Skip to main content
SpringerLink
Log in

Neuroanatomical and functional alterations of insula in mild traumatic brain injury patients at the acute stage

  • ORIGINAL RESEARCH
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

Cognitive impairment is a major cause of disability and decline in quality of life in mild traumatic brain injury (mTBI) survivors, but the underlying pathophysiology is still poorly understood. The insula has extensive connections to other cortex and is believed to responsible for integrating external and internal processes and controlling cognitive functions. To explore this hypothesis, we investigated early alterations in the gray matter volume (GMV) and brain functional connectivity (FC) of insula in mTBI patients within 7 days after injury and any possible correlations with cognitive function. A total of 58 mTBI patients at the acute stage and 32 matched healthy controls were recruited and underwentT1-weighted magnetic resonance imaging (MRI)andresting-state functional MRI scans within 7 days of injury. FC was characterized using seed-based region of interest analysis method. The patients’ cognitive function was evaluated with Montreal Cognitive Assessment (MoCA) score. The resulting of GMV and FC of insula were correlated with cognitive alterations. We found that the GMV was significantly reduced only in the right insula in mTBI patients and no significant GMV increase was observed in either hemisphere. mTBI patients demonstrated decreased FC in the right parahippocampal gyrus and increased FC in the right supramargianl gyrus. In addition, compared to the healthy controls, the mTBI patients in the acute stage presented a decline in the visuospatial/executive (p = 0.013) and attention (p = 0.038) subcategories. In the mTBI group, the changes in GMV in the right insula were positively correlated with poor attention performance (r = 0.316, p = 0.016). Our data demonstrated alterations of the GMV and resting-stateFC of the right insula in mTBI patients at the acute stage. These early changes in GMV and resting-state FC perhaps serve as a potential biomarker for improving the understanding of cognitive decline for mTBI in the acute setting.

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

Similar content being viewed by others

References

  • Augustine, J. R. (1996). Circuitry and functional aspects of the insular lobe in primates including humans. Brain Research. Brain Research Reviews, 22, 229–244.

    Article  CAS  PubMed  Google Scholar 

  • Bigler, E. D. (2013). Traumatic brain injury, neuroimaging, and neurodegeneration. Frontiers in Human Neuroscience, 7, 395.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bonnelle, V., Ham, T. E., Leech, R., Kinnunen, K. M., Mehta, M. A., Greenwood, R. J., & Sharp, D. J. (2012). Salience network integrity predicts default mode network function after traumatic brain injury. Proceedings of the National Academy of Sciences of the United States of America, 109, 4690–4695.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carlozzi, N. E., Kirsch, N. L., Kisala, P. A., & Tulsky, D. S. (2015). An examination of the Wechsler adult intelligence scales, fourth edition (WAIS-IV) in individuals with complicated mild, moderate and severe traumatic brain injury (TBI). The Clinical Neuropsychologist, 29, 21–37.

    Article  PubMed  Google Scholar 

  • Chao-Gan, Y., & Yu-Feng, Z. (2010). DPARSF: A MATLAB toolbox for "pipeline" data analysis of resting-state fMRI. Frontiers in Systems Neuroscience, 4, 13.

    PubMed  PubMed Central  Google Scholar 

  • Dall'Acqua, P., Johannes, S., Mica, L., Simmen, H. P., Glaab, R., Fandino, J., Schwendinger, M., Meier, C., Ulbrich, E. J., Muller, A., Jancke, L., & Hanggi, J. (2016). Connectomic and surface-based morphometric correlates of acute mild traumatic brain injury. Frontiers in Human Neuroscience, 10, 127.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dall'Acqua, P., Johannes, S., Mica, L., Simmen, H. P., Glaab, R., Fandino, J., Schwendinger, M., Meier, C., Ulbrich, E. J., Muller, A., Jancke, L., & Hanggi, J. (2017). Prefrontal cortical thickening after mild traumatic brain injury: A one-year magnetic resonance imaging study. Journal of Neurotrauma, 34, 3270–3279.

