Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Alterations in regional homogeneity and functional connectivity associated with cognitive impairment in patients with hypertension: a resting-state functional magnetic resonance imaging study

Hypertension Research volume 46, pages 1311–1325 (2023)Cite this article

A Comment to this article was published on 08 March 2023

Abstract

Our study aims to investigate the alterations and diagnostic efficiency of regional homogeneity (ReHo) and functional connectivity (FC) in hypertension patients with cognitive impairment. A total of 62 hypertension patients with cognitive impairment (HTN-CI), 59 hypertension patients with normal cognition (HTN-NC), and 58 healthy controls (HCs) with rs-fMRI data were enrolled in this study. Univariate analysis (based on whole-brain ReHo and seed-based FC maps) was performed to observe brain regions with significant differences among the three groups. Multiple voxel pattern analysis (MVPA) was applied to evaluate the diagnostic accuracy in classifying HTN-CI from HTN-NC and HCs. Compared with the HCs and HTN-NC, HTN-CI exhibited decreased ReHo in the right caudate, left postcentral gyrus, posterior cingulate gyrus, insula, while increased ReHo in the left superior occipital gyrus and superior parietal gyrus. HTN-CI showed increased FC between seed regions (left posterior cingulate gyrus, insula, postcentral gyrus) with many specific brain regions. MVPA analysis (based on whole-brain ReHo and seed-based FC maps) displayed high classification ability in distinguishing HTN-CI from HTN-NC and HCs. The ReHo values (right caudate) and the FC values (left postcentral gyrus seed to left posterior cingulate gyrus) were positively correlated with the MoCA scores in HTN-CI. HTN-CI was associated with decreased ReHo and increased FC mainly in the left posterior cingulate gyrus, postcentral gyrus, insula compared to HTN-NC and HC. Besides, MVPA analysis yields excellent diagnostic accuracy in classifying HTN-CI from HTN-NC and HCs. The findings may contribute to unveiling the underlying neuropathological mechanism of HTN-CI.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

The datasets used or analyzed during the current study are included in the article.

Code availability

MATLAB 2013b (The Mathworks, Natick, MA, USA), Statistical Parametric Mapping, version 12 (SPM12, http://www.fil.ion.ucl.ac.uk/spm) and DPABI (http://rfmri.org/dparbi) software were used for resting-state image preprocessing. MVPA was performed on the MATLAB platform by using pattern recognition for neuroimaging (PRoNTo) baggage (http://www.mlnl.cs.ucl.ac.uk/pronto).

References

  1. Iadecola C, Yaffe K, Biller J, Bratzke LC, Faraci FM, Gorelick PB, et al. Impact of hypertension on cognitive function: a scientific statement from the American Heart Association. Hypertension. 2016;68:e67–e94.

    Article  CAS  PubMed  Google Scholar 

  2. Zhou H, Zhu Z, Liu C, Bai Y, Zhan Q, Huang X, et al. Effect of hypertension duration and blood pressure control during early adulthood on cognitive function in middle age. J Alzheimers Dis. 2022;85:779–89. https://doi.org/10.3233/JAD-215070.

  3. Sanchez-Nieto JM, Rivera-Sanchez UD, Mendoza-Nunez VM. Relationship between arterial hypertension with cognitive performance in elderly. Systematic review and meta-analysis. Brain Sci. 2021;11:1445.

  4. Triantafyllou A, Ferreira JP, Kobayashi M, Micard E, Xie Y, Kearney-Schwartz A, et al. Longer duration of hypertension and MRI microvascular brain alterations are associated with lower hippocampal volumes in older individuals with hypertension. J Alzheimers Dis. 2020;74:227–35.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Li H, Sun D, Lu D, Zhang J, Zeng J. Low hippocampal dentate gyrus volume associated with hypertension-related cognitive impairment. Am J Alzheimers Dis Other Demen. 2020;35:1533317520949782.

    Article  PubMed  Google Scholar 

  6. Luo DH, Tseng WI, Chang YL. White matter microstructure disruptions mediate the adverse relationships between hypertension and multiple cognitive functions in cognitively intact older adults. Neuroimage. 2019;197:109–19.

