Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Mapping brain activity at scale with cluster computing

Abstract

Understanding brain function requires monitoring and interpreting the activity of large networks of neurons during behavior. Advances in recording technology are greatly increasing the size and complexity of neural data. Analyzing such data will pose a fundamental bottleneck for neuroscience. We present a library of analytical tools called Thunder built on the open-source Apache Spark platform for large-scale distributed computing. The library implements a variety of univariate and multivariate analyses with a modular, extendable structure well-suited to interactive exploration and analysis development. We demonstrate how these analyses find structure in large-scale neural data, including whole-brain light-sheet imaging data from fictively behaving larval zebrafish, and two-photon imaging data from behaving mouse. The analyses relate neuronal responses to sensory input and behavior, run in minutes or less and can be used on a private cluster or in the cloud. Our open-source framework thus holds promise for turning brain activity mapping efforts into biological insights.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A platform for large-scale neural analytics.
Figure 2: Performance benchmarks for Thunder.
Figure 3: Maps of in vivo two-photon calcium imaging data from mouse cortex revealing response modulation by locomotion.
Figure 4: Direction tuning maps of whole-brain neural activity measured in a larval zebrafish with light-sheet microscopy while zebrafish were presented visual stimuli.
Figure 5: Maps of sensorimotor responses in larval zebrafish.
Figure 6: Dynamical portraits of larval zebrafish whole-brain activity via dimensionality reduction.
Figure 7: Analysis of whole-brain spontaneous activity by ICA reveals functionally defined networks.

Similar content being viewed by others

References

  1. Grewe, B.F., Langer, D., Kasper, H., Kampa, B.M. & Helmchen, F. High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision. Nat. Methods 7, 399–405 (2010).

    Article  CAS  PubMed  Google Scholar 

  2. Broxton, M. et al. Wave optics theory and 3-D deconvolution for the light field microscope. Opt. Express 21, 25418–25439 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Quirin, S., Peterka, D.S. & Yuste, R. Instantaneous three-dimensional sensing using spatial light modulator illumination with extended depth of field imaging. Opt. Express 21, 16007–16021 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Prevedel, R. et al. Simultaneous whole-animal 3D imaging of neuronal activity using light-field microscopy. Nat. Methods 11, 727–730 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Churchland, M.M. et al. Neural population dynamics during reaching. Nature 487, 51–56 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Holekamp, T.F., Turaga, D. & Holy, T.E. Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy. Neuron 57, 661–672 (2008).

    Article  CAS  PubMed  Google Scholar 

  7. Ahrens, M.B., Orger, M.B., Robson, D.N., Li, J.M. & Keller, P.J. Whole-brain functional imaging at cellular resolution using light-sheet microscopy. Nat. Methods 10, 413–420 (2013).

    Article  CAS  PubMed  Google Scholar 

  8. Panier, T. et al. Fast functional imaging of multiple brain regions in intact zebrafish larvae using Selective Plane Illumination Microscopy. Front. Neural Circuits 7, 65 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Portugues, R., Feierstein, C.E., Engert, F. & Orger, M.B. Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior. Neuron 81, 1328–1343 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Alivisatos, A.P. et al. Neuroscience. The brain activity map. Science 339, 1284–1285 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Briggman, K.L., Abarbanel, H. & Kristan, W.B. Optical imaging of neuronal populations during decision-making. Science 307, 896–901 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Ahrens, M.B. et al. Brain-wide neuronal dynamics during motor adaptation in zebrafish. Nature 485, 471–477 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Churchland, M.M., Yu, B.M., Sahani, M. & Shenoy, K.V. Techniques for extracting single-trial activity patterns from large-scale neural recordings. Curr. Opin. Neurobiol. 17, 609–618 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Huber, D. et al. Multiple dynamic representations in the motor cortex during sensorimotor learning. Nature 484, 473–478 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dean, J. & Ghemawat, S. MapReduce: simplified data processing on large clusters. Commun. ACM 51.1, 107–113 (2008).

