Skip to main content

Advertisement

SpringerLink
Log in

Hemispheric coupling between structural and functional asymmetries in clinically asymptomatic carotid stenosis with cognitive impairment

  • Research
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

Advanced carotid stenosis is a known risk factor for ischemic stroke and vascular dementia, and it is associated with multidomain cognitive impairment as well as asymmetric alterations in hemispheric structure and function. Here we introduced a novel measure—the asymmetry index of amplitude of low-frequency fluctuations (ALFF_AI)—derived from resting-state functional magnetic resonance imaging. This measure captures the hemispheric asymmetry of intrinsic brain activity using high-dimensional registration. We aimed to investigate functional brain asymmetric alterations in patients with severe asymptomatic carotid stenosis (SACS). Furthermore, we extended the analyses of ALFF_AI to different frequencies to detect frequency-specific alterations. Finally, we examined the coupling between hemispheric asymmetric structure and function and the relationship between these results and cognitive tests, as well as the white matter hyperintensity burden. SACS patients presented significantly decreased ALFF_AI in several clusters, including the visual, auditory, parahippocampal, Rolandic, and superior parietal regions. At low frequencies (0.01–0.25 Hz), the ALFF_AI exhibited prominent group differences as frequency increased. Further structure-function coupling analysis indicated that SACS patients had lower coupling in the lateral prefrontal, superior medial frontal, middle temporal, superior parietal, and striatum regions but higher coupling in the lateral occipital regions. These findings suggest that, under potential hemodynamic burden, SACS patients demonstrate asymmetric hemispheric configurations of intrinsic activity patterns and a decoupling between structural and functional asymmetries.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

Data Availability

Datasets analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

References

  • Ashburner, J. (2007). A fast diffeomorphic image registration algorithm. Neuroimage, 38(1), 95–113.

    Article  PubMed  Google Scholar 

  • Avelar, W. M., D’Abreu, A., et al. (2015). Asymptomatic carotid stenosis is associated with gray and white matter damage. International Journal of Stroke : Official Journal of the International Stroke Society, 10(8), 1197–1203.

    Article  PubMed  Google Scholar 

  • Biswal, B. B. (2012). Resting state fMRI: A personal history. Neuroimage, 62(2), 938–944.

    Article  PubMed  Google Scholar 

  • Chang, T. Y., Huang, K. L., et al. (2016). Graph theoretical analysis of functional networks and its relationship to cognitive decline in patients with carotid stenosis. Journal of Cerebral Blood Flow and Metabolism, 36(4), 808–818.

    Article  PubMed  Google Scholar 

  • Chen, Y., Jiang, Y., et al. (2021). Common and unique structural plasticity after left and right hemisphere Stroke. Journal of Cerebral Blood Flow & Metabolism, 41(12), 3350–3364.

    Article  Google Scholar 

  • Cheng, L., Zhang, Y., et al. (2021). Connectional asymmetry of the inferior parietal lobule shapes hemispheric specialization in humans, chimpanzees, and rhesus macaques. Elife, 10, e67600.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • de Weerd, M., Greving, J. P., et al. (2014). Prediction of asymptomatic carotid artery stenosis in the general population: Identification of high-risk groups. Stroke, 45(8), 2366–2371.

    Article  PubMed  PubMed Central  Google Scholar 

  • Demarin, V., Zavoreo, I., et al. (2012). Carotid artery Disease and cognitive impairment. Journal of the Neurological Sciences, 322(1), 107–111.

    Article  PubMed  Google Scholar 

  • Dichgans, M., & Leys, D. (2017). “Vascular cognitive impairment " Circulation research 120 (3): 573–591.

    PubMed  CAS  Google Scholar 

  • Duering, M., Gonik, M. (2013). Identification of a strategic brain network underlying processing speed deficits in vascular cognitive impairment. NeuroImage 66: 177–183.

  • Fischer, F., Malherbe, C., et al. (2022). Intrinsic functional brain connectivity is resilient to chronic hypoperfusion caused by unilateral carotid artery stenosis. NeuroImage. Clinical, 34, 103014.

    Google Scholar 

  • Floresco, S. B. (2015). The nucleus accumbens: An interface between cognition, emotion, and action. Annu Rev Psychol, 66, 25–52.

    Article  PubMed  Google Scholar 

  • Folstein, M. F., Folstein, S. E., et al. (1975). Mini-mental state: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198.

    Article  PubMed  CAS  Google Scholar 

  • Frisby, S. L., Halai, A. D. (2023). Decoding semantic representations in mind and brain. Trends in cognitive sciences.

  • Friston, K. J., Williams, S., et al. (1996). Movement-related effects in fMRI time-series. Magnetic Resonance in Medicine, 35(3), 346–355.

