Research Article
No access
Published Online: 20 August 2019

Frequency-Dependent Changes in Resting State Electroencephalogram Functional Networks after Traumatic Brain Injury in Piglets

Publication: Journal of Neurotrauma
Volume 36, Issue Number 17


Traumatic brain injury (TBI) is a major health concern in children, as it can cause chronic cognitive and behavioral deficits. The lack of objective involuntary metrics for the diagnosis of TBI makes prognosis more challenging, especially in the pediatric context, in which children are often unable to articulate their symptoms. Resting state electroencephalograms (EEG), which are inexpensive and non-invasive, and do not require subjects to perform cognitive tasks, have not yet been used to create functional brain networks in relation to TBI in children or non-human animals; here we report the first such study. We recorded resting state EEG in awake piglets before and after TBI, from which we generated EEG functional networks from the alpha (8–12 Hz), beta (16.5–25 Hz), broad (1–35 Hz), delta (1–3.5 Hz), gamma (30–35 Hz), sigma (13–16 Hz), and theta (4–7.5 Hz) frequency bands. We hypothesize that mild TBI will induce persistent frequency-dependent changes in the 4-week-old piglet at acute and chronic time points. Hyperconnectivity was found in several frequency band networks after TBI. This study serves as proof of concept that the study of EEG functional networks in awake piglets may be useful for the development of diagnostic metrics for TBI in children.

Get full access to this article

View all available purchase options and get full access to this article.


