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Biomedical subjects

T M Darcey

Publications and source records attributed to T M Darcey.

31 records · Page 2Linked to original sources

Chronic focal epilepsy induced by microinjection of tetanus toxin into the cat motor cortex.

The tetanus toxin model of epilepsy, involving direct microinjection of toxin into the mammalian brain, has a number of advantages relative to other chronic models. However, chronic seizure foci have been confined primarily to the hippocampus. In the present study, 5 cats received total doses of 7.5-22.5 ng of tetanus toxin applied to the left primary motor cortex through an epidural cannula. After 2-18 days, all 5 cats exhibited similar persistent epileptiform syndromes. Three distinct types of spontaneous seizures were noted: focal motor seizures of variable complexity, focal motor seizures with secondary generalization, and epilepsia partialis continua. All cats required anticonvulsant therapy. Simple focal motor seizures, which predominated, were electrographically characterized by 3-5 Hz spike-sharp wave activity, originating in the left motor cortex, associated with contralateral shoulder and forepaw clonus and jacksonian spread. Electrographic activity quickly spread to ipsilateral neocortical structures, and in longer episodes to the cingulate gyri. Seizure foci were still active as long as 37 days after toxin injection. Light microscopic damage attributable to the toxin was absent. These experiments further generalized the tetanus toxin model and confirmed its advantages.

Animals↗

Human cortical potentials evoked by stimulation of the median nerve. I. Cytoarchitectonic areas generating short-latency activity.

1. The anatomic generators of human median nerve somatosensory evoked potentials (SEPs) in the 40 to 250-ms latency range were investigated in 54 patients by means of cortical-surface and transcortical recordings obtained during neurosurgery. 2. Contralateral stimulation evoked three groups of SEPs recorded from the hand representation area of sensorimotor cortex: P45-N80-P180, recorded anterior to the central sulcus (CS) and maximal on the precentral gyrus; N45-P80-N180, recorded posterior to the CS and maximal on the postcentral gyrus; and P50-N90-P190, recorded near and on either side of the CS. 3. P45-N80-P180 inverted in polarity to N45-P80-N180 across the CS but was similar in polarity from the cortical surface and white matter in transcortical recordings. These spatial distributions were similar to those of the short-latency P20-N30 and N20-P30 potentials described in the preceding paper, suggesting that these long-latency potentials are generated in area 3b of somatosensory cortex. 4. P50-N90-P190 was largest over the anterior one-half of somatosensory cortex and did not show polarity inversion across the CS. This spatial distribution was similar to that of the short-latency P25-N35 potentials described in the preceding paper and, together with our and Goldring et al. 1970; Stohr and Goldring 1969 transcortical recordings, suggest that these long-latency potentials are generated in area 1 of somatosensory cortex. 5. SEPs of apparently local origin were recorded from several regions of sensorimotor cortex to stimulation of the ipsilateral median nerve. Surface and transcortical recordings suggest that the ipsilateral potentials are generated not in area 3b, but rather in other regions of sensorimotor cortex perhaps including areas 4, 1, 2, and 7. This spatial distribution suggests that the ipsilateral potentials are generated by transcallosal input from the contralateral hemisphere. 6. Recordings from the periSylvian region were characterized by P100 and N100, recorded above and below the Sylvian sulcus (SS) respectively. This distribution suggests a tangential generator located in the upper wall of the SS in the second somatosensory area (SII). In addition, N125 and P200, recorded near and on either side of the SS, suggest a radial generator in a portion of SII located in surface cortex above the SS. 7. In comparison with the short-latency SEPs described in the preceding paper, the long-latency potentials were more variable and were more affected by intraoperative conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain↗

The magnetic and electric fields agree with intracranial localizations of somatosensory cortex.

We measured the magnetoencephalogram (MEG), electroencephalogram (EEG), and electrocorticogram (ECoG) after stimulation of contralateral median nerve in four patients with partial epilepsy evaluated for surgery. Quantitative localization estimates from equivalent source modeling were compared with locations of central fissure in hand sensorimotor area determined by cortical stimulations, intraoperative photographs, and examination after excision in frontal lobe. We also measured MEG and EEG in nine control subjects. MEG and EEG localizations were within 2.5 cm of the estimated location of central fissure in all 13 subjects. In the three patients who had complete mapping of all three fields, the average distance of localizations from central fissure was approximately 4 mm in both MEG and EEG, 3 mm in ECoG, and 3 mm in combined MEG and EEG. MEG was simpler than EEG, which was simpler than ECoG. MEG resolved ambiguities in both EEG and ECoG. The combination of the three fields added information about the spatiotemporal activity of somatosensory cortex. Localization of central fissure was essential to surgical treatment.

Brain Mapping↗

The magnetic field of complex partial seizures agrees with intracranial localizations.

The magnetoencephalogram (MEG) was recorded during 63 complex partial seizures in 4 patients. The MEG showed large biomagnetic signals occurring at the same time as discharges recorded from scalp electroencephalogram (EEG). These MEG signals had the same morphology and frequency as the discharges from the EEG. The location of the seizure focus was verified by depth electrode recordings in 2 patients and by lesions shown on computed tomographic scan and magnetic resonance imaging in the other 2. In each patient, MEG localization estimates were consistent with the location of the seizure focus shown by other methods. When seizures were recorded repeatedly and mapped with a single-channel magnetometer placed at different scalp locations in a single patient, the MEG localization agreed with the electrographic seizure focus localized from depth electrodes. In the maps, the MEG resolved an ambiguity in the scalp EEG and therefore increased the confidence of localization. MEG recordings of seizures may help localize epileptic foci noninvasively.

