Ketamine-induced Electroconvulsive Phenomena in the Human Limbic and Thalamic Regions

Ferrer-Allado, Theresa; Brechner, Verne L.; Dymond, Anthony M.; Cozen, Harry; Crandall, Paul H.

doi:10.1097/00000542-197304000-00006

Cited by 130 publications

(43 citation statements)

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“…In a previous study [Walczak & Jayakar, 1997], the sensitivity of an initial EEG in humans with epilepsy was 29-55%, which improved to 80-90% after serial studies were conducted. The greater sensitivity of scalp EEG observed in the present study may have been due in part to our use of ketamine, which has dose-dependent pro-and anticonvulsant effects [Ferrer-Allado et al, 1973;Arfel et al, 1976]. The specificity, on the other hand, may have been underestimated, as some of the controls may have had unwitnessed seizures, or the ketamine may have lowered the IED threshold in animals with a genetic or acquired predisposition to seizures.…”

Section: Ketaminementioning

confidence: 68%

“…It provoked seizures acutely after intramuscular administration, and activated discharges even in baboons with otherwise normal studies. Ketamine's proconvulsant effect was noted transiently at doses of o10 mg/kg [Ferrer-Allado et al, 1973;Arfel et al, 1976]. Intravenous doses of 0.5-4 mg/kg led to progressively more severe seizure activity.…”

Section: Ketaminementioning

confidence: 99%

“…papio with epileptogenic cerebral lesions [Ferrer-Allado et al, 1973], and in susceptible humans and animals with epileptogenic lesions [Bennett et al, 1973;Arfel et al, 1976]. Therefore, we also evaluated the electroclinical effects of ketamine in both seizure and asymptomatic animals.…”

Section: Ketamine Effectmentioning

confidence: 99%

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Scalp EEG for the diagnosis of epilepsy and photosensitivity in the baboon

Szabó

Leland

Sztonák

et al. 2004

American J Primatol

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Spontaneous seizures have been observed in several baboon species housed at the Southwest National Primate Research Center (SNPRC), including Papio hamadryas anubis and cynocephalus/anubis, hamadryas/anubis, and papio/anubis hybrids. The goal of this study was to establish a noninvasive, reliable electroencephalographic technique to characterize epilepsy phenotypes and assess photosensitivity in these subspecies. Thirty baboons with witnessed seizures, and 15 asymptomatic baboons underwent scalp electroencephalograms (EEGs) with photic stimulation (PS). The sensitivity and specificity of surface EEG for identifying interictal epileptic discharges (IEDs) in baboons with witnessed seizures were examined. The morphology of IEDs, electroclinical features of seizures and responses to PS, reproducibility of EEG findings, and intrarater reliability were also evaluated. Twenty-three seizure baboons (77%) demonstrated IEDs, predominantly with frequencies of 4-6 Hz in 18 baboons and 2-3 Hz in six baboons. Two seizure animals had a mixture of 2-3-Hz and 4-6-Hz IEDs. All animals with 2-3-Hz IEDs were 3 years old or younger. Myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were recorded in 13 baboons (43%). PS activated IEDs in 15 baboons (50%) and seizures in nine baboons. The presence of IEDs or seizures was not associated with a particular gender or species (Fisher exact test, alpha=0.05). Seizures were more common in animals >3 years old, while PS-induced IEDs and seizures were more prevalent in P.h. anubis/cynocephalus crosses compared to P.h. anubis. In the asymptomatic controls, IEDs were recorded in five baboons (33%), and photoparoxysmal responses were observed in two (13%). Surface EEG is a sensitive and reliable instrument for characterizing the epilepsy encountered in Papio species. Electroclinically, the seizure animals had generalized epilepsy with photosensitivity. The variation in IED morphology may be age-related or it may reflect different epileptic phenotypes. Ketamine provoked IEDs and seizures in most seizure animals and only in a few asymptomatic baboons; therefore, it may enhance the sensitivity of surface EEG for detecting a predisposition to epilepsy.

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Section: Ketaminementioning

confidence: 68%

Section: Ketaminementioning

confidence: 99%

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Scalp EEG for the diagnosis of epilepsy and photosensitivity in the baboon

Szabó

Leland

Sztonák

et al. 2004

American J Primatol

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“…Results of the original EEG studies (7-9, [18][19][20] suggested that the central effects of ketamine are mediated by depressing activity of somatosensory thalamocortical areas while activating limbic areas. Whereas our finding that somatosensory responses in the SI cortex are strongly suppressed by ketamine agrees with this theory, our discovery of strong excitatory influences on some neurons does not.…”

Section: Discussionmentioning

confidence: 99%

Ketamine Effects on Somatosensory Cortical Single Neurons and on Behavior in Rats

