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Single-neuron dynamics in human focal epilepsy

Nature Neuroscience volume 14, pages 635–641 (2011)Cite this article

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Abstract

Epileptic seizures are traditionally characterized as the ultimate expression of monolithic, hypersynchronous neuronal activity arising from unbalanced runaway excitation. Here we report the first examination of spike train patterns in large ensembles of single neurons during seizures in persons with epilepsy. Contrary to the traditional view, neuronal spiking activity during seizure initiation and spread was highly heterogeneous, not hypersynchronous, suggesting complex interactions among different neuronal groups even at the spatial scale of small cortical patches. In contrast to earlier stages, seizure termination is a nearly homogenous phenomenon followed by an almost complete cessation of spiking across recorded neuronal ensembles. Notably, even neurons outside the region of seizure onset showed significant changes in activity minutes before the seizure. These findings suggest a revision of current thinking about seizure mechanisms and point to the possibility of seizure prevention based on spiking activity in neocortical neurons.

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Figure 1: Heterogeneous neuronal spiking patterns during seizure.
Figure 2: Transient suppression of neuronal spiking during the seizure and at seizure termination.
Figure 3: Reproducibility of neuronal spiking modulation patterns across consecutive seizures.
Figure 4: Preictal and ictal modulations in spiking rates.
Figure 5: Preictal and ictal sample path deviations with respect to an interictal period.

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Acknowledgements

The authors thank the patients who participated in this study, as well as the nursing and physician staff at each facility. We also thank A.M. Chan, C.J. Keller, A. Dykstra and J.E. Cormier for technical assistance, and J.P. Donoghue and K.J. Staley for critical reading of the manuscript. This research is funded by a CIMIT grant and US National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) NS062092 to S.S.C.; an NIH–NINDS Career Award (5K01NS057389) to W.T.; NIH NS018741 to E.H.; NINDS K08NS066099-01A1 to W.S.A.; US National Eye Institute EY017658, US National Institute on Drug Abuse NS063249, US National Science Foundation IOB 0645886, Howard Hughes Medical Institute and the Klingenstein Foundation to E.N.E.; NIH Director's Pioneer Award DP1OD003646 to E.N.B.; US Department of Veterans Affairs Career Development Transition Award, Doris Duke Charitable Foundation–Clinical Scientist Development Award, Massachusetts General Hospital–Deane Institute for Integrated Research on Atrial Fibrillation and Stroke, and NIH-NIDCD R01DC009899 to L.R.H. The contents do not represent the views of the Department of Veterans Affairs or the United States government.

Author information

Author notes

  1. Wilson Truccolo and Jacob A Donoghue: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Wilson Truccolo, Jacob A Donoghue, Leigh R Hochberg & Sydney S Cash

  2. Department of Neuroscience, Brown University, Providence, Rhode Island, USA

    Wilson Truccolo

  3. Institute for Brain Science, Brown University, Providence, Rhode Island, USA

    Wilson Truccolo & Leigh R Hochberg

  4. Department of Veterans Affairs, Rehabilitation Research and Development Service, Providence, Rhode Island, USA

    Wilson Truccolo & Leigh R Hochberg

  5. School of Engineering, Brown University, Providence, Rhode Island, USA

    Leigh R Hochberg

  6. Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Emad N Eskandar

  7. Nayef Al-Rodhan Laboratories for Cellular Neurosurgery and Neurosurgical Technology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Emad N Eskandar

  8. Department of Neurosurgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Joseph R Madsen

  9. Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Joseph R Madsen & William S Anderson

  10. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Emery N Brown

  11. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Emery N Brown

  12. Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Emery N Brown

  13. Department of Radiology, University of California, San Diego, San Diego, California, USA.,

    Eric Halgren

  14. Department of Neurosciences, University of California, San Diego, San Diego, California, USA.,

    Eric Halgren

  15. Department of Psychiatry, University of California, San Diego, San Diego, California, USA.,

    Eric Halgren

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  1. Wilson Truccolo
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Contributions

W.T., S.S.C. and J.A.D. wrote the paper. W.T. and J.A.D. conducted the data analysis. Data collection and preprocessing were done by J.A.D., W.T. and S.S.C. S.S.C., L.R.H., W.T. and E.H. conceived and planned the research. E.N.B. provided guidance on methods of data analysis and interpretation. E.N.E., W.S.A. and J.R.M. performed the surgeries and microelectrode array implantations. All authors participated in editing the manuscript.

Corresponding author

Correspondence to Wilson Truccolo.

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Competing interests

L.R.H. reports receiving research support from Massachusetts General Hospital and Spaulding Rehabilitation Hospital, which in turn received clinical trial support from Cyberkinetics (CKI). CKI ceased operation in 2009.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–11 and Supplementary Table 1 (PDF 1968 kb)

Supplementary Movie 1

Spiking activity on the microelectrode array (subject A, seizure 1). The movie shows the spiking rate of one single unit per electrode in the microelectrode array as a function of time. The largest unit recorded in each electrode was selected. Seizure onset, based on ECoG inspection, is at time zero. Electrodes at the darkest blue locations did not record activity that could be sorted into single units. Spiking rates are shown in spikes per second and were estimated based on 100-ms time bins. The ECoG at four locations is shown below. Location of electrodes OccS2 and GR50 are shown in Fig. 1, main text. The other two are nearby electrodes. (MPG 9226 kb)

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Truccolo, W., Donoghue, J., Hochberg, L. et al. Single-neuron dynamics in human focal epilepsy. Nat Neurosci 14, 635–641 (2011). https://doi.org/10.1038/nn.2782

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