Magnetic field profiles in normal human breast during the menstrual cycle.

OBJECTIVE: To investigate the subtle magnetic fields produced by living normal breast tissue during the menstrual cycle. METHODS: The magnetic activity of the breast was recorded in four young women, 26-28 years old; two had regular and two irregular menstrual cycles. The recordings were accomplished with a biomagnetometer and covered two complete menstrual cycles. The results were correlated with estrogen and progesterone levels on days 7, 14 and 21 of the menstrual cycle. RESULTS: The magnetic breast recordings in the two young women with the regular cycling endometrium showed a biphasic magnetic curve, apparently corresponding to the proliferative and secretory phase of the menstrual cycle. By contrast, the two young women with irregular menstrual cycles showed a monophasic magnetic curve. CONCLUSION: It is suggested that a biphasic, but not a monophasic, pattern of magnetic activity in the breast is indicative of an ovulatory endometrial cycle.

Encoding of visual information: correlation of EEG response to intracellular response.

The intracellular average evoked response to full field flash in cat visual cortex was seen to have constant PSP correlates in every individual response, with a less constant relationship to spike activity. All components of the averaged evoked response in the gross EEG are explicable in the response of a single cell, including a component of latency 100 ms for which there is evidence of initiation at the apical dendrites. The data support the hypothesis that information about photostimulation is encoded at the level of the individual cell, with distortion resulting from extraneous "noise".

Differences in human visual evoked potentials during the perception of colour as revealed by a bootstrap method to compare cortical activity. A prospective study.

The aim of this prospective study was to investigate the colour related information in cortical activity as it is recorded from the scalp, by comparing the shape of the potential fields. Six healthy volunteers and two volunteers with known protanopsia were used to record multichannel visual evoked potentials after stimulation with chromatic stimuli of equally perceived brightness. The scalp fields resulting from each of the four chromatic stimuli were compared in pairs, in every possible combination and for each time point, using Efron's bootstrap method. It was found that, in comparison to other stimuli responses, the long dominant wavelength stimulus results in significant differences of cortical activity. These are mainly identified in two time periods: (a) at mid-latency responses, usually during the onset and development of P100 component, and (b) after the peak (on the decline) of P100 component. Similar but less evident behaviour was identified when the responses from the short dominant wavelength stimulus were compared with those from the other stimuli. Colour effects were not significant in protanops. The proposed method can be used to locate in time and quantify the differences in cortical activity during colour perception.

Filling of microelectrodes: an expedient solution.

Micropipettes of small diameter filled with an electrolyte solution have been used widely to record electrophysiological potentials. Filling micropipettes is a major problem for many researchers. We describe an expedient and reliabel method of solving this problem by using parts that can be easily found in any research laboratory. Among the most important parts are; a vacuum pump, two stands, a container, tubes and a few clamps. The filling of these micropipettes can then be easily done by using negative pressure through the fine tip. With the drop in pressure distilled water or an electrolyte is forced downward inside the pipette thus filling the electiode tip.

MEG measurements with SQUID as a diagnostic tool for epileptic patients.

In experimental studies with a SQUID (Super-conducting QUantum Interference Device) second order gradiometer, we recently registered the magnetoencephalogram (MEG) from different subjects under different physiological and psychological conditions from which we will determine normal and abnormal function of the human brain. Thus with our first measurements using the MEG spectra, we have succeeded in identifying the exact location of the abnormality in the human brain as shown in several individuals.

Spatiotemporal stationarity of epileptic focal activity evaluated by analyzing magnetoencephalographic (MEG) data and the theoretical implications.

BACKGROUND: The emitted brain neuromagnetic activity was recorded from patients suffering from idiopathic epilepsy, using a Superconductive Quantum Interference Device (SQUID). This activity will be referred as magnetoencephalogram (MEG). METHODS: The MEG recording which were obtained from 32 equal spaced points of a rectangular 4 x 8 matrix were analysed using Fourier statistical analysis. Then, a two dimensional brain mapping technique was utilized in order to detect the possible existence and the accurate localization of epileptic foci. The applied technique was based on the construction of ISO contour maps which are lines of equal power spectral amplitudes of the scalp spatial distribution of the recorded MEGs specific frequency bands. These maps will be referred as ISO-SA maps. A number of more than 200 epileptic patients were examined using this method. For each patient the magnetic brain activity was recorded for the temporal lobes, the frontal lobe and the occipital lobe. ISO-SA mappings were reconstructed for the frequency bands of the compound delta and theta rhythms (2-7 Hz), the alpha rhythm (8-13 Hz), and the beta rhythm (14-25 Hz). In these mappings epileptic (pathological) foci are represented as points emitting abnormal high magnetic power in the frequency band of 2-7 Hz. RESULTS: Systematic MEG measurements showed that the abnormal activity of a certain cortex region, when present, is stationary, i.e., time-invariant. CONCLUSIONS: Brain magnetic fields on the order of magnitude a picotesia are considered as to their possible physiologic nature, and a query is made as to what physical mechanisms might be involved in this propitiation.

