We used the salamander electroencephalogram (EEG) pattern as a means to monitor for possible direct effects of high-strength magnetic fields applied along a specific axis through the head (1). The field induced the onset of a slow or delta-wave pattern, and a large fluctuation in activity was seen as the field was slowly decreased from 1000 gauss to zero (see fig. 2.5). These observations were confirmed and extended by Kholodov (2) in 1966 in the rabbit EEG. He found that the presence of delta waves and the number of spindles (brief bursts of 8-12 Hz waves) were both increased by 1-3 minutes' exposure at 200-1000 gauss. In about half the animals tested these reactions lasted at least 30 seconds. In addition to these changes, which occurred after a latent period of the order of 10 seconds, Kholodov sometimes observed a desynchronization reaction (an abrupt change in the main rhythm) 2-10 seconds after the field was turned on (in I4% of the cases), or off (24%). He attributed the increase in spindles and slow waves to a direct action of the magnetic field on the nervous system and the more rapid, and relatively less frequent, desynchronization reaction to the electric field which was induced in the tissue as a result of the change in magnetic field during the turn-on turn-off. Chizhenkova (3) confirmed this hypothesis by exposing rabbits to 300 gauss for either 1 minute or 1.5 seconds. At the longer exposure period, the changes reported by Kholodov were observed, but following 1.5-second exposures only the desynchronization reaction occurred. In addition, Chizhenkova showed that a ten-factor reduction in the induced electric field (achieved by changing the magnetic field more slowly) had no effect on the number of spindles. Similar changes in the EEG due to EMFs of frequencies ranging from 50 Hz to 3 GHz have been reported (4, 72).
Fig. 5.1. Change in number of spindles in the rabbit induced by exposure to 300 gauss. N is the average number of spindles per 10 second periods that occurred during 604 exposures.
Three additional aspects of the Kholodov-Chizhenkova studies deserve mention: (1) the number of spindles observed after a change in the magnetic field increased regardless of whether the change was on-to-off or off-to-on (Fig. 5.1); (2) there was an after-effect in which the number of spindles remained elevated even when the field was tumed off (Fig. 5.1); (3) the most reactive regions were the hypothalamus and the cortex, and the least reactive region was the reticular formation of the midbrain.
Kholodov found a desynchronization reaction, but no changes in spindles or delta waves, when rabbits were exposed for 1 minute to 500 kv/m DC electric fields (2). Lott and McCain (5) measured the total integrated EEG in rats before, during, and after exposure to a DC field of 10 kv/m (Fig. 5.2). They found a transient increase associated with either the application or removal of the field, a steady response that persisted during application of the field, and an after-effect. A 640 Hz pulsed field, 40 v/m maximum, also increased the total integrated EEG, particularly for readings from the hypothalmic region.
Fig. 5.2. Total brain activity of anesthetized rats exposed to a DC electric field of 10kv/m. Each point represents a mean of 9 experiments; readings were not taken for 6 minutes following application of the EMF.
At high frequencies, a different effect on the total integrated electrical activity was observed. Goldstein (68) exposed rabbits for 5 minutes to 700-2.800 µW/cm2, 9.3 GHz, and found no EEG changes during the exposure period. Commencing about I0 minutes after exposure, however, there occurred an interval of decreased total integrated EEG that persisted for up to 15 minutes. The authors reported that the observed changes in the EEG resembled those induced by hallucinogenic drugs.
The nature of the EMF-induced EEG after-effect is determined by the exposure conditions and the physiological characteristics of the subject (6-11). For example, following a 30 minute exposure at 100 µW/cm2, 3 GHz, most of the rabbits tested exhibit either depressed or elevated slow-wave activity, and the relative number in each group varied with the location from which the EEG was recorded (6) (Fig. 5.3). The activity in the hypothalamus and the cortex was highly correlated in individual animals-it was either elevated or depressed simultaneously in both regions. After a 1 week exposure (1 hr./day) depressed EEG activity was the characteristic response (6), and after 3-4 weeks the after-effect phenomenon was no longer present (7). Dumanskiy observed a similar pattern in rabbits from exposure to 1.9-10 µW/cm2, 50 MHz (8); after 2 weeks, EEG activity was elevated, but after 2. months' exposure significant slowwave inhibition occurred. Such inhibition was also found after 4 months' exposure at 1-10.5 µW/cm2, 2.5 GHz (9).
Fig. 5.3. Relation of EEG response from the cortex, hypothalamus, and brainstem due to exposure at 3 GHz. The numbers indicate rabbits with a given response.
Servantie showed that the EEG could be entrained by a pulsed EMF (10). For 1-2 minutes after a 10-day irradiation period at 5000 ,µW/cm2 the EEG of rats exhibited the pulse-modulation frequency of the applied 3-GHz field. Bawin (44) also observed the production of specific EEG rhythms, and the reinforcement of spontaneous rhythms, by pulsed EMFs. Effects of EMFs have been reported on other aspects of neuroelectric behavior, such as evoked potentials (12, 13, 73), neuronal firing rate (14, 15), latency and voltage threshold (16),and response to drugs (73).
