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Biomedical subjects

J A Wada

Publications and source records attributed to J A Wada.

At least 55 records · Page 3Linked to original sources

Bifunctional roles of catecholamines in the development of amygdala kindling demonstrated by continuous intra-amygdala infusion of 6-hydroxydopamine.

Details of seizure stage progression in amygdala kindling were studied in the cat under local denervation of catecholamine input to the amygdala. A chemitrode was used for both electrical stimulation and continuous infusion of 6-hydroxydopamine. The extent of denervation was confirmed by fluorescence histochemistry. The result has indicated that catecholamine afferents to the amygdala exert biphasic roles in normal kindling: inhibitory in the early local and late generalized seizure stages, whereas facilitatory in the intermediate stage.

Amygdala↗

Role of the forebrain commissure and hemispheric independence in photosensitive response of epileptic baboon, Papio papio.

The effect of monocular intermittent light stimulation (ILS) of either hemivisual field (HVF) of the full visual field (FVF) was examined in Papio papio with or without forebrain bisection. ILS of the HVF or the FVF in non-bisected baboons produced bisymmetrical and bisynchronous spike and wave which was followed by a self-sustained seizure without EEG evidence of hemispheric independence. ILS of the FVF in bisected baboons also produced bilateral spike and wave and self-sustained seizures of a similar nature. With ILS of the HVF in bisected baboons, EEG seizures lateralized largely to the contralateral hemisphere and when the ILS of the HVF was switched to the other eye similarly lateralized spike and wave and a self-sustained seizure were produced in the other hemisphere. These findings suggest that (a) the forebrain commissure, most probably the corpus callosum (and possibly the hippocampal commissure), plays a major but not unique role in the bisynchronization and generalization of the ILS-induced spike and wave and the self-sustained seizures, and (b) each hemisphere possesses independent cerebral excitability to the ILS.

Animals↗

Midline thalamic lesion and feline amygdaloid kindling. I. Effect of lesion placement prior to kindling.

Nine cats with electrolytic lesion in the massa intermedia (MI, N = 8) and ipsilateral nucleus centrum medianum (CM, N = 1) underwent primary and secondary site amygdaloid (AM) kindling and primary site retest. During primary site kindling, MI- but not CM-lesioned animals showed a pattern of seizure development strikingly similar to that of forebrain-bisected cats and the development of contralateral hemiconvulsive seizure was coincident with the onset of afterdischarge (AD) in the ipsilateral motor cortex. Unlike the forebrain-bisected ones, the MI-lesioned animals eventually developed bisymmetrical clonic convulsion with initial contralateral and then ipsilateral clonic involvement. At the secondary site, no positive transfer effect was noted in 1 CM-lesioned and 6/7 MI-lesioned cats. When the primary site was retested, a marked interference effect was observed. The lesion site responsible for these unique kindling features was in the rostral half of the MI with varying involvement of the nucleus centralis medialis (NCM). It is concluded that the MI plays an important role both for transhemispheric ictal propagation and for positive transfer effect in feline AM kindling. However, the mechanisms underlying these two phenomenon are unlikely to be the same since these effects can be totally divorced.

Amygdala↗

Midline thalamic lesion and feline amygdaloid kindling. II. Effect of lesion placement upon completion of primary site kindling.

Lesion placement in the massa intermedia (MI) prior to amygdaloid (AM) kindling distinctively modifies the pattern of transhemispheric ictal transmission to one similar to that of forebrain-bisected cats, and eliminates the positive transfer effect (Hiyoshi and Wada 1988). Since the mechanism of AM seizure development is not the same as that for maintenance of AM-kindled seizure susceptibility, the effect of MI lesioning on established primary site AM-kindled seizures and secondary site AM kindling was studied in 8 cats. Upon the first primary site AM restimulation following MI lesioning, all animals responded with established bisymmetrical generalized tonic-clonic convulsions. Subsequent secondary site AM kindling showed (1) a distinctively modified seizure pattern identical to that observed during primary site kindling in cats with 'prior-to-kindling' MI lesions, and (2) complete absence of positive transfer effects. At primary site retest, the animals again responded with an established bisymmetrical convulsion and a marked interference effect (negative aftereffect) was noted. It is concluded that (1) the positive transfer effect at the contralateral homotopic AM is primary site hemisphere dependent, (2) the MI is critically involved in this effect, (3) the MI is not critical for maintaining the bisymmetrical pattern of AM-kindled convulsions, and (4) the mechanisms underlying the transhemispheric positive and negative transfer effects are different.