    Article  Google Scholar 

  16. Isard, M. et al. Dryad: distributed data-parallel programs from sequential building blocks. ACM SIGOPS Operating Systems Review 41, 59–72 (2007).

    Article  Google Scholar 

  17. Shvachko, K., Kuang, H., Radia, S. & Chansler, R. The Hadoop Distributed File System. in IEEE 26th Symposium on Mass Storage Systems and Technologies 1–10 (2010).

  18. Chu, C.-T. et al. Map-reduce for machine learning on multicore. Adv. Neural Inf. Process. Syst. 19, 281 (2007).

    Google Scholar 

  19. Zaharia, M., Chowdhury, M., Das, T., Dave, A. & Ma, J. Resilient distributed datasets: A fault-tolerant abstraction for in-memory cluster computing. in Proceedings of the 9th USENIX conference on Networked Systems Design and Implementation 2–15 (2012).

  20. Vladimirov, N. et al. Light-sheet functional imaging in behaving zebrafish. Nat. Methods http://www.nature.com/doifinder/10.1038/nmeth.3040 (27 July 2014).

  21. Naumann, E.A., Kampff, A.R., Prober, D.A., Schier, A.F. & Engert, F. Monitoring neural activity with bioluminescence during natural behavior. Nat. Neurosci. 13, 513–520 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Roweis, S. EM algorithms for PCA and SPCA. Adv. Neural Inf. Process. Syst. 626–632 (1998).

  23. Sofroniew, N.J., Cohen, J.D., Lee, A.K. & Svoboda, K. Natural whisker-guided behavior by head-fixed mice in tactile virtual reality. J. Neurosci. 34, 9537–9550 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Chen, T.-W. et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Keller, G.B., Bonhoeffer, T. & Hübener, M. Sensorimotor mismatch signals in primary visual cortex of the behaving mouse. Neuron 74, 809–815 (2012).

    Article  CAS  PubMed  Google Scholar 

  26. Niell, C.M. & Stryker, M.P. Modulation of visual responses by behavioral state in mouse visual cortex. Neuron 65, 472–479 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Valmianski, I. et al. Automatic identification of fluorescently labeled brain cells for rapid functional imaging. J. Neurophysiol. 104, 1803–1811 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Borst, A., Haag, J. & Reiff, D.F. Fly motion vision. Annu. Rev. Neurosci. 33, 49–70 (2010).

    Article  CAS  PubMed  Google Scholar 

  29. Niell, C.M. & Stryker, M.P. Highly selective receptive fields in mouse visual cortex. J. Neurosci. 28, 7520–7536 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Grama, A. & Engert, F. Direction selectivity in the larval zebrafish tectum is mediated by asymmetric inhibition. Front. Neural Circuits 6, 59 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Nikolaou, N. et al. Parametric functional maps of visual inputs to the tectum. Neuron 76, 317–324 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gabriel, J.P., Trivedi, C.A., Maurer, C.M., Ryu, S. & Bollmann, J.H. Layer-specific targeting of direction-selective neurons in the zebrafish optic tectum. Neuron 76, 1147–1160 (2012).

    Article  CAS  PubMed  Google Scholar 

  33. Del Bene, F. et al. Filtering of visual information in the tectum by an identified neural circuit. Science 330, 669–673 (2010).

    Article  CAS  PubMed  Google Scholar 

  34. Kubo, F. et al. Functional architecture of an optic flow-responsive area that drives horizontal eye movements in zebrafish. Neuron 81, 1344–1359 (2014).

    Article  CAS  PubMed  Google Scholar 

  35. Niell, C.M. & Smith, S.J. Functional imaging reveals rapid development of visual response properties in the zebrafish tectum. Neuron 45, 941–951 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. Dreosti, E., Vendrell Llopis, N., Carl, M., Yaksi, E. & Wilson, S.W. Left-right asymmetry is required for the habenulae to respond to both visual and olfactory stimuli. Curr. Biol. 24, 440–445 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Akerboom, J. et al. Optimization of a GCaMP calcium indicator for neural activity imaging. J. Neurosci. 32, 13819–13840 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Park, H.C. et al. Structural comparison of zebrafish Elav/Hu and their differential expressions during neurogenesis. Neurosci. Lett. 279, 81–84 (2000).