    Article  PubMed  Google Scholar 

  • de Guise, E., Alturki, A. Y., LeBlanc, J., Champoux, M. C., Couturier, C., Lamoureux, J., Desjardins, M., Marcoux, J., Maleki, M., & Feyz, M. (2014). The Montreal cognitive assessment in persons with traumatic brain injury. Applied Neuropsychology. Adult, 21, 128–135.

    Article  PubMed  Google Scholar 

  • Duning, T., Kloska, S., Steinstrater, O., Kugel, H., Heindel, W., & Knecht, S. (2005). Dehydration confounds the assessment of brain atrophy. Neurology, 64, 548–550.

    Article  CAS  PubMed  Google Scholar 

  • Floden, D., & Stuss, D. T. (2006). Inhibitory control is slowed in patients with right superior medial frontal damage. Journal of Cognitive Neuroscience, 18, 1843–1849.

    Article  PubMed  Google Scholar 

  • Gao, X., & Chen, J. (2011). Mild traumatic brain injury results in extensive neuronal degeneration in the cerebral cortex. Journal of Neuropathology and Experimental Neurology, 70, 183–191.

    Article  PubMed  PubMed Central  Google Scholar 

  • Good, C. D., Johnsrude, I. S., Ashburner, J., Henson, R. N., Friston, K. J., & Frackowiak, R. S. (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage, 14, 21–36.

    Article  CAS  PubMed  Google Scholar 

  • Govindarajan, K. A., Narayana, P. A., Hasan, K. M., Wilde, E. A., Levin, H. S., Hunter, J. V., Miller, E. R., Patel, V. K., Robertson, C. S., & McCarthy, J. J. (2016). Cortical thickness in mild traumatic brain injury. Journal of Neurotrauma, 33, 1809–1817.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hasan, K. M., Wilde, E. A., Miller, E. R., Kumar Patel, V., Staewen, T. D., Frisby, M. L., Garza, H. M., McCarthy, J. J., Hunter, J. V., Levin, H. S., Robertson, C. S., & Narayana, P. A. (2014). Serial atlas-based diffusion tensor imaging study of uncomplicated mild traumatic brain injury in adults. Journal of Neurotrauma, 31, 466–475.

    Article  PubMed  Google Scholar 

  • Hillary, F. G., Slocomb, J., Hills, E. C., Fitzpatrick, N. M., Medaglia, J. D., Wang, J., Good, D. C., & Wylie, G. R. (2011). Changes in resting connectivity during recovery from severe traumatic brain injury. International journal of psychophysiology : official journal of the International Organization of Psychophysiology, 82, 115–123.

    Article  CAS  Google Scholar 

  • Iraji, A., Benson, R. R., Welch, R. D., O'Neil, B. J., Woodard, J. L., Ayaz, S. I., Kulek, A., Mika, V., Medado, P., Soltanian-Zadeh, H., Liu, T., Haacke, E. M., & Kou, Z. (2015). Resting state functional connectivity in mild traumatic brain injury at the acute stage: Independent component and seed-based analyses. Journal of Neurotrauma, 32, 1031–1045.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jagoda, A. S., Bazarian, J. J., Bruns, J. J., Jr., Cantrill, S. V., Gean, A. D., Howard, P. K., Ghajar, J., Riggio, S., Wright, D. W., Wears, R. L., Bakshy, A., Burgess, P., Wald, M. M., & Whitson, R. R. (2008). Clinical policy: Neuroimaging and decisionmaking in adult mild traumatic brain injury in the acute setting. Annals of Emergency Medicine, 52, 714–748.

    Article  PubMed  Google Scholar 

  • Jamora, C. W., Young, A., & Ruff, R. M. (2012). Comparison of subjective cognitive complaints with neuropsychological tests in individuals with mild vs more severe traumatic brain injuries. Brain Injury, 26, 36–47.