1. Bryan M.A., Rowhani-Rahbar A., Comstock R.D., Rivara F., and Collaborative, on behalf of the S. S. C. R. (2016). Sports- and recreation-related concussions in US youth. Pediatrics 138, e20154635.
2. Faul M., Xu L., Wald M., Coronado V. (2010). Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations and Deaths 2002–2006. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control: Atlanta.
3. Davis G.A., Anderson V., Babl F.E., Gioia G.A., Giza C.C., Meehan W., Moser R.S., Purcell L., Schatz P., Schneider K.J., Takagi M., Yeates K.O., and Zemek R. (2017). What is the difference in concussion management in children as compared with adults? A systematic review. Br. J. Sports Med. 51, 949–957.
4. Nadlonek N.A., Acker S.N., Bensard D.D., Bansal S., and Partrick D.A. (2015). Early diffuse slowing on electroencephalogram in pediatric traumatic brain injury: impact on management and prognosis. J. Pediatr. Surg. 50, 1338–1340.
5. Nuwer M.R. (2016). Measuring outcomes for neurophysiological intraoperative monitoring. Clin. Neurophysiol. 127, 3–4
6. Schmitt S., and Dichter M.A. (2015). Electrophysiologic recordings in traumatic brain injury. Handb. Clin. Neurol. 127, 319–339.
7. Bartolomei F., Bosma I., Klein M., Baayen J.C., Reijneveld J.C., Postma T.J., Heimans J.J., van Dijk B.W., de Munck J.C., de Jongh A., Cover K.S., Stam C.J. (2006). Disturbed functional connectivity in brain tumour patients: Evaluation by graph analysis of synchronization matrices. Clin. Neurophysiol. 117, 2039–2049.
8. De V.F., Baluch F., Astolfi L., Subramanian D., Zouridakis G., Babiloni F. (2010). Structural organization of functional networks from eeg signals during motor learning tasks. Int J Bifurc Chaos. 20, 905–912.
9. Nishida K., Morishima Y., Yoshimura M., Isotani T., Irisawa S., Jann K., Dierks T., Strik W., Kinoshita T., Koenig T. (2013). EEG microstates associated with salience and frontoparietal networks in frontotemporal dementia, schizophrenia and Alzheimer's disease. Clin Neurophysiol. 124, 1106–1114.
10. Boersma M., Smit D.J., de Bie H.M., Van Baal G.C., Boomsma D.I., de Geus E.J., Delemarre-van de Waal H.A., and Stam C.J. (2011). Network analysis of resting state EEG in the developing young brain: structure comes with maturation. Hum. Brain Mapp. 32, 413–425.
11. Knyazev G.G., Savostyanov A.N., Bocharov A.V., Slobodskaya H.R., Bairova N.B. (2017). Personality and resting state networks in children: A longitudinal EEG study. Personal Individ Differ. 118, 39–43.
12. Mantini D., Perrucci M.G., Del G., Romani G.L., and Corbetta M. (2007). Electrophysiological signatures of resting state networks in the human brain. Proc. Natl. Acad. Sci. U. S. A. 104, 13170–13175.
13. Musso F., Brinkmeyer J., Mobascher A., Warbrick T., and Winterer G. (2010). Spontaneous brain activity and EEG microstates. a novel EEG/fMRI analysis approach to explore resting-state networks. NeuroImage 52, 1149–1161.
14. Zheng L., Zhang Z.-Q., Wang Z.-G., Wang M.-X., Yuan C.-P., Shen L.-F., Chen G.-H., Yang F., Tan Q.-F., Jiao Q., Lu G.-M. (2012). EEG-fMRI study of resting-state networks in childhood absence epilepsy. Chin J Contemp Neurol Neurosurg. 12, 558–562.
15. Lind N.M., Moustgaard A., Jelsing J., Vajta G., Cumming P., and Hansen A.K. (2007). The use of pigs in neuroscience: modeling brain disorders. Neurosci. Biobehav. Rev. 31, 728–751.
16. Pareja J.C.M., Keeley K., Duhaime A.-C., and Dodge C.P. (2016). Modeling pediatric brain trauma: piglet model of controlled cortical impact, in: Injury Models of the Central Nervous System. Humana Press: New York, pps. 345–356.
17. Saito T., Watanabe Y., Nemoto T., Kasuya E., and Sakumoto R. (2005). Radiotelemetry recording of electroencephalogram in piglets during rest. Physiol. Behav. 84, 725–731.
