EEG recurrence markers and sleep quality.

OBJECTIVES: To show that EEG markers formed using the variable percent recurrence reliably quantified two related aspects of sleep quality, sleep depth and sleep fragmentation. As hypotheses, the depth marker would increase and the fragmentation marker decrease in patients where improved sleep quality occurred when assessed by polysomnography. METHODS: The patients (N=20) had been diagnosed with obstructive sleep apnea during diagnostic polysomnography (dPSG), and had exhibited increased REM sleep (clinical indication of improved sleep quality) during subsequent polysomnography to titrate the pressure of a treatment device (cPSG). Percent recurrence was computed second-by-second from the EEG; sleep-depth and sleep-stability markers were obtained algorithmically. By assumption, the markers contained temporal information regarding the extent of deterministic (non-random) brain activity. Marker means were compared between the dPSG and the cPSG for NREM and REM sleep. RESULTS: Sleep depth was greater and sleep fragmentation was less during cPSG, as hypothesized (P<0.05). The effects occurred during NREM and REM sleep, but were greater during NREM sleep (P<0.05). At least one of the predicted changes occurred in 95% of the patients. CONCLUSIONS: The factors generally regarded as responsible for subjective sleep quality were objectively quantified on the basis of dynamical changes in the EEG.

Continuous EEG-based dynamic markers for sleep depth and phasic events.

Sleep architecture is characterized by classifying polysomnographic epochs into mutually exclusive stages. Notwithstanding the clinical importance of staging, it has the drawback of representing sleep as a discrete process. Metrics based on the electroencephalogram (EEG) are needed to supplement conventional sleep staging by allowing a description of sleep in terms of unitary, continuous markers. Traditional linear and nonlinear techniques for achieving this goal have not proved sufficient. Employing recurrence analysis, we developed a method for capturing and quantifying the dynamical states of the brain during sleep. The method yields markers for continuously determining sleep depth, for detecting sleep-specific phasic events, and for objectively defining potentially useful sleep markers and indices. Recurrence markers captured the coarse- and fine-grained temporal activity of the sleep EEG, thereby permitting continuous quantitation of brain electrical activity on any desired time scale. The markers were validated with respect to the tonic behavior (time scale of seconds) of the sleep EEG by establishing that they disambiguated the stages of sleep that are defined solely on the basis of EEG activity. Validation of the markers over time scales of milliseconds was achieved by showing that common types of sleep-EEG phasic events could be detected by recurrence analysis. The method was also used to define a generalized EEG arousal index that quantified previously unrecognized sleep-stage-dependent deterministic properties of brain electrical activity. Using nonlinear analysis that quantified the recurrence properties of the EEG, we described a novel method for producing dynamic markers of brain states during sleep.

Increased determinism in brain electrical activity occurs in association with multiple sclerosis.

OBJECTIVE: Increased determinism (decreased complexity) of brain electrical activity has been associated with some brain diseases. Our objective was to determine whether a similar association occurred for multiple sclerosis (MS). METHODS: Ten subjects with a relapsing-remitting course of MS who were in remission were studied; the controls were age- and gender-matched clinically normal subjects. Recurrence plots were calculated using representative electroencephalogram (EEG) epochs (1-7 seconds) from six derivations; the plots were quantified using the nonlinear variables percent recurrence (%R) and percent determinism (%D). The results were averaged over all derivations for each participant, and the means were compared between the groups. As a linear control procedure the groups were also compared using spectral analysis. RESULTS: The mean±SD of %R for the MS subjects was 6·6±1·3%, compared with 5·1±1·3% in the normal group (P = 0·017), indicating that brain activity in the subjects with MS was less complex, as hypothesized. The groups were not distinguishable using %D or spectral analysis. DISCUSSION: Taken together with our earlier report that %R could be used to discriminate between MS and normal subjects based on the ability to exhibit evoked potentials, the evidence suggests that complexity analysis of the EEG has potential for development as a diagnostic test for MS.

Electromagnetic hypersensitivity: evidence for a novel neurological syndrome.

OBJECTIVE: We sought direct evidence that acute exposure to environmental-strength electromagnetic fields (EMFs) could induce somatic reactions (EMF hypersensitivity). METHODS: The subject, a female physician self-diagnosed with EMF hypersensitivity, was exposed to an average (over the head) 60-Hz electric field of 300 V/m (comparable with typical environmental-strength EMFs) during controlled provocation and behavioral studies. RESULTS: In a double-blinded EMF provocation procedure specifically designed to minimize unintentional sensory cues, the subject developed temporal pain, headache, muscle twitching, and skipped heartbeats within 100 s after initiation of EMF exposure (p < .05). The symptoms were caused primarily by field transitions (off-on, on-off) rather than the presence of the field, as assessed by comparing the frequency and severity of the effects of pulsed and continuous fields in relation to sham exposure. The subject had no conscious perception of the field as judged by her inability to report its presence more often than in the sham control. DISCUSSION: The subject demonstrated statistically reliable somatic reactions in response to exposure to subliminal EMFs under conditions that reasonably excluded a causative role for psychological processes. CONCLUSION: EMF hypersensitivity can occur as a bona fide environmentally inducible neurological syndrome.

