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PubMed1997

Possibilities and limitations of magnetic source imaging of methohexital-induced epileptiform patterns in temporal lobe epilepsy patients.

The usefulness of MEG-based techniques in lateralizing and localizing the epileptogenic area was investigated in the present study. Spontaneous and methohexital-induced spikes were studied in a group of 15 patients with temporomesial epilepsy using a 37-channel neuromagnetometer. The accuracy of the magnetic source imaging was compared to the results of electrocorticographic (ECoG) recordings. Differences of drug-induced spike densities in the MEG recordings between both sides confirmed a similar lateralizing power of the MEG and ECoG recordings. Source location analyses based on a moving dipole model resp. a rotating dipole model were performed using a spherical head model. After subdivision of the volume of each patient's head, 8 cm3 cubicles containing at least 3 source locations were projected onto the individual MRI scan and resulted in source locations within or close to the presurgically defined primary epileptogenic area only in 3 of the 15 patients. Spike induction by methohexital has the advantage of shortening the recording period as compared to recordings of interictal epileptiform discharges. However, the correlation analyses of spike densities from MEG and ECoG recordings and the source location analyses from MEG recordings indicate that spike generated in deep temporomesial structures may escape the MEG registration.

Adolescent↗

PubMed1998

Measurement of serosal temperatures and depth of thermal injury generated by thermal balloon endometrial ablation in ex vivo and in vivo models.

OBJECTIVE: To evaluate the safety profile of endometrial ablation performed with a thermal balloon as defined by serosal temperature elevation and depth of injury. DESIGN: Observational study with histopathologic correlation conducted in ex vivo and in vivo phases. SETTING: Academic medical center. PATIENT(S): Twenty patients undergoing total abdominal hysterectomy. INTERVENTION(S): Endometrial ablation with a thermal balloon. MAIN OUTCOME MEASURE(S): Serosal temperature elevation and histologic depth of injury. RESULT(S): Ex vivo phase results revealed serosal temperatures remained within a safe physiologic range (<45 degrees C). Greatest depth of myometrial injury in the premenopausal uteri was 5.8 mm over the anterior lower uterine segment. In postmenopausal uterus. the greatest depth of myometrial injury was 3.8 mm in the anterior midline. In vivo phase results revealed mean (+/- SD) peak serosal temperatures of 36.1 +/- 1.6 degrees C. As with the ex vivo phase. histologic examination revealed deep endometrial and superficial myometrial damage to all areas. The greatest depth of myometrial injury occurred in the midfundus at 3.4 mm. CONCLUSION(S): No patients experienced complications or adverse events secondary to treatment. Results showed that transuterine thermal injury is a highly unlikely scenario. In both phases of this study, histologic examination revealed that temperatures exposed to the endometrial layer were sufficient to cause tissue damage.

Adult↗

PubMed2025

Efficient Detection and Characterization of Targets of Natural Selection Using Transfer Learning.

Natural selection leaves detectable patterns of altered spatial diversity within genomes, and identifying affected regions is crucial for understanding species evolution. Recently, machine learning approaches applied to raw population genomic data have been developed to uncover these adaptive signatures. Convolutional neural networks (CNNs) are particularly effective for this task, as they handle large data arrays while maintaining element correlations. However, shallow CNNs may miss complex patterns due to their limited capacity, while deep CNNs can capture these patterns but require extensive data and computational power. Transfer learning addresses these challenges by utilizing a deep CNN pretrained on a large dataset as a feature extraction tool for downstream classification and evolutionary parameter prediction. This approach reduces extensive training data generation requirements and computational needs while maintaining high performance. In this study, we developed TrIdent, a tool that uses transfer learning to enhance detection of adaptive genomic regions from image representations of multilocus variation. We evaluated TrIdent across various genetic, demographic, and adaptive settings, in addition to unphased data and other confounding factors. TrIdent demonstrated improved detection of adaptive regions compared to recent methods using similar data representations. We further explored model interpretability through class activation maps and adapted TrIdent to infer selection parameters for identified adaptive candidates. Using whole-genome haplotype data from European and African populations, TrIdent effectively recapitulated known sweep candidates and identified novel cancer, and other disease-associated genes as potential sweeps.

Selection, Genetic↗

PubMed1988

Extraction of "deep" components from scalp EEG.

