Skip to main content
Log in

Functional connectivity in disorders of consciousness: methodological aspects and clinical relevance

  • Review Article
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

This is a Quick Guide about the role of the functional connectivity in the Disorders of Consciousness (DOC). Recent studies on resting state (RS) in DOC, by using functional magnetic resonance imaging (fMRI), showed that functional connectivity is severely impaired above all in the default mode network (DMN). In the vegetative and minimally conscious state, DMN integrity seems to correlate with the level of remaining consciousness, offering the possibility of using this information for diagnostic and prognostic purposes. Although the two principal approaches used in the RS analysis showed several methodological difficulties, especially in DOC patients, functional brain imaging is currently being validated as a valuable addition to the standardized clinical assessments that are already in use.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Achard, S., Delon-Martin, C., Vértes, P. E., Renard, F., Schenck, M., Schneider, F., et al. (2012). Hubs of brain functional networks are radically reorganized in comatose patients. Proceedings of the National Academy of Sciences of the United States of America, 109(50), 20608–20613. doi:10.1073/pnas.1208933109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amico, E., Gomez, F., Di Perri, C., Vanhaudenhuyse, A., Lesenfants, D., Boveroux, P., et al. (2014). Posterior cingulate cortex-related co-activation patterns: a resting state FMRI study in propofol-induced loss of consciousness. PloS One, 9(6):e100012. doi:10.1371/journal.pone.0100012.

    Article  PubMed  PubMed Central  Google Scholar 

  • Andronache, A., Rosazza, C., Sattin, D., Leonardi, M., D’Incerti, L., & Minati, L. (2013). Coma Research Centre (CRC) – Besta Institute. Impact of functional MRI data preprocessing pipeline on default-mode network detectability in patients with disorders of consciousness. Front Neuroinform, 7–16. doi:10.3389/fninf.2013.00016.

  • Boly, M., Tshibanda, L., Vanhaudenhuyse, A., Noirhomme, Q., Schnakers, C., Ledoux, D., et al. (2009). Functional connectivity in the sefault network during resting state is preserved in a vegetative but not in a brain dead patient. Human Brain Mapping, 30(8), 2393–2400. doi:10.1002/hbm.20672.

    Article  CAS  PubMed  Google Scholar 

  • Bodart, O., Laureys, S., & Gosseries, O. (2013). Coma and disorders of consciousness: scientific advances and practical considerations for clinicians. Seminars in Neurology, 33(2):83–90. doi: 10.1055/s-0033–1348965.

  • Cauda, F., Micon. B. M., Sacco, K., Duca, S., D’Agata, F., Geminiani, G. et al. (2009). Disrupted intrinsic functional connectivity in the vegetative state. Journal of Neurology, Neurosurgery, and Psychiatry, 80:429–431 doi:10.1136/jnnp.2007.142349.

  • Crone, J. S., Ladurner, G., Höller, Y., Golaszewski, S., Trinka, E., & Kronbichler M. (2011). Deactivation of the default mode network as a marker of impaired consciouness: an fMRI study. PloS One, 6(10): e26373. doi: 10.1371/journal.pone.0026373.

  • Crone, J. S., Soddu, A., Höller, Y., Vanhaudenhuyse, A., Schurz, M., Bergmann, J., et al. (2014). Altered network properties of the fronto-parietal network and the thalamus in impaired consciousness. Neuroimage Clinical, 4, 240–248.

    Article  PubMed  Google Scholar 

  • De Salvo, S., Bramanti, P., & Marino, S. (2012). Clinical differentiation and outcome evaluation in vegetative and minimally conscious state patients: the neurophysiological approach. Functional Neurology, 27(3), 155–162.

    PubMed  Google Scholar 

  • Demertzi, A., Gómez, F., Crone, J. S., Vanhaudenhuyse, A., Tshibanda, L., Noirhomme, Q., et al. (2014). Multiple fMRI system-level baseline connectivity is disrupted in patients with consciousness alterations. Cortex, 52, 35–46. doi:10.1016/j.cortex.2013.11.005.

    Article  PubMed  Google Scholar 

  • Demertzi, A., Vanhaudenhuyse, A., Bredart, S., Heine, L., Di Perri, C., & Laureys, S. (2013). Looking for the self in pathological unconsciousness. Frontiers in Human Neuroscience, 7, 538.

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Perri, C., Bastianello, S., Bartsch, A. J., Pistarini, C., Maggioni, G., Magrassi, L., et al. (2013). Limbic hyperconnectivity in the vegetative state. Neurology, 81(16), 1417–1424. doi:10.1212/WNL.0b013e3182a43b78.

    Article  PubMed  Google Scholar 

  • Di Perri, C., Stender, J., Laureys, S., & Gosseries, O. (2014). Functional neuroanatomy of disorders of consciousness. Epilepsy & Behavior, 30, 28–32. doi:10.1016/j.yebeh.2013.09.014.

    Article  Google Scholar 

  • Filippini, N., Macintosh, B. J., Hough, M. G., Goodwin, G. M., Frisoni, G. B., Smith, S. M., et al. (2009). Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proceedings of the National Academy of Sciences of the United States of America, 106(17), 7209–7214. doi:10.1073/pnas.0811879106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fingelkurts, A. A., Fingelkurts, A. A., Bagnato, S., Boccagni, C., & Galardi, G. (2012). DMN operational synchrony relates to self-consciousness: evidence from patients in vegetative and minimally conscious states. Open Neuroimaging Journal, 6, 55–68. doi:10.2174/1874440001206010055.

    Article  PubMed  PubMed Central  Google Scholar 

  • Golland, Y., Golland, P., Bentin, S., & Malach, R. (2008). Data-driven clustering reveals a fundamental subdivision of the human cortex into two global systems. Neuropsychologia, 46, 540–553.