    Article  PubMed  Google Scholar 

  • Jarrett, M., Tam, R., Hernandez-Torres, E., Martin, N., Perera, W., Zhao, Y., Shahinfard, E., Dadachanji, S., Taunton, J., Li, D. K., & Rauscher, A. (2016). A prospective pilot investigation of brain volume, white matter Hyperintensities, and hemorrhagic lesions after mild traumatic brain injury. Frontiers in Neurology, 7, 11.

    Article  PubMed  PubMed Central  Google Scholar 

  • Killgore, W. D. S., Singh, P., Kipman, M., Pisner, D., Fridman, A., & Weber, M. (2016). Gray matter volume and executive functioning correlate with time since injury following mild traumatic brain injury. Neuroscience Letters, 612, 238–244.

    Article  CAS  PubMed  Google Scholar 

  • Kou, Z., Wu, Z., Tong, K. A., Holshouser, B., Benson, R. R., Hu, J., & Haacke, E. M. (2010). The role of advanced MR imaging findings as biomarkers of traumatic brain injury. The Journal of Head Trauma Rehabilitation, 25, 267–282.

    Article  PubMed  Google Scholar 

  • Lamm, C., Decety, J., & Singer, T. (2011). Meta-analytic evidence for common and distinct neural networks associated with directly experienced pain and empathy for pain. NeuroImage, 54, 2492–2502.

    Article  PubMed  Google Scholar 

  • Lange, R. T., Brickell, T. A., French, L. M., Merritt, V. C., Bhagwat, A., Pancholi, S., & Iverson, G. L. (2012). Neuropsychological outcome from uncomplicated mild, complicated mild, and moderate traumatic brain injury in US military personnel. Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists, 27, 480–494.

    Article  Google Scholar 

  • Ledberg, A., Akerman, S., & Roland, P. E. (1998). Estimation of the probabilities of 3D clusters in functional brain images. NeuroImage, 8, 113–128.

    Article  CAS  PubMed  Google Scholar 

  • Len, T. K., & Neary, J. P. (2011). Cerebrovascular pathophysiology following mild traumatic brain injury. Clinical Physiology and Functional Imaging, 31, 85–93.

    CAS  PubMed  Google Scholar 

  • Lipton, M. L., Gulko, E., Zimmerman, M. E., Friedman, B. W., Kim, M., Gellella, E., Gold, T., Shifteh, K., Ardekani, B. A., & Branch, C. A. (2009). Diffusion-tensor imaging implicates prefrontal axonal injury in executive function impairment following very mild traumatic brain injury. Radiology, 252, 816–824.

    Article  PubMed  Google Scholar 

  • List, J., Ott, S., Bukowski, M., Lindenberg, R., & Floel, A. (2015). Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults. Frontiers in Human Neuroscience, 9, 228.

    Article  PubMed  PubMed Central  Google Scholar 

  • Livny, A., Biegon, A., Kushnir, T., Harnof, S., Hoffmann, C., Fruchter, E., & Weiser, M. (2017). Cognitive deficits post-traumatic brain injury and their association with injury severity and gray matter volumes. Journal of Neurotrauma, 34, 1466–1472.

    Article  PubMed  Google Scholar 

  • Lu, L., Wei, X., Li, M., Li, Y., & Li, W. (2014). Emerging MRI and metabolic neuroimaging techniques in mild traumatic brain injury. Neurology India, 62, 487–491.

    Article  PubMed  Google Scholar 

  • Marquez de la Plata, C. D., Garces, J., Shokri Kojori, E., Grinnan, J., Krishnan, K., Pidikiti, R., Spence, J., Devous, M. D., Sr., Moore, C., McColl, R., Madden, C., & Diaz-Arrastia, R. (2011). Deficits in functional connectivity of hippocampal and frontal lobe circuits after traumatic axonal injury. Archives of Neurology, 68, 74–84.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mayer, A. R., Hanlon, F. M., & Ling, J. M. (2015). Gray matter abnormalities in pediatric mild traumatic brain injury. Journal of Neurotrauma, 32, 723–730.

