MEG evaluation of pico-Tesla external TMS on multiple sclerosis patients.

Magnetoencephalographic (MEG) recordings of 10 multiple sclerosis (MS) patients (2 men, 8 women, mean 41.3±9.5 years, mean disease duration 12.7±7.2 years) were obtained using a whole-head 122 - channel MEG system in a magnetically shielded room of low magnetic noise. Our experimental design was double-blind in order to look for possible effect of external pico - Tesla Transcranial Magnetic Stimulation (pT-TMS). The external pT-TMS was applied on the MS patients with proper field characteristics (magnetic field amplitude: 1-7.5pT, frequency: the alpha-rhythm of the patient 8-13Hz) which were obtained prior to the application of pT-TMS. Each MS patient had two separate recording sessions consisting of 3 runs in between where were given real or sham pT-TMS. It was then tried to predict the real and sham stimulation sessions based on the changes in the mean peak frequency difference (MPFD) observed in the brain of the patients in the 2-7Hz frequency band. After unblinding it was found a significant effect of an increase of frequencies in the range of 2-7Hz across the subjects followed by an improvement and normalization of the MEG.

Meg recordings of patients with CNS disorders before and after external magnetic stimulation.

Magnetoencephalographic (MEG) recordings of patients with CNS disorders were obtained using a whole-head 122-channel magnetometer SQUID and analyzed using Fourier statistical analysis. External transcranial magnetic stimulation in the order of pico Tesla (pTMS) was applied to the above patients with proper characteristics (magnetic intensity 1-7.5 pT; frequency: 8-13 Hz) which were obtained with MEG recordings prior to pTMS. The MEG recordings after the application of pTMS showed a rapid attenuation of the high abnormal activity followed by an increase in the number of the low frequency components toward the patients alpha-rhythm. The possible mechanisms of the effects of external magnetic stimulation on the pineal gland in the brain are presented.

A mathematical description of the diurnal variation of radon progeny.

The variation of the alpha radioactivity in the air near the ground and the ground-level total gamma radiation has been monitored in North-eastern Greece over several days. Meteorological information regarding the temperature of the air and humidity has been simultaneously recorded. The alpha-radioactivity shows a periodic diurnal variation with a peak in the morning followed by a decrease in the afternoon; then, the variation rises again to the peak the next morning. The variation of the ground gamma-radiation follows that of the air alpha-radioactivity. Furthermore, their significant dependence on the air temperature and humidity is confirmed, rising with an increase in humidity and a decrease in temperature. Hence, a mathematical function has been developed to describe the diurnal variation of the alpha-radioactivity in terms of the ground-level gamma-radiation and the meteorological variables of temperature and humidity.

MEG evaluation of Parkinson's diseased patients after external magnetic stimulation.

Magnetoencephalographic (MEG) recordings of Parkinson's diseased (PD) patients were obtained using a whole-head 122-channel magnetometer and analyzed with Fourier statistical analysis. External transcranial magnetic stimulation (TMS) in the order of pico Tesla was applied on the above patients with proper field characteristics (magnetic amplitude : 1-7.5 pT, frequency : the alpha-rhythm of the patient: 8-13 Hz) which were obtained prior to TMS. The MEG recordings after the application of TMS showed a rapid attenuation of the high abnormal activity followed by an increase of the low frequency components toward the patients' alpha-rhythm. The patients responded to the TMS with a feeling of relaxation and partial or complete disappearance of tremor, muscular ache and levodopa induced dyskinesias as well as rapid reversed visuospatial impairment, which were followed by a corresponding improvement and normalization of the MEG.

Transcranial magnetic stimulation. A case report and review of the literature.

OBJECTIVE: Transcranial magnetic stimulation (TMS) is a non-invasive tool for the electrical stimulation of neural tissue. TMS can be applied as single pulses of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. CASE REPORT: A 2-years-old male infant was referred to our department with a history of Epstein-Barr virus (EBV) encephalitis, treated with foscarnet and steroids, for he developed mutism and ataxia and loss of the ability to eat, walk and talk. Brain imaging revealed loss of white matter around ventricles and progressive global brain atrophy, findings consistent with encephalopathy. Serology for antibodies against EBV infection was positive and the diagnosis of acute and prolonged EBV infection was made. There was an improvement of the clinical findings after the application of TMS with proper field characteristics (intensity: 1-7.5 pT, frequency: 8-13 Hz). CONCLUSIONS: Our case illustrates the possibility of therapeutic applications of TMS (in the order of pT) with proper field characteristics to normalize pathologically decreased levels of brain cortex activity. TMS might provide novel insights into the pathophysiology of the neural circuitry, be developed into clinically useful diagnostic and prognostic tests, and have therapeutic uses in various diseases.