Action Potentials↗

The clinical use of EEG in a general psychiatric setting.

In a university teaching hospital, the charts of 150 psychiatric inpatients consecutively referred for EEG were reviewed to survey the clinical use of the EEG by psychiatrists. Individual psychiatrists referred between 18 and 31 percent of their caseloads, and 11.3 percent of the EEGs were abnormal. The only clinical indications significantly associated with an abnormal EEG were a history of epilepsy and suspicion of a recent seizure. The presence of an organic factor, which was previously identified in the history, mental status examination, or physical examination of 58 percent of the patients, was significantly associated with an abnormal EEG. However, none of the abnormal EEGs helped identify an organic etiology that was not already diagnosed, and in three cases clinicians appeared to ignore abnormal EEG results. Based on these data, the authors discourage the routine use of the EEG for psychiatric patients, recommending that an EEG be considered only when the clinical history and findings suggest an underlying organic disorder.

Adolescent↗

Results of anterior corpus callosum section in 24 patients with medically intractable seizures.

Twenty-four medically refractory seizure patients, who did not qualify for excisional surgery, had anterior two-thirds corpus callosum section. Three to 11 years' postoperative follow-up suggests that this procedure can (1) lateralize a frontal lobe focus, which may lead to subsequent localized excision and (2) significantly reduce seizure frequency and severity in 75% of the patients without giving any permanent neurologic deficits. Patients with an ictal focus confined to one frontal lobe did best (8/8 improved), followed by patients with secondarily generalized seizures and multifocal bilateral foci (5/6 improved). Patients with mental retardation benefited less frequently (5/10 improved), but 4/4 from this group with ictal falls associated with Lennox-Gastaut syndrome did benefit. In this series, the improvements following the anterior partial section were lasting if present at 1 year of follow-up. Anterior corpus callosum section should be considered as a diagnostic (lateralizing) and therapeutic option in appropriately defined medically refractory patients who do not qualify for excisional surgery.

Adolescent↗

A role of the striatum in premotor cortical seizure development.

Striatal function in partial seizure development induced by low frequency cortical stimulation of the ipsilateral premotor cortex was investigated by either electrolytic lesion placement or microinjection of putative neurotransmitter-related drugs into the ipsilateral striatum. Unilateral striatal lesioning and intrastriatal injection of muscimol, a GABA-agonist, and glutamic acid diethylester, a presumed antagonist for glutamatergic neurotransmission, were effective in suppressing seizure development, whereas intrastriatal injection of a subconvulsive dose of carbamylcholine chloride (carbachol), a cholinergic agonist, decreased the seizure threshold. In contrast to the ipsilaterally dominant metabolic activation in the intact animal, an inverse asymmetry due to a considerable reduction of deoxyglucose uptake in the ipsilateral thalamus, entopeduncular nucleus, substantia nigra, striatum and surrounding cortex of the focus was found in those brains with striatal lesion. Altogether, the findings suggest that experimental reduction of the inhibitory striatal outputs to both the entopeduncular nucleus and the substantia nigra enhances tonic activities of the projection GABAergic neurons in those nuclei, thereby inhibiting seizure development.

Animals↗

Bidirectional transfer between kindling induced by excitatory amino acids and electrical stimulation.

