Increased thalamo-cortical functional connectivity in patients with diabetic painful neuropathy: A resting-state functional MRI study

Xiaomei Liu, Xianghong Xu, Cunnan Mao, Peng Zhang, Qing Zhang, Lanlan Jiang, Yuyin Yang, Jianhua Ma, Lei Ye, Kok-Onn Lee, Jindan Wu, Zhijian Yao, Xiaomei Liu, Xianghong Xu, Cunnan Mao, Peng Zhang, Qing Zhang, Lanlan Jiang, Yuyin Yang, Jianhua Ma, Lei Ye, Kok-Onn Lee, Jindan Wu, Zhijian Yao

Abstract

Functional changes in the brain of patients with painful diabetic neuropathy (PDN) have remained largely elusive. The aim of the present study was to explore changes in thalamo-cortical functional connectivity (FC) of patients with PDN using resting-state functional MRI. A total of 20 patients with type 2 diabetes mellitus (T2DM) with non-painful diabetic neuropathy (Group NDN), 19 patients with T2DM with PDN (Group-PDN) and 13 age-, sex- and education-matched healthy controls were recruited. The differences in thalamo-cortical FC among the three groups were compared. Patients in Group PDN had increased FC in the left thalamus, the right angular gyrus and the occipital gyrus as compared to those in Group NDN. Furthermore, patients in Group PDN had increased FC in the right thalamus and angular gyrus as compared to those in Group NDN. In conclusion, the present results suggested that the thalamo-cortical FC is increased in patients with T2DM and PDN. Furthermore, the increased FC in the thalamic-parietal-occipital connectivity may be a central pathophysiological mechanism for PDN. The study was retrospectively registered at ClinicalTrials.gov on 3 October 2018 (identifier no. NCT03700502).

Keywords: diabetes mellitus; functional connectivity; imaging; painful neuropathy; resting-state functional MRI; thalamo-cortical.

Conflict of interest statement

The authors declare that they have no competing interests.

Copyright: © Liu et al.

Figures

Figure 1
Figure 1
Differences in functional connectivity in the thalamus among the three groups. The blue dots represent brain regions that had abnormal activity among the three groups. (A) Brain regions exhibiting different activity among three groups when considering the left thalamus as the ROI. (B) Brain regions exhibiting different activity among the three groups when considering the right thalamus as the ROI. ROI, region of interest.
Figure 2
Figure 2
Differences of functional connectivity in the thalamus between Group-PDN and Group-NDN. The blue dots represent brain regions that had significantly increased activity in Group PDN when compared with Group NDN. (A) Brain regions exhibiting different activity between the two groups when considering the left thalamus as the ROI. (B) Brain regions exhibiting different activity between two groups when considering the right thalamus as the ROI. ROI, region of interest; Group-PDN, T2DM with painful neuropathy; Group-NDN, T2DM with non-painful neuropathy.