    Article  CAS  PubMed  Google Scholar 

  39. Kimura, Y. et al. Hindbrain V2a neurons in the excitation of spinal locomotor circuits during zebrafish swimming. Curr. Biol. 23, 843–849 (2013).

    Article  CAS  PubMed  Google Scholar 

  40. Kinkhabwala, A. et al. A structural and functional ground plan for neurons in the hindbrain of zebrafish. Proc. Natl. Acad. Sci. USA 108, 1164–1169 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fox, M.D. & Raichle, M.E. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat. Rev. Neurosci. 8, 700–711 (2007).

    Article  CAS  PubMed  Google Scholar 

  42. Hyvärinen, A. Fast and robust fixed-point algorithms for independent component analysis. IEEE Trans. Neural Netw. 10, 626–634 (1999).

    Article  PubMed  Google Scholar 

  43. Satou, C. et al. Transgenic tools to characterize neuronal properties of discrete populations of zebrafish neurons. Development 140, 3927–3931 (2013).

    Article  CAS  PubMed  Google Scholar 

  44. Bock, D.D. et al. Network anatomy and in vivo physiology of visual cortical neurons. Nature 471, 177–182 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Briggman, K.L., Helmstaedter, M. & Denk, W. Wiring specificity in the direction-selectivity circuit of the retina. Nature 471, 183–188 (2011).

    Article  CAS  PubMed  Google Scholar 

  46. Oberlaender, M. et al. Automated three-dimensional detection and counting of neuron somata. J. Neurosci. Methods 180, 147–160 (2009).

    Article  PubMed  Google Scholar 

  47. Mukamel, E.A., Nimmerjahn, A. & Schnitzer, M.J. Automated analysis of cellular signals from large-scale calcium imaging data. Neuron 63, 747–760 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pillow, J.W. et al. Spatio-temporal correlations and visual signalling in a complete neuronal population. Nature 454, 995–999 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Paninski, L. et al. A new look at state-space models for neural data. J. Comput. Neurosci. 29, 107–126 (2010).

    Article  PubMed  Google Scholar 

  50. Dale, A.M. Optimal experimental design for event-related fMRI. Hum. Brain Mapp. 8, 109–114 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Pologruto, T.A., Sabatini, B.L. & Svoboda, K. ScanImage: flexible software for operating laser scanning microscopes. Biomed. Eng. Online 2, 13 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lister, J.A., Robertson, C.P., Lepage, T., Johnson, S.L. & Raible, D.W. nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate. Development 126, 3757–3767 (1999).

    CAS  PubMed  Google Scholar 

  53. White, R.M. et al. Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell 2, 183–189 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Urasaki, A., Morvan, G. & Kawakami, K. Functional dissection of the Tol2 transposable element identified the minimal cis-sequence and a highly repetitive sequence in the subterminal region essential for transposition. Genetics 174, 639–649 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kanda, T., Sullivan, K.F. & Wahl, G.M. Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells. Curr. Biol. 8, 377–385 (1998).

    Article  CAS  PubMed  Google Scholar 

  56. Sato, T., Takahoko, M. & Okamoto, H. HuC:Kaede, a useful tool to label neural morphologies in networks in vivo. Genesis 44, 136–142 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Fisher, S., Grice, E.A., Vinton, R.M. & Bessling, S.L. Evaluating the biological relevance of putative enhancers using Tol2 transposon-mediated transgenesis in zebrafish. Nat. Protoc. 1, 1297–1305 (2006).