In an attempt to delineate the relative contribution of surface versus deep components in the EEG of patients with 3 per second generalized spike-wave discharges and clinical petit mal seizures, a mathematical method was devised which allows the splitting of the EEG into two major subsystems. It is based on the observation that broad electrical fields tend to represent activity at deeper structures while discrete narrow fields centered at one electrode position tend to be of more superficial origin. Since source derivation intentionally suppresses broad potential fields, a differentiation between superficial and deep activity can be achieved by subtracting the source density values from the corresponding electrode potential values. This will provide those aspects of the EEG which are contributed mainly by deep generators. The resultant data can then be subjected to eigenfunction analysis which yields few uncorrelated components. The percentage of contribution of each electrode to the total component thus derived can then be displayed as a topographic map. When this methodology was applied to ictal EEGs of three patients consistent results were obtained. The "deep" data yielded mainly two components with mutually perpendicular directions.

Cerebral Cortex↗

PubMed1993

[Photoablation of the cornea with pulsed 2790 nm ErCr:YSGG laser irradiation. Basic studies].

The potential of 3 microns solid-state lasers as an alternative to excimer lasers for photoablative corneal surgery was investigated. A Q-switched ErCr:YSGG laser (2790 nm, 200 ns) was used for irradiation of porcine corneas and agar-agar samples. Mechanical tissue effects (stroma, endothelium) were documented by micromorphology. Laser-induced shock-waves were analyzed by piezo-electric transducers. No sharp ablation threshold, as in excimer laser photoablation, could be determined. Energy fluences < 2 J/cm2 led to dehydration of the irradiated samples. Higher fluences are necessary for the evaporation of tissue water to be so vigorous that the tissue matrix is expelled along with the organic matrix. At high fluences, the ablation rate exceeds the absorption depth of the laser radiation (up to 25 microns/pulse). At fluences between 2.5 and 28 J/cm2 the thermal necrosis zone adjacent to the crater was 7 +/- 3 microns. The intensity of the laser-induced acoustic shock waves can peak to some hundred bar. Small gas bubbles up to 1 mm were found in the surrounding area of the ablation crater. Apparently, they were pressed between the collagen lamellas by the explosive force of the ablative process. In deep excisions (> 75%) endothelial defects underneath the beam axis could be documented. Large-area tissue ablation, with a resolution in the range of 1 micron, as necessary in myopia correction, will not be possible with the present generation of ErCr:YSGG lasers. Its high ablation rate makes this laser suitable as a cutting (astigmatism, keratoplasty, vitreous surgery) and drilling (glaucoma) device.

Animals↗

PubMed2025

Efficient detection and characterization of targets of natural selection using transfer learning.

Natural selection leaves detectable patterns of altered spatial diversity within genomes, and identifying affected regions is crucial for understanding species evolution. Recently, machine learning approaches applied to raw population genomic data have been developed to uncover these adaptive signatures. Convolutional neural networks (CNNs) are particularly effective for this task, as they handle large data arrays while maintaining element correlations. However, shallow CNNs may miss complex patterns due to their limited capacity, while deep CNNs can capture these patterns but require extensive data and computational power. Transfer learning addresses these challenges by utilizing a deep CNN pre-trained on a large dataset as a feature extraction tool for downstream classification and evolutionary parameter prediction. This approach reduces extensive training data generation requirements and computational needs while maintaining high performance. In this study, we developed TrIdent, a tool that uses transfer learning to enhance detection of adaptive genomic regions from image representations of multilocus variation. We evaluated TrIdent across various genetic, demographic, and adaptive settings, in addition to unphased data and other confounding factors. TrIdent demonstrated improved detection of adaptive regions compared to recent methods using similar data representations. We further explored model interpretability through class activation maps and adapted TrIdent to infer selection parameters for identified adaptive candidates. Using whole-genome haplotype data from European and African populations, TrIdent effectively recapitulated known sweep candidates and identified novel cancer, and other disease-associated genes as potential sweeps.

Journal Article↗

PubMed1993

Laboratory evaluation of a low prime closed-circuit cardiopulmonary bypass system.

