Y.C.C. collected the data, performed the analysis and wrote the manuscript. W.X designed the experiment and revised the manuscript. C.Q., J.D., S.J. and G.J.T contributed to the discussion and manuscript revision.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87# Dingjiaqiao Road, Nanjing, 210009, China

    Yu-Chen Chen, Cheng Qian, Jie Ding, Shenghong Ju & Gao-Jun Teng

  2. Medical School, Southeast University, Nanjing, China

    Wenqing Xia

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  1. Yu-Chen Chen
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Correspondence to Gao-Jun Teng.

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Yu-Chen Chen and Wenqing Xia contributed equally to this paper.

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Chen, YC., Xia, W., Qian, C. et al. Thalamic resting-state functional connectivity: disruption in patients with type 2 diabetes. Metab Brain Dis 30, 1227–1236 (2015). https://doi.org/10.1007/s11011-015-9700-2

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