Action potential alterations and cell-type specific activity through ictal recruitment in humans

E.M. Merricks, E.H. Smith, G.M. McKhann, II, R.R. Goodman, S.A. Sheth, B. Greger, P.A. House, A.J. Trevelyan, C.A. Schevon

Affiliations & Contact

EMM, CAS: Dept. Neurology, Columbia University Medical Center; EHS: Dept. Neurosurgery, University of Utah; GMM: Dept. Neurological Surgery, Columbia University Medical Center; RRG: Dept. Neurosurgery, Icahn School of Medicine at Mount Sinai; SAS: Baylor College of Medicine; BG: School of Engineering, Arizona State University; PAH: Intermountain Healthcare, UT; AJT: Institute of Neuroscience, Newcastle University, UK
Contact:
em3217@cumc.columbia.edu (EMM) / cas2044@cumc.columbia.edu (CAS)

References

  1. Bower, M.R., et al. (2012) Epilepsia. 53 (5), 807—816.
  2. Goldensohn, E.S. & Purpura, D.P. (1963) Science. 139 (3557), 840—2.
  3. Merricks, E.M., et al. (2015) Brain. 138 (10), 2891—2906.
  4. Miri, M.L., et al. (2018) eLife. 7, e40750.
  5. Misra, A., et al. (2014) J Neural Eng. 11 (2), 026013.
  6. Schevon, C.A., et al. (2012) Nat Commun. 3 (1), 1060.
  7. Traub, R.D. & Wong, R.K. (1982) Science. 216 (4547), 745—747.

Conclusions

  • Waveform alterations found during seizures are enough to cause traditional cluster cutting to fail. Single units can be traced through the ictal transition using a combination of template matching and waveform similarity metrics
  • The distinction between tissue that has been recruited to the seizure versus penumbra is maintained at the level of single neurons. Waveshape changes are a suitable proxy for ictal recruitment and are in keeping with the paroxysmal depolarizing shift (Traub & Wong, 1982)
  • Interneuronal firing was maintained throughout all recruited seizures (n = 7; 4 patients), suggesting that a process such as altered GABAergic conductance or K+ concentration is responsible for inhibitory failure that permits ictal recruitment
  • Transient out-of-phase firing in interneurons with respect to low frequency rhythms suggests effects from the approaching seizure