Cerebral Cortex↗

Spatio-temporal EEG measures and their application to human intracranially recorded epileptic seizures.

We describe analysis methods which involve the computation of band-integrated, intrachannel spectral measures from the EEG. These measures require only very general assumptions, have a simple interpretation and achieve significant data reduction, while providing a quantitative assessment of significant EEG modification at seizure or onset or in the course of seizure evolution. In developing these measures, we experimented with various measures derived from spatio-temporal power spectra. Bandpass (8-30 Hz) integrated relative energy measures appear to be the most useful since they objectively measure paroxysmal modification. Two such measures are illustrated in this report: the band-integrated power z-score (BIPZ), which is a quantitative measure designed to allow significance testing, and the band-integrated power ratio (BIPR), which is a simply calculated qualitative measure that behaves very similarly to the BIPZ measure and may be useful for real-time data screening. In addition to developing these intrachannel measures, we have also developed methods of displaying these measures in a format appropriate to the analysis of interchannel relationships. In a general sense, the displays provide objective information regarding the spatio-temporal dynamics of the EEG in a condensed format which is still readily understandable to the electroencephalographer. This analysis was applied to 29 spontaneous, depth-recorded seizures in 14 patients with the aim of identifying the initial locus of seizure activity in each seizure episode. The initial locus was defined as that location (or set of locations) to first exhibit statistically significant values of the BIPZ measure. The method was very effective in this regard, as shown by correspondence between the conclusions of this automated analysis and conventional visual analysis.

Brain↗

Spatio-temporal visually evoked scalp potentials in response to partial-field patterned stimulation.

Visually evoked scalp potentials (VESP) have been recorded at 40 electrode sites from each of 3 subjects. Pattern appearance/disappearance was used for whole field and partial field stimulation. The data are displayed as equipotential maps. The topographical features of the equipotential maps show periods of stable organization followed by periods of relatively rapid change. The structure of the maps changes in a consistent pattern with the region of the retina stimulated; the first peak fits well within the framework of the cruciform model of striate cortex. The first and second peaks of the VESP appear to be caused by independent neural generators. The work reported in this paper shows major agreement with other authors and reconciles some points of disagreement between them.

Electroencephalography↗

The dimensionality of the human visual evoked scalp potential.

A small number of processes can account for most of the evoked potentials activity in the two subjects studied. Principal components analysis indicates that six independent processes can account for approximately 97% of the variability in the data. Moreover, the factor analysis and plots of the factor coefficients yield indications that the times during which these principal factors are active agree quite well with the times at which the equipotential maps show some organized activity. The question of dipoles being the underlying cause of the observed activity is not answered by the factor analysis. The principal factors are not unique, but models which have a small number of parameters are more justifiable in light of the results of this study.

Brain↗

Chronic/semichronic limbic epilepsy produced by microinjection of tetanus toxin in cat hippocampus.

We describe an animal preparation in which a semichronic or chronic limbic epileptiform syndrome can be produced reliably by unilateral microinjection of tetanus toxin in cat ventral hippocampus. Injections were given at 1-week intervals until abnormal EEG activity was observed. After two to five injections, the animals abruptly began to exhibit intermittent spikes and subclinical discharges that soon gave way to spontaneous and recurrent behavioral seizures which gradually increased in frequency, duration, and severity in the next 12-48 h. Anticonvulsant therapy (phenobarbital, PB) was required within the first 3 days of the syndrome, since life-threatening generalized tonic-clonic seizures (GTCS) and status epilepticus would develop if the animal were left untreated. If severe seizures were prevented by antiepileptic drugs (AEDs) there was complete remission of the syndrome and repeat injection was necessary to reinitiate seizures. Animals that experienced severe seizures or that were reinjected after remission developed a chronic seizure syndrome and could be maintained with AEDs for long times (greater than 1 year) without significant debilitation. Although early spikes and subclinical discharges were typically focal to ipsilateral limbic sites, initial seizures appeared explosively in the form of a high-amplitude, high-frequency discharge, which often had an apparently bilateral limbic onset. On the other hand, chronic seizures had much more gradual onset and spread, often consisting of periodic sharp waves or low-amplitude sinusoidal discharge that was more clearly focal to ipsilateral limbic sites. Throughout the syndrome, ictal behavioral manifestations were highly stereotyped and very comparable to those described by other investigators in studies of clinical and experimental limbic epilepsy. All animals exhibited signs of independent contralateral involvement during the syndrome, ranging from independent contralateral spikes to subclinical discharges with a clear contralateral onset. None of the animals exhibited structural lesions on histologic examination at the level of light microscopy.

Amygdala↗

Experimental models of chronic focal epilepsy: a critical review of four models.

A number of experimental (i.e., animal) models have been developed to induce chronic focal epilepsy. Three of the most commonly employed are the alumina cream, kainic acid, and the electrical kindling techniques. A fourth approach involving the application of minute quantities of tetanus toxin to discrete brain sites, although relatively under-utilized, may be favorably compared to the aforementioned models.

Aluminum Oxide↗