Chemical (C) kindling by means of repeated spaced injections into the amygdala (AM) of a subconvulsive dose of L-glutamate and L-aspartate combined in a molar ratio of 1:3. (Glu/Asp) produced progressive seizure development culminating in generalized convulsion strikingly similar to electrically kindled Stage 5 seizure in rats. These C-kindled AM sites responded readily to electrical stimulation with very rapid development of kindled seizure. When a separate group of rats electrically kindled at the AM were subjected to identical C-kindling at the kindled AM site, a similar positive transfer effect was observed. In addition, 30 days following the last injection, kindled Stage 5 seizure was triggered with a single injection of Glu/Asp, one-half of the dose used for C-kindling. These results suggest that the glutamate and/or aspartate systems participate in the development and persistence of increased seizure susceptibility induced by AM kindling.

Amygdala↗

Facilitation of premotor cortical seizure development by intranigral muscimol.

The role of the substantia nigra in seizure development was investigated using a chronic model of partial onset generalized seizure induced by low frequency cortical stimulation. Unilateral intranigral micro-injection of muscimol, a GABA receptor agonist, was found to facilitate partial onset seizure development, but did not affect developed seizures. This finding suggested that a non-dopaminergic, presumably GABAergic, mechanism was involved since the facilitatory effect of intranigral muscimol was not modified by haloperidol pretreatment.

Animals↗

Transcallosal response (TCR) in the chronic photosensitive baboon preparation, Papio papio. I. Premotor cortical stimulation, recovery cycle and neurotropic drug effect.

Transcallosal response (TCR) and its recovery cycle were studied in the chronic photosensitive baboon, Papio papio. Bipolar premotor intracortical stimulation evoked early positive (P1) and negative (N1) sequences followed by late small positivity (P2) and large negativity (N2) in the contralateral homotopic site. The sequential pattern of P1 and N1 was similar to that previously described in acute preparations. The recovery cycle as measured by means of paired stimuli with varying inter-stimulus intervals (ISI) showed a marked supernormality of P1 and N1 at an ISI of 15-200 msec with maximal facilitation up to 250-300% of the conditioning response at an ISI of 30-50 msec. Pentobarbital (10 mg/kg) suppressed this supernormality without causing a constant TCR amplitude change. In contrast, a significant increase in both the TCR amplitude and the supernormality of the recovery cycle was observed with a subconvulsive dose (3 mg/kg) of Megimide, a presumed antagonist of pentobarbital. Our results suggest that (a) the recovery cycle is a more sensitive measure than amplitude for assessing the effect of neurotropic drugs on TCR, and (b) the P1, N1 amplitudes and the supernormality may represent different neuronal processes involved in the TCR.

Animals↗

Transcallosal response (TCR) in the chronic photosensitive baboon preparation, Papio papio. II. Effect of premotor cortical kindling.

The chronological pattern of transcallosal response (TCR) and its recovery cycle were studied by single or paired stimulation of the homotopic primary and the secondary (contralateral) cortical site before, during and after primary site premotor cortical kindling in Papio papio. Prior to kindling, the sequential pattern of TCR was early positive (P1), negative (N1), late small positive (P2) and large negative (N2) components. The recovery cycle of both P1 and N1 showed a marked supernormal phase at an inter-stimulus interval of 15-200 msec with a peak at about 30 msec, showing maximal facilitation up to 300%. Kindling, with or without prior low frequency cortical stimulation, resulted in a long-lasting amplitude potentiation of both P1 and N1 and a significant modification of the late components. However, a transient amplitude reduction was noted immediately following completion of stage 5 kindling, presumably due to repeated generalized convulsions. These changes occurred only during primary (kindling), but not secondary, homotopic site stimulation. These findings suggest that a persistently increased callosal transmission is probably due to primary site kindling-induced functional alteration of the synaptic site at the homotopic secondary site cortex. In contrast, the supernormal phase of the TCR recovery cycle was suppressed significantly at the secondary site cortex. Since a similar suppressive effect was observed with a small dose of pentobarbital in naive baboons, kindling is considered to produce enhancement of the inhibitory mechanism. However, a diminished suppressive effect on the supernormality 20 days after the termination of kindling suggests that this suppressive effect is transient. It is probably related to the repeated kindled convulsive seizures rather than to the kindling process itself.