    Article  PubMed  CAS  Google Scholar 

  • Gao, L., Wang, T., et al. (2019). Severe asymptomatic carotid stenosis is associated with robust reductions in homotopic functional connectivity. NeuroImage. Clinical, 24, 102101.

    Google Scholar 

  • Gao, L., Ruan, Z., et al. (2021). Surface-based Cortical Morphometry, White Matter Hyperintensity, and Multidomain Cognitive performance in asymptomatic carotid stenosis. " Neuroscience, 467, 16–27.

    Article  PubMed  CAS  Google Scholar 

  • Gao, L., Xiao, Y., et al. (2021). Gray Matter asymmetry in asymptomatic carotid stenosis. Human Brain Mapping, 42(17), 5665–5676.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gong, Z., & Zuo, X. (2023). Connectivity gradients in spontaneous brain activity at multiple frequency bands. Cerebral Cortex, 33(17), 9718–9728.

    Article  PubMed  Google Scholar 

  • Gotts, S. J., Jo, H. J., et al. (2013). Two distinct forms of functional lateralization in the human brain. Proc Natl Acad Sci U S A, 110(36), E3435–E3444.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Güntürkün, O., & Ocklenburg, S. (2017). “Ontogenesis of lateralization " Neuron 94 (2): 249–263.

    Article  PubMed  Google Scholar 

  • Güntürkün, O., Ströckens, F. (2020). “Brain Lateralization: A Comparative Perspective " Physiological reviews 100 (3): 1019–1063.

    PubMed  Google Scholar 

  • Han, Y., Wang, J., et al. (2011). Frequency-dependent changes in the amplitude of low-frequency fluctuations in amnestic mild cognitive impairment: A resting-state fMRI study. Neuroimage, 55(1), 287–295.

    Article  PubMed  Google Scholar 

  • Hao, X., Wang, K., et al. (2013). Individual differences in brain structure and resting brain function underlie cognitive styles: Evidence from the embedded figures test. " PLoS One, 8(12), e78089.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  • Hu, B., Yan, L. F., et al. (2019). Disturbed neurovascular coupling in type 2 Diabetes Mellitus patients: Evidence from a comprehensive fMRI analysis. Neuroimage Clin, 22, 101802.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hu, B., Yu, Y., et al. (2019). Multi-modal MRI reveals the neurovascular coupling dysfunction in chronic migraine. " Neuroscience, 419, 72–82.

    Article  ADS  PubMed  CAS  Google Scholar 

  • Hu, R., Gao, L., et al. (2020). How do you feel now? The Salience Network Functional Connectivity in End-Stage Renal Disease. Frontiers in Neuroscience, 14, 533910–533910.

    Article  PubMed  PubMed Central  Google Scholar 

  • Joliot, M., Jobard, G., et al. (2015). AICHA: An atlas of intrinsic connectivity of homotopic areas. Journal of Neuroscience Methods, 254, 46–59.

    Article  PubMed  Google Scholar 

  • Karolis, V. R., Corbetta, M., et al. (2019). The architecture of functional lateralisation and its relationship to callosal connectivity in the human brain. Nature Communications, 10(1), 1417.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  • Kim, G. H., Jeon, S., et al. (2012). Topography of cortical thinning areas associated with hippocampal atrophy (HA) in patients with Alzheimer’s Disease (AD). Archives of Gerontology and Geriatrics, 54(2), e122–e129.

    Article  PubMed  Google Scholar 

  • Kucewicz, M. T., Berry, B. M., et al. (2018). Evidence for verbal memory enhancement with electrical brain stimulation in the lateral temporal cortex. Brain, 141(4), 971–978.

    Article  PubMed  Google Scholar 

  • Kurth, F., Gaser, C., et al. (2015). A 12-step user guide for analyzing voxel-wise gray matter asymmetries in statistical parametric mapping (SPM). Nature Protocols, 10(2), 293–304.

    Article  ADS  PubMed  CAS  Google Scholar 

  • Lal, B. K., Dux, M. C., et al. (2017). Asymptomatic carotid stenosis is associated with cognitive impairment. Journal of Vascular Surgery, 66(4), 1083–1092.

    Article  PubMed  Google Scholar 

  • Lattanzi, S., Carbonari, L., et al. (2018). Neurocognitive functioning and cerebrovascular reactivity after carotid endarterectomy. Neurology, 90(4), e307–e315.

    Article  PubMed  Google Scholar 

  • Li, P., Mu, J., et al. (2021). Neurovascular coupling dysfunction in end-stage renal Disease patients related to cognitive impairment. Journal of Cerebral Blood Flow and Metabolism, 41(10), 2593–2606.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liang, X., Zou, Q., et al. (2013). Coupling of functional connectivity and regional cerebral blood flow reveals a physiological basis for network hubs of the human brain. Proceedings of the National Academy of Sciences, 110(5), 1929–1934.