References

    1. Feldman EL, Nave KA, Jensen TS, Bennett DLH. New horizons in diabetic neuropathy: Mechanisms, bioenergetics, and pain. Neuron. 2017;93:1296–1313. doi: 10.1016/j.neuron.2017.02.005.
    1. Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012;13:715–724. doi: 10.1016/j.jpain.2012.03.009.
    1. Fayaz A, Croft P, Langford RM, Donaldson LJ, Jones GT. Prevalence of chronic pain in the UK: A systematic review and meta-analysis of population studies. BMJ Open. 2016;6(e010364) doi: 10.1136/bmjopen-2015-010364.
    1. Dermanovic Dobrota V, Hrabac P, Skegro D, Smiljanic R, Dobrota S, Prkacin I, Brkljacic N, Peros K, Tomic M, Lukinovic-Skudar V, Basic Kes V. The impact of neuropathic pain and other comorbidities on the quality of life in patients with diabetes. Health Qual Life Outcomes. 2014;12(171) doi: 10.1186/s12955-014-0171-7.
    1. Tesfaye S, Selvarajah D, Gandhi R, Greig M, Shillo P, Fang F, Wilkinson ID. Diabetic peripheral neuropathy may not be as its name suggests: Evidence from magnetic resonance imaging. Pain. 2016;157 (Suppl 1):S72–S80. doi: 10.1097/j.pain.0000000000000465.
    1. Modha DS, Singh R. Network architecture of the long-distance pathways in the macaque brain. Proc Natl Acad Sci USA. 2010;107:13485–13490. doi: 10.1073/pnas.1008054107.
    1. Yen CT, Lu PL. Thalamus and pain. Acta Anaesthesiol Taiwan. 2013;51:73–80. doi: 10.1016/j.aat.2013.06.011.
    1. Selvarajah D, Wilkinson ID, Maxwell M, Davies J, Sankar A, Boland E, Gandhi R, Tracey I, Tesfaye S. Magnetic resonance neuroimaging study of brain structural differences in diabetic peripheral neuropathy. Diabetes Care. 2014;37:1681–1688. doi: 10.2337/dc13-2610.
    1. Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995;34:537–541. doi: 10.1002/mrm.1910340409.
    1. Zuo XN, Kelly C, Di Martino A, Mennes M, Margulies DS, Bangaru S, Grzadzinski R, Evans AC, Zang YF, Castellanos FX, Milham MP. Growing together and growing apart: Regional and sex differences in the lifespan developmental trajectories of functional homotopy. J Neurosci. 2010;30:15034–15043. doi: 10.1523/JNEUROSCI.2612-10.2010.
    1. Gorges M, Muller HP, Lule D, Ludolph AC, Pinkhardt EH, Kassubek J. Functional connectivity within the default mode network is associated with saccadic accuracy in Parkinson's disease: A resting-state FMRI and videooculographic study. Brain Connect. 2013;3:265–272. doi: 10.1089/brain.2013.0146.
    1. Zhang Q, Zhang P, Yan R, Xu X, Mao C, Liu X, Li F, Ma J, Ye L, Yao Z, Wu J. A single-blinded trial using resting-state functional magnetic resonance imaging of brain activity in patients with type 2 diabetes and painful neuropathy. Diabetes Ther. 2019;10:135–147. doi: 10.1007/s13300-018-0534-x.
    1. Gabir MM, Hanson RL, Dabelea D, Imperatore G, Roumain J, Bennett PH, Knowler WC. The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes. Diabetes Care. 2000;23:1108–1112. doi: 10.2337/diacare.23.8.1108.
    1. Essmat A, Hussein MS. Green tea extract for mild-to-moderate diabetic peripheral neuropathy A randomized controlled trial. Complement Ther Clin Pract. 2021;43(101317) doi: 10.1016/j.ctcp.2021.101317.
    1. Garoushi S, Johnson MI, Tashani OA. Translation and cultural adaptation of the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale into Arabic for use with patients with diabetes in Libya. Libyan J Med. 2017;12(1384288) doi: 10.1080/19932820.2017.1384288.
    1. Chao-Gan Y, Yu-Feng Z. DPARSF: A MATLAB toolbox for ‘Pipeline’ data analysis of resting-state fMRI. Front Syst Neurosci. 2010;4(13) doi: 10.3389/fnsys.2010.00013.
    1. Salvador R, Suckling J, Schwarzbauer C, Bullmore E. Undirected graphs of frequency-dependent functional connectivity in whole brain networks. Philos Trans R Soc Lond B Biol Sci. 2005;360:937–946. doi: 10.1098/rstb.2005.1645.
    1. Liu Y, Yu C, Liang M, Li J, Tian L, Zhou Y, Qin W, Li K, Jiang T. Whole brain functional connectivity in the early blind. Brain. 2007;130:2085–2096. doi: 10.1093/brain/awm121.
    1. Hale JR, White TP, Mayhew SD, Wilson RS, Rollings DT, Khalsa S, Arvanitis TN, Bagshaw AP. Altered thalamocortical and intra-thalamic functional connectivity during light sleep compared with wake. Neuroimage. 2016;125:657–667. doi: 10.1016/j.neuroimage.2015.10.041.
    1. Song XW, Dong ZY, Long XY, Li SF, Zuo XN, Zhu CZ, He Y, Yan CG, Zang YF. REST: A toolkit for resting-state functional magnetic resonance imaging data processing. PLoS One. 2011;6(e25031) doi: 10.1371/journal.pone.0025031.