Animals↗

Role of the corpus callosum and hippocampal commissure on transfer phenomenon in amygdala-kindled cats.

Forebrain-bisected cats underwent kindling at primary and secondary amygdala sites. The behavioral effect of amygdala kindling was then examined according to the extent of the surgical lesion in the forebrain commissures. Bisection of the corpus callosum with or without lesion of the hippocampal commissure modified both kindling and kindled symmetrical generalized seizure into a lateralized and asymmetrical form. Lesion of the hippocampal commissure was correlated with the loss of the expected positive transfer effect at the secondary amygdala site. These results suggest that whereas the corpus callosum plays a major role in patterning convulsive generalization and generalized convulsion, the hippocampal commissure is involved in mediation of the transhemispheric positive transfer effect. Evidence of a callosal inhibitory influence on amygdala kindling was not obtained.

Amygdala↗

An epileptic syndrome caused by mesial frontal lobe seizure foci.

We describe an epileptic syndrome of bilaterally coordinated limb movements, axial movements, vocalization, and nonmasticatory oral activity. EEG and physiologic evidence indicates the syndrome is caused by ictal discharge in the mesial frontal lobes. Two of 12 patients were not helped by anterior temporal lobectomy, and 3 others improved after section of the anterior two-thirds of the corpus callosum.

Adolescent↗

Automation of the seizure investigation unit at the University of British Columbia Health Sciences Centre Hospital.

At the University of British Columbia Health Sciences Centre Hospital we have constructed an automated Seizure Investigation Unit for long term monitoring of epileptic patients. A central component of this system is a new device, developed at the University of British Columbia, which prevents video and EEG records of seizures recorded on video tape from being over-recorded. Computer technology is relied upon to a considerable degree in our unit. Computers are seen, in this phase of development of the SIU, as a means of making patient monitoring less dependent on supervision. They can help to redirect human energy towards complex analysis rather than time consuming and simple monitoring tasks.

Automation↗

Suppression of amygdala-kindled seizure in cats by enhanced GABAergic transmission in the substantia innominata.

The chronological effect of intracerebral injection of GABAergic drugs, either muscimol or gabaculine, into the substantia innominata, was examined in amygdala-kindled cats. Results obtained indicate: that the substantia innominata may play a significant role in ictal linkage between a nonmotor system such as the amygdala and the motor mechanism responsible for amygdala-kindled convulsion, and that the GABA terminals in the substantia innominata exert a suppressive action toward convulsive seizure generalization of amygdala origin.

Amygdala↗

A study of somatostatin receptors in amygdaloid-kindled rat brain.

The present study indicates that in kindled rats there are no differences in the total number or affinity of the binding sites in the temporal cortex and a slight increase in the total number of binding sites in the cortex when compared with controls. These results, in view of our other observations, suggest that in the kindled rat brain there may be an increased release of SRIF but no down-regulation of SRIF receptors in the temporal cortex and cortex. There appears to be a significant decrease in the number of SRIF receptors in kindled hippocampus. The mechanism by which this occurs remains unclear.

Amygdala↗

Cerebral organization of affect suggested by temporal lobe seizures.

A right-handed woman with independent left- and right-sided temporal lobe discharges was studied by continuous EEG and videotape monitoring for 3 weeks. Changes in affect were noted in the immediate and extended postictal periods and varied with the side of discharge. After a left-sided discharge, she became globally aphasic and depressed. Right-sided discharges evoked laughing and postictal hypomania. These manifestations were attributed to contralateral hemispheric disinhibition after ipsilateral seizure inactivation. This case provides evidence that the speech-dominant hemisphere subserves positive feelings and the nondominant hemisphere negative ones.

Adult↗