We have explored the potential advantages of a low prime closed-circuit cardiopulmonary bypass (CPB) system using a non-human primate model. Although manufacturers have reduced priming volumes in individual CPB components, the standard circuit volume remains high because of the tubing diameter and length necessary for gravity drainage. By replacing gravity drainage with the negative pressure generated by a centrifugal pump, we can realize significant tubing volume reduction. Closed-circuit bypass was conducted on 13 baboons ranging from 5-15 kg. The circuit consisted of a centrifugal pump, a hollow fiber oxygenator, and 1/4" arterial and venous tubing. The design of the circuit included the capacity to remove a limited amount of venous air. Circulatory arrest during deep hypothermia with volume displacement into a reservoir was also accomplished with this circuit. The potential benefits of this low prime closed-circuit bypass system include blood conservation and reduction in blood surface area contact. The future safe clinical use of this type of closed-circuit bypass for routine open heart surgery will depend upon the incorporation of a device in the venous line to remove air. This is the greatest threat to patient safety in a closed circuit system and its use for open chest surgery must wait until an efficient venous air elimination device is available.

Blood Transfusion, Autologous↗

PubMed1976

Vitamin-A-induced mucous metaplasia. An in vitro system for modulating tight and gap junction differentiation.

Stratified squamous epithelia from 14-day chick embryo shank skin contain rare tight-junctional strands and only small gap junctions. Exposure of this tissue to retinoic acid (vitamin-A) (20 U/ml) in organ culture, however, induces mucous metaplasia, accompanied by tight-junction formation and gap-junction growth; untreated specimens continue to keratinize. To investigate sequential stages of junctional assembly and growth, we examined thin sections and freeze-fracture replicas at daily intervals for 3 days. During the metaplastic process, tight junctions assemble in midepidermal and upper regions, beginning on day 1 and becoming maximal on day 3. Two tight-junctional patterns could be tentatively identified as contributing to the emergence of fully formed zonulae occludentes: (a) the formation of individual ridges along the margins of gap junctions; (b) de novo generation of continuous ramifying strands by fusion of short strand segments and linear particulate aggregates near cellular apices. Gap junction enlargement, already maximal at day 1, occurs primarily three to four cell layers deep. Growth appears to occur by annexation of islands of 20-40 8.5-nm particles into larger lattices of islands separated by particle-free aisles. Eventually, a single gap junction may occupy much of the exposed membrane face in freeze-fractured tissue, but during apical migration of the cells such junctions disappear. The vitamin- A chick-skin system is presented as a responsive model for the controlled study of junction assembly.

Animals↗

PubMedDate not supplied

Estimates of the net excitatory currents evoked by visual stimulation of identified neurons in cat visual cortex.

The action potential discharge response of single neurons to both visual stimulation and injections of current were obtained during intracellular recordings in cat visual cortex in order to estimate the net excitatory current arriving at the soma during visual stimulation. Of 45 neurons recorded intracellularly, 19 pyramidal neurons and one basket cell were labelled with horseradish peroxidase. The discharge of all neurons adapted to constant current. For 40 neurons, a single exponential provided a good fit to the adapting discharge (r2 = 0.73 +/- 0.03) for all current intensities. Superficial layer neurons were significantly faster adapting [P < 0.001, mean (+/- SEM) time constant of adaptation = 11.5 +/- 1.3 ms; n = 20] than deep layer neurons (mean time constant of adaptation = 51.4 +/- 6.4 ms; n = 10). The percentage adaptation of the spike frequency, %(peak - adapted rate)/peak, was determined from the fitted exponential. Superficial layer neurons adapted significantly more strongly (P < 0.01, mean = 67 +/- 3%) than deep layer neurons (mean = 51 +/- 5%). The mean firing frequency in response to a current step of 320 ms duration had a linear relationship to the amplitude of the injected current (slope 66 spikes/s/nA; origin zero, mean r2 = 0.94; n = 33). This relationship provided a means of estimating the net peak excitatory current generated by visual stimuli. The estimated mean peak somatic current during the passage of a bar across the receptive field was 1.1 nA and the average current for the duration of the visually evoked discharge was 0.64 nA (n = 17). The transfer response of real and model neurons was obtained by differentiating the discharge response to a step input current and was then used to predict the output of the neuron following an arbitrary input. When these transfer responses were convolved with known input signals in model neurons, the predicted output was close to the simulated response of the model neuron to the same input waveforms. The transfer response was calculated for eight real neurons. Estimates of the net excitatory current arriving at the soma during visual stimulation was obtained by deconvolution. The mean peak somatic current for these neurons was 0.62 nA.

Action Potentials↗

PubMed1991

Neuroblastoma grafts are noninvasively removed within mouse neocortex by selective laser activation of intracellular photolytic chromophore.