One of the American scientists who pioneered the study of EMF effects on the nervous system is Allen Frey; his work has induded studies of the effects on evoked potentials (12.), behavior (17), and hearing phenomena (18). In 1975 Frey reported an increase in the permeability of the bloodbrain barrier (the selective process by which capillaries in the brain regulate transport of substances between the blood and the surrounding neuropil) of rats exposed to 2400 µW/cm2 (continuous) or 200 µW/cm2 (pulsed) at 1.2 GHz (19). Frey found that dye injected into the bloodstream appeared in the brain of exposed animals, but not the control animals, and that the pulsed EMF was more effective than the continuous signal in opening the barrier, even though the average power level of the pulsed signal was only one-tenth that of the continuous signal. Frey's findings were confirmed and extended by Oscar and Hawkins in 1977 (20). They reported that continuous and pulsed EMFs both increased brain-tissue permeability, but that, depending on the particular pulse characteristics, pulsed energy could be either more or less effective than continuous-wave energy. Effects were observed at average powers as low as 30 ,µW/cm2. Preston et al., on the other hand, failed to find an effect on the permeability of the blood-brain barrier even at thermal-level EMFs (21). Frey concluded that Preston's failure resulted from an inappropriate choice of statistical procedures (11).
Biochemical studies of EMF-induced changes in brain tissue have yielded remarkably similar results at widely different frequencies. Fischer et al. (22) found that 50Hz, 5300 v/m, resulted in an initial rise of norepinephrine in rat brain, and a subsequent decline below the control level (Fig. 5.4 A). Grin (23 ) observed the same sequence of changes at 2.4 GHz, 500 µW/cm2 Fig. 5.4 B); at 50 µW/cm2, however, the norepinephrine level in Grin's study rose continuously throughout the exposure period.
Noval et al. (24) found that the activity of choline acetyltransferase (ChAC)-a neuronal enzyme which catalyses the synthesis of acetylcholine-was significantly reduced in the brainstem portion of brains from rats exposed to 10-100 v/m, 45 Hz, for 30-40 days; ChAC activity in the cerebral hemispheres was not affected by the field. Cytochrome oxidase activity in rat-brain mitochondria was significantly reduced after 1 month's exposure at 1000 and 1000 ,µW/cm2, 2.4 GHz; no effect was found at 10 µW/cm2 (25).
Cholinesterase is the neuronal enzyme that destroys acetylcholine, thereby permitting re-establishment of the membrane potential; alteration in blood cholinesterase levels reflects changes in the functional state of the nervous system. Chronic exposure to both low-frequency (22 ) and highfrequency (32) EMFs have produced lowered blood cholinesterase levels.
Fig.5.4. Norepinephrine levels in rat brain following exposure to EMFs:A, 5300 v/m, 50 Hz; B,500 µW/cm2, 2.4 GHz.
Microscopic studies of brain tissue of EMF-exposed animals have disclosed several kinds of functional histopathological effects. Kholodov (2 ) reported changes in brain tissue of rabbits and cats exposed to 200-300 gauss for up to 70 hours. In the sensorimotor cortex he found hyperplasia, hypertrophy, atrophy. and dystrophic nerve lesions. In an attempt to confirm11-210 gauss DC and 5-11 gauss at 0.1-0.2 Hz for up to 60 hours. Four of the 12. exposed rabbits and 2 of the 13 controls exhibited some histopathological change consisting principally of scattered granulomata in the meninges and the cortex, often associated with vascular proliferation, leukocyte infiltration, and small Gram-positive organisms. They concluded that their results could not be reconciled with those of Kholodov, but rather were consistent with a sub-clinical encephalitozoonosis which was exacerbated by a stressor effect of the magnetic field. In a subsequent electronmicroscopic study, Kholodov and his colleagues demonstrated EMF-induced changes-granular material in the Golgi complex in the rat pituitary-which seem clearly to be related to increased synthesis, and not a zoonosis (27). Tolgskaya and colleagues have conducted many studies of the histopathological effects of EMFs (28). In 1973 they described results of a time study of the effects of 3 GHz, 60-320 µW/cm2 (1hr/day for 22 weeks) on the morphology of the hypothalamus of the rat (29). After 2-3 weeks of exposure there was an increase in neurosecretory material in cells in the anterior region and along fibers of the hypothalamohypophysial tract. At 4-5 weeks similar results were seen, but at 22 weeks the picture was quite different-neurons were smaller with some atrophy, and little secretory material was seen. Six weeks following termination of exposure the rats exhibited a normal histological appearance.