Summary:Purpose: To test the sensitivity of extracranial magnetoencephalography (MEG) for epileptic spikes in different cerebral sites.Methods: We simultaneously recorded MEG and electrocorticography (ECoG) by using subdural electrodes with 1-cm interelectrode distances for one patient with lateral frontal epilepsy and one patient with basal temporal epilepsy. We analyzed MEG spikes associated with ECoG spikes and compared the maximal amplitude and number of electrodes involved. We estimated and evaluated the locations and moments of the equivalent current dipoles (ECDs) of MEG spikes.Results: In patient 1, MEG detected 100 (53%) of 188 ECoG lateral frontal spikes, including 31 (46%) of 67 spikes that activated three subdural electrodes. MEG spike amplitudes correlated with ECoG spike amplitudes and the number of electrodes activated (p < 0.01). ECDs were perpendicular to the superior frontal sulcus. In patient 2, MEG detected 31 (26%) of 121 ECoG basal temporal spikes, but none that activated only three subdural electrodes. ECDs were localized in the entorhinal and parahippocampal gyri, oriented perpendicular to those basal temporal cortical surfaces. The ECD strength was 136.6 ± 71.5 nAm in the frontal region, but 274.5 ± 150.6 nAm in the temporal region (p < 0.01).Conclusions: When lateral frontal ECoG spikes extend >3 cm 2 across the fissure, MEG can detect >50%, correlating with spatial activation and voltage. In the basal temporal region, MEG requires higher-amplitude discharges over a more extensive area. MEG shows a significantly higher sensitivity to lateral convexity epileptic discharges than to discharges in isolated deep basal temporal regions. Key Words: Magnetoencephalography-Electrocorticography-Epilepsy-Extent of epileptic spikes-Sensitivity.Magnetoencephalography (MEG) measures the extracranial magnetic fields generated by intraneuronal electric currents with superconducting quantum interference devices (1). Extracranial magnetic fields result from intracranial tangential currents, such as neuronal activity, in the fissural cortex, which makes up two thirds of the surface of the human brain (2). During MEG analysis, magnetic field recordings are fitted to an equivalent current dipole (ECD) model to localize sources of intracranial activity, such as epileptic spikes; the spike source locations are then overlaid onto magnetic resonance (MR) images of corresponding areas of the brain. Because magnetic fields are relatively unaffected by the different electrical conductivities of the brain, cerebral spinal fluid, skull, and skin, MEG can accurately localize the source of intraneuronal electric currents that contribute to extracranial magnetic fields (3).Electroencephalography (EEG) dipole recordings delineate both radial and tangential currents (4). However, the electrical fields, as measured by EEG, are affected by the conductivities of different tissues.MEG has clinical application for patients with partial epilepsy. Neurosurgeons use advanced multisensor helmet-shaped, whole-head neuromagnetomete...

Summary:Purpose: The h current (Ih) is an inwardly mixed cationic conductance activated by membrane hyperpolarization and distributed predominantly in the apical dendrites of hippocampal pyramidal neurons. To verify a hypothesis that an anomalous hyperpolarization generates an abnormal excitation by way of Ih channels, we examined the effects of Ih blockers (CsCl and ZD7288) on electrically induced paroxysmal discharges (PADs).Methods: Fifty-three adult male rabbits were used. We measured the PAD threshold elicited by stimulation to the apical dendritic layer of the hippocampal CA1 region before and after injecting 50 l of each Ih blocker or saline extracellularly into the same region.Results: In Ih blocker injection groups (n ‫ס‬ 26), we obtained a significant increase in PAD threshold (1 mM CsCl: 163%, p < 0.01; 10 mM CsCl: 265%, p < 0.01; 100 mM CsCl: 199%, p < 0.01; 100 M ZD7288: 192%, p < 0.05; 1 mM ZD7288: 246%, p < 0.05). Conversely, we did not obtain the increase in PAD threshold in a saline injection group (n ‫ס‬ 10, 107%). The magnitude as well as duration of the effect had a tendency to depend on concentration of Ih blockers, although a saturated or declining tendency was observed with the 100 mM CsCl injection.Conclusions: We concluded that Ih channels might contribute to hippocampal epileptiform discharges in vivo. Our hypothesis for epileptogenesis demonstrated in the present experiment offers an idea to develop a new type of antiepileptic drug based on Ih blockers for the treatment of epileptic disorders refractory to current medications. Key Words: EpilepsyHippocampus-Paroxysmal discharge-Hyperpolarizationactivated current-In vivo physiology.Multiple ionic channels regulate neuronal activity. In the hippocampal CA1 region, Na + and Ca 2+ channels activate and inactivate neuronal membrane depolarizations and contribute to the generation of excitatory postsynaptic potentials (1-3). Before as well as after the membrane excitation, the release of ␥-aminobutyric acid from inhibitory interneurons induces inhibitory postsynaptic potentials (IPSPs) and suppresses/terminates the depolarizing potentials (4-6). Previous hypotheses for epileptogenesis were based on imbalance between such excitatory and inhibitory currents (7).Recently the h current (Ih) has been investigated (8-24), and the following characteristics of Ih were reported: (a) Ih is a voltage-gated nonselective cationic conductance activated by membrane hyperpolarization, not by depolarization (8,14); (b) Ih is blocked by cesium chloride (CsCl) or 4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride (ZD7288) instead of tetrodotoxin (8,13,15); and (c) Ih channels occur in higher density in the apical dendrites than in the soma (8,14). In spite of many in vitro reports on Ih channels (8-24) as well as in vivo studies on the pacemaking function of Ih (25-28), any contributions of Ih to epileptic activity are unknown in vivo, except for the one that showed the long-lasting enhancement of the widely expressed intrinsic Ih that converts...