Studies of neural cell transplantation would be aided by the ability to damage or destroy, noninvasively and extremely selectively, grafted cells at defined times following their initial implantation. Mechanisms of graft integration and performance could be investigated, also providing insight into natural injury and repair mechanisms. At long wavelengths between 650 and 850 nm, laser energy can penetrate several millimeters of brain tissue without absorption or damage to the unpigmented tissue. However, targeted cells are selectively damaged by illumination at these long wavelengths if they contain latex nanospheres with incorporated cytolytic chromophores (e.g., chlorin e6). Light penetration allows many thousands of cells to be lesioned simultaneously, noninvasively, and deep within a surrounding matrix of other tissue. Such laser-activated damage has been termed laser photolysis (PL). We studied damage to C1300 neuroblastoma (NB) cells grafted into mouse neocortex in vivo by this process of PL. NB cells provided a simple and reproducible model of neural grafting, allowing direct histologic assessment of cellular growth and viability by distinct morphologic and mitotic criteria. Cells were cultured by standard methods, labeled in vitro by brief exposure to nanospheres containing chlorin e6, and grafted to sites within deep layers of mouse neocortex. Mice were exposed to transcranial, fractionated, unfocused pulses of 670-nm-wavelength energy totaling 90-120 J/cm2. We histologically assessed graft growth and cellular viability over a period from 2 d to 4 weeks, measured graft volumes quantitatively during the period of early rapid growth in controls (2 and 7 d), and generated 3-D reconstructions from serial sections to assist in visual analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

[Changes in the sleep-wakefulness cycle in experimental Parkinson's syndrome].

It was demonstrated in rat experiments that in modelling the akinetico-rigid parkinsonian syndrome by injecting kainic acid into the caudate nuclei the phases of wakefulness and light slow-wave sleep decreased while the phase of deep slow-wave sleep increased. In the tremorogenic from of the parkinsonian syndrome induced by reserpine the phases of wakefulness and deep slow-wave sleep decreased in the rats while the phases of light slow-wave and paradoxical sleep increased. In destruction of the substantia nigra with kainic acid the phase of paradoxical sleep reduced. The results of the study are discussed from the standpoint of the generator mechanisms of the development of neuropathological syndromes and the mechanisms of the interrelations of parkinsonism and epilepsy.

Animals↗

PubMed1985

Infusion strategies to investigate the pharmacokinetics and pharmacodynamics of hypnotic drugs: etomidate as an example.

Etomidate was administered to six healthy volunteers by microprocessor controlled infusions, to generate three cycles of linearly increasing plasma levels, with an anticipated slope of 0.05 microgram ml-1 min-1. The infusions were stopped when a deep hypnotic state was obtained, as indicated by burst suppressions in the EEG. The infusions were restarted when the volunteers were fully orientated to person, place and time. The mean (+/-SD) doses of etomidate delivered by the first, second and third infusion were 165 +/- 30, 137 +/- 25 and 157 +/- 26 mg, respectively. Certain clinical signs were observed and related to the plasma concentrations of etomidate. Pharmacokinetic analysis was undertaken using an open two-compartment model. The therapeutic window was in a range of plasma concentrations between 0.3 and 1.0 microgram ml-1 of etomidate. Pharmacokinetic analysis gave a volume for the central compartment of 50 +/- 11 litre, an apparent volume of distribution of 252 +/- 51 litre and a total clearance of 1693 +/- 504 ml min-1. Microprocessor controlled infusions can serve as a powerful tool for research in clinical pharmacology. The achievement of linearly increasing plasma levels of etomidate allowed further pharmacokinetic and pharmacodynamic modelling concepts to be realized.

Adult↗

PubMed1997

Reaction of Nitrogen Chelates with the [Rh(2)](4+) Core: Bis-Chelate Products and Demonstration of Reversible, Chelate-Based Reduction Processes.