18. Gavilanes A.W., Vles J.S., von Siebenthal K., Reulen J.P., Nieman F.H., van Sprundel R., Blanco C.E. (2001). Electrocortical brain activity, cerebral haemodynamics and oxygenation during progressive hypotension in newborn piglets. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 112, 52–59.
19. Ioroi T., Peeters-Scholte C., Post I., Leusink C., Groenendaal F., van Bel F. (2002). Changes in cerebral haemodynamics, regional oxygen saturation and amplitude-integrated continuous EEG during hypoxia-ischaemia and reperfusion in newborn piglets. Exp Brain Res. 144, 172–177.
20. Esslinger C., Walter H., Kirsch P., Erk S., Schnell K., Arnold C., Haddad L., Mier D., Opitz von Boberfeld C., Raab K., Witt S.H., Rietschel M., Cichon S., and Meyer-Lindenberg A. (2009). Neural mechanisms of a genome-wide supported psychosis variant. Science 324, 605–605
21. Armstead W.M. (2000). Age-dependent cerebral hemodynamic effects of traumatic brain injury in newborn and juvenile pigs. Microcirculation 7, 225–235.
22. Armstead W.M. (2005). Age and cerebral circulation. Pathophysiology 12, 5–15.
23. Buckley N.M. (1986). Maturation of circulatory system in three mammalian models of human development. Comp. Biochem. Physiol. A Physiol. 83, 1–7.
24. Dickerson J.W.T., and Dobbing J. (1967). Prenatal and postnatal growth and development of the central nervous system of the pig. Proc. R. Soc. Lond. B Biol. Sci. 166, 384–395.
25. Duhaime A.C. (1998). Age-specific therapy for traumatic injury of the immature brain: experimental approaches. Pathophysiology 5, 236.
26. Eucker S.A., Smith C., Ralston J., Friess S.H., and Margulies S.S. (2011). Physiological and histopathological responses following closed rotational head injury depend on direction of head motion. Exp. Neurol. 227, 79–88.
27. Ibrahim N.G., Ralston J., Smith C., Margulies S.S. (2010). Physiological and pathological responses to head rotations in toddler piglets. J. Neurotrauma 27, 1021–1035.
28. Maltese M.R. (2012). Traumatic brain injury thresholds in the pre-adolescent juvenile. 1–184.
29. Nuwer M.R., Comi G., Emerson R., Fuglsang-Frederiksen A., Guérit J.M., Hinrichs H., Ikeda A., Luccas F.J., and Rappelsburger P. (1998). IFCN standards for digital recording of clinical EEG. International Federation of Clinical Neurophysiology. Electroencephalogr. Clin. Neurophysiol. 106, 259–261.
30. Modarres M.H., Kuzma N.N., Kretzmer T., Pack A.I., and Lim M.M. (2017). EEG slow waves in traumatic brain injury: Convergent findings in mouse and man. Neurobiol. Sleep Circadian Rhythms 2, 59–70.
31. Nuwer M. (1997). Assessment of digital EEG, quantitative EEG, and EEG brain mapping: report of the American Academy of Neurology and the American Clinical Neurophysiology Society. Neurology 49, 277–292.
32. Nuwer M.R. (1996). Quantitative EEG analysis in clinical settings. Brain Topogr. 8, 201–208.
33. Nuwer M.R., Hovda D.A., Schrader L.M., and Vespa P.M. (2005). Routine and quantitative EEG in mild traumatic brain injury. Clin. Neurophysiol. 116, 2001–2025.
34. Fulop S.A., and Fitz K. (2006). Algorithms for computing the time-corrected instantaneous frequency (reassigned) spectrogram, with applications. 119, 360–371.
35. MATLAB R (2015). The MathWorks Inc., Natick, MA.
36. Chu C.J., Kramer M.A., Pathmanathan J., Bianchi M.T., Westover M.B., Wizon L., Cash S.S. (2012). Emergence of Stable Functional Networks in Long-Term Human Electroencephalography. J Neurosci. 32, 2703–2713.
37. Saby J.N., and Marshall P.J. (2012). The utility of EEG band power analysis in the study of infancy and early childhood. Dev. Neuropsychol. 37, 253–273.
38. Kramer M. A.Eden U.T., Lepage K.Q., Kolaczyk E.D., Bianchi M.T., and Cash S.S. (2011). Emergence of persistent networks in long-term intracranial EEG recordings. J. Neurosci. 31, 15757–15767.