    Article  PubMed  Google Scholar 

  7. Naumczyk P, Sabisz A, Witkowska M, Graff B, Jodzio K, Gasecki D, et al. Compensatory functional reorganization may precede hypertension-related brain damage and cognitive decline: a functional magnetic resonance imaging study. J Hypertens. 2017;35:1252–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yang F, Ma H, Yuan J, Wei Y, Xu L, Zhang Y, et al. Correlation of abnormalities in resting state fMRI with executive functioning in chronic schizophrenia. Psychiatry Res. 2021;299:113862.

    Article  PubMed  Google Scholar 

  9. Yang Y, Liu S, Jiang X, Yu H, Ding S, Lu Y, et al. Common and specific functional activity features in schizophrenia, major depressive disorder, and bipolar disorder. Front Psychiatry. 2019;10:52.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ma X, Zheng W, Li C, Li Z, Tang J, Yuan L, et al. Decreased regional homogeneity and increased functional connectivity of default network correlated with neurocognitive deficits in subjects with genetic high-risk for schizophrenia: a resting-state fMRI study. Psychiatry Res. 2019;281:112603.

    Article  PubMed  Google Scholar 

  11. Xing Y, Fu S, Li M, Ma X, Liu M, Liu X, et al. Regional neural activity changes in Parkinson’s disease-associated mild cognitive impairment and cognitively normal patients. Neuropsychiatr Dis Treat. 2021;17:2697–706.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Li MG, Liu TF, Zhang TH, Chen ZY, Nie BB, Lou X, et al. Alterations of regional homogeneity in Parkinson’s disease with mild cognitive impairment: a preliminary resting-state fMRI study. Neuroradiology. 2020;62:327–34.

    Article  PubMed  Google Scholar 

  13. Li X, Liang Y, Chen Y, Zhang J, Wei D, Chen K, et al. Disrupted frontoparietal network mediates white matter structure dysfunction associated with cognitive decline in hypertension patients. J Neurosci. 2015;35:10015–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang Z, Yuan Y, Jiang Y, You J, Zhang Z. Identification of specific neural circuit underlying the key cognitive deficit of remitted late-onset depression: a multi-modal MRI and machine learning study. Prog Neuropsychopharmacol Biol Psychiatry. 2021;108:110192.

    Article  PubMed  Google Scholar 

  15. Gao Y, Wang X, Xiong Z, Ren H, Liu R, Wei Y, et al. Abnormal fractional amplitude of low-frequency fluctuation as a potential imaging biomarker for first-episode major depressive disorder: a resting-state fMRI Study and support vector machine analysis. Front Neurol. 2021;12:751400.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Yan B, Xu X, Liu M, Zheng K, Liu J, Li J, et al. Quantitative identification of major depression based on resting-state dynamic functional connectivity: a machine learning approach. Front Neurosci. 2020;14:191.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Tian ZY, Qian L, Fang L, Peng XH, Zhu XH, Wu M, et al. Frequency-specific changes of resting brain activity in Parkinson’s disease: a machine learning approach. Neuroscience. 2020;436:170–83.

    Article  CAS  PubMed  Google Scholar 

  18. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007;28:1462–536.

    PubMed  Google Scholar 

  19. Uiterwijk R, Staals J, Huijts M, van Kuijk SMJ, de Leeuw PW, Kroon AA, et al. Hypertensive organ damage predicts future cognitive performance: a 9-year follow-up study in patients with hypertension. J Clin Hypertens (Greenwich). 2018;20:1458–63.

    Article  CAS  PubMed  Google Scholar 

  20. Gu Y, Liu R, Qin R, Chen X, Zou J, Jiang Y, et al. Characteristic changes in the default mode network in hypertensive patients with cognitive impairment. Hypertens Res. 2019;42:530–40.

    Article  PubMed  Google Scholar 

  21. Guo P, Lang S, Jiang M, Wang Y, Zeng Z, Wen Z, et al. Alterations of regional homogeneity in children with congenital sensorineural hearing loss: a resting-state fMRI study. Front Neurosci. 2021;15:678910.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Zuo M, Xu Y, Zhang X, Li M, Jia X, Niu J, et al. Aberrant brain regional homogeneity and functional connectivity of entorhinal cortex in vascular mild cognitive impairment: a resting-state functional MRI study. Front Neurol. 2018;9:1177.