The biological effects of magnetic stimulation in epileptic patients.

BACKGROUND: The magnetoencephalogram (MEG) is the magnetic activity emitted by the brain, which can be measured using a superconductive quantum interference device (SQUID). This is a totally non-invasive method for localizing functional healthy, epileptic and other CNS brain disorders. METHODS: Using the MEG brain activity recorded from epileptic patients we were able to obtain a mapping technique characterized by the ISO-spectral amplitude of scalp distribution of the MEG Fourier power spectrum. In addition, by utilizing the above recorded MEG activity we energize an electronic device, which emits back to the abnormal brain points of the epileptic patients magnetic fields with proper frequencies and intensities. RESULTS: Using this method we present here in more detail three randomly selected epileptic patients in which application of external magnetic fields of low intensities and frequencies produced a substantial attenuation of their abnormal brain activity. Furthermore, we present a statistical analysis of 50 randomly selected epileptic patients who underwent magnetic stimulation for the treatment of their seizures and we found that the anticonvulsant response to magnetic stimulation was statistically significant (chi 2 = 6.55, df = 1, p < 0.02). CONCLUSIONS: Our findings indicate that the use of low external magnetic fields produce substantial attenuation in seizure activity in epileptic patients and therefore it may open new ways in the future for management of epileptic activity.

Nonlinear analysis of biomagnetic signals recorded from the umbilical artery in normal and pre-eclamptic pregnancies.

OBJECTIVE: In this study we investigated the hemodynamics of the feto-placental circulation in normal and pre-eclamptic near term pregnancies using the biomagnetometer SQUID. Thirteen abnormal and 25 normal pregnancies were included in this study. STUDY DESIGN: The biomagnetic signals were analyzed using nonlinear analysis in order to differentiate these two types of pregnancies. RESULTS: The application of nonlinear analysis reveal a clear saturation dimension value for pre-eclamptic and non-saturation for normal pregnancies. These findings were statistically significant and were correlated with fetal heart rate monitoring, pH and Apgar score: high biomagnetic cases (140-300 fT/square root Hz) were related with normal patterns, pH>7.25 and Apgar >7, while low biomagnetic recordings (50-110 fT/square root Hz) were connected with abnormal patterns, pH<7.25 and Apgar <7. CONCLUSIONS: It is suggested that the biomagnetic measurements with SQUID and the application of nonlinear analysis, is a promising procedure in assessing fetal health, especially in high risk pregnancies.

Biomagnetic measurements in uterine leiomyomas using a superconducting quantum interference device (SQUID).

Using the biomagnetometer superconducting quantum interference device (SQUID), the magnetic signals relating to spontaneous uterine activity were measured for the first time in 25 women with uterine leiomyomas, and 12 women with normal, non-leiomyomatous, uteri. Magnetic radiation, in the range of low frequency (below 2 Hz), was of low amplitudes in normal uterine tissues and of high amplitudes in benign leiomyomas. The observed differences were confirmed by the corresponding power spectra obtained from the statistical Fourier analysis. It is suggested that biomagnetic measurements may facilitate the detection of uterine leiomyomas in equivocal cases.

Differential diagnosis of breast lesions by use of biomagnetic activity and non-linear analysis.

PURPOSE: Breast cancer mortality rates have not changed during the past 60 years despite significant advances in screening methods. It is tempting therefore to use novel technology in order to better understand breast oncology. In this study we investigated the biomagnetic activity obtained in benign and malignant breast lesions using a single channel biomagnetometer SQUID (Superconducting Quantum Interference Device) in order to assess the method's efficacy in the differential diagnosis of these two types of lesions and its establishment as a screening technique. METHOD: Magnetic recordings were obtained from 21 patients with palpable breast lumps. Of these 11 were invasive carcinomas and 10 were benign breast lesions. We used non-linear analysis to investigate whether there is any biological differentiation in the dynamics in these two types of lesions. RESULTS: High amplitudes characterized the waveform of a malignant breast lesion whereas in benign breast lesions the corresponding amplitudes were low. Using the application of non-linear analysis we observed a clear saturation value for the dimension of malignant breast lesions and no saturation for benign ones. DISCUSSION: Biomagnetic measurements with the SQUID and the application of non-linear analysis are promising procedures in assessing and differentiating breast tumors.

