Beta-adrenergic drugs do not affect phrenic nerve afterdischarge

Summary In anesthetized cats, a carotid sinus nerve was stimulated electrically. After this stimulation the time course of the afterdischarge in the phrenic nerve activity was studied in the control situation, during infusion of isoprenalin and after administration of metoprolol. The time courses were identical in all situations.It is concluded that in spite of the fact that the beta-adrenergic drugs change the steady state phrenic nerve activity, the afterdischarge is unchanged and therefore probably mediated by a separate mechanism. A comparison is made with analogous findings in patients with a hyperventilation syndrome.     

Cocaine and "pharmacological kindling" in the rat

The concept of "pharmacological kindling" has been used to explain the behavioral sensitization to cocaine produced by repeated administration of subconvulsive doses. This idea was tested by the repeated administration of cocaine to rats followed by electrical kindling of the olfactory bulb (a site at which cocaine has prominent electrophysiologic effects). No significant effect of cocaine on kindling was found. The relationship of this finding to studies using other drugs is discussed.     

Cortico-cortical evoked potential by single-pulse electrical stimulation is a generally safe procedure

ObjectiveCortico-cortical evoked potential (CCEP) by single-pulse electrical stimulation (SPES) is useful to investigate effective connectivity and cortical excitability. We aimed to clarify the safety of CCEPs.MethodsWe retrospectively analyzed 29 consecutive patients with intractable partial epilepsy undergoing chronic subdural grid implantation and CCEP recording. Repetitive SPES (1 Hz) was systematically applied to a pair of adjacent electrodes over almost all electrodes. We evaluated the incidences of afterdischarges (ADs) and clinical seizures.ResultsOut of 1283 electrode pairs, ADs and clinical seizures were observed in 12 and 5 pairs (0.94% and 0.39%, per electrode pair) in 7 and 3 patients (23.3% and 10.0%, per patient), respectively. Of the 18–82 pairs per patient, ADs and clinical seizures were induced in 0–4 and 0–3 pairs, respectively. Stimulating 4 SOZ (seizure onset zone) (2.5%) and 8 non-SOZ pairs (0.75%) resulted in ADs. We observed clinical seizures in stimulating 4 SOZ (2.5%) and 1 non-SOZ pair (0.09%). The incidence of clinical seizures varied significantly between SOZ and non-SOZ stimulations (p = 0.001), while the difference in AD incidence tended towards significance (p = 0.058).ConclusionAlthough caution should be taken in stimulating SOZ, CCEP is a safe procedure for presurgical evaluation.SignificanceCCEP is safe under the established protocol.     

Effects of amygdala lesions on dorsal hippocampus kindling in rats

In two experiments, bilateral amygdala lesions were shown to facilitate the rate of kindling from the dorsal hippocampus. This facilitation was produced equally by an amygdala lesion ipsilateral to the kindled focus, whereas a lesion contralateral to the focus was ineffective. An interesting negative correlation emerged between the kindling rate and latency to onset of forelimb clonus, i.e., the faster the kindling, the longer the convulsion latencies.     

Phencyclidine inhibition of the rate of development of amygdaloid kindled seizures

Administration of (5, 10, 20 or 35 mg/kg, i.p.) phencyclidine (PCP) 15 min prior to each stimulation significantly reduced the rate of kindling induced by daily electrical stimulation of the amygdala in the rat. All four doses significantly reduced the rate of kindling measured by the behavioral ranking (BR) and the afterdischarge duration (AD). The drug at 2.5 mg/kg had no significant effect on the rate of kindling. The 20- and 35-mg/kg PCP doses significantly reduced the afterdischarge duration evoked by the first stimulation to 40.2 ± 16.1% and 13.5 ± 9.2% (mean ± se) of the control value. The 5- and 10-mg/kg doses reduced the initial AD to approximately 65% of control. After switching from PCP to normal saline all rats kindled. The 5-mg/kg group which was injected 12 days with PCP required 15.0 ± 0.9 stimulations to develop a maximal BR whereas the control group required only 10.2 ± 0.5 stimulations. The saline controls were injected with 5 mg/kg PCP after their BR was maximal. This dose minimally reduced the AD to 88.8 ± 6.8% of the previous two stimulations and had no effect on the BR. It is apparent that 5 mg/kg PCP will inhibit the initial afterdischarge and the rate of kindling while minimally affecting fully kindled seizure activity. Naloxone at 6 mg/kg failed to reverse the inhibition of the rate of kindling produced by 5 mg/kg PCP daily. Neither 5 mg/kg morphine, an opiate agonist, nor 5 mg/kg quipazine, a serotonergic agonist, significantly affected the rate of kindling in similar experiments. Pretreatment of rats with 10 or 20 mg/kg PCP once daily for 4 days prior to the beginning of daily kindling stimulations did not affect the rate of kindling.     

