Neurocritical Care

, Volume 23, Issue 2, pp 262–273 | Cite as

Early Quantitative Gamma-Band EEG Marker is Associated with Outcomes After Cardiac Arrest and Targeted Temperature Management

  • Ruoxian Deng
  • Matthew A. Koenig
  • Leanne Moon Young
  • Xiaofeng JiaEmail author
Translational Research



Brain recovery after cardiac arrest (CA) is sensitive to temperature. Yet the effect of temperature management on different EEG frequency bands has not been elucidated. A novel quantitative EEG algorithm, sub-band information quantity (SIQ), was applied to evaluate EEG recovery and outcomes after CA.


Twenty-four Wistar rats undergoing 7-min CA were randomly assigned to immediate hypothermia (32–34 °C), normothermia (36.5–37.5 °C), or hyperthermia (38.5–39.5 °C) (n = 8). EEG was recorded continuously for the first 8 h and then for serial 30-min epochs daily. The neurologic deficit score (NDS) at 72-h was the primary functional outcome. Another four rats without brain injury were added as a control.


Better recovery of gamma-band SIQ was found in the hypothermia group (0.60 ± 0.03) compared with the normothermia group (0.40 ± 0.03) (p < 0.01) and in the normothermia group compared with the hyperthermia group (0.34 ± 0.03) (p < 0.05). The NDS was also improved in the lower temperature groups: hypothermia [median (25th, 75th), 74 (61, 74)] versus normothermia [49 (47, 61)] versus hyperthermia [43 (0, 50)] (p < 0.01). Throughout the 72-h experiment, the gamma-band SIQ showed the strongest correlation at every time point (ranging 0.520–0.788 from 30-min to 72-h post-resuscitation, all p < 0.05) whereas the delta-band SIQ had poor correlation with the 72-h NDS. No significant difference of sub-band EEG was found with temperature manipulation alone.


Recovery of gamma-band SIQ-qEEG was strongly associated with functional outcomes after CA. Induced hypothermia was associated with faster recovery of gamma-band SIQ and improved functional outcomes. Targeted temperature management primarily affected gamma frequency oscillations but not delta rhythm.


Cardiac arrest Targeted temperature management Hypothermia EEG Gamma-band EEG Functional outcome 



The work was supported by R01HL118084 from NIH (to XJ) and 09SDG2110140 from American Heart Association (to XJ). Deng and Jia were supported by NIH R01HL118084 and AHA 09SDG2110140. Dr. Jia was supported in partial by Maryland Stem Cell Research Fund (2013-MSCRFE-146-00) (to XJ).

Conflict of interest

The authors declare no competing financial interests.

Supplementary material

12028_2015_157_MOESM1_ESM.doc (24 kb)
Supplementary material 1 (DOC 24 kb)
12028_2015_157_MOESM2_ESM.doc (74 kb)
Supplementary material 1 (DOC 74 kb)