Evaluation of CNS-function in CAPD patients using magnetoencephalography (MEG): comparison with hemodialysis patients.

In order to evaluate the CNS-function of uremic patients, the magnetic activity emitted from the brain of 20 pts (10 pts on CAPD and 10 on HD) was measured. MEG consisted of taking 32 consecutive records from the 32 equally spaced points chosen on the skull in uremic pts around our reference points T3, T4, P4, F3, F4 of the international 10-20 electrode placement point system. MEG data were converted using an AD-converter with sampling frequency 256 Hz and stored in a P/C. Our results showed significant differences between the two groups. In all HD pts there was abnormal magnetic brain activity with high spectral amplitudes (in the band 2-7 Hz) which was more prominent in pts in hemo for more than 4 years. The magnetic activity was within normal ranges in all CAPD pts. We conclude that: 1) There is high magnetic brain activity in HD pts, which in accordance with the EEG findings are signs of diffuse encephalopathy. 2) CAPD pts show a very low magnetic brain activity which must be interpreted as normal brain function, and 3) MEG can be useful in further measurement of adequacy of dialysis.

A neural model theory leading to kindling effect of epilepsy.

The dynamics of neural nets constructed of discrete populations of formal neurons were investigated, beginning with the study of single probabilistic nets which were called netlets. The dynamics of these netlets was extended to include steady or slowly varying excitatory or inhibitory inputs. Results obtained with this approach showed simple hysteresis phenomena. However, by considering that the neural connections can be set up by means of chemical markers carried by the individual neurons the dynamics of such systems exhibits not only simple hysteresis but also multiple phenomena. Such hysteresis loops may be considered to represent the basis for short-term memory. The later study of probabilistic neural nets with chemical markers was generalized by considering the intrinsic noise of the system, caused by the spontaneous release of synaptic transmitter substance. On the basis of these studies of noisy neural nets we proposed a model for epileptic phenomena and a theory leading to kindling effect of epilepsy.

Localization of epileptiform foci by means of MEG measurements.

Systematic studies of the magnetoencephalogram (MEG) in normal and pathological subjects (mainly with focal epilepsies) showed that the MEG may evidence significant brain activities even if they are not identifiable in the electroencephalogram (EEG). They also showed that the MEG has a considerably higher spatial resolution than the EEG. A two-dimensional mapping technique was used to get such a representation of the data that would enable the investigator to draw his conclusions mainly from inspecting the plots. The technique is characterized by an isospectral synchronized power (iso-SSP) mapping of the scalp distribution of specified frequency bands of the MEG power spectrum. In this way the precise projection on the scalp of an epileptiform focus can be determined without applying a strong eliciting stimulus or relying on the analysis of the simultaneously recorded EEG. Our results compare very favourably with the clinical picture of our pathological subjects.

Neural net simulation of the corpus callosum.

The effects of simulated anatomical and physiological parameters were investigated in a "neural net" model, where two neural nets corresponding to two small patches of cerebral cortex were connected by a simulated "corpus callosum." The isolated neural nets have previously been shown to exhibit oscillatory activity similar to the raw EEG. By connecting the nets with fibers which have a specified percentage of inhibition and a specified percentage of homotopicity, the effects of such parameters on the cyclic activity of the nets were studied. It was found that, regardless of the inhibitory-excitatory nature of the simulated corpus callosum, the cyclic activity established in one hemisphere is more readily transferred to the contralateral hemisphere, the greater the percentage of homotopic callosal fibers. Learning was more rapid when the effect of the corpus callosum was primarily excitatory, but learning also took place over inhibitory or mixed callosal tracts. The simulation does not therefore resolve the issue of the predominant physiological effect of the corpus callosum, but does indicate that, given the assumptions of the simulation, "learning" can occur regardless of the percentage of excitatory or inhibitory fibers. It is noteworthy that homotopicity was more important for learning across an inhibitory tract than across an excitatory tract.

Localization and cure of epileptic foci with the use of MEG measurements.

Systematic studies with pathological subjects with focal and general epilepsies using magnetoencephalographic (MEG) measurements showed significant brain activities even if they are not present in the electroencephalogram EEG. Using a mapping technique characterized by an isospectral amplitude (ISO-SA) of the scalp distribution of specified spectral components or frequency bands of the MEG power spectrum we were able to localize the epileptic foci. This localization of epileptic foci gives us information on the emitted magnetic field intensity and frequency for each focal point on the map of the patient. Using this information we can cure the patient by adjusting an electronic device which can emit back to the specific scalp point a magnetic field of the same intensity and frequency as the one which-is emitted from it. The principle of this technique is based on the physical phenomenon of Young's double-slit experiment by which under certain condition light plus light gives darkness.