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We investigated aberrant cortical excitability in malformations of cortical development From subdural electrodes, we recorded afterdischarges lasting > or = 6 seconds in 12 of 13 patients with malformations of cortical development and 6 of 10 pediatric patients with nonmalformations of cortical development and reviewed amperage thresholds, distribution of afterdischarges, and motor responses. In patients with malformation of cortical development, motor response thresholds were high; afterdischarge and motor response thresholds, which essentially overlapped, inversely correlated with age (P < .01); afterdischarge thresholds declined with age; and 8 patients showed afterdischarges in remote sites. In nonmalformation of cortical development, afterdischarge thresholds did not significantly correlate with age; motor response thresholds tended to decline with age; and 2 patients had remote afterdischarges. Adolescent patients with malformations of cortical development had lower afterdischarge thresholds than adolescents with nonmalformation of cortical development (P < .05). From their high afterdischarge (and motor response) thresholds, we concluded that preadolescent patients with malformation of cortical development have less excitable, immature cortices, whereas adolescent patients with malformation of cortical development with low afterdischarge thresholds have hyperexcitable cortices. Remote afterdischarges over focal dysplastic cortex suggest aberrant cortical excitability and neural circuits.

Kindling has been recognized as an animal model of human epilepsy. The standard kindling paradigm, first described by Goddard et al. (1,2), involves the repeated delivery of an electrical current through an implanted electrodc to a single forebrain site in mammals (3-6) of sufficient intensity to evoke an afterdischarge (AD). Recently, a modification of the standard kindling model known as alternate-site kindling has been reported (7-13). 11 involves the concurrent, alternate stimulation of two forebrain structures, which induces a functional disparity in seizure development between the two sites where one (dominant) site undergoes typical seizure development, and the seizure development from the other (suppressed) site is incomplete and goes no further, despite continued stimulation (1 3). The phenomenon, known as kindling antagonism, is a potentially useful Accepted March 17, 2000. Address corrcspondence and reprint requests to Dr. S. Kogure at Dcpartment 0 1 Bioengineering, Soka University, 1-236 Taogi-cho, Hachioji, Tokyo, 192-8577, Japan. E-mail: kogureQt.soka.ac.jp tool in discovering the mechanisms that facilitate and oppose seizure progression and gcneralization.Timofeeva and Peterson (14), using the singlc-site kindling of the rabbit hippocampus, showed a relationship between bilateral hippocampal interictal spiking and seizure generalization. We have also demonstrated that thc same procedure divided animals into two groups: kindled (K) and incomplete-kindling (IK) groups ( I 5-17). Furthermore, a complex type of interictal discharges (TIDs), of which the intracellular counterpart in CAI pyramidal cells was initial depolarization with a superimposed spike burst followed by a relatively shorter lasting hyperpolarization, increased its frequency during the kindling of the K group. In contrast, the IK group had a higher rate of the simple type of HDs, particularly B type, of which the intracellular counterpart corresponded to a (smaller) depolarization-(longer) hyperpolarization sequence.Based on our previous studies of unilateral kindling (UK) of the rabbit hippocampus, the bilateral kindling (BK) procedure was examined to see whether it would accelerate or decelerate kindling. 929

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Summary:Purpose: Alternate-site kindling (AK), which has been known to induce so-called kindling antagonism, was performed in the bilateral hippocampi to reveal neural mechanisms underlying hippocampal kindling.Methods: Ten adult rabbits were used. Daily kindling stimulation consisted of a 1-s train of 50 pulses (pulse duration, 1 ms) of 80 to 200 A (base-to-peak), which was higher than the afterdischarge (AD) threshold. The concurrent alternating stimulations were delivered to the right and left hippocampus once every 24 h.Results: All animals developed a stage 5 convulsion with a mean of 28.1 ± 3.3 (mean ± SEM) stimulations. The right and left hippocampus received 14.8 ± 1.7 and 14.6 ± 1.6 stimulations, respectively. Behavioral stages induced by stimulation of the right or left hippocampus evolved to generalized seizures along a similar course. Kindling antagonism was not observed.The two sides showed similar increases in AD duration, and similar chronologic changes in interictal discharge (IID) frequency. Simple A-type IID and complex types of IID appeared at higher rates, whereas simple B-type IID remained at a relatively low level.Conclusions: The present AK procedure did not induce kindling antagonism, but it induced progression of kindling manifestations. The origin of simple B-type IID is known to be in the contralateral side, and its intracellular counterpart corresponds to a sequence of small depolarization followed by large hyperpolarization, suggesting that plastic changes in the feedforward inhibitory system play an important role in hippocampal kindling.

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