    Article  ADS  CAS  Google Scholar 

  • Lin, C., Tu, P., et al. (2014). Connectivity features for identifying cognitive impairment in Presymptomatic Carotid stenosis. " PLOS ONE, 9(1), e85441.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  • Lineback, C. M., Stamm, B., et al. (2023). Carotid Disease, cognition, and aging: Time to redefine asymptomatic Disease? " Geroscience, 45(2), 719–725.

    Article  PubMed  Google Scholar 

  • Liu, Y., Spulber, G., et al. (2011). Diffusion tensor imaging and tract-based spatial statistics in Alzheimer’s Disease and mild cognitive impairment. Neurobiology of Aging, 32(9), 1558–1571.

    Article  PubMed  Google Scholar 

  • Liu, F., Guo, W., et al. (2013). Abnormal amplitude low-frequency oscillations in medication-naive, first-episode patients with major depressive disorder: A resting-state fMRI study. Journal of Affective Disorders, 146(3), 401–406.

    Article  MathSciNet  PubMed  Google Scholar 

  • Liu, X., Wang, S., et al. (2014). Abnormal amplitude of low-frequency fluctuations of intrinsic brain activity in Alzheimer’s Disease. Journal of Alzheimer’s Disease, 40, 387–397.

    Article  PubMed  Google Scholar 

  • Liu, J., Zhang, X., et al. (2016). Impaired parahippocampus connectivity in mild cognitive impairment and Alzheimer’s Disease. Journal of Alzheimer’s Disease, 49(4), 1051–1064.

    Article  PubMed  Google Scholar 

  • Liu, X., Xu, D., et al. (2023). Altered callosal morphology and connectivity in asymptomatic carotid stenosis. " Journal of Magnetic Resonance Imaging.

  • Luo, F. F., Wang, J. B., et al. (2020). Higher sensitivity and reproducibility of Wavelet-based amplitude of resting-state fMRI. " Front Neurosci, 14, 224.

    Article  PubMed  PubMed Central  Google Scholar 

  • Murphy, K., & Fox, M. D. (2017). Towards a consensus regarding global signal regression for resting state functional connectivity MRI. Neuroimage, 154, 169–173.

    Article  PubMed  Google Scholar 

  • Nasreddine, Z. S., Phillips, N. A., et al. (2005). The Montreal Cognitive Assessment, MoCA: A brief Screening Tool for mild cognitive impairment. Journal of the American Geriatrics Society, 53(4), 695–699.

    Article  PubMed  Google Scholar 

  • Power, J. D., Barnes, K. A., et al. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage, 59(3), 2142–2154.

    Article  PubMed  Google Scholar 

  • Quandt, F., Fischer, F., et al. (2020). Normalization of reduced functional connectivity after revascularization of asymptomatic carotid stenosis. Journal of Cerebral Blood Flow and Metabolism, 40(9), 1838–1848.

    Article  PubMed  Google Scholar 

  • Raichle, M. E. (2015). The brain’s default Mode Network. Annual Review of Neuroscience, 38(1), 433–447.

    Article  PubMed  CAS  Google Scholar 

  • Raut, R. V., Snyder, A. Z., et al. (2021). Global waves synchronize the brain’s functional systems with fluctuating arousal. Science Advances, 7(30), eabf2709.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  • Schmidt, P., Gaser, C., et al. (2012). An automated tool for detection of FLAIR-hyperintense white-matter lesions. In Multiple Sclerosis " NeuroImage, 59(4), 3774–3783.

    PubMed  Google Scholar 

  • Silberman, E. K., & Weingartner, H. (1986). Hemispheric lateralization of functions related to emotion. Brain and Cognition, 5(3), 322–353.

    Article  PubMed  CAS  Google Scholar 

  • Sulter, G., Steen, C., et al. (1999). Use of the Barthel index and modified Rankin scale in acute Stroke trials. Stroke, 30(8), 1538–1541.

    Article  PubMed  CAS  Google Scholar 

  • Sztriha, L. K., Nemeth, D., et al. (2009). Carotid stenosis and the cognitive function. Journal of the Neurological Sciences, 283(1–2), 36–40.

    Article  PubMed  Google Scholar 

  • Tuo, J., He, W., et al. (2021). Disrupted Topological Organization of Functional Networks in asymptomatic carotid plaque without significant carotid stenosis: A resting-state fMRI study. Frontiers in Human Neuroscience, 15, 685763.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang, Z., Yan, C., et al. (2011). Spatial patterns of intrinsic brain activity in mild cognitive impairment and alzheimer’s Disease: A resting-state functional MRI study. Human Brain Mapping, 32(10), 1720–1740.