    Article  PubMed  Google Scholar 

  • McCrory, P., Meeuwisse, W., Aubry, M., Cantu, B., Dvorak, J., Echemendia, R., Engebretsen, L., Johnston, K., Kutcher, J., Raftery, M., Sills, A., Benson, B., Davis, G., Ellenbogen, R., Guskiewicz, K., Herring, S. A., Iverson, G., Jordan, B., Kissick, J., McCrea, M., McIntosh, A., Maddocks, D., Makdissi, M., Purcell, L., Putukian, M., Schneider, K., Tator, C., & Turner, M. (2013). Consensus statement on concussion in sport - the 4th international conference on concussion in sport held in Zurich, November 2012. Physical therapy in sport : official journal of the Association of Chartered Physiotherapists in Sports Medicine, 14, e1–e13.

    Article  Google Scholar 

  • Menon, V., & Uddin, L. Q. (2010). Saliency, switching, attention and control: A network model of insula function. Brain Structure & Function, 214, 655–667.

    Article  Google Scholar 

  • Metting, Z., Rodiger, L. A., De Keyser, J., & van der Naalt, J. (2007). Structural and functional neuroimaging in mild-to-moderate head injury. The Lancet. Neurology, 6, 699–710.

    Article  PubMed  Google Scholar 

  • Narayana, P. A., Yu, X., Hasan, K. M., Wilde, E. A., Levin, H. S., Hunter, J. V., Miller, E. R., Patel, V. K., Robertson, C. S., & McCarthy, J. J. (2015). Multi-modal MRI of mild traumatic brain injury. NeuroImage. Clinical, 7, 87–97.

    Article  PubMed  Google Scholar 

  • Nasreddine, Z. S., Phillips, N. A., Bedirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J. L., & Chertkow, H. (2005). The Montreal cognitive assessment, MoCA: A brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society, 53, 695–699.

    Article  PubMed  Google Scholar 

  • Piras, F., Piras, F., Chiapponi, C., Girardi, P., Caltagirone, C., & Spalletta, G. (2015). Widespread structural brain changes in OCD: A systematic review of voxel-based morphometry studies. Cortex; a journal devoted to the study of the nervous system and behavior, 62, 89–108.

    Article  PubMed  Google Scholar 

  • Rigg, J. L., & Mooney, S. R. (2011). Concussions and the military: Issues specific to service members. PM & R : The Journal of Injury, Function, and Rehabilitation, 3, 380–386.

    Article  Google Scholar 

  • Rutland-Brown, W., Langlois, J. A., Thomas, K. E., & Xi, Y. L. (2006). Incidence of traumatic brain injury in the United States, 2003. The Journal of Head Trauma Rehabilitation, 21, 544–548.

    Article  PubMed  Google Scholar 

  • Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., & Greicius, M. D. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of neuroscience : the official journal of the Society for Neuroscience, 27, 2349–2356.

    Article  CAS  Google Scholar 

  • Shumskaya, E., Andriessen, T. M., Norris, D. G., & Vos, P. E. (2012). Abnormal whole-brain functional networks in homogeneous acute mild traumatic brain injury. Neurology, 79, 175–182.

    Article  PubMed  Google Scholar 

  • Slobounov, S. M., Zhang, K., Pennell, D., Ray, W., Johnson, B., & Sebastianelli, W. (2010). Functional abnormalities in normally appearing athletes following mild traumatic brain injury: A functional MRI study. Experimental Brain Research, 202, 341–354.

    Article  PubMed  Google Scholar 

  • Sours, C., Zhuo, J., Janowich, J., Aarabi, B., Shanmuganathan, K., & Gullapalli, R. P. (2013). Default mode network interference in mild traumatic brain injury - a pilot resting state study. Brain Research, 1537, 201–215.