Magnelic stimulation can modulate seizures in epileptic patients.

OBJECTIVE: The aim of this study is to investigate the influence of external magnetic stimulation (EMS) in epileptic patients using magnetoencephalographic (MEG) measurements and non-linear analytic techniques. METHODS: The examined group consisted of 15 men aged 19-56 years (mean: 39.5 +/- 11.3) and 15 women aged 15-53 years (mean: 36.7 +/- 11.4). For each one the magnetic activity was recorded from 32 points for each temporal lobe. External magnetic stimulation (EMS) with proper field characteristics (intensity: 1-7.5 pT, frequency: the alpha-rhythm of the patient (8-13 Hz)) was applied in the frontal, occipital and temporal lobes for 2 to 6 minutes and the emitted brain magnetic activity was recorded again. In order to investigate if there is any alteration in the MEG complexity underlying the neural dynamics characterizing the pathologic brain before and after the EMS, chaotic analysis approach was applied for the estimation of the dimensional analysis of the existing strange attractors. RESULTS: The application of EMS resulted in rapid attenuation of the MEG activity of epileptic patients. The obtained results of the dimensionality calculation provide a shift from lower to higher dimensional values. Such a shift is an indication that we are dealing with a chaotic system similar with the one characterizing normal subjects. CONCLUSIONS: The increased values of the dimensional complexity and the lower activity of the MEG after the application of EMS strongly supports the beneficial effects of EMS in epileptic patients.

Nonlinear analysis of brain activity in magnetic influenced Parkinson patients.

Magnetoencephalogram (MEG) recordings were obtained from the brain of patients suffering from Parkinson's disease (PD) using the Superconductive Quantum Interference Device (SQUID). For each patient the magnetic activity was recorded from a total of 64 points of the skull (32 points from each temporal lobe) as defined by a recording reference system, which is based on the 10-20 Electrode Placement System. Some of the recorded points were observed to exhibit abnormal rhythmic activity, characterized by high amplitudes and low frequencies. External magnetic stimulation (EMS) with intensity 1-7.5pT, and frequency the alpha-rhythm of the patient (8-13 Hz) was applied in the left-right temporal, frontal-occipital and vertex (2 minutes over each of the above regions) and the brain magnetic activity was recorded again. The application of the EMS resulted in rapid attenuation of the MEG activity of PD patients. Furthermore, chaotic dynamic methods were used, in order to estimate the correlation dimension D of the reconstructed phase spaces. The estimated values of D, in conjunction with the results derived from the other data analysis methods, strongly support the existence of low dimension chaotic structures in the dynamics of cortical activity of PD patients. In addition, the increased values of D of the MEG after the application of EMS when compared with the corresponding ones obtained from the MEGs prior to the EMS, suggest that the neural dynamics are strongly influenced by the application of EMS.

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.

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.

Short-time neutron activation gamma-ray spectroscopy.

Short-time instrumental neutron activation analysis, with high throughput, sensitivity and accuracy without matrix interferences, can be achieved in spite of the initial high count rate from both short and long-lived nuclide activation, if the experimental conditions are optimized by the combination of techniques. Thus the initial usually high counting rate can be faced by a loss-free counting system to avoid blocking or distortion of the system. The rapid radioactive decay and the consequent low counting statistics of short lived nuclides can be compensated by source-detector distance variation during the counting period and by cyclic and cumulative activation. Matrix spectral interferences can be reduced by ion exchange before activation for selective element preseparation and by neutron spectrum optimization such as epithermal neutron activation for selective element peak enhancement.

Advanced short-lived nuclide NAA with application in the life sciences.

A new technique for short-lived nuclide activation analysis has been developed that compensates the rapid radioactive decay during the counting period by simultaneous approach of the sample holder to the detector with a mechanical device, permitting prolongation of the counting time and reduction of the required complementary cyclic activation to avoid sample container damage. The operation of the analytical system is automated by a programmable logic controller (PLC). This improvement of short-lived nuclide activation analysis, providing a high throughput, is important in biological and environmental research, where often a large number of samples has to be analyzed for sufficient sampling statistics.

Magnetic fields mimic the behavioral effects of REM sleep deprivation in humans.