    Article  PubMed  Google Scholar 

  • Hannawi, Y., Lindquist, M. A., Caffo, B. S., Sair, H. I., & Stevens, R. D. (2015). Resting brain activity in disorders of consciousness: a systematic review and meta-analysis. Neurology, 84(12), 1272–1280.

    Article  PubMed  PubMed Central  Google Scholar 

  • He, J. H., Yang, Y., Zhang, Y., Qiu, S. Y., Zhou, Z. Y., Dang, Y. Y., et al. (2014). Hyperactive external awareness against hypoactive internal awareness in disorders of consciousness using resting-state functional MRI: highlighting the involvement of visuo-motor modulation. NMR in Biomedicine, 27, 880–886.

    Article  PubMed  Google Scholar 

  • Heine, L., Soddu, A., Gómez, F., Vanhaudenhuyse, A., Tshibanda, L., Thonnard, M., et al. (2012). Resting state networks and consciousness: alterations of multiple resting state network connectivity in physiological, pharmacological, and pathological consciousness states. Frontiers in Psychology, 27(3), 295. doi:10.3389/fpsyg.2012.00295.

    Google Scholar 

  • Höller, Y., Thomschewski, A., Bergmann, J., Kronbichler, M., Crone, J.S., & Schmid, E.V., et al, (2014). Connectivity biomarkers can differentiate patients with different levels of consciousness. Clinical Neurophysiology, 125(8):1545–1555. doi: 10.1016/j.clinph.2013.12.095.

  • Kotchoubey, B., Merz, S., Lang, S., Markl, A., Müller, F., Yu T., & Schwarzbauer, C. (2013). Global functional connectivity reveals highly significant differences between the vegetative and the minimally conscious state. Journal of Neurology, 260(4), 975–983. doi:10.1007/s00415-012-6734-9.

    Article  PubMed  Google Scholar 

  • Laureys, S., & Schiff, N. D. (2012). Coma and consciousness: paradigms (re)framed by neuroimaging. NeuroImage, 61(2), 478–491. doi:10.1016/j.neuroimage.2011.12.041.

    Article  PubMed  Google Scholar 

  • Laureys, S., Perrin, F., & Bredart, S. (2007). Self-consciousness in non-communicative patients. Consciousness and Cognition, 16, 722–741.

    Article  PubMed  Google Scholar 

  • Mäki-Marttunen, V., Diez, I., Cortes, J. M., Chialvo, D. R., & Villarreal, M. (2013). Disruption of transfer entropy and inter-hemispheric brain functional connectivity in patients with disorder of consciousness. Frontiers in Neuroinformatics, 24(7), 1–11.

    Google Scholar 

  • Margulies, D. S., Kelly, A. M. C., Uddin, L. Q., Biswal, B. B., Castellanos, F. X., & Milham, M. P. (2007). Mapping the functional connectivity of anterior cingulate cortex. NeuroImage, 37(2), 579–588.

    Article  PubMed  Google Scholar 

  • Marino, S., & Bramanti, P. (2009). Neurofunctional imaging in differential diagnosis and evaluation of outcome in vegetative and minimally conscious state. Functional Neurology, 24(4), 185–188.

    PubMed  Google Scholar 

  • Murphy, K., Birn, R. M., Handwerker, D. A., Jones, T. B., & Bandettini, P. A. (2009). The impact of global signal regression on resting state correlations: are anti-correlated networks Introduced? NeuroImage, 44(3), 893–905.

    Article  PubMed  Google Scholar 

  • Ovadia-Caro, S., Nir, Y., Soddu, A, Hesselmann, G., Vanhaudenhuyse, A., Dinstein, I., et al. (2012). Reduction in inter-hemispheric connectivity in disorders of consciousness. PloS One, 7:e37238.

  • Riganello, F., Cortese, M.D., Dolce, G., Lucca, L.F., Sannita, W.G. (2015). The autonomic system functional state predicts responsiveness in DOC. J Neurotrauma. 2015. [Epub ahead of print].

  • Soddu, A., Vanhaudenhuyse, A., Demertzi, A., Bruno, M. A., Tshibanda, L., Di, H., et al. (2011). Resting state activity in patients with disorders of consciousness. Functional Neurology, 26(1), 37–43.

    PubMed  PubMed Central  Google Scholar 

  • Soddu, A., Vanhaudenhuyse, A., Bahri, M. A., Bruno, M. A., Boly, M., Demertzi, A., et al. (2012). Identifying the default-mode component in spatial IC analyses of patients with disorders of consciousness. Human Brain Mapping, 33(4), 778–796. doi:10.1002/hbm.21249.

    Article  PubMed  Google Scholar 

  • Vanhaudenhuyse, A., Noirhomme, Q., Tshibanda, L. J., Bruno, M. A., Boveroux, P., Schnakers, C., et al. (2010). Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain, 133(Pt1), 161–171. doi:10.1093/brain/awp313.

    Article  PubMed  Google Scholar 

  • Zhang, J., Li, X., Li, C., Lian, Z., Huang, X., Zhong, G., et al. (2014). Inferring functional interaction and transition patterns via dynamic Bayesian variable partition models. Human Brain Mapping, 35(7), 3314–3331.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

Silvia Marino, Lilla Bonanno, and Antonio Giorgio declare that they have no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Silvia Marino.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marino, S., Bonanno, L. & Giorgio, A. Functional connectivity in disorders of consciousness: methodological aspects and clinical relevance. Brain Imaging and Behavior 10, 604–608 (2016). https://doi.org/10.1007/s11682-015-9417-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-015-9417-1

Keywords

Navigation