    Article  PubMed  Google Scholar 

  23. Qiu M, Zhang H, Mellor D, Shi J, Wu C, Huang Y, et al. Aberrant neural activity in patients with bipolar depressive disorder distinguishing to the unipolar depressive disorder: a resting-state functional magnetic resonance imaging study. Front Psychiatry. 2018;9:238.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Yu H, Li ML, Li YF, Li XJ, Meng Y, Liang S, et al. Anterior cingulate cortex, insula and amygdala seed-based whole brain resting-state functional connectivity differentiates bipolar from unipolar depression. J Affect Disord. 2020;274:38–47.

    Article  PubMed  Google Scholar 

  25. Wang L, Wei Q, Wang C, Xu J, Wang K, Tian Y, et al. Altered functional connectivity patterns of insular subregions in major depressive disorder after electroconvulsive therapy. Brain Imaging Behav. 2020;14:753–61.

    Article  PubMed  Google Scholar 

  26. Jung J, Choi S, Han KM, Kim A, Kang W, Paik JW, et al. Alterations in functional brain networks in depressed patients with a suicide attempt history. Neuropsychopharmacology. 2020;45:964–74.

    Article  PubMed  Google Scholar 

  27. Chand GB, Wu J, Qiu D, Hajjar I. Racial differences in insular connectivity and thickness and related cognitive impairment in hypertension. Front Aging Neurosci. 2017;9:177.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Xin H, Wen H, Feng M, Gao Y, Sui C, Zhang N, et al. Disrupted topological organization of resting-state functional brain networks in cerebral small vessel disease. Hum Brain Mapp. 2022;43:2607–20.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Yang H, Chen X, Chen ZB, Li L, Li XY, Castellanos FX, et al. Disrupted intrinsic functional brain topology in patients with major depressive disorder. Mol Psychiatry. 2021;26:7363–71.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Xiong Y, Chen X, Zhao X, Fan Y, Zhang Q, Zhu W. Altered regional homogeneity and functional brain networks in Type 2 diabetes with and without mild cognitive impairment. Sci Rep. 2020;10:21254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Xiong Y, Tian T, Fan Y, Yang S, Xiong X, Zhang Q, et al. Diffusion tensor imaging reveals altered topological efficiency of structural networks in type-2 diabetes patients with and without mild cognitive impairment. J Magn Reson Imaging. 2022;55:917–27.

    Article  PubMed  Google Scholar 

  32. Carnevale L, Maffei A, Landolfi A, Grillea G, Carnevale D, Lembo G. Brain functional magnetic resonance imaging highlights altered connections and functional networks in patients with hypertension. Hypertension. 2020;76:1480–90.

    Article  CAS  PubMed  Google Scholar 

  33. Guo W, Jin W, Li N, Gao J, Wang J, Chang Y, et al. Brain activity alterations in patients with Parkinson’s disease with cognitive impairment based on resting-state functional MRI. Neurosci Lett. 2021;747:135672.

    Article  CAS  PubMed  Google Scholar 

  34. Yuan Q, Qi W, Xue C, Ge H, Hu G, Chen S, et al. Convergent functional changes of default mode network in mild cognitive impairment using activation likelihood estimation. Front Aging Neurosci. 2021;13:708687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang Y, Jiang M, Huang L, Meng X, Li S, Pang X, et al. Altered functional brain network in systemic lupus erythematosus patients without overt neuropsychiatric symptoms based on resting-state functional magnetic resonance imaging and multivariate pattern analysis. Front Neurol. 2021;12:690979.

    Article  PubMed  PubMed Central  Google Scholar 

  36. McIntosh RC, Lobo JD, Yang A, Schneiderman N. Brainstem network connectivity with mid-anterior insula predicts lower systolic blood pressure at rest in older adults with hypertension. J Hum Hypertens. 2021;35:1098–108.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Liu G, Jiao K, Zhong Y, Hao Z, Wang C, Xu H, et al. The alteration of cognitive function networks in remitted patients with major depressive disorder: an independent component analysis. Behav Brain Res. 2021;400:113018.

    Article  PubMed  Google Scholar 

  38. Shang S, Zhang H, Feng Y, Wu J, Dou W, Chen YC, et al. Region-specific neurovascular decoupling associated with cognitive decline in Parkinson’s disease. Front Aging Neurosci. 2021;13:770528.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Chen CY, Tsai TY, Chen BH. Effects of black garlic extract and nanoemulsion on the deoxy corticosterone acetate-salt induced hypertension and its associated mild cognitive impairment in rats. Antioxidants (Basel). 2021;10:1611.