The discovery of rapid eye movement (REM) sleep by Aserinsky and Kleitman in 1953 initiated the impetus for sleep research and specifically the investigations of the effects of REM sleep deprivation (RSD) on animal and human behavior. The behavioral effects of RSD include the enhancement of motivational and "drive"-related behaviors. In laboratory animals, RSD has been reported to increase appetite, sexual behavior, aggressiveness, and locomotor activity. Moreover, RSD reportedly improves mood in patients with endogenous depression and heightens appetite and sexual interest in normal subjects. Since "drive"-related behaviors are thought to involve activation of limbic dopaminergic reward sites, RSD may enhance motivational behaviors through an action on limbic dopaminergic functions. In the present communication, we present two patients (one with multiple sclerosis and the other with Parkinson's disease) in whom treatment with magnetic fields produced behavioral effects which paralleled those observed in REM-sleep-deprived animals and humans. We propose, therefore, that the behavioral and mental effects of treatment with magnetic fields may be mediated via RSD and, by inference, involve activation of limbic dopaminergic reward sites.

Melatonin as a proconvulsive hormone in humans.

The pineal gland and melatonin exert a major influence in the control of brain electrical activity and have been shown to be involved in seizure and sleep mechanisms. Since pinealectomy has been reported to result in seizures in experimental animals, it is assumed that melatonin has anticonvulsant properties. Indeed, limited studies in humans with temporal lobe epilepsy indicate that melatonin attenuates seizure activity. In the present communication we present evidence, based on magnetoencephalographic (MEG) brain measurements, that melatonin may exert proconvulsive activity in humans as well. The proconvulsive properties of melatonin may explain several phenomena associated with epilepsy such as the increased occurrence of seizures at night when melatonin plasma levels are 5 to 8-fold higher than during the day and the observed exacerbation of seizures premenstrually and during pregnancy as well as the attenuation of seizures in the menopause. Furthermore, our findings suggest that anticonvulsants which decrease melatonin secretion, such as the benzodiazepines, may exert their antiepileptic activity by attenuating nocturnal melatonin secretion. Finally, we propose that patients with nocturnal epilepsy or those experiencing exacerbation of seizures premenstrually may benefit from the administration of agents which block the secretion or action of melatonin.

Magnetic fields in the treatment of Parkinson's disease.

Levodopa-induced dyskinesias are a common complication of chronic dopaminergic therapy in patients with Parkinson's disease (PD). The overall prevalence of levodopa-induced dyskinesias ranges from 40%-90% and is related to the underlying disease process, pharmacologic factors, and to the duration of high dose levodopa therapy. The mechanisms underlying the emergence of levodopa-induced dyskinesias are unknown, although most investigators favor the theory that striatal dopamine receptor supersensitivity is directly responsible for the development of these abnormal movements. In laboratory animals, the pineal hormone melatonin has been shown to regulate striatal dopaminergic activity and block levodopa-induced dyskinesias (Cotzias et al., 1971). Since the pineal gland is known to be a magnetosensitive organ and as application of external magnetic fields has been shown to alter melatonin secretion, we studied the effects of application of external artificial weak magnetic fields in a Parkinsonian patient with severe levodopa-induced dyskinesias ("on-off"). Application of weak magnetic fields with a frequency of 2 Hz and intensity of 7.5 picotesla (pT) for a 6 minute period resulted in a rapid and dramatic attenuation of Parkinsonian disability and an almost complete resolution of the dyskinesias. This effect persisted for about 72 hours after which the patient regressed to his pretreatment state. To ascertain if the responses elicited in the laboratory were reproducible, the patient was instructed to apply magnetic fields of the same characteristics daily at home. These subsequent treatments paralleled the initial response with a sustained improvement being maintained during an observation period lasting at least one month. This case demonstrates the efficacy of weak magnetic fields in the treatment of Parkinsonism and motor complications of chronic levodopa therapy.

Is postmenopausal osteoporosis related to pineal gland functions?

There is currently considerable interest in the pathogenesis of postmenopausal osteoporosis, which is the most common metabolic bone disease. Osteoporosis affects approximately 20 million persons in the United States, 90% of whom are postmenopausal women. Although there is evidence that estrogen deficiency is an important contributory factor, the pathogenesis of osteoporosis is multifactorial and presently poorly understood. There is evidence that pineal melatonin is an anti-aging hormone and that the menopause is associated with a substantial decline in melatonin secretion and an increased rate of pineal calcification. Animal data indicate that pineal melatonin is involved in the regulation of calcium and phosphorus metabolism by stimulating the activity of the parathyroid glands and by inhibiting calcitonin release and inhibiting prostaglandin synthesis. Hence, the pineal gland may function as a "fine tuner" of calcium homeostasis. In the following communication, we propose that the fall of melatonin plasma levels during the early stage of menopause may be an important contributory factor in the development of postmenopausal osteoporosis. Consequently, plasma melatonin levels taken in the early menopause could be used as an indicator or perhaps as a marker for susceptibility to postmenopausal osteoporosis. Moreover, light therapy, administration of oral melatonin (2.5 mg at night) or agents which induce a sustained release of melatonin secretion such as 5-methoxypsoralen, could be useful agents in the prophylaxis and treatment of postmenopausal osteoporosis. Finally, since application of external artificial magnetic fields has been shown to synchronize melatonin secretion in experimental animals and humans, we propose that treatment with artificial magnetic fields may be beneficial for postmenopausal osteoporosis.