Transient and steady-state magnetic fields induce increased fluorodeoxyglucose uptake in the rat hindbrain.

We inquired into the biophysical basis of the ability of weak electromagnetic fields (EMFs) to trigger onset and offset evoked potentials, and to produce steady-state changes in the electroencephalogram (EEG). Rats were exposed to a 2.5-G, 60-Hz magnetic field and the neuroanatomical region of glucose activation associated with the effect of the field on the EEG was identified by positron emission tomography (PET) using fluorodeoxyglucose (FDG). Paired emission scans from the same animal with and without field treatment were differenced and averaged, and t values of the brain voxels computed using the pooled standard deviation were compared with a calculated critical t value to identify the field-activated voxels. Increased glucose utilization occurred in hindbrain voxels when the field was applied orthogonally to the sagittal plane, but not when the angle between the field and the sagittal plane varied randomly. Distinct FDG activation effects were observed in response to transient (both onset and offset) and steady-state magnetic stimuli. Observations of increased glucose utilization induced by magnetic stimuli and its dependence on the direction of the field suggested that signal transduction was mediated by a force detector and that the process and/or early post-transduction processing occurred in the hindbrain.

Simulated MR magnetic field induces steady-state changes in brain dynamics: Implications for interpretation of functional MR studies.

We examined whether a magnetic field comparable to one of the fields produced during MRI induced steady-state changes in brain electrical activity while the field was applied (called a presence effect to distinguish it from evoked potentials). The electroencephalogram was measured from standard scalp locations in the presence and absence of 100-200 microT, 60 Hz, and the effect of the field was evaluated by nonlinear (recurrence analysis) and linear techniques; individual subjects served as their own controls. Using recurrence analysis, changes in brain activity lasting 1 sec (the longest interval considered) were found in 21 of 22 subjects (P < 0.05 for each subject). The presence effect was not detected using linear analysis and was reversible, as indicated by a return of brain activity to baseline levels in all subjects within 2 sec of field offset. The possible role of artifacts or systematic errors was ruled out by studies using electrical phantoms and by analyses of electroencephalograms recorded during sham exposure. It is reasonable to expect that actual scanner magnetic fields also produce nonlinear steady-state perturbations of brain dynamical activity. The effect may influence the picture of brain connectivity inferred in some functional MR studies.

Numerical analysis of recurrence plots to detect effect of environmental-strength magnetic fields on human brain electrical activity.

Environmental magnetic fields may activate the neuroendocrine stressor system leading to some human diseases. The stressor theory predicts that the fields can trigger changes in brain electrical activity, like known stressors. We exposed subjects to 1 and 5 µT, 60 Hz while recording electroencephalograms (EEGs) from six derivations, and used a novel method based on numerical analysis of recurrence plots computed from the signals to detect brain electrical potentials evoked by onset and/or offset of the field. The EEGs were also analyzed using linear methods (time averaging). Evoked potentials occurred in all 22 subjects (family-wise error rate less than 0.05 for each subject); the average latency was 250 ms, as expected based on earlier studies using stronger magnetic fields. Field-induced changes in brain electrical activity were not found using time averaging. Control procedures and measurements obtained from electrical phantoms reasonably excluded recording artifacts or chance as explanations for the effects. Onset and offset of magnetic fields produced immediate changes in brain electrical activity, suggesting that the fields were detected by sensory transduction, like ordinary somatic stressors.

Multiple sclerosis impairs ability to detect abrupt appearance of a subliminal stimulus.

OBJECTIVES: The study was designed to find evidence that brain electrical activity associated with processing the abrupt appearance or disappearance of a sensory stimulus differed in the presence and absence of the neuropathological changes that are characteristic of multiple sclerosis (MS). METHODS: A subliminal stimulus (electrical field) was applied, and the onset and offset responses from patients with MS were compared with the responses of study participants in two age- and gender-matched control groups, using a novel type of non-linear dynamical analysis that had been developed in earlier studies. RESULTS: An onset response occurred in 27% of the patients with MS, compared with 85% in the control groups. Among the three patients who exhibited onset-induced changes in brain electrical activity, the average latency of the effect was less and the magnitude of the change was greater than the corresponding values in the control group. DISCUSSION: Non-linear analysis of electroencephalograms recorded during the sudden presentation of a subliminal stimulus potentially could serve as the basis of a functional test to help diagnose MS. A larger cohort of patients with MS needs to be assessed to validate the results of this study.