  1. 1.
    Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, et al. Heart disease and stroke statistics–2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28–292.CrossRefPubMedGoogle Scholar
  2. 2.
    Neumar RW, Nolan JP, Adrie C, Aibiki M, Berg RA, Bottiger BW, Callaway C, Clark RS, Geocadin RG, Jauch EC, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation. 2008;118(23):2452–83.CrossRefPubMedGoogle Scholar
  3. 3.
    Leary M, Grossestreuer AV, Iannacone S, Gonzalez M, Shofer FS, Povey C, Wendell G, Archer SE, Gaieski DF, Abella BS. Pyrexia and neurologic outcomes after therapeutic hypothermia for cardiac arrest. Resuscitation. 2013;84(8):1056–61.CrossRefPubMedGoogle Scholar
  4. 4.
    Bro-Jeppesen J, Hassager C, Wanscher M, Soholm H, Thomsen JH, Lippert FK, Moller JE, Kober L, Kjaergaard J. Post-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arrest. Resuscitation. 2013;84(12):1734–40.CrossRefPubMedGoogle Scholar
  5. 5.
    Hypothermia after Cardiac Arrest Study G. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549–56.CrossRefGoogle Scholar
  6. 6.
    Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. New Engl J Med. 2002;346(8):557–63.CrossRefPubMedGoogle Scholar
  7. 7.
    Thomassen A, Sorensen K, Wernberg M. The prognostic value of EEG in coma survivors after cardiac arrest. Acta Anaesthesiol Scand. 1978;22(5):483–90.CrossRefPubMedGoogle Scholar
  8. 8.
    Binnie CD, Prior PF, Lloyd DS, Scott DF, Margerison JH. Electroencephalographic prediction of fatal anoxic brain damage after resuscitation from cardiac arrest. Br Med J. 1970;4(5730):265–8.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Berger H. Über das elektrenkephalogramm des menschen. Eur Arch Psychiatry Clin Neurosci. 1929;87(1):527–70.Google Scholar
  10. 10.
    Buzsaki G, Draguhn A. Neuronal oscillations in cortical networks. Science. 2004;304(5679):1926–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Uhlhaas PJ, Pipa G, Lima B, Melloni L, Neuenschwander S, Nikolic D, Singer W. Neural synchrony in cortical networks: history, concept and current status. Front Integr Neurosci. 2009;3:17.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Uhlhaas PJ, Singer W. Abnormal neural oscillations and synchrony in schizophrenia. Nat Rev Neurosci. 2010;11(2):100–13.CrossRefPubMedGoogle Scholar
  13. 13.
    Jia X, Koenig MA, Nickl R, Zhen G, Thakor NV, Geocadin RG. Early electrophysiologic markers predict functional outcome associated with temperature manipulation after cardiac arrest in rats. Crit Care Med. 2008;36(6):1909–16.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Shin HC, Tong S, Yamashita S, Jia X, Geocadin RG, Thakor NV. Quantitative EEG and effect of hypothermia on brain recovery after cardiac arrest. IEEE Trans Biomed Eng. 2006;53(6):1016–23.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Shin HC, Jia X, Nickl R, Geocadin RG, Thakor NV. A subband-based information measure of EEG during brain injury and recovery after cardiac arrest. IEEE Trans Biomed Eng. 2008;55(8):1985–90.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Jia X, Koenig MA, Venkatraman A, Thakor NV, Geocadin RG. Post-cardiac arrest temperature manipulation alters early EEG bursting in rats. Resuscitation. 2008;78(3):367–73.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Jia X, Koenig MA, Shin HC, Zhen G, Pardo CA, Hanley DF, Thakor NV, Geocadin RG. Improving neurological outcomes post-cardiac arrest in a rat model: immediate hypothermia and quantitative EEG monitoring. Resuscitation. 2008;76(3):431–42.PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Uhlhaas PJ, Singer W. Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology. Neuron. 2006;52(1):155–68.CrossRefPubMedGoogle Scholar
  19. 19.
    Fugate JE, Wijdicks EF, Mandrekar J, Claassen DO, Manno EM, White RD, Bell MR, Rabinstein AA. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol. 2010;68(6):907–14.CrossRefPubMedGoogle Scholar
  20. 20.
    Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557–63.CrossRefPubMedGoogle Scholar
  21. 21.
    Horn M, Schlote W, Henrich HA. Global cerebral ischemia and subsequent selective hypothermia. A neuropathological and morphometrical study on ischemic neuronal damage in cat. Acta Neuropathol. 1991;81(4):443–9.CrossRefPubMedGoogle Scholar
  22. 22.
    D’Cruz BJ, Fertig KC, Filiano AJ, Hicks SD, DeFranco DB, Callaway CW. Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation. J Cereb Blood Flow Metab. 2002;22(7):843–51.CrossRefPubMedGoogle Scholar
  23. 23.
    Hicks SD, DeFranco DB, Callaway CW. Hypothermia during reperfusion after asphyxial cardiac arrest improves functional recovery and selectively alters stress-induced protein expression. J Cereb Blood Flow Metab. 2000;20(3):520–30.CrossRefPubMedGoogle Scholar
  24. 24.
    Jia X, Kohn A. Gamma rhythms in the brain. PLoS Biol. 2011;9(4):e1001045.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Singer W, Gray CM. Visual feature integration and the temporal correlation hypothesis. Annu Rev Neurosci. 1995;18:555–86.CrossRefPubMedGoogle Scholar
