Brain Imaging and Behavior

, Volume 12, Issue 1, pp 296–302 | Cite as

Decoupling between the hand territory and the default mode network after bilateral arm transplantation: four-year follow-up case study

  • Carlos R. Hernandez-Castillo
  • Jörn Diedrichsen
  • Erika Aguilar-Castañeda
  • Martin Iglesias
Case Study


Several studies have suggested both a local and network reorganization of the sensorimotor system following amputation. Transplantation of a new limb results in a new shifting of cortical activity in the local territory of the transplanted limb. However, there is a lack of information about the reversibility of the abnormalities at the network level. The objective of this study was to characterize the functional connectivity changes between the cortical territory of the new hand and two intrinsic network of interest: the sensorimotor network (SMN) and the default mode network (DMN) of one patient whom received bilateral forearm transplants. Using resting-state fMRI these two networks were identified across four different time points, starting four months after the transplantation surgery and during three consecutive years while the patient underwent physical rehabilitation. The topology of the SMN was disrupted at the first acquisition and over the years returned to its canonical pattern. Analysis of the DMN showed the normal topology with no significant changes across acquisitions. Functional connectivity between the missing hand’s cortical territory and the SMN increased over time. Accordingly, functional connectivity between the missing hand’s cortical territory and the DMN became anticorrelated over time. Our results suggest that after transplantation a new reorganization occurs at the network level, supporting the idea that extreme behavioral changes can affect not only the local rewiring but also the intrinsic network organization in neurologically healthy subjects. Overall this study provides new insight on the complex dynamics of brain organization.


Resting state Motor network Transplantation Hand Default mode network 


Compliance with ethical standards


This study was funded by Consejo Nacional De Ciencia y Tecnologia (3157 to CRHC).

Conflict of interest

The Authors declare they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Instituto Nacional de Neurología y Neurocirugía in Mexico City and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