Kindling in sensory systems: Neocortex

The kindling response of the visual and auditory neocortex (areas 17 and 41) was assessed in the hooded rat. Most subjects in these groups developed generalized convulsions after approximately 13 to 17 afterdischarges had been evoked. The convulsions shared many of the basic properties of limbic-type convulsions, but differed in various details, suggesting that a different neural mechanism was involved. The results demonstrate that sensory neocortex can be kindled in the rat.     

Potassium activity and changes in glial and neuronal membrane potentials during initiation and spread of afterdischarge in cerebral cortex of cat

Trains of electrical stimuli of increasing intensity were applied to the surface of the anterior suprasylvian gyrus to produce afterdischarges (AD) that remained localized or spread to a recording site 2 cm posteriorly in the same gyrus. The local afterdischarge was associated with a negative steady potential (SP) shift and increases in [K⁺]₀ that were maximal at or near the surface and gradually decreased in magnitude at deeper layers of the cortex.During spreading AD, recordings at the stimulus site showed a secondary increase in both the SP shift and [K⁺]₀ at about 400 to 1400 μm below the cortical surface. As the AD invaded the distant recording site it was associated with a comparable negative SP shift and increase in [K+]o. Neither the appearance of local AD nor its spread to the distant recording site were contingent upon critical elevations of [K⁺]₀.During secondary increases in [K+]o glial depolarizations were less than would be predicted if the membrane potential were determined solely by changes in the ratio of intra- to extracellular [K⁺]. Smaller deviations from the Nernst equation also occurred during the repolarizing phase of glial depolarization produced by weaker stimuli that did not produce a secondary increase in [K⁺]₀. Only immediately after the stimulus train did the relationship between glial depolarization and [K⁺]₀ approach the expected slope of a K⁺ electrode.Simultaneous intracellular recording of neurons and [K⁺]₀ did not show an increase in neuronal firing rate or membrane depolarization to account for the additional increase in [K⁺]₀ during spreading AD.The possible sources of the secondary increase in [K⁺]₀ and the significance of the failure of glia to depolarize to levels predicted by the Nernst equation are discussed.     

Cognitive effort decreases beta,alpha, and theta coherence and ends afterdischarges in human brain

ObjectiveMental activation has been reported to modify the occurrence of epileptiform activity. We studied its effect on afterdischarges.MethodIn 15 patients with implanted electrodes we presented cognitive tasks when afterdischarges occurred. We developed a wavelet cross-coherence function to analyze the electrocorticography before and after the tasks and compared findings when cognitive tasks did or did not result in afterdischarge termination. Six patients returned for functional MRI (fMRI) testing, using similar tasks.ResultsCognitive tasks often could terminate afterdischarges when direct abortive stimulation could not. Wavelet cross-coherence analysis showed that, when afterdischarges stopped, there was decreased coherence throughout the brain in the 7.13–22.53 Hz frequency ranges (p values 0.008–0.034). This occurred a) regardless of whether an area activated on fMRI and b) regardless of whether there were afterdischarges in the area.ConclusionsIt is known that cognitive tasks can alter localized or network synchronization. Our results show that they can change activity throughout the brain. These changes in turn can terminate localized epileptiform activity.SignificanceCognitive tasks result in diffuse brain changes that can modify focal brain activity. Combined with a seizure detection device, cognitive activation might provide a non-invasive method of terminating or modifying seizures.