Interictal spikes are periodic, very brief bursts of neuronal activity that are observed in the electroencephalogram of patients with chronic epilepsy. These spikes are useful diagnostically, but we do not know why they are so strongly associated with the spontaneous seizures that characterize chronic epilepsy. Interictal spikes appear before the first spontaneous seizures in animal models of acquired epilepsy, and spikes are sufficient to induce long-term changes in synaptic connections between neurons. Thus, spikes may guide the development of the neuronal circuits that initiate spontaneous seizures. If so, then attempts to prevent or cure epilepsy may best be directed at spikes rather than seizures.
Al-Asmi A, Benar CG, Gross DW, Khani YA, Andermann F, Pike B, and others. 2003. fMRI activation in continuous and spike-triggered EEG-fMRI studies of epileptic spikes. Epilepsia44(10):1328-1339.
2.
Angeleri F, Majkowski J, Cacchio G, Sobieszek A, D’Acunto S, Gesuita R, and others. 1999. Posttraumatic epilepsy risk factors: one-year prospective study after head injury. Epilepsia40(9): 1222-1230.
3.
Annegers JF, Hauser WA, Coan SP, Rocca WA. 1998. A population based study of seizures after traumatic brain injuries. N Engl J Med338(1):20-24.
4.
Bains JS, Longacher JM, Staley KJ. 1999. Reciprocal interactions between CA3 network activity and strength of recurrent collateral synapses. Nat Neurosci2(8):720-726.
5.
Barry E, Sussman NM, O’Connor MJ, Harner RN. 1992. Presurgical electroencephalographic patterns and outcome from anterior temporal lobectomy. Arch Neurol49(1):21-27.
6.
Barth DS, Sutherling W, Engle J Jr, Beatty J.1984. Neuromagnetic evidence of spatially distributed sources underlying epileptiform spikes in the human brain. Science223:2936.
7.
Ben-Ari Y, Cherubini E, Corradetti R, Gaiarsa JL. 1989. Giant synaptic potentials in immature rat CA3 hippocampal neurones. J Physiol416:303-325.
8.
Berg AT, Shinnar S.1997. Do seizures beget seizures? An assessment of the clinical evidence in humans. J Clin Neurophysiol14:102-110.
9.
Buckmaster PS, Dudek FE. 1997. Network properties of the dentate gyrus in epileptic rats with hilar neuron loss and granule cell axon reorganization. J Neurophysiol77:2685-2696.
10.
Buckmaster PS, Dudek FE. 1999. In vivo intracellular analysis of granule cell axon reorganization in epileptic rats. J Neurophysiol81:712-721.
11.
Buzsaki G.1989. Two-stage model of memory trace formation: a role for “noisy” brain states. Neuroscience31(3):551-570.
12.
Buzsaki G, Bayardo F, Miles R, Wong RK, Gage FH. 1989. The grafted hippocampus: an epileptic focus. Exp Neurol105:10-22.
13.
Buzsaki G, Hsu M, Slamka C, Gage FH, Horvath Z.1991. Emergence and propagation of interictal spikes in the subcortically denervated hippocampus. Hippocampus1:163-180.
14.
Buzsaki G, Ponomareff GL, Bayardo F, Ruiz R, Gage FH. 1989. Neuronal activity in the subcortically denervated hippocampus: a chronic model for epilepsy. Neuroscience28:527-538.
15.
Cavazos JE, Das I, Sutula TP. 1994. Neuronal loss induced in limbic pathways by kindling: evidence for induction of hippocampal sclerosis by repeated brief seizures. J Neurosci14:3106-3121.
16.
Cukiert A, Buratini JA, Machado E, Sousa A, Vieira JO, Argentoni M, and others. 2001. Results of surgery in patients with refractory extratemporal epilepsy with normal or nonlocalizing magnetic resonance findings investigated with subdural grids. Epilepsia42(7):889-894.
17.
Dichter M, Spencer WA. 1969. Penicillin-induced interictal discharges from the cat hippocampus. I. Characteristics and topographical features. J Neurophysiol32:649-662.
18.
Esclapez M, Hirsch JC, Ben-Ari Y, Bernard C.1999. Newly formed excitatory pathways provide a substrate for hyperexcitability in experimental temporal lobe epilepsy. J Comp Neurol408:449-460.
19.
Gastaut H, Broughton R.1972. Epileptic seizures: clinical and electrographic features, diagnosis and treatment. Springfield (IL): Thomas.
20.
Gotman J.1991. Relationships between interictal spiking and seizures: human and experimental evidence. Can J Neurol Sci18 (4 Suppl): 573-576.
21.
Gotman J, Ives JR, Gloor P.1979. Automatic recognition of inter-ictal epileptic activity in prolonged EEG recordings. Electroencephalogr Clin Neurophysiol46:510-520.
22.