Magnetic fields alter the circadian periodicity of seizures.

We have recently reported that application of external, weak magnetic fields attenuated seizures in epileptic patients (Anninos et al., 1991). However, the mechanisms by which magnetic stimulation reduces seizure activity are unknown. We present four non-selected epileptic patients the first to be rated by the senior author, in whom treatment with magnetic fields attenuated the severity of seizures and also altered the circadian occurrence of seizures. The first patient, a 27-year old woman, had generalized tonic-clonic seizures which occurred almost exclusively at night. Following treatment with magnetic fields she experienced attenuation of seizures which then occurred only after waking up in the morning. The second patient, a 42-year old man, had generalized tonic-clonic seizures which occurred randomly during the day and night. Treatment with magnetic fields resulted in disappearance of nocturnal seizures with seizures now occurring exclusively during the day. The third patient, a 21-year old woman had generalized tonic-clonic seizures which occurred randomly during the day. After treatment with magnetic fields she was free of seizures for 7 months, but recently experienced one attack in the morning hours while sleeping. The fourth patient, a 39-year old woman had secondary generalized seizures since the age of 12. Prior to treatment with magnetic fields she had 8-10 seizures daily which occurred randomly during the day and night hours. Magnetic treatment resulted in attenuation in seizure frequency (1-2/day) with seizures now occurring only during the day. We propose, therefore, that since the pineal gland is a magnetosensitive organ which "transduces" environmental information of the light-dark cycle and of the earth's magnetic field into an endocrine message mediated via the circadian release of melatonin, and since it is recognized that melatonin attenuates seizure activity, artificial magnetic fields attenuate seizure activity by altering the functions of the pineal gland.

Attenuation of epilepsy with application of external magnetic fields: a case report.

We have previously demonstrated that magnetoencephalographic (MEG) brain measurements in patients with seizure disorders show significant MEG activity often in the absence of conventional EEG abnormalities. We localized foci of seizure activity using the mapping technique characterized by the ISO-Spectral Amplitude (ISO-SA) on the scalp distribution of specified spectral components or frequency bands of the emitted MEG Fourier power spectrum. In addition, using an electronic device, we utilized the above recorded activity to emit back the same intensity and frequency of magnetic field to the presumed epileptic foci. Using this method we were able, over the past two and one-half years, successfully to attenuate seizure activity in a cohort of over 150 patients with various forms of epilepsy. We present a patient with severe epilepsy and behavioral disturbances in whom application of an external artificial magnetic field of low intensity produced a substantial attenuation of seizure frequency which coincided with an improvement in the patient's behavior. This case demonstrates that artificial magnetic treatment may be a valuable adjunctive procedure in the management of epilepsy.

Effect of structure on function in model nerve nets.

A theoretical analysis has been made on the effect of the pattern of interneuronal connectivity in model nerve nets on the activity of these nets. Two types of nets have been investigated: one in which the likelihood of a connection between a given neuron and any other element in the net is given by a Poisson probability distribution, and a second type in which the pattern of interconnection follows a Gaussian distribution. An analytical treatment is presented of the equations for noiseless nets in these two conditions. The principal result is that nets with Poisson connectivity law are activated by extraneous firing of a single neuron and continue in spontaneous activity indefinitely. On the other hand, similar nets in which the connections are, however, distributed according to a normal connectivity law, exhibit a definite threshold and produce spontaneous activity only subsequent to extraneous activation of a substantial fraction of the population. Moreover, spontaneous activity in Gaussian nets, but not in Poisson nets, becomes extinguished if the number of active neurons falls below the critical threshold. Some neuroanatomical implications are discussed which suggest that the pyramidal system of the cerebral cortex and other neuronal systems histologically characterized by large numbers of synapses per neuron may incorporate a Gaussian connectivity law, whereas a Poisson law may be characteristic of these cortical layers and nuclei primarily containing granule cells.

A neural net model for the alpha-rhythm.

Because of the enormous complexity which characterizes the activity of the brain a special effort has been made toward the development of neural models. These models are necessarily based on fundamental simplification of neural structures, and neural mechanisms. It is however necessary that any assumed mechanism be based on acceptable physiological criteria. We have developed such a model in the past (Anninos, 1969; Anninos et al., 1970) and in this paper we elaborate on it and attempt to incorporate in it a mechanism which will give rise to alpha-rhythm activity.