    Article  ADS  PubMed  Google Scholar 

  • Wang, D., Buckner, R. L., et al. (2014). Functional specialization in the human brain estimated by intrinsic hemispheric interaction. Journal of Neuroscience, 34(37), 12341–12352.

    Article  PubMed  CAS  Google Scholar 

  • Wang, H., Yu, M., et al. (2023). Neuroanatomical correlates of cognitive impairment following basal ganglia-thalamic post-hemorrhagic Stroke: Uncovering network-wide alterations in hemispheric gray matter asymmetry. Brain Research, 1820, 148559.

    Article  PubMed  CAS  Google Scholar 

  • Whitney, C., Jefferies, E., et al. (2011). Heterogeneity of the left temporal lobe in semantic representation and control: Priming multiple versus single meanings of ambiguous words. Cerebral Cortex, 21(4), 831–844.

    Article  PubMed  Google Scholar 

  • Yang, C., Zhong, S., et al. (2017). The abnormality of Topological asymmetry between Hemispheric Brain White Matter Networks in Alzheimer’s Disease and mild cognitive impairment. Frontiers in Aging Neuroscience, 9, 261.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yarkoni, T., Poldrack, R. A., et al. (2011). Large-scale automated synthesis of human functional neuroimaging data. Nature Methods, 8(8), 665–670.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yu, X., Gao, L., et al. (2019). Neuroanatomical changes underlying Vertical HIV Infection in adolescents. " Front Immunol, 10, 814.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zang, Y. F., He, Y., et al. (2007). Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. " Brain Dev, 29(2), 83–91.

    Article  PubMed  Google Scholar 

  • Zhu, J., Jin, Y., et al. (2015). Frequency-dependent changes in the regional amplitude and synchronization of resting-state functional MRI in Stroke. PLoS One, 10(4), e0123850.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zou, Q., Zhu, C., et al. (2008). An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: Fractional ALFF. Journal of Neuroscience Methods, 172(1), 137–141.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zuo, X., Di Martino, A. (2010). “The oscillating brain: complex and reliable " Neuroimage 49 (2): 1432–1445.

    PubMed  Google Scholar 

  • Zuo, X., & Xing, X. (2014). Test-retest reliabilities of resting-state FMRI measurements in human brain functional connectomics: A systems neuroscience perspective. Neuroscience & Biobehavioral Reviews, 45, 100–118.

    Article  Google Scholar 

Download references

Funding

This study was supported by the National Key R&D Program of China (No. 2021ZD0111101), the National Natural Science Foundation of China (No. 82001799) and the Fundamental Research Funds for the Central Universities (No. 2042023kf0055) to LG.

Author information

Author notes

  1. Chenhong Fan, Dan Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Zhongnan Hospital of Wuhan University, Wuchang District, 430071, Wuhan City, Hubei Province, China

    Chenhong Fan, Hao Mei, Xiaoli Zhong, Jinxia Ren, Jiaojiao Ma, Zhao Ruan, Jinfeng Lv, Xitong Liu, Huan Wang, Lei Gao & Haibo Xu

  2. Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuchang District, 430071, Wuhan City, Hubei Province, China

    Dan Xu

  3. The Interventional Diagnostic and Therapeutic Center, Zhongnan Hospital of Wuhan University, Wuchang District, 430071, Wuhan City, Hubei Province, China

    Chenhong Fan

Authors
  1. Chenhong Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hao Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoli Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jinxia Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiaojiao Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhao Ruan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jinfeng Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xitong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Huan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Lei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Haibo Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CF and DX analyzed data, drafted manuscript; LG supervised the neuroimaging analyses; HM, XZ, JM, ZR, XL collected data and wrote manuscript; JR, JL and HW contributed to data analyses and wrote manuscript; LG and HX conceived idea and contributed to manuscript editing.

Corresponding authors

Correspondence to Lei Gao or Haibo Xu.

Ethics declarations

Institutional review board statement

The study was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University, China.

Data sharing statement

Datasets analyzed during the current study are available from the corresponding author on reasonable request.

Conflict of interest

The authors declare that there are no conflicts of interest associated with this manuscript.

Ethics approval

The study was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University, China.

Additional information

Publisher’s Note

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

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

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

Fan, C., Xu, D., Mei, H. et al. Hemispheric coupling between structural and functional asymmetries in clinically asymptomatic carotid stenosis with cognitive impairment. Brain Imaging and Behavior 18, 192–206 (2024). https://doi.org/10.1007/s11682-023-00823-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-023-00823-0

Keywords

Search

Navigation