The pineal gland and spontaneous abortions: implications for therapy with melatonin and magnetic field.

Spontaneous abortion, the termination of pregnancy prior to 20 weeks of gestation, is estimated to occur in 40%-50% of all pregnancies and in 12%-15% of identified pregnancies. The causes of spontaneous abortion can be divided into two main categories: those arising from chromosomal anomalies and those arising from abnormalities in the intrauterine environment. In the following communication, we propose that deficient pineal melatonin functions in early pregnancy may be causally related to the development of spontaneous abortions in cases where chromosomal anomalies or structural abnormalities of the uterus have been excluded. This hypothesis is based on the findings that: (a) melatonin plasma levels normally increase by 200%-300% in the first 20 weeks of pregnancy; (b) melatonin decreases uterine contractility in the rat; (c) melatonin stimulates the secretion of progesterone, which decreases uterine contractility and prevents immunological rejection of the trophoblast; (d) melatonin inhibits the synthesis of prostaglandins, which are potent inducers of uterine contractility and labor, and (e) pinealectomy increases the number of spontaneous abortions in pregnant rats. In addition, since melatonin is a hormone with immunosuppressant properties, we propose that the increased melatonin production in early pregnancy may contribute to a state of "transplantation immunity" to the paternal histocompatibility antigens preventing immunological rejection of the trophoblast. If this hypothesis is correct, then plasma melatonin, levels during early pregnancy could be used as an indicator for increased risk of spontaneous abortions.(ABSTRACT TRUNCATED AT 250 WORDS)

Is the pineal gland involved in the pathogenesis of endometrial carcinoma.

The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic stimulation in the treatment of partial seizures.

We have recently 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 years, successfully to attenuate seizure activity in a cohort of over 100 patients with various forms of epilepsy. We now present in more detail three randomly selected patients with partial seizures in whom application of an external artificial magnetic field of low intensity produced a substantial attenuation of seizure frequency during an observation period extending from 10 to 14 months. All patients had previously obtained only partial response to conventional anticonvulsant therapy. Attenuation in seizure frequency was associated with normalization of the MEG activity. These cases demonstrate that artificial magnetic treatment may be a valuable adjunctive procedure in the management of partial seizures. The possible mechanisms underlying the anticonvulsant properties of magnetic stimulation at both cellular and systemic levels are discussed. Specifically, since the pineal gland has been shown to be a magnetosensitive organ which forms part of a combined compass-solar clock system, and since it exerts an inhibitory action on seizure activity in both experimental animals and humans, we discuss the potential pivotal role of the pineal gland in the long term anticonvulsant effects of external artificial magnetic stimulation.

Age-related disruption of circadian rhythms: possible relationship to memory impairment and implications for therapy with magnetic fields.

Disorganization of circadian rhythms, a hallmark of aging, may be related causally to the progressive deterioration of memory functions in senescence and possibly Alzheimer's disease (AD). In experimental animals, disruption of circadian rhythms produces retrograde amnesia by interfering with the circadian organization of memory processes. The circadian system is known to be synchronized to external 24 h periodicities of ambient light by a neural pathway extending from the retina to the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. There is also evidence that the earth's magnetic field is a time cue ("Zeitgeber") of circadian organization and that shielding of the ambient magnetic field leads to disorganization of the circadian rhythms in humans. Since aging is associated with a delay of the circadian rhythm phase, and since light, which phase advances circadian rhythms, mimics the effects of magnetic fields on melatonin secretion, we postulate that application of magnetic fields might improve memory functions in the elderly as a result of resynchronization of the circadian rhythms. Moreover, since the circadian rhythm organization is more severely disrupted in patients with AD, it is possible that magnetic treatment might prove useful also in improving memory functions in these patients. If successful, application of magnetic fields might open new avenues in the management of memory disturbances in the elderly and possibly in AD.