    Article  CAS  PubMed  Google Scholar 

  • Stam, C. J. (2014). Modern network science of neurological disorders. Nature Reviews. Neuroscience, 15, 683–695.

    Article  CAS  PubMed  Google Scholar 

  • Stevens, M. C., Lovejoy, D., Kim, J., Oakes, H., Kureshi, I., & Witt, S. T. (2012). Multiple resting state network functional connectivity abnormalities in mild traumatic brain injury. Brain Imaging and Behavior, 6, 293–318.

    Article  PubMed  Google Scholar 

  • Tops, M., & Boksem, M. A. (2011). A potential role of the inferior frontal gyrus and anterior insula in cognitive control, brain rhythms, and event-related potentials. Frontiers in Psychology, 2, 330.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tu, Y., Yu, T., Wei, Y., Sun, K., Zhao, W., & Yu, B. (2016). Structural brain alterations in hemifacial spasm: A voxel-based morphometry and diffusion tensor imaging study. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 127, 1470–1474.

    Article  Google Scholar 

  • Uddin, L. Q., Kinnison, J., Pessoa, L., & Anderson, M. L. (2014). Beyond the tripartite cognition-emotion-interoception model of the human insular cortex. Journal of Cognitive Neuroscience, 26, 16–27.

    Article  PubMed  Google Scholar 

  • Vakhtin, A. A., Calhoun, V. D., Jung, R. E., Prestopnik, J. L., Taylor, P. A., & Ford, C. C. (2013). Changes in intrinsic functional brain networks following blast-induced mild traumatic brain injury. Brain Injury, 27, 1304–1310.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou, Y., Milham, M. P., Lui, Y. W., Miles, L., Reaume, J., Sodickson, D. K., Grossman, R. I., & Ge, Y. (2012). Default-mode network disruption in mild traumatic brain injury. Radiology, 265, 882–892.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou, Y., Kierans, A., Kenul, D., Ge, Y., Rath, J., Reaume, J., Grossman, R. I., & Lui, Y. W. (2013). Mild traumatic brain injury: Longitudinal regional brain volume changes. Radiology, 267, 880–890.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhu, D. C., Covassin, T., Nogle, S., Doyle, S., Russell, D., Pearson, R. L., Monroe, J., Liszewski, C. M., DeMarco, J. K., & Kaufman, D. I. (2015). A potential biomarker in sports-related concussion: Brain functional connectivity alteration of the default-mode network measured with longitudinal resting-state fMRI over thirty days. Journal of Neurotrauma, 32, 327–341.

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (No.81870563), Jiangsu Provincial Special Program of Medical Science (BE2017614), Youth Medical Talents of Jiangsu Province (No. QNRC2016062), 14th “Six Talent Peaks” Project of Jiangsu Province (No. YY-079), and the Nanjing Medical University grant (No. 2017NJMU123).

Author information

Author notes

  1. Fengfang Li and Liyan Lu contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Nanjing First Hospital, Nanjing Medical University, No.68, Changle Road, Nanjing, 210006, China

    Fengfang Li, Liyan Lu, Huiyou Chen, Peng Wang, Yu-Chen Chen & Xindao Yin

  2. Department of Radiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China

    Hong Zhang

Authors
  1. Fengfang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liyan Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huiyou Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu-Chen Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xindao Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yu-Chen Chen or Xindao Yin.

Ethics declarations

Conflict of interests

The authors declare that there is no potential conflict of interests regarding the publication of this paper.

Ethical approval

The current study was approved by the Research Ethics Committee of the Nanjing Medical University.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, F., Lu, L., Chen, H. et al. Neuroanatomical and functional alterations of insula in mild traumatic brain injury patients at the acute stage. Brain Imaging and Behavior 14, 907–916 (2020). https://doi.org/10.1007/s11682-019-00053-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-019-00053-3

Keywords

Search

Navigation