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


  1. Barnes, S. J., & Finnerty, G. T. (2010). Sensory experience and cortical rewiring. The Neuroscientist: A Review Journal Bringing Neurobiology, Neurology and Psychiatry, 16(2), 186–198. doi: 10.1177/1073858409343961.CrossRefGoogle Scholar
  2. Beaton, D. E., Katz, J. N., Fossel, A. H., Wright, J. G., Tarasuk, V., & Bombardier, C. (2001). Measuring the whole or the parts? Validity, reliability, and responsiveness of the disabilities of the arm, shoulder and hand outcome measure in different regions of the upper extremity. Journal of Hand Therapy : Official Journal of the American Society of Hand Therapists, 14(2), 128–146. doi: 10.1016/S0894-1130(01)80043-0.CrossRefGoogle Scholar
  3. Beckmann, C. F., DeLuca, M., Devlin, J. T., & Smith, S. M. (2005). Investigations into resting-state connectivity using independent component analysis. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 360(1457), 1001–1013. doi: 10.1098/rstb.2005.1634.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Biswal, B., Zerrin Yetkin, F., Haughton, V. M., & Hyde, J. S. (1995). Functional connectivity in the motor cortex of resting human brain using echo-planar mri. Magnetic Resonance in Medicine, 34(4), 537–541. doi: 10.1002/mrm.1910340409.CrossRefPubMedGoogle Scholar
  5. Brenneis, C., Löscher, W. N., Egger, K. E., Benke, T., Schocke, M., Gabl, M. F., et al. (2005). Cortical motor activation patterns following hand transplantation and replantation. Journal of Hand Surgery, 30(5), 530–533. doi: 10.1016/j.jhsb.2005.05.012.CrossRefGoogle Scholar
  6. Chou, Y. H., Panych, L. P., Dickey, C. C., Petrella, J. R., & Chen, N. K. (2012). Investigation of long-term reproducibility of intrinsic connectivity network mapping: a resting-state fMRI study. American Journal of Neuroradiology, 33(5), 833–838.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Damoiseaux, J. S., Rombouts, S. A. R. B., Barkhof, F., Scheltens, P., Stam, C. J., Smith, S. M., & Beckmann, C. F. (2006). Consistent resting-state networks across healthy subjects. Proceedings of the National Academy of Sciences of the United States of America, 103(37), 13848–13853. doi: 10.1073/pnas.0601417103.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Ejaz, N., Hamada, M., & Diedrichsen, J. (2015). Hand use predicts the structure of representations in sensorimotor cortex. Nature Neuroscience, 18(7), 1034–1040.CrossRefPubMedGoogle Scholar
  9. Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences of the United States of America, 102(27), 9673–9678. doi: 10.1073/pnas.0504136102.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Fox, M. D., Corbetta, M., Snyder, A. Z., Vincent, J. L., & Raichle, M. E. (2006). Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. Proceedings of the National Academy of Sciences of the United States of America, 103(26), 10046–10051. doi: 10.1073/pnas.0604187103.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Gagné, M., Hétu, S., Reilly, K. T., & Mercier, C. (2011). The map is not the territory: motor system reorganization in upper limb amputees. Human Brain Mapping, 32(4), 509–519.CrossRefPubMedGoogle Scholar
  12. Giraux, P., Sirigu, A., Schneider, F., & Dubernard, J. M. (2001). Cortical reorganization in motor cortex after graft of both hands. Nature Neuroscience, 4(7), 691–692.CrossRefPubMedGoogle Scholar
  13. Guo, C. C., Kurth, F., Zhou, J., Mayer, E. A., Eickhoff, S. B., Kramer, J. H., & Seeley, W. W. (2012). One-year test–retest reliability of intrinsic connectivity network fMRI in older adults. NeuroImage, 61(4), 1471–1483.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Hernandez-Castillo, C. R., Alcauter, S., Galvez, V., Barrios, F. A., Yescas, P., Ochoa, A., et al. (2013). Disruption of visual and motor connectivity in spinocerebellar ataxia type 7. Movement Disorders, 28(12), 1708–1716. doi: 10.1002/mds.25618.CrossRefPubMedGoogle Scholar
  15. Hernandez-Castillo, C. R., Galvez, V., Mercadillo, R. E., Díaz, R., Yescas, P., Martinez, L., et al. (2015). Functional connectivity changes related to cognitive and motor performance in spinocerebellar ataxia type 2. Movement Disorders, 30(10), 1391–1399. doi: 10.1002/mds.26320.CrossRefPubMedGoogle Scholar
  16. Hernandez-Castillo, C. R., Aguilar-Castañeda, E., Iglesias, M., & Fernandez-Ruiz, J. (2016). Motor and sensory cortical reorganization after bilateral forearm transplantation: four-year follow up fMRI case study. Magnetic Resonance Imaging. doi: 10.1016/j.mri.2015.12.025.PubMedGoogle Scholar
  17. Iglesias, M., Butron, P., Moran-Romero, M., Cruz-Reyes, A., Alberu-Gomez, J., Leal-Villalpando, P., et al. (2016). Bilateral forearm transplantation in Mexico: 2-year outcomes. Transplantation, 100(1), 233–238.CrossRefPubMedGoogle Scholar
  18. Jenkinson, M., Bannister, P., Brady, M., & Smith, S. (2002). Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage, 17(2), 825–841. doi: 10.1006/nimg.2002.1132.CrossRefPubMedGoogle Scholar
  19. Makin, T. R., Cramer, A. O., Scholz, J., Hahamy, A., Slater, D. H., Tracey, I., & Johansen-Berg, H. (2013). Deprivation-related and use-dependent plasticity go hand in hand. eLife, 2, e01273.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Makin, T. R., Filippini, N., Duff, E. P., Henderson Slater, D., Tracey, I., & Johansen-Berg, H. (2015). Network-level reorganisation of functional connectivity following arm amputation. NeuroImage, 114, 217–225. doi: 10.1016/j.neuroimage.2015.02.067.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage, 59(3), 2142–2154. doi: 10.1016/j.neuroimage.2011.10.018.CrossRefPubMedGoogle Scholar
  22. Qi, H.-X., Stepniewska, I., & Kaas, J. H. (2000). Reorganization of primary motor cortex in adult macaque monkeys with long-standing amputations. Journal of Neurophysiology, 84, 2133–2147. doi: 10.1016/j.neubiorev.2010.08.008.CrossRefPubMedGoogle Scholar
  23. Röricht, S., Meyer, B. U., Niehaus, L., & Brandt, S. A. (1999). Long-term reorganization of motor cortex outputs after arm amputation. Neurology, 53(1), 106–106.CrossRefPubMedGoogle Scholar
  24. Seeley, W. W., Crawford, R. K., Zhou, J., Miller, B. L., & Greicius, M. D. (2009). Neurodegenerative diseases target large-scale human brain networks. Neuron, 62(1), 42–52. doi: 10.1016/j.neuron.2009.03.024.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Wu, C. W. H., & Kaas, J. H. (1999). Reorganization in primary motor cortex of primates with long-standing therapeutic amputations. The Journal of Neuroscience, 19(17), 7679–7697.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Carlos R. Hernandez-Castillo
    • 1
    • 2
  • Jörn Diedrichsen
    • 2
  • Erika Aguilar-Castañeda
    • 3
  • Martin Iglesias
    • 4
  1. 1.CONACYT – Instituto de NeuroetologiaUniversidad VeracruzanaXalapaMexico
  2. 2.The Brain and Mind InstituteWestern UniversityLondonCanada
  3. 3.Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suarez”Ciudad de MéxicoMexico
  4. 4.Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”Ciudad de MéxicoMexico

Personalised recommendations