Patel

Chapin

1990

Anesthesia & Analgesia

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The neurophysiological effects of ketamine were studied at the single-neuron level in the somatosensory cortex of unanesthetized rats behaving in a treadmill movement paradigm. Chronically implanted 25-microns microwire electrodes were used to record spontaneous discharge, sensory responses, and sensorimotor-correlated activity of single neurons before and after ketamine administration. Extracellular action potentials of up to six single neurons were simultaneously recorded for several days, allowing ketamine effects to be tested repeatedly on the same neurons. Videotaped recordings obtained during each experiment were used to measure both the sensorimotor properties of the neurons and the changes in these measures caused by different doses of ketamine. Behaviorally, ketamine produced restless-hyperactive behavior at subanesthetic doses from 5 to 20 mg/kg (intramuscularly). At higher doses (30-50 mg/kg) the rats became cataleptic and immobile after the initial hyperactive period. Whereas the spontaneous rates of most neurons were reduced or unchanged after subanesthetic doses, a subgroup (27% of the total) exhibited markedly increased firing rates. This excitation was of a tonic nature, persisting for a dose-dependent duration in a manner that was not correlated with any of the behavioral effects of the drug. In further analyses, ketamine suppressed the sensory responses of virtually all of the recorded neurons. In particular, low doses of ketamine suppressed "sensorimotor" firing (mainly proprioceptive responses) of neurons in relation to active limb movement. It also suppressed virtually all neuronal sensory responses to the sudden onset of treadmill movement, although the time-course of this effect varied from neuron to neuron. These results reveal two separable effects of ketamine: (a) a strong inhibition of all somatosensory responsiveness in this area and (b) a tonic excitatory influence expressed heterogeneously on a subgroup of neurons. This coexistence of cortical neuronal excitation and sensory suppression in the same cortical region may explain in part the mechanism of dissociative anesthesia and hallucinatory side effects observed in humans during emergence from ketamine anesthesia.

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“…The electrophysiological consequences of systemic administration of ketamine are complex, with some regions showing inhibition and other regions exhibiting excitation that can progress to seizure-like activity. 47,63,64 By contrast, iontophoretic application of ketamine to neurons uniformly antagonizes NMDAevoked excitatory responses. [65][66][67][68] The well documented ability of ketamine to inhibit excitatory actions of NMDA at the cellular level, and induce excitatory responses after systemic administration, suggests that the excitatory effects of ketamine result from disruption of inhibitory neural circuits (ie from disinhibition).…”

Section: Neurobiological Consequences Of Nmda Antagonist Administrationmentioning

confidence: 99%

Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia

1999

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Available evidence indicates that clozapine is the most effective antipsychotic currently used for the pharmacotherapy of schizophrenia. Unfortunately, clozapine can cause serious side effects that limit the use of the drug. The therapeutic mechanism of action of clozapine is poorly understood, and accordingly, it has been difficult to design new drugs with the advantageous therapeutic properties of clozapine. Based on hypotheses that dopaminergic and serotonergic receptor-blocking properties of clozapine account for its clinical efficacy, several novel antipsychotic drugs have been introduced recently. There is currently insufficient data to reach definitive conclusions regarding the efficacy of the newer 'atypical' antipsychotics in comparison to clozapine. However, most published studies, and general clinical impressions, suggest that none of the newer drugs are as effective as clozapine in treating patients resistant to typical antipsychotic drug therapy. The present paper briefly reviews the clinical experience with the newer 'atypical' antipsychotic drugs and then discusses clinical and preclinical data potentially relevant to mechanisms of action of clozapine in relation to the NMDA receptor hypofunction hypothesis of schizophrenia.Keywords: clozapine; olanzapine; risperidone; ziprasidone; quetiapine; antipsychotic; schizophrenia; dopamine; NMDA The introduction of clozapine for the pharmacotherapy of schizophrenia represented a significant advance in the treatment of this devastating mental illness. Clozapine is superior to typical neuroleptic drugs (eg haloperidol) in treating positive and negative symptoms, and is effective in many patients who are refractory to typical antipsychotics. [1][2][3] In addition, clozapine does not induce the extrapyramidal side effects (EPS) commonly caused by the typical agents. Because of these properties, clozapine was termed atypical and represents the prototype drug of this class. Although clozapine is the most efficacious antipsychotic currently available, serious side effects induced by the drug, including agranulocytosis, impose substantial limitations on its use. Concerted research and development efforts have been made to produce an antipsychotic drug with the therapeutic advantages of clozapine, without the properties contributing to its serious side effects. However, the specific pharmacological characteristics of clozapine that confer its therapeutic properties are poorly understood. Clozapine binds to a diverse number of neurotransmitter receptors (see Table 1) but it is unclear whether actions at specific serotonin, dopamine, or adrenergic receptors, alone or in combination, account for its clinical efficacy.A number of specific hypotheses concerning mechanisms of action of clozapine have directed drug discovery efforts and led to clinical trials of drugs with widely different receptor-binding characteristics. The clinical experience with drugs whose development was inspired by clozapine will be briefly reviewed and then actions of clozapine and other antip...

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Ketamine-induced Electroconvulsive Phenomena in the Human Limbic and Thalamic Regions

Cited by 130 publications

References 0 publications

Scalp EEG for the diagnosis of epilepsy and photosensitivity in the baboon

Scalp EEG for the diagnosis of epilepsy and photosensitivity in the baboon

Ketamine Effects on Somatosensory Cortical Single Neurons and on Behavior in Rats

Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia

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