    Article  CAS  PubMed  Google Scholar 

  58. Westerfield, M. The Zebrafish (University of Oregon Press, 1993).

  59. Ahrens, M.B., Huang, K.H., Narayan, S., Mensh, B.D. & Engert, F. Two-photon calcium imaging during fictive navigation in virtual environments. Front. Neural Circuits 7, 104 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Cheng, A., Gonçalves, J.T., Golshani, P., Arisaka, K. & Portera-Cailliau, C. Simultaneous two-photon calcium imaging at different depths with spatiotemporal multiplexing. Nat. Methods 8, 139–142 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Fisher, N.I. Statistical Analysis of Circular Data (Cambridge University Press, 1995).

Download references

Acknowledgements

We thank K. Carlisle and R. Lines for help installing and running Spark on the Janelia Farm Research Campus Compute Cluster, D. Ganguli and M. Zaharia for advice on using Spark, G. Merlino for advice on benchmarking, C. Ziemba, C. Stock and T.J. Florence for help testing EC2 installation procedures, P. Keller for his help and advice in building the light-sheet microscope, B. Coop and T. Tabachnik for their help with hardware design, M. Coleman for writing the light-sheet microscope control software Zebrascope and continuing support, S. Narayan for help with zebrafish experiments, K. Svoboda and S. Peron for help setting up the mouse two-photon imaging, B. MacLennan for help with mouse surgeries, D.G.C. Hildebrand and M. Koyama for discussions, the Janelia Farm Research Campus vivarium staff for fish and mouse husbandry, and V. Jayaraman, G. Murphy, K. Svoboda and P. Keller for comments on an earlier draft of the manuscript. This work was supported by the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

Authors

Contributions

J.F. and M.B.A. conceived of the project. J.F. developed the analysis library and analyzed the data. N.V., M.B.A. and T.K. developed the zebrafish light-sheet imaging experimental preparation. N.V., M.B.A., Y.M., T.K. and J.F. collected the zebrafish data. N.J.S. developed the mouse experimental preparation, collected the data reported in Figure 3 and helped develop the analysis of those data. D.V.B. contributed to zebrafish experiments. J.R. contributed code to the analysis library. C.-T.Y. and L.L.L. developed the Tg(elavl3:H2B-GCaMP6s)jf5 transgenic fish line. J.F. and M.B.A. wrote the paper, with input from all authors.

Corresponding authors

Correspondence to Jeremy Freeman or Misha B Ahrens.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Protocol (PDF 118 kb)

Direction tuning, planes.

Maps of direction tuning from individual planes (MOV 1188 kb)

Direction tuning, volume.

Volumetric rendering of direction tuning maps (MOV 2206 kb)

Principal component analysis, planes.

Maps of sensorimotor responses from individual planes (MOV 351 kb)

Swimming-related responses, volume.

Volumetric rendering of sensorimotor response maps (MOV 1148 kb)

Swimming-related responses, planes.

Maps of swimming-related responses from individual planes (MOV 3449 kb)

Swimming-related responses, volume.

Volumetric rendering of swimming-related response maps (MOV 2840 kb)

Swim-related trajectories.

State-space trajectories showing how neural activity on individual trials evolves through a low-dimensional space. Each trace is a trial. Size of dot indicates strength of swimming. (MOV 757 kb)

Direction-related trajectories.

State-space trajectories showing how neural activity on individual trials evolves through a low-dimensional space recovered to capture variability related to different stimulus directions. Each trace is a trial. Color indicates stimulus direction. (MOV 3277 kb)

Independent component analysis, planes.

Maps of spontaneous functional networks from individual planes. (MOV 486 kb)

Independent component analysis, volume.

Volumetric rendering of spontaneous functional network maps. (MOV 1148 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Freeman, J., Vladimirov, N., Kawashima, T. et al. Mapping brain activity at scale with cluster computing. Nat Methods 11, 941–950 (2014). https://doi.org/10.1038/nmeth.3041

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth.3041

This article is cited by

Search

Quick links

Nature Briefing AI and Robotics

Sign up for the Nature Briefing: AI and Robotics newsletter — what matters in AI and robotics research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: AI and Robotics