The preparations and properties are described of a series of [Rh(2)](4+) complexes possessing carboxylates and N-based chelates as ligands. Treatment of Rh(2)(O(2)CR)(4)(MeOH)(2) (R = Me (1), Et (2), Ph (3) or CF(3) (4)) with 2 equiv of 2,2'-bipyridine (bpy) in refluxing MeCN leads to the [Rh(2)(O(2)CR)(2)(bpy)(2)](2+) cation (in complexes 5-9). Reaction of 1 with 1,10-phenanthroline (phen), 4,4'-dimethyl-2,2'-bipyridine (Me(2)bpy), 4,4'-diphenyl-2,2'-bipyridine (Ph(2)bpy), and 4,7-diphenyl-1,10-phenanthroline (Ph(2)phen) leads to the analogous cations of complexes 10-13. Complex 6a, [Rh(2)(OAc)(2)(bpy)(2)(MeCN)(2)](PF(6))(2).2MeCN, crystallizes in monoclinic space group P2(1)/a with the following cell parameters at -172 degrees C: a = 14.433(2) Å, b = 12.810(1) Å, c = 22.78(3) Å, beta = 104.42(3) degrees, Z = 4, and V = 3971.2 Å(3). Complex 9, [Rh(2)(O(2)CCF(3))(4)(bpy)(2)].Me(2)CO, crystallizes in triclinic space group P&onemacr; with the following cell parameters at 20 degrees C: a = 14.260(4) Å, b = 15.375(4) Å, c = 9.709(2) Å, alpha = 105.98(2) degrees, beta = 97.49(2) degrees, gamma = 70.32(2) degrees, Z = 2, and V = 1925.2 Å(3). Both 6a and 9 contain a singly-bonded [Rh(2)](4+) unit with two cis bridging RCO(2)(-) groups and two syn-bpy chelate groups in a near-eclipsed conformation about the Rh-Rh vector. Reaction of [Rh(2)(tpy)(2)(MeCN)(4)](BF(4))(4) (15) (tpy = 2,2':6',2"-terpyridine) with NBu(n)(4)(O(2)CPh) gives [Rh(2)(O(2)CPh)(tpy)(2)(MeCN)(2)](BF(4))(3).MeCN (16). Complex 16 crystallizes in triclinic space group P&onemacr; with the following cell parameters at -168 degrees C: a = 11.684(4) Å, b = 20.373(8) Å, c = 10.451(3) Å, alpha = 93.47(2) degrees, beta = 110.53(1) degrees, gamma = 100.03(2) degrees, Z = 2, and V = 2274.1 Å(3). The cation of 16 consists of a [Rh(2)](4+) unit with a bridging PhCO(2)(-) group and two chelating tpy groups. The solution (1)H NMR properties of complexes 6-13 and 16 show the complexes to retain their solid-state structures on dissolution. The electrochemical properties of 6-13 and 16 were investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in MeCN. The bis(bpy) and -(phen) complexes 6-8, 10, and 11 show a reversible, one-electron reduction in the range -0.83 to -0.91 V vs ferrocene and an additional, irreversible reduction and an irreversible oxidation; the Ph(2)bpy (12) and Ph(2)phen (13) complexes show a two-electron reversible reduction at -0.61 to -0.76 and a reversible one-electron oxidation at 0.68-0.89 V. Consideration of the potentials as a function of carboxylate and chelate identity leads to the conclusion that the reductions are ligand (chelate)-based. This is supported by an extended Hückel calculation on the model compound [Rh(2)(O(2)CH)(2)(bpy)(2)(HCN)(2)](2+), which shows the LUMO to be a bpy-based orbital comprising in-phase, sigma overlap of two bpy pi orbitals, one on each of the syn-bpy groups. In contrast, complex 16 shows no reversible reduction processes. Complex 6b, [Rh(2)(OAc)(2)(bpy)(2)(MeCN)(2)](BF(4))(2), in MeCN may be reduced with sodium acenaphthylenide in THF to give deep blue [Rh(2)(OAc)(2)(bpy)(2)(MeCN)(2)](BF(4)) (14) in high yield. The cation of 14 may also be generated by controlled potential electrolysis of 6a in MeCN at -0.99 V and by heating of a solution of 6a or 6b in alcohol.

Journal Article↗

PubMed2026

Fast, accurate construction of multiple sequence alignments from protein language embeddings.

Multiple sequence alignment (MSA) is a foundational task in computational biology, underpinning protein structure prediction, evolutionary analysis, and domain annotation. Traditional MSA algorithms rely on pairwise amino acid substitution matrices derived from conserved protein families. While effective for aligning closely related sequences, these scoring schemes struggle in the low-identity "twilight zone." Here, we present a new approach for constructing MSAs leveraging amino acid embeddings generated by protein language models (PLMs), which capture rich evolutionary and contextual information from massive and diverse sequence datasets. We introduce a windowed reciprocal-weighted embedding similarity metric that is surprisingly effective in identifying corresponding amino acids across sequences. Building on this metric, we develop ARIES (Alignment via RecIprocal Embedding Similarity), an algorithm that constructs a PLM-generated template embedding and aligns each sequence to this template via dynamic time warping in order to build a global MSA. Across diverse benchmark datasets, ARIES achieves higher accuracies than existing state-of-the-art approaches, especially in low-identity regimes where traditional methods degrade, while scaling almost linearly with the number of sequences to be aligned. Together, these results provide the first large-scale demonstration of the power of PLMs for accurate and scalable MSA construction across protein families of varying sizes and levels of similarity, highlighting the potential of PLMs to transform comparative sequence analysis.