  26. 26.
    Basar E, Basar-Eroglu C, Rahn E, Schurmann M. Sensory and cognitive components of brain resonance responses. An analysis of responsiveness in human and cat brain upon visual and auditory stimulation. Acta Otolaryngol Suppl. 1991;491:25–34 discussion 35.CrossRefPubMedGoogle Scholar
  27. 27.
    Adrian ED. Olfactory reactions in the brain of the hedgehog. J Physiol. 1942;100(4):459–73.PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Kaiser J, Lutzenberger W. Human gamma-band activity: a window to cognitive processing. Neuroreport. 2005;16(3):207–11.CrossRefPubMedGoogle Scholar
  29. 29.
    Pulvermuller F, Lutzenberger W, Preissl H, Birbaumer N. Spectral responses in the gamma-band: physiological signs of higher cognitive processes? Neuroreport. 1995;6(15):2059–64.CrossRefPubMedGoogle Scholar
  30. 30.
    Miltner WH, Braun C, Arnold M, Witte H, Taub E. Coherence of gamma-band EEG activity as a basis for associative learning. Nature. 1999;397(6718):434–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Llinas R, Ribary U. Coherent 40-Hz oscillation characterizes dream state in humans. Proc Natl Acad Sci USA. 1993;90(5):2078–81.PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Elbert T, Rockstroh B, Lutzenberger W, Birbaumer N. Self-regulation of the brain and behavior. Berlin: Springer; 1984.CrossRefGoogle Scholar
  33. 33.
    Steriade M, Amzica F, Contreras D. Synchronization of fast (30–40 Hz) spontaneous cortical rhythms during brain activation. J Neurosci. 1996;16(1):392–417.PubMedGoogle Scholar
  34. 34.
    Traub RD, Bibbig A, LeBeau FE, Buhl EH, Whittington MA. Cellular mechanisms of neuronal population oscillations in the hippocampus in vitro. Annu Rev Neurosci. 2004;27:247–78.CrossRefPubMedGoogle Scholar
  35. 35.
    Wang XJ, Buzsaki G. Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model. J Neurosci. 1996;16(20):6402–13.PubMedGoogle Scholar
  36. 36.
    White BC, Sullivan JM, DeGracia DJ, O’Neil BJ, Neumar RW, Grossman LI, Rafols JA, Krause GS. Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J Neurol Sci. 2000;179(S 1-2):1–33.CrossRefPubMedGoogle Scholar
  37. 37.
    Oku K, Kuboyama K, Safar P, Obrist W, Sterz F, Leonov Y, Tisherman SA. Cerebral and systemic arteriovenous oxygen monitoring after cardiac arrest. Inadequate cerebral oxygen delivery. Resuscitation. 1994;27(2):141–52.CrossRefPubMedGoogle Scholar
  38. 38.
    Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischemic stroke: an integrated view. Trends Neurosci. 1999;22(9):391–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Morimoto T, Nagao H, Yoshimatsu M, Yoshida K, Matsuda H. Pathogenic role of glutamate in hyperthermia-induced seizures. Epilepsia. 1993;34(3):447–52.CrossRefPubMedGoogle Scholar
  40. 40.
    Suehiro E, Fujisawa H, Ito H, Ishikawa T, Maekawa T. Brain temperature modifies glutamate neurotoxicity in vivo. J Neurotrauma. 1999;16(4):285–97.CrossRefPubMedGoogle Scholar
  41. 41.
    Qu L, Liu X, Wu C, Leung LS. Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats. Neurobiol Dis. 2007;27(3):320–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Busto R, Globus MY, Dietrich WD, Martinez E, Valdes I, Ginsberg MD. Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke. 1989;20(7):904–10.CrossRefPubMedGoogle Scholar
  43. 43.
    Nolan JP, Morley PT, Vanden Hoek TL, Hickey RW, Kloeck WG, Billi J, Bottiger BW, Morley PT, Nolan JP, Okada K, et al. Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. Circulation. 2003;108(1):118–21.CrossRefPubMedGoogle Scholar
  44. 44.
    Sharbrough FW, Messick JM Jr, Sundt TM Jr. Correlation of continuous electroencephalograms with cerebral blood flow measurements during carotid endarterectomy. Stroke. 1973;4(4):674–83.CrossRefPubMedGoogle Scholar
  45. 45.
    Hossmann KA. Viability thresholds and the penumbra of focal ischemia. Ann Neurol. 1994;36(4):557–65.CrossRefPubMedGoogle Scholar
  46. 46.
    Jordan KG. Emergency EEG and continuous EEG monitoring in acute ischemic stroke. J Clin Neurophysiol. 2004;21(5):341–52.PubMedGoogle Scholar
  47. 47.
    Kawakami S, Hossmann KA. Electrophysiological recovery after compression ischemia of the rat brain. J Neurol. 1977;217(1):31–42.CrossRefPubMedGoogle Scholar
  48. 48.
    Amzica F, Kroeger D. Cellular mechanisms underlying EEG waveforms during coma. Epilepsia. 2011;52(Suppl 8):25–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringThe Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of NeurosurgeryUniversity of Maryland School of MedicineBaltimoreUSA
  3. 3.Department of MedicineThe University of Hawaii John A. Burns School of MedicineHonoluluUSA
  4. 4.Neuroscience InstituteThe Queen’s Medical CenterHonoluluUSA
  5. 5.Department of Anesthesiology and Critical Care MedicineThe Johns Hopkins University School of MedicineBaltimoreUSA
  6. 6.Department of OrthopaedicsUniversity of Maryland School of MedicineBaltimoreUSA

Personalised recommendations