Graber KD, Prince DA. 2000. Alterations of neuronal connectivity in area CA1 of hippocampal slices from temporal lobe epilepsy patients and from pilocarpine-treated epileptic rats. Epilepsia41(Suppl 6):S190-S194.
23.
Hanson MG, Landmesser LT. 2004. Normal patterns of spontaneous activity are required for correct motor axon guidance and the expression of specific guidance molecules. Neuron43(5):687-701.
24.
Hellier JL, Dudek FE. 1999. Spontaneous motor seizures of kainate-induced epileptic rats: effect of time of day and activity state. Epilepsy Res35:47-57.
25.
Hellier JL, Patrylo PR, Dou P, Nett M, Rose GM, Dudek FE. 1999. Assessment of inhibition and epileptiform activity in the septal dentate gyrus of freely behaving rats during the first week after kainate treatment. J Neurosci19(22):10053-10064.
26.
Hufnagel A, Dumpelmann M, Zentner J, Schijns O, Elger CE. 2000. Clinical relevance of quantified intracranial interictal spike activity in presurgical evaluation of epilepsy. Epilepsia41:467-478.
27.
Ishibashi H, Simos PG, Wheless JW, Baumgartner JE, Kim HL, Castillo EM, and others. 2002. Localization of ictal and interictal bursting epileptogenic activity in focal cortical dysplasia: agreement of magnetoencephalography and electrocorticography. Neurol Res24(6):525-530.
28.
Katz LC, Shatz CJ. 1996. Synaptic activity and the construction of cortical circuits. Science274(5290):1133-1138.
29.
Kelley MS, Steward O.1997. Injury-induced physiological events that may modulate gene expression in neurons and glia. Rev Neurosci8:147-177.
30.
Khazipov R, Sirota A, Leinekugel X, Holmes GL, Ben-Ari Y, Buzsaki G.2004. Early motor activity drives spindle bursts in the developing somatosensory cortex. Nature432(7018):758-761.
31.
Kobayashi M, Buckmaster PS. 2003. Reduced inhibition of dentate granule cells in a model of temporal lobe epilepsy. J Neurosci23(6):2440-2452.
32.
Krakow K, Woermann FG, Symms MR, Allen PJ, Lemieux L, Barker GJ, and others. 1999. EEG-triggered functional MRI of interictal epileptiform activity in patients with partial seizures. Brain122(Pt 9):1679-1688.
33.
Krauss GL, Niedermeyer E.1991. Electroencephalogram and seizures in chronic alcoholism. Electroencephalogr Clin Neurophysiol78:97-104.
34.
Lehmann TN, Gabriel S, Kovacs R, Eilers A, Kivi A, Schulze K, and others. 2000. Alterations of neuronal connectivity in area CA1 of hippocampal slices from temporal lobe epilepsy patients and from pilocarpine-treated epileptic rats. Epilepsia41(Suppl 6):S190-S194.
35.
Leite JP, Babb TL, Pretorius JK, Kuhlman PA, Yeoman KM, Mathern GW. 1996. Neuron loss, mossy fiber sprouting, and interictal spikes after intrahippocampal kainate in developing rats. Epilepsy Res26:219-231.
36.
Lemieux L, Salek-Haddadi A, Josephs O, Allen P, Toms N, Scott C, and others. 2001. Event-related fMRI with simultaneous and continuous EEG: description of the method and initial case report. Neuroimage14(3):780-787.
37.
Leung LW. 1990. Spontaneous hippocampal interictal spikes following local kindling: time-course of change and relation to behavioral seizures. Brain Res513:308-314.
38.
Lisman J.1989. A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. Proc Natl Acad Sci U S A86(23):9574-9578.
39.
Lynch M, Sutula T.2000. Recurrent excitatory connectivity in the dentate gyrus of kindled and kainic acid-treated rats. J Neurophysiol83:693-704.
40.
Malenka RC, Nicoll RA. 1999. Long-term potentiation—a decade of progress?Science285(5435):1870-1874.
41.
Malow BA, Lin X, Kushwaha R, Aldrich MS. 1998. Interictal spiking increases with sleep depth in temporal lobe epilepsy. Epilepsia39:1309-1316.
42.
Matsumoto H, Ajmone-Marsan CA. 1964. Cortical cellular phenomena in experimental epilepsy: interictal manifestations. Exp Neurol9:286-304.
43.
Maytal J, Steele R, Eviatar L, Novak G.2000. The value of early postictal EEG in children with complex febrile seizures. Epilepsia41:219-221.
44.
Okazaki MM, Molnar P, Nadler JV. 1999. Recurrent mossy fiber pathway in rat dentate gyrus: synaptic currents evoked in presence and absence of seizure-induced growth. J Neurophysiol81:1645-1660.
45.