Deep Learning↗

PubMed2025

CASTER-DTA: Equivariant Graph Neural Networks for Predicting Drug-Target Affinity.

Accurately determining the binding affinity of a ligand with a protein is important for drug design, development, and screening. With the advent of accessible protein structure prediction methods such as AlphaFold, predicted protein 3D structures are readily available; however, methods for predicting binding affinity currently do not take full advantage of 3D protein information. Here, we present CASTER-DTA (Cross-Attention with Structural Target Equivariant Representations for Drug-Target Affinity), which uses an equivariant graph neural network to learn more robust protein representations alongside a standard graph neural network to learn molecular representations to predict drug-target affinity. We augment these representations by incorporating an attention-based mechanism between protein residues and drug atoms to improve interpretability. We show that CASTER-DTA represents a state-of-the-art improvement on multiple benchmarks for predicting drug-target affinity and that it generates novel insights for several related tasks. We then apply CASTER-DTA to create a large resource of the binding affinities of every FDA-approved drug against every protein in the human proteome and make these predictions freely available for download. We also make available a web server for researchers to apply a pretrained CASTER-DTA model for predicting binding affinities between arbitrary proteins and drugs.

deep learning↗

PubMed1980

Heating patterns produced by 434 MHz erbotherm UHF 69.

Thermal distributions of 434 MHz Erbotherm H 69 hyperthermia/diathermy generators in tissue-equivalent medium have been investigated. Thermocouples were used to measure temperatures at a set of grid points. Cylindrical and abdominal phantoms were heated and sectioned after heating to measure the temperatures at depth. Results indicate that there is potential for heating deep-seated tumors. The distributions were influenced by the number, shape and geometry of the applicators employed.

Diathermy↗

PubMed1997

The vanishing defibrillator syndrome: incidence, mechanism, and clinical relevance.

Intraperitoneal migration of an abdominally implanted cardioverter defibrillator is a complication not yet fully described. In a consecutive series of 195 patients, migration occurred between 1 and 20 months in 5 (8%) of the 63 patients in whom a subrectus abdomini placement of the generator was chosen. It was unrelated to the patients' clinical characteristics or the defibrillator model. Dysuria and inability to interrogate the device were present in every subject, and the diagnosis was confirmed by the characteristic abdominal x-ray appearance and the findings at the time of surgery. Adhesions involving the omentum, and in one case, the small bowels, were present in three patients and seem to be related to the length of intraabdominal permanence of the generator. Because this complication may be due to specific anatomical characteristics of the aponeurosis of the abdominal muscles, it is likely that its incidence will be unchanged by the use of smaller devices. A close follow-up of the generators implanted deep to the rectus fascia is therefore advisable.

Abdomen↗

PubMed1998

Pain processing traced by magnetoencephalography in the human brain.

The temporal and spatial processing of pain perception in human was traced by magnetoencephalography (MEG). We applied a painful CO2 laser beam to the forearm of 11 normal subjects, and estimated the activated areas using a single equivalent current dipole (ECD) at each time point, and a brain electric source analysis (BESA) as a spatio-temporal multiple source analysis method. The four-source model was found to be the most appropriate; sources 1 and 2 at the secondary sensory cortex (SII) contralateral and ipsilateral to the stimulation, and sources 3 and 4 at the anterior medial temporal area (probably the amygdalar nuclei or hippocampal formation) contralateral and ipsilateral to the stimulation, respectively. Activities in all 4 areas were temporally overlapped. Activity in the primary sensory cortex (SI) contralateral to the stimulated site was not identified. Activity in the cingulate cortex was also not clearly identified. These results are probably due to one or more of the following factors; (1) the cingulate cortex is too deep, (2) the ECDs generated in the cingulate cortex are mainly oriented radially, and (3) the ECDs generated in bilateral hemispheres interfere with each other. No significant or consistent magnetic fields were recorded after 500 msec following the stimulation, probably due to the complicated spatial and temporal overlapping of activities in multiple areas.

Adult↗