  40. Liu X, Cheng R, Chen L, Gong J, Luo T, Lv F. Altered neurovascular coupling in subcortical ischemic vascular disease. Front Aging Neurosci. 2021;13:598365.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Lyu D, Li T, Lyu X. Resting-state functional reorganisation in Alzheimer’s disease and amnestic mild cognitive impairment: protocol for a systematic review and meta-analysis. BMJ Open. 2021;11:e049798.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Liang S, Xue K, Wang W, Yu W, Ma X, Luo S, et al. Altered brain function and clinical features in patients with first-episode, drug naive major depressive disorder: a resting-state fMRI study. Psychiatry Res Neuroimaging. 2020;303:111134.

    Article  PubMed  Google Scholar 

  43. Harricharan S, Nicholson AA, Thome J, Densmore M, McKinnon MC, Theberge J, et al. PTSD and its dissociative subtype through the lens of the insula: anterior and posterior insula resting-state functional connectivity and its predictive validity using machine learning. Psychophysiology. 2020;57:e13472.

    Article  PubMed  Google Scholar 

  44. Zhang Q, Wang Q, He C, Fan D, Zhu Y, Zang F, et al. Altered regional cerebral blood flow and brain function across the Alzheimer’s disease spectrum: a potential biomarker. Front Aging Neurosci. 2021;13:630382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhang Z, Cui L, Huang Y, Chen Y, Li Y, Guo Q. Changes of regional neural activity homogeneity in preclinical Alzheimer’s disease: compensation and dysfunction. Front Neurosci. 2021;15:646414.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Bohaterewicz B, Sobczak AM, Podolak I, Wojcik B, Metel D, Chrobak AA, et al. Machine learning-based identification of suicidal risk in patients with schizophrenia using multi-level resting-state fMRI features. Front Neurosci. 2020;14:605697.

    Article  PubMed  Google Scholar 

  47. Hilbert K, Lueken U, Muehlhan M, Beesdo-Baum K. Separating generalized anxiety disorder from major depression using clinical, hormonal, and structural MRI data: a multimodal machine learning study. Brain Behav. 2017;7:e00633.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Wang S, Zhang Y, Lv L, Wu R, Fan X, Zhao J, et al. Abnormal regional homogeneity as a potential imaging biomarker for adolescent-onset schizophrenia: a resting-state fMRI study and support vector machine analysis. Schizophr Res. 2018;192:179–84.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank all the patients and healthy controls who joined the present study.

Funding

This work was supported by grants from the National Natural Science Foundation of China (81871507 and 81471389), and the Beijing Natural Science Foundation of China (7212200).

Author information

Author notes

  1. These authors contributed equally: Dan Liao, Zhu-Qing Zhang.

Authors and Affiliations

  1. Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China

    Dan Liao, Zhi-Peng Guo, Zhu-Qing Zhang, Ming-Hao Yang & Chun-Hong Liu

  2. Department of Radiology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, China

    Dan Liao & Rong-Ping Wang

  3. Department of Radiology and Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, 100032, China

    Li-Rong Tang & Yue Gao

Authors
  1. Dan Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhi-Peng Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li-Rong Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yue Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhu-Qing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ming-Hao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rong-Ping Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chun-Hong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study’s conception and design. C-HL contributed to the conception of the study. DL and Z-PG performed the experiment. DL and Z-QZ contributed significantly to the analysis and manuscript preparation. M-HY performed the data analyses and wrote the manuscript. C-HL helped perform the analysis with constructive discussions. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Rong-Ping Wang or Chun-Hong Liu.

Ethics declarations

Ethics approval and consent to participate

This study received approval from the Medical Ethics Committee of Beijing Anding Hospital, Capital Medical University, and this study was performed in line with the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants before the experiment.

Consent for publication

The participants have consented to the submission of the original research to the journal.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liao, D., Guo, ZP., Tang, LR. et al. Alterations in regional homogeneity and functional connectivity associated with cognitive impairment in patients with hypertension: a resting-state functional magnetic resonance imaging study. Hypertens Res 46, 1311–1325 (2023). https://doi.org/10.1038/s41440-023-01168-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-023-01168-3

Keywords

This article is cited by

Search

Advanced search

Quick links