Overweg J, Binnie CD, Oosting J, Rowan AJ. 1987. Clinical and EEG prediction of seizure recurrence following antiepileptic drug withdrawal. Epilepsy Res1:272-283.
46.
Perez Y, Morin F, Beaulieu C, Lacaille JC. 1996. Axonal sprouting of CA1 pyramidal cells in hyperexcitable hippocampal slices of kainate-treated rats. Eur J Neurosci8:736-748.
47.
Prince DA. 1968. The depolarization shift in “epileptic” neurons. Exp Neurol21(4):467-485.
48.
Prince DA, Connors BW. 1986. Mechanisms of interictal epileptogenesis. Adv Neurol44:275-299.
49.
Quigg M, Clayburn H, Straume M, Menaker M, Bertram EH 3rd. 2000. Effects of circadian regulation and rest-activity state on spontaneous seizures in a rat model of limbic epilepsy. Epilepsia41:502-509.
50.
Roseman & Woodhall, Assoc. 1946. Res Nerv Ment Dis Proc 201-19.
51.
Salanova V, Markand O, Worth R.1999. Longitudinal follow-up in 145 patients with medically refractory temporal lobe epilepsy treated surgically between 1984 and 1995. Epilepsia40:1417-1423.
52.
Santhakumar V, Bender R, Frotscher M, Ross ST, Hollrigel GS, Toth Z, and others. 2000. Granule cell hyperexcitability in the early post traumatic rat dentate gyrus: the ‘irritable mossy cell’ hypothesis. J Physiol524(Pt 1):117-134.
53.
Schauwecker PE, Ramirez JJ, Steward O.2000. Genetic dissection of the signals that induce synaptic reorganization. Exp Neurol161:139-152.
54.
Shao LR, Dudek FE. 2004. Increased excitatory synaptic activity and local connectivity of hippocampal CA1 pyramidal cells in rats with kainate-induced epilepsy. J Neurophysiol92(3):1366-1373.
55.
Sjostrom PJ, Turrigiano GG, Nelson SB. 2001. Rate, timing, and cooperativity jointly determine cortical synaptic plasticity. Neuron20;32(6):1149-1164.
56.
Smith BN, Dudek FE. 2001. Short- and long-term changes in CA1 network excitability after kainate treatment in rats. J Neurophysiol85(1):1-9.
57.
Smith BN, Dudek FE. 2002. Network interactions mediated by new excitatory connections between CA1 pyramidal cells in rats with kainate-induced epilepsy. J Neurophysiol87(3):1655-1658.
58.
Staley KJ, Bains JS, Yee A, Hellier J, Longacher JM. 2001. Statistical model relating CA3 burst probability to recovery from burst induced depression at recurrent collateral synapses. J Neurophysiol86(6):2736-2747.
59.
Steward O, Cotman CW, Lynch GS. 1974. Growth of a new fiber projection in the brain of adult rats: re-innervation of the dentate gyrus by the contralateral entorhinal cortex following ipsilateral entorhinal lesions. Exp Brain Res20:45-66.
60.
Sundaram M, Sadler RM, Young GB, Pillay N.1999. EEG in epilepsy: current perspectives. Can J Neurol Sci26:255-262.
61.
Sutula T, He XX, Cavazos J, Scott G.1988. Synaptic reorganization in the hippocampus induced by abnormal functional activity. Science239:1147-1150.
62.
Tauck DL, Nadler JV. 1985. Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats. J Neurosci5:1016-1022.
63.
Toth Z, Hollrigel GS, Gorcs T, Soltesz I.1997. Instantaneous perturbation of dentate interneuronal networks by a pressure wave-transient delivered to the neocortex. J Neurosci17(21):8106-8117.
64.
Traub RD, Jefferys JG, Whittington MA. 1999. Functionally relevant and functionally disruptive (epileptic) synchronized oscillations in brain slices. Adv Neurol79:709-724.
65.
Traub RD, Miles R.1991. Synaptic function and organization in CA3. In: Neuronal networks of the hippocampus. Cambridge (UK): Cambridge University Press. Chap 3.
66.
Verrotti A, Morresi S, Cutarella R, Morgese G, Chiarelli F.2000. Predictive value of EEG monitoring during drug withdrawal in children with cryptogenic partial epilepsy. Neurophysiol Clin30(4):240-245.
67.
Wennberg R, Quesney F, Olivier A, Rasmussen T.1998. Electrocorticography and outcome in frontal lobe epilepsy. Electroencephalogr Clin Neurophysiol106:357-368.
68.
Wuarin JP, Dudek FE. 1996. Electrographic seizures and new recurrent excitatory circuits in the dentate gyrus of hippocampal slices from kainate-treated epileptic rats. J Neurosci16(14):4438-4448.
69.
Wuarin JP, Dudek FE. 2001. Excitatory synaptic input to granule cells increases with time after kainate treatment. J Neurophysiol85(3):1067-1077.