39. Gazzellini S., Napolitano A., Bauleo G., Bisozzi E., Lispi M.L., Ardu E., Castelli E., Benso F. (2016). Time-frequency analyses of reaction times and theta/beta EEG ratio in pediatric patients with traumatic brain injury: A preliminary study. Dev Neurorehabilitation. 1–15.
40. Rubinov M., and Sporns O. (2010). Complex network measures of brain connectivity: uses and interpretations. NeuroImage 52, 1059–1069.
41. Davison A.C., Hinkley D.V. (1997). Bootstrap Methods and Their Application. 1st edition. Cambridge, NY: Cambridge University Press; 1997.
42. Gao X. (2008). Nonparametric multiple comparison procedures for unbalanced one-way factorial designs. JSPI. 138, 2574–2591.
43. R Core Team. (2017). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna.
44. Konietschke F., Placzek M., Schaarschmidt Hothorn. (2015). nparcomp: An R Software Package for Nonparametric Multiple Comparisons and Simultaneous Confidence Intervals. J Stat Softw. 64, 1–17.
45. Hillary F.G., Slocomb J., Hills E.C., Fitzpatrick N.M., Medaglia J.D., Wang J., Good D.C., Wylie G.R. (2011). Changes in resting connectivity during recovery from severe traumatic brain injury. Int J Psychophysiol. 82, 115–123.
46. Kasahara M., Menon D.K., Salmond C.H., Outtrim J.G., Tavares J.V.T., Carpenter T.A., Pickard J.D., Sahakian B.J., Stamatakis E.A. (2011). Traumatic brain injury alters the functional brain network mediating working memory. Brain Inj. 25, 1170–1187.
47. Mayer A.R., Mannell M.V., Ling J., Gasparovic C. and Yeo R.A. (2011). Functional connectivity in mild traumatic brain injury. Hum. Brain Mapp. 32, 1825–1835.
48. Palacios E.M., Yuh E.L., Chang Y.-S., Yue J.K., Schnyer D.M., Okonkwo D.O., Valadka A.B., Gordon W.A., Maas A.I.R., Vassar M., Manley G.T., Mukherjee P. (2017). Resting-State Functional Connectivity Alterations Associated with Six-Month Outcomes in Mild Traumatic Brain Injury. J Neurotrauma. 34, 1546–1557.
49. Rigon A., Duff M.C., McAuley E., Kramer A.F., and Voss M.W. (2015). Is traumatic brain injury associated with reduced inter-hemispheric functional connectivity? A study of large-scale resting state networks following traumatic brain injury. J. Neurotrauma 33, 977–989.
50. Sharp D.J., Beckmann C.F., Greenwood R., Kinnunen K.M., Bonnelle V., De Boissezon X., Powell J.H., Counsell S.J., Patel M.C., Leech R. (2011). Default mode network functional and structural connectivity after traumatic brain injury. Brain J Neurol. 134, 2233–2247.
51. Risen S.R., Barber A.D., Mostofsky S.H., and Suskauer S.J. (2015). Altered functional connectivity in children with mild to moderate TBI relates to motor control. J. Pediatr. Rehabil. Med. 8, 309–319.
52. Virji-Babul N., Hilderman C.G.E., Makan N., Liu A., Smith-Forrester J., Franks C., Wang Zj. (2014). Changes in Functional Brain Networks following Sports-Related Concussion in Adolescents. J Neurotrauma. 31, 1914–1919.
53. Porter S., Torres I.J., Panenka W., Rajwani Z., Fawcett D., Hyder A., Virji-Babul N. (2017). Changes in brain-behavior relationships following a 3-month pilot cognitive intervention program for adults with traumatic brain injury. Heliyon. 3, e00373.
54. Slobounov S., Gay M., Johnson B., and Zhang K. (2012). Concussion in athletics: ongoing clinical and brain imaging research controversies. Brain Imaging Behav. 6, 224–243.
55. Thatcher R.W., Biver C., McAlaster R., Camacho M., and Salazar A. (1998). Biophysical linkage between MRI and EEG amplitude in closed head injury. NeuroImage 7, 352–367.
56. Haneef Z., Levin H.S., Frost J.D., and Mizrahi E.M. (2012). Electroencephalography and quantitative electroencephalography in mild traumatic brain injury. J. Neurotrauma 30, 653–656.
57. Koufen H., and Dichgans J. (1978). Frequency and course of posttraumatic EEG-abnormalities and their correlations with clinical symptoms: a systematic follow up study in 344 adults [in German]. Fortschr. Neurol. Psychiatr. Grenzgeb. 46, 165–177.
58. Tebano M.T., Cameroni M., Gallozzi G., Loizzo A., Palazzino G., Pezzini G., and Ricci G.F. (1988). EEG spectral analysis after minor head injury in man. Clin. Neurophysiol. 70, 185–189.
59. von Bierbrauer A., Weissenborn K., Hinrichs H., Scholz M., and Künkel H. (1992). Automatic (computer-assisted) EEG analysis in comparison with visual EEG analysis in patients following minor cranio-cerebral trauma (a follow-up study) [in German]. EEG EMG Z. Elektroenzephalogr. Elektromyogr. Verwandte Geb. 23, 151–157.
60. Fenton G.W. (1994). The postconcussional syndrome: new insights. J. R. Soc. Med. 87, 499–500.
61. Fenton G.W. (1996). The postconcussional syndrome reappraised. Clin. Electroencephalogr. 27, 174–182.
62. Gosselin N., Lassonde M., Petit D., Leclerc S., Mongrain V., Collie A., and Montplaisir J. (2009). Sleep following sport-related concussions. Sleep Med. 10, 35–46.
63. McClelland R.J., Fenton G.W., and Rutherford W. (1994). The postconcussional syndrome revisited. J.R. Soc. Med. 87, 508–510.
64. Moeller J.J., Tu B., and Bazil C.W. (2011). Quantitative and qualitative analysis of ambulatory electroencephalography during mild traumatic brain injury. Arch. Neurol. 68, 1595–1598.
65. Thompson J., Sebastianelli W., and Slobounov S. (2005). EEG and postural correlates of mild traumatic brain injury in athletes. Neurosci. Lett. 377, 158–163.
66. Buzsáki G., Logothetis N., Singer W. (2013). Scaling brain size, keeping timing: evolutionary preservation of brain rhythms. Neuron 80, 751–764.
67. Harmony T. (2013). The functional significance of delta oscillations in cognitive processing. Front Integr Neurosci. 7, 1–10.
68. Fedor M., Berman R.F., Muizelaar J.P., and Lyeth B.G. (2010). Hippocampal θ dysfunction after lateral fluid percussion injury. J. Neurotrauma 27, 1605–1615.
69. Lee D.Y., Xun Z., Platt V., Budworth H., Canaria C.A., McMurray C.T. (2013). Distinct Pools of Non-Glycolytic Substrates Differentiate Brain Regions and Prime Region-Specific Responses of Mitochondria. Dzeja P, ed. PLoS ONE. 8, e68831.
70. Dixon C.E., Lyeth B.G., Povlishock J.T., Findling R.L., Hamm R.J., Marmarou A., Young H.F., and Hayes R.L. (1987). A fluid percussion model of experimental brain injury in the rat. J. Neurosurg. 67, 110–119.
71. Ishige N., Pitts L.H., Berry I., Carlson S.G., Nishimura M.C., Moseley M.E., Weinstein P.R. (1987). The effect of hypoxia on traumatic head injury in rats: alterations in neurologic function, brain edema, and cerebral blood flow. J Cereb Blood Flow Metab. 7, 759–767.
72. McIntosh T.K., Noble L., Andrews B., and Faden A.I. (1987). Traumatic brain injury in the rat: characterization of a midline fluid-percussion model. Cent. Nerv. Syst. Trauma 4, 119–134.
73. Paterno R., Metheny H., Xiong G., Elkind J., and Cohen A.S. (2016). Mild traumatic brain injury decreases broadband power in area CA1. J. Neurotrauma 33, 1645–1649.
74. Borich M.R., Brown K.E., Lakhani B., and Boyd L.A. (2015). Applications of electroencephalography to characterize brain activity: perspectives in stroke. J. Neurol. Phys. Ther. 39, 43–51.
75. Frieboes R.M., Müller U., Murck H., von Cramon D.Y., Holsboer F., Steiger A. (1999). Nocturnal hormone secretion and the sleep EEG in patients several months after traumatic brain injury. J Neuropsychiatry Clin Neurosci. 11, 354–360.
76. Parsons L.C., Crosby L.J., Perlis M., Britt T., and Jones P. (1997). Longitudinal sleep EEG power spectral analysis studies in adolescents with minor head injury. J. Neurotrauma 14, 549–559.
77. Nakamura T., Hillary F.G., and Biswal B.B. (2009). Resting network plasticity following brain injury. PloS One 4, e8220.
78. Stevens M.C., Lovejoy D., Kim J., Oakes H., Kureshi I., Witt S.T. (2012). Multiple resting state network functional connectivity abnormalities in mild traumatic brain injury. Brain Imaging Behav. 6, 293–318.
79. Friston K. (2002). Functional integration and inference in the brain. Prog Neurobiol. 68, 113–143.
80. Hillary F.G., Rajtmajer S.M., Roman C.A., Medaglia J.D., Slocomb-Dluzen J.E., Calhoun V.D., Good D.C., Wylie G.R. (2014). The rich get richer: brain injury elicits hyperconnectivity in core subnetworks. PloS One. 9, e104021.
81. Hillary F.G., Roman C.A., Venkatesan U., Rajtmajer S.M., Bajo R., Castellanos N.D. (2015). Hyperconnectivity is a fundamental response to neurological disruption. Neuropsychology. 29, 59–75.
82. Nunez P.L., Srinivasan R., Fields R.D. (2015). EEG functional connectivity, axon delays and white matter disease. Clin Neurophysiol. 126, 110–120.
83. Harris N.G., Verley D.R., Gutman B.A., Thompson P.M., Yeh H.J., Brown J.A. (2016). Disconnection and hyper-connectivity underlie reorganization after TBI: A rodent functional connectomic analysis. Exp Neurol. 277, 124–138.
84. Mishra A.M., Bai X., Sanganahalli B.G., Waxman S.G., Shatillo O., Grohn O., Hyder F., Pitkänen A., Blumenfeld H. (2014). Decreased Resting Functional Connectivity after Traumatic Brain Injury in the Rat. PLoS ONE. 9, e95280.
85. Han K., Mac Donald C.L., Johnson A.M., Barnes Y., Wierzechowski L., Zonies D., Oh J., Flaherty S., Fang R., Raichle M.E., Brody D.L. (2014). Disrupted modular organization of resting-state cortical functional connectivity in U.S. military personnel following concussive “mild” blast-related traumatic brain injury. NeuroImage. 84, 76–96.
86. Alexander-Bloch A.F., Gogtay N., Meunier D., Birn R., Clasen L., Lalonde F., Lenroot R., Giedd J., Bullmore E.T. (2010). Disrupted modularity and local connectivity of brain functional networks in childhood-onset schizophrenia. Front Syst Neurosci. 4, 147.
87. Pevzner A., Izadi A., Lee D.J., Shahlaie K., and Gurkoff G.G. (2016). Making waves in the brain: what are oscillations, and why modulating them makes sense for brain injury. Front. Syst. Neurosci. 10, 30.
88. Luo Q., Xu D., Roskos T., Stout J., Kull L., Cheng X., Whitson D., Boomgarden E., Gfeller J., Bucholz R.D. (2013). Complexity Analysis of Resting State Magnetoencephalography Activity in Traumatic Brain Injury Patients. J Neurotrauma. 30, 1702–1709.
89. Douw L. Schoonheim M.M., Landi D., van der Meer M.L., Geurts J.J., Reijneveld J.C., Klein M., and Stam C.J. (2011). Cognition is related to resting-state small-world network topology: an magnetoencephalographic study. Neuroscience 175, 169–177.
90. Olsen K.S., Madsen P.L., Børme T., and Schmidt J.F. (1993). The effect of ketanserin on cerebral blood flow and oxygen metabolism in healthy volunteers. Acta Neurochir. (Wien) 125, 83–85.
91. Cucchiara R.F., Theye R.A., and Michenfelder J.D. (1974). The effects of isoflurane on canine cerebral metabolism and blood flow. Anesthesiology 40, 571–574.
92. Todd M.M., and Weeks J. (1996). Comparative effects of propofol, pentobarbital, and isoflurane on cerebral blood flow and blood volume. J. Neurosurg. Anesthesiol. 8, 296–303.
93. Kochs E., Hoffman W.E., Werner C., Albrecht R.F., and Schulte am Esch J. (1993). Cerebral blood flow velocity in relation to cerebral blood flow, cerebral metabolic rate for oxygen, and electroencephalogram analysis during isoflurane anesthesia in dogs. Anesth. Analg. 76, 1222–1226.
94. Gelman S., Fowler K.C., and Smith L.R. (1984). Regional blood flow during isoflurane and halothane anesthesia. Anesth. Analg. 63, 557–565.
95. Smith J.H., Karsli C., Lagacé A., Luginbuehl I., Barlow R., and Bissonnette B. (2005). Cerebral blood flow velocity increases when propofol is changed to desflurane, but not when isoflurane is changed to desflurane in children. Acta Anaesthesiol. Scand. 49, 23–27.
96. O'Connor C.A., Cernak I., and Vink R. (2003). Interaction between anesthesia, gender, and functional outcome task following diffuse traumatic brain injury in rats. J. Neurotrauma 20, 533–541.
97. Statler K.D., Kochanek P.M., Dixon C.E., Alexander H.L., Warner D.S., Clark R.S.b., Wisniewski S.R., Graham S.H., Jenkins L.W., Marion D.W., Safar P.J. (2000). Isoflurane Improves Long-Term Neurologic Outcome Versus Fentanyl After Traumatic Brain Injury in Rats. J Neurotrauma. 17, 1179–1189.
98. Hertle D., Beynon C., Zweckberger K., Vienenkötter B., Jung C.S., Kiening K., Unterberg A., Sakowitz O.W. (2012). Influence of Isoflurane on Neuronal Death and Outcome in a Rat Model of Traumatic Brain Injury. In: Intracranial Pressure and Brain Monitoring XIV. Springer: Vienna. pps 383–386.
99. Bruins B., Kilbaugh T.J., Margulies S.S., and Friess S.H. (2013). The anesthetic effects on vasopressor modulation of cerebral blood flow in an immature swine model. Anesth. Analg. 116, 838–844.
100. Brady K.M., Lee J.K., Kibler K.K., Easley R.B., Koehler R.C., Czosnyka M., Smielewski P., Shaffner D.H. (2009). The lower limit of cerebral blood flow autoregulation is increased with elevated intracranial pressure. Anesth Analg. 108, 1278–1283.
101. Weeks D., Sullivan S., Kilbaugh T., Smith C., and Margulies S.S. (2014). Influences of developmental age on the resolution of diffuse traumatic intracranial hemorrhage and axonal injury. J. Neurotrauma 31, 206–214.
102. Atlan L.S., Smith C., Margulies S.S. (2017). Improved prediction of direction-dependent, acute axonal injury in piglets. J Neurosci Res. 96, 536–544.
103. Sullivan S., Friess S.H., Ralston J., Smith C., Propert K.J., Rapp P.E., and Margulies S.S. (2013). Behavioral deficits and axonal injury persistence after rotational head injury are direction dependent. J. Neurotrauma 30, 538–545.
104. Sullivan S., Friess S.H., Ralston J., Smith C., Propert K.J., Rapp P.E., and Margulies S.S. (2013). Improved behavior, motor, and cognition assessments in neonatal piglets. J. Neurotrauma 30, 1770–1779.
105. Rowson S., Duma S.M., Beckwith J.G., Chu J.J., Greenwald R.M., Crisco J.J., Brolinson P.G., Duhaime A.C., McAllister T.W., and Maerlender A.C. (2012). Rotational head kinematics in football impacts: an injury risk function for concussion. Ann. Biomed. Eng. 40, 1–13.

Information & Authors


Published In

cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 36Issue Number 17September 1, 2019
Pages: 2558 - 2578
PubMed: 30909806


Published in print: September 1, 2019
Published online: 20 August 2019
Published ahead of print: 23 May 2019
Published ahead of production: 26 March 2019


Request permissions for this article.




Lorre S. Atlan
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.
Susan S. Margulies [email protected]
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.


Address correspondence to: Susan S. Margulies, PhD, Georgia Tech, The U.A. Whitaker Biomedical Engineering Building, 313 Ferst Drive, Atlanta, GA 30332-0535 [email protected]

Author Disclosure Statement

No competing financial interests exist.

Metrics & Citations



Export citation

Select the format you want to export the citations of this publication.

View Options

Get Access

Access content

To read the fulltext, please use one of the options below to sign in or purchase access.

Society Access

If you are a member of a society that has access to this content please log in via your society website and then return to this publication.

Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

View options


View PDF/ePub

Full Text

View Full Text







Copy the content Link

Share on social media

Back to Top