    1. 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. doi: 10.1006/nimg.2001.0978.
    1. Zhu X, He Z, Luo C, Qiu X, He S, Peng A, Zhang L, Chen L. Altered spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder: A resting-state fMRI study. J Neurol Sci. 2018;386:29–35. doi: 10.1016/j.jns.2018.01.010.
    1. Tose K, Yoshihara Y, Takahashi H. FMRI neurofeedback and its application to psychiatric disorders. Brain Nerve. 2018;70:1209–1216. doi: 10.11477/mf.1416201166.
    1. Tadayonnejad R, Deshpande R, Ajilore O, Moody T, Morfini F, Ly R, O'Neill J, Feusner JD. Pregenual anterior cingulate dysfunction associated with depression in OCD: An integrated multimodal fMRI/(1)H MRS study. Neuropsychopharmacology. 2018;43:1146–1155. doi: 10.1038/npp.2017.249.
    1. Shen Z, Jiang L, Yang S, Ye J, Dai N, Liu X, Li N, Lu J, Liu F, Lu Y, et al. Identify changes of brain regional homogeneity in early and later adult onset patients with first-episode depression using resting-state fMRI. PLoS One. 2017;12(e0184712) doi: 10.1371/journal.pone.0184712.
    1. Head H, Holmes G. Sensory disturbances from cerebral lesions. Brain. 1911;34:102–254.
    1. Selvarajah D, Wilkinson ID, Gandhi R, Griffiths PD, Tesfaye S. Microvascular perfusion abnormalities of the Thalamus in painful but not painless diabetic polyneuropathy: A clue to the pathogenesis of pain in type 1 diabetes. Diabetes Care. 2011;34:718–720. doi: 10.2337/dc10-1550.
    1. Bellana B, Liu Z, Anderson JAE, Moscovitch M, Grady CL. Laterality effects in functional connectivity of the angular gyrus during rest and episodic retrieval. Neuropsychologia. 2016;80:24–34. doi: 10.1016/j.neuropsychologia.2015.11.004.
    1. Seghier ML. The angular gyrus: Multiple functions and multiple subdivisions. Neuroscientist. 2013;19:43–61. doi: 10.1177/1073858412440596.
    1. Greicius MD, Supekar K, Menon V, Dougherty RF. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex. 2009;19:72–78. doi: 10.1093/cercor/bhn059.
    1. Napadow V, LaCount L, Park K, As-Sanie S, Clauw DJ, Harris RE. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum. 2010;62:2545–2555. doi: 10.1002/art.27497.
    1. Garza-Villarreal EA, Jiang Z, Vuust P, Alcauter S, Vase L, Pasaye EH, Cavazos-Rodriguez R, Brattico E, Jensen TS, Barrios FA. Music reduces pain and increases resting state fMRI BOLD signal amplitude in the left angular gyrus in fibromyalgia patients. Front Psychol. 2015;6(1051) doi: 10.3389/fpsyg.2015.01051.
    1. Craggs JG, Price DD, Robinson ME. Enhancing the placebo response: Functional magnetic resonance imaging evidence of memory and semantic processing in placebo analgesia. J Pain. 2014;15:435–446. doi: 10.1016/j.jpain.2013.12.009.
    1. Xiang CQ, Liu WF, Xu QH, Su T, Yong-Qiang S, Min YL, Yuan Q, Zhu PW, Liu KC, Jiang N, et al. Altered spontaneous brain activity in classical trigeminal neuralgia as determined by changes in regional homogeneity: A resting-state functional MRI study. Pain Pract. 2018;19:397–406. doi: 10.1111/papr.12753.
    1. Anurova I, Renier LA, De Volder AG, Carlson S, Rauschecker JP. Relationship between cortical thickness and functional activation in the early blind. Cereb Cortex. 2015;25:2035–2048. doi: 10.1093/cercor/bhu009.
    1. Tu Y, Wei Y, Sun K, Zhao W, Yu B. Altered spontaneous brain activity in patients with hemifacial spasm: A resting-state functional MRI study. PLoS One. 2015;10(e0116849) doi: 10.1371/journal.pone.0116849.
    1. Ching YY, Wang C, Tay T, Loke YM, Tang PH, Sng BL, Zhou J. Altered sensory insular connectivity in chronic postsurgical pain patients. Front Hum Neurosci. 2018;12(483) doi: 10.3389/fnhum.2018.00483.
    1. Chen X, Chen Z, Dong Z, Liu M, Yu S. Morphometric changes over the whole brain in caffeine-containing combination-analgesic-overuse headache. Mol Pain. 2018;14(1744806918778641) doi: 10.1177/1744806918778641.
    1. Chen Y, Meng Z, Zhang Z, Zhu Y, Gao R, Cao X, Tan L, Wang Z, Zhang H, Li Y, Fan Q. The right thalamic glutamate level correlates with functional connectivity with right dorsal anterior cingulate cortex/middle occipital gyrus in unmedicated obsessive-compulsive disorder: A combined fMRI and 1H-MRS study. Aust N Z J Psychiatry. 2019;53:207–218. doi: 10.1177/0004867418806370.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel