Event Abstract Back to Event Tractometry and the hunt for the missing link: a physicist perspective Derek Jones1, 2* and Markus Nilsson3 1 Cardiff University, School of Psychology, United Kingdom 2 Cardiff University, Neuroscience and Mental Health Research Institute, United Kingdom 3 Lund University, Lund University Bioimaging Center, Sweden This article focuses attention on the pressing need to think carefully and deeply about the current state of the art in using measurements of tissue microstructure derived from MRI to explain individual differences in brain function, electrophysiology and or cognitive function. Although initial effort in the application of microstructural imaging was on voxel-based metrics derived from diffusion tensor magnetic resonance imaging (DT-MRI), such as fractional anisotropy (FA) and the mean diffusivity (MD), there is increasing realisation of the limitations of this approach both in terms of biological specificity and in terms of interpretability of any results that emerge. This has led to the development of alternative approaches that are (i) looking at topologies of networks derived from diffusion-MRI-based fibre-tracking approaches, (ii) adopting ‘advanced’ diffusion MRI metrics that go beyond the tensor model, or (iii) by looking at data from non-diffusion-based MRI contrasts, such as those based on magnetization transfer, multi-component relaxometry, or susceptibility-weighted imaging. With the increasing availability of methods to extract such metrics, and ease of access, it should be stressed that our application of such methods is outpacing our understanding of what aspect of biology the metrics are actually capturing. As such, there is a danger of operating in an unprincipled and unstructured fashion. This article argues that the ‘missing link’ is a non-invasive neuroimaging metric that is not only well understood, but which also can reasonably be expected to explain variance in brain function from a biological perspective, rather than a metric that is used purely as a matter of convenience. We begin, not in the brain, but by considering properties of the UK national rail network and ‘leaves on the line’, before moving on to a consideration of brain networks and network usage. This then leads to consideration of the current status of the search for the ‘Missing Link’, exploring current microstructural metrics and what they offer, and argues that even if we had ‘Quantitative, interpretable metrics’ of white matter microstructure (with the emphasis on ‘interpretable’) there is still a quantum leap to be made before we can reliably link structure to function. Acknowledgements The authors wish to thank Dr Mark Drakesmith, Cardiff University for helpful comments on the manuscript. DKJ is also grateful to the Wellcome Trust, United Kingdom, for supporting this work through an Investigator Award. References Aboitiz, F., Scheibel, A. B., Fisher, R. S., and Zaidel, E. (1992). Brain Res. 598, 154–161. Ajilore, O., Lamar, M., and Kumar, A. (2014). Am. J. Geriatr. Psychiatry 22, 102–110. Alexander, A. L., et al. (2011). Brain Connect. 1, 423–446. Alexander, D. C., et al. (2010). Neuroimage 52, 1374–1389. Anderson, R. E., and Jakobsson, J. G. (2004). Br. J. Anaesth. 92, 167–170. Arlotta, P. (2014). Science 344, 319–324. Assaf, Y., et al. (2013). Neuroimage 80, 273–282. Assaf, Y., et al. (2002). Magn. Reson. Med. 47, 115–126. Assaf, Y., Blumenfeld-Katzir, T., Yovel, Y., and Basser, P. J. (2008). Magn. Reson. Med. 59, 1347–1354. Assaf, Y., Freidlin, R. Z., Rohde, G. K., and Basser, P. J. (2004). Magn. Reson. Med. 52, 965–978. Baker, G. E., and Stryker, M. P. (1990). Nature 344, 342–345. Basser, P. J., and Pierpaoli, C. (1996). J. Magn. Reson. B 111, 209–219. Beaulieu, C. (2002). NMR Biomed. 15, 435–455. Behrens, T. E., and Sporns, O. (2012). Curr. Opin. Neurobiol. 22, 144–153. Bells, S., et al. (2011). Proceedings of ISMRM 19th Annual Meeting, Montreal, QC. Biswal, B., Yetkin, F. Z., Haughton, V. M., and Hyde, J. S. (1995). Magn. Reson. Med. 34, 537–541. Bracht, T., Doidge, A. N., Keedwell, P. A., and Jones, D. K. (2015). Psychol. Med. 45, 865–874. Broser, P. J., Groeschel, S., Hauser, T. K., Lidzba, K., and Wilke, M. (2012). Neuroimage 63, 1561–1570. Bullmore, E., and Sporns, O. (2009). Nat. Rev. Neurosci. 10, 186–198. []erratum in: Nature Reviews Neuroscience 10, 312], Campbell, J. S. W., Stikov, N., Dougherty, R. F., and Pike, G. B. (2014). Proceedings of the ISMRM 22nd Annual Meeting, Milan. Chen, Z. J., He, Y., Rosa-Neto, P., Germann, J., and Evans, A. C. (2008). Cereb. Cortex 18, 2374–2381. Cohen, Y., and Assaf, Y. (2002). NMR Biomed. 15, 516–542. De Santis, S., Drakesmith, M., Bells, S., Assaf, Y., and Jones, D. K. (2014). Neuroimage 89, 35–44. Deoni, S. C., Rutt, B. K., Arun, T., Pierpaoli, C., and Jones, D. K. (2008). Magn. Reson. Med. 60, 1372–1387. Drakesmith, M., et al (2014). Proceedings of the ISMRM (Milan), 279. Dyrby, T. B., Søgaard, L. V., Hall, M. G., Ptito, M., and Alexander, D. C. (2012). Magn. Reson. Med. 70, 711–721. Fanelli, D. (2010). PLoS ONE 5:e10068. Ferizi, U., et al. (2014). Magn. Reson. Med. 72, 1785–1792. Fields, R. D. (2008). Trends Neurosci. 7, 361–370. Francis, G. (2014). Psychon. Bull. Rev. 21, 1180–1187. Friston, K. (2011). Brain Connect. 1, 13–36. Griffa, A., Baumann, P. S., Thiran, J. P., and Hagmann, P. (2013). Neuroimage 80, 515–526. Haacke, E. M., Liu, S., Buch, S., Zheng, W., Wu, D., and Ye, Y. (2015). Magn. Reson. Imaging 33, 1–25. Hagmann, P., et al. (2008). PLoS Biol. 6:e159. He, Y., Chen, Z. J., and Evans, A. C. (2007). Cereb. Cortex 17, 2407–2419. Hecht, E. E., et al (2013). Cereb. Cortex 23, 1014–1024. Henkelman, R. M., et al (1993). Magn. Reson. Med. 29, 759–766. Henkelman, R. M., Stanisz, G. J., and Graham, S. J. (2001). NMR Biomed. 14, 57–64. Hess, A., and Young, J. Z. (1952). Philos. Trans. R. Soc. Lond. B Biol. Sci. 140, 301–320. Horowitz, A., Barazany, D., Tavor, I., Bernstein, M., Yovel, G., and Assaf, Y. (2014). Brain Struct. Funct. Huang, S. Y., et al. (2015). Neuroimage 106, 464–472. Hursh, J. B. (1939). Am. J. Physiol. 127, 131–139. Ioannidis, J. P. (2011). Arch. Gen. Psychiatry 68, 773–780. Iturria-Medina, Y., et al. (2007). Neuroimage 36, 645–660. Jensen, J. H., and Helpern, J. A. (2010). NMR Biomed. 23, 698–710. Johansen-Berg, H. (2010). Curr. Opin. Neurol. 23, 351–358. Jones, D. K. (2008). Cortex 44, 936–952. Jones, D. K. (2010). Imaging Med. 2, 341–355. Jones, D. K., et al. (2005a). Am. J. Geriatr. Psychiatry 13, 1092–1099. Jones, D. K., Catani, M., Pierpaoli, C., Reeves, S. J., Shergill, S. S., O’Sullivan, M., et al. (2005b). Hum. Brain Mapp. 273, 230–238. Jones, D. K., and Cercignani, M. (2010). NMR Biomed. 23, 803–820. Jones, D. K., Horsfield, M. A., and Simmons, A. (1999). Magn. Reson. Med. 42, 515–525. Jones, D. K., Knoesche, T., and Turner, R. (2013). Neuroimage 73, 239–254. Jones, D. K., and Leemans, A. (2011). Methods Mol. Biol. 71, 127–144. Kaiser, M. A. (2011). Neuroimage 57, 892–907. Kanaan, R. A., Shergill, S. S., Barker, G. J., Catani, M., Ng, V. W., Howard, R., et al. (2006). Psychiatry Res. 146, 73–82. Kanai, R., and Rees, G. (2011). Nat. Rev. Neurosci. 231–242. Keedwell, P. A., Chapman, R., Christiansen, K., and Jones, D. K. (2012). Biol. Psychiatry 72, 296–302. King, M. D., et al (1994). Magn. Reson. Med. 32, 707–713. Langer, N., Pedroni, A., and Jäncke, L. (2013). PLoS ONE 8:e53199. Lasič, S., Nilsson, M., Lätt, J., Ståhlberg, F., and Topgaard, D. (2011). Magn. Reson. Med. 66, 356–365. Laule, C., Vavasour, I. M., et al. (2007). Neurotherapeutics 4, 460–484. Leemans, A., Jeurissen, B., Sijbers, J., and Jones, D. K. (2009). Proceedings ISMRM 17th Annual Meeting (Honolulu), 3536. Liu, C., Li, W., Tong, K. A., Yeom, K. W., and Kuzminski, S. (2014). J. Magn. Reson. Imaging. MacKay, A., Whittall, K., Adler, J., Li, D., Paty, D., and Graeb, D. (1994). Magn. Reson. Med. 6, 673–677. McNab, J. A., Edlow, B. L., Witzel, T., Huang, S. Y., Bhat, H., Heberlein, K., et al. (2014). Med. Image Comput. Comput. Assist. Interv. 17, 268–275. Nilsson, M., Lätt, J., Ståhlberg, F., van Westen, D., and Hagslätt, H. (2012). NMR Biomed. 25, 795–805. Nilsson, M., van Westen, D., Ståhlberg, F., Sundgren, P. C., and Lätt, J. (2013a). MAGMA 26, 345–370. Nilsson, M., Lätt, J., van Westen, D., Brockstedt, S., Lasič, S., Ståhlberg, F., et al. (2013b). Magn. Reson. Med. 69, 1573–1581. Pajevic, S., Basser, P. J., and Fields, R. D. (2014). Neuroscience 276, 135–147. Parker, G. J., et al (2005). Neuroimage 24, 656–666. Perge, J. A., Koch, K., Miller, R., Sterling, P., and Balsubramanian, V. (2009). J. Neurosci. 29, 7917–7928. Petrella, J. R. (2011). Radiology 259, 317–320. Pierpaoli, C., and Basser, P. J. (1996). Magn. Reson. Med. 36, 893–906. [Erratum in: Magnetic Resonance in Medicine 37, 972], Pierpaoli, C., Jezzard, P., Basser, P. J., Barnett, A., and Di Chiro, G. (1996). Radiology 201, 637–648. Postans, M., Hodgetts, C., Mundy, M., Jones, D. K., Lawrence, A., and Graham, K. S. (2014). J. Neurosci. Qi, H., Wan, B., and Zhao, L. (2004). Computer and Information Technology (IEEE Computer Society), 885–889. Ramani, A., Dalton, C., Miller, D. H., Tofts, P. S., and Barker, G. J. (2002). Magn. Reson. Imaging 20, 721–731. Roberts, R. E., Anderson, E. J., and Husain, M. (2013a). Neuroscientist. 19, 8–15. Roberts, R. E., Bain, P. G., Day, B. L., and Husain, M. (2013b). Cereb. Cortex 23, 2282–2292. Rushton, W. A. H. (1951). J. Physiol. 115, 101–122. Schoffelen, J.-M., and Gross, J. (2009). Hum. Brain Mapp. 30, 1857–1865. Setsompop, K., et al. (2013). Neuroimage 80, 220–233. Sled, J. G., and Pike, G. B. (2001). Magn. Reson. Med. 46, 923–931. Smith, S. M., Jenkinson, M., Johansen-Berg, H., Rueckert, D., Nichols, T. E., Mackay, C. E., et al. (2006). Neuroimage 3, 1487–1505. Sporns, O. (2010). Networks of the Brain. MIT Press. Stanford, L. R. (1987). Science 238, 358–360. Stikov, N., Campbell, J. S. W., Lavallée, M., Stroh, T., Frey, S., Novek, J., et al. (2014). Proceedings of the ISMRM 22nd Annual Meeting, Milan. Stikov, N., et al. (2011). Neuroimage 54, 1112–1121. Sugihara, I., Lang, E. J., and Llinás, R. (1993). J. Physiol. 470, 243–271. Szczepankiewicz, F., et al. (2015). Neuroimage 104, 241–252. Tasaki, I., and Matsumoto, G. (2002). Bull. Math. Biol. 64, 1069–1082. Tisdall, M. D., Folkerth, R. D., Kinney, H. C., and Wald, L. L. (2013). Neuroimage 80, 234–245. Tomassy, G. S., Berger, D. R., Chen, H. H., Kasthuri, N., Hayworth, K. J., Vercelli, A., et al. (1988). J. Neurophysiol. 59, 41–55. Tuch, D. S., et al. D. (2005). Proc. Natl. Acad. Sci. U.S.A. 102, 12212–12217. van den Heuvel, et al. (2010). J. Neurosci. 30, 15915–15926. van den Heuvel, M. P., Stam, C. J., Kahn, R. S., and Hulshoff Pol, H. E. (2009). J. Neurosci. 29, 7619–7624. Vorburger, R. S., Reischauer, C., and Boesiger, P. (2013). Neuroimage 66, 426–435. Wang, J. et al (2012). Neuroimage 60, 1127–1138. Wang, S. S. (2008). Brain Behav. Evol. 72, 159–167. Wang, S. S., Shultz, J. R., Burish, M. J., Harrison, K. H., Hof, P. R., Towns, L. C., et al. (2008). J. Neurosci. 28, 4047–4056. Waxman, S. G. (1980). Muscle Nerve 3, 141–150. Waxman, S. G., and Bennett, M. V. L. (1972). Nat. New Biol. 238, 217–219. Weiler, M., et al. (2014). Psychiatry Res. 223, 15–22. Wharton, S., and Bowtell, R. (2012). Proc. Natl. Acad. Sci. U.S.A. 109, 18559–18564. Wharton, S., and Bowtell, R. (2014). Magn. Reson. Med. Wheeler-Kingshott, C. A., and Cercignani, M. (2009). Magn. Reson. Med. 61, 1255–1260. Wolff, S. D., and Balaban, R. S. (1989). Magn. Reson. Med. 10, 135–144. Wu, E. X., and Cheung, M. M. (2010). NMR Biomed. 23, 836–848. Xu, J., Li, H., Harkins, K. D., Jiang, X., Xie, J., Kang, H., et al. (2014). Neuroimage. Yendiki, A., Koldewyn, K., Kakunoori, S., Kanwisher, N., and Fischl, B. (2013). Neuroimage. Zhang, H., Schneider, T., Wheeler-Kingshott, C. A., and Alexander, D. C. (2012). Neuroimage 61, 1000–1016. Keywords: Axons, connectivity, DTI, graph theory, microstructure, myelin, networks, tractography, Tractometry, white matter Conference: Microstructures of Learning: Novel methods and approaches for assessing structural and functional changes underlying knowledge acquisition in the brain, Lund, Sweden, 23 May - 23 May, 2014. Presentation Type: Oral presentation Topic: Neuroscience Citation: Jones D and Nilsson M (2015). Tractometry and the hunt for the missing link: a physicist perspective. Front. Neurosci. Conference Abstract: Microstructures of Learning: Novel methods and approaches for assessing structural and functional changes underlying knowledge acquisition in the brain. doi: 10.3389/conf.fnins.2015.88.00008 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 06 Mar 2015; Published Online: 06 Mar 2015. * Correspondence: Prof. Derek Jones, Cardiff University, School of Psychology, Cardiff, United Kingdom, jonesd27@cardiff.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Derek Jones Markus Nilsson Google Derek Jones Markus Nilsson Google Scholar Derek Jones Markus Nilsson PubMed Derek Jones Markus Nilsson Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.