Mobile-phone pulse triggers evoked potentials.

If mobile-phone electromagnetic fields (EMFs) are hazardous, as suggested in the literature, processes or mechanisms must exist that allow the body to detect the fields. We hypothesized that the low-frequency pulses produced by mobile phones (217 Hz) were detected by sensory transduction, as evidenced by the ability of the pulses to trigger evoked potentials (EPs). Electroencephalograms (EEGs) were recorded from six standard locations in 20 volunteers and analyzed to detect brain potentials triggered by a pulse of the type produced by mobile phones. Evoked potentials having the expected latency were found in 90% of the volunteers, as assessed using a nonlinear method of EEG analysis. Evoked potentials were not detected when the EEG was analyzed using time averaging. The possibility of systematic error was excluded by sham-exposure analyses. The results implied that mobile-phones trigger EP at the rate of 217 Hz during ordinary phone use. Chronic production of the changes in brain activity might be pertinent to the reports of health hazards among mobile-phone users.

The effects of mobile-phone electromagnetic fields on brain electrical activity: a critical analysis of the literature.

We analyzed the reports in which human brain electrical activity was compared between the presence and absence of radio-frequency and low-frequency electromagnetic fields (EMFs) from mobile phones, or between pre- and post-exposure to the EMFs. Of 55 reports, 37 claimed and 18 denied an EMF-induced effect on either the baseline electro encephalogram (EEG), or on cognitive processing of visual or auditory stimuli as reflected in changes in event-related potentials. The positive reports did not adequately consider the family-wise error rate, the presence of spike artifacts in the EEG, or the confounding role of the two different EMFs. The negative reports contained neither positive controls nor power analyses. Almost all reports were based on the incorrect assumption that the brain was in equilibrium with its surroundings. Overall, the doubt regarding the existence of reproducible mobile-phone EMFs on brain activity created by the reports appeared to legitimate the knowledge claims of the mobile-phone industry. However, it funded, partly or wholly, at least 87% of the reports. From an analysis of their cognitive framework, the common use of disclaimers, the absence of information concerning conflicts of interest, and the industry's donations to the principal EMF journal, we inferred that the doubt was manufactured by the industry. The crucial scientific question of the pathophysiology of mobile-phone EMFs as reflected in measurements of brain electrical activity remains unanswered, and essentially unaddressed.

The electric field is a sufficient physical determinant of the human magnetic sense.

PURPOSE: The onset and offset of weak low-frequency magnetic fields triggered evoked potentials in human subjects that could be detected using nonlinear analysis, but not by means of time averaging. Because the magnetic fields and their induced electric fields were both present in the brain, their respective role in producing the effect on brain activity could not be ascertained. We inquired whether a biophysical coupling mechanism involving only the electric field could explain the occurrence of the brain potentials. MATERIALS AND METHODS: An external electric field capable of producing a brain electric field comparable to that induced by the magnetic stimuli was identified by finite-element analysis. The electroencephalogram from 23 subjects was measured from six scalp derivations in the presence and absence of the external electric field, and the presence of evoked potentials was assessed using nonlinear and linear analyses. RESULTS: Evoked potentials were observed in all but one subject (p < 0.05 in each subject); the potentials had the same latency, duration, and distribution of magnitudes as seen in the earlier studies, and were detectable only by means of nonlinear analysis. Using a realistic physical model of an ion channel, we showed that transduction of an electric field could be explained by assuming that the field exerted a force on glycocalyx molecules attached to a channel gate. CONCLUSION: The evoked potentials described here, as well as those observed previously in response to magnetic stimuli, were probably triggered by the induced electric field.

Evidence that transduction of electromagnetic field is mediated by a force receptor.

Low-strength magnetic fields triggered onset and offset evoked potentials, indicating that the detection process was a form of sensory transduction; whether the field interacted directly with an ion channel or indirectly via a signaling cascade is unknown. By analogy with electrosensory transduction in lower life forms, we hypothesized that the evoked potentials were initiated by a force exerted by the induced electric field on an ion channel in the plasma membrane. We applied a rapid magnetic stimulus (0.2 ms) and found that it produced evoked potentials indistinguishable in latency, magnitude, and frequency from those found previously when the stimulus was 50 times slower. The ability of the field-detection system in human subjects to respond to the rapid stimulus supported the theory that the receptor potentials necessary for production of evoked potentials originated from a direct interaction between the field and an ion channel in the plasma membrane that resulted in a change in the average probability of the channel to be in the open state.

Magnetosensory function in rats: localization using positron emission tomography.

The aim of this study was to show that low-strength electromagnetic fields (EMFs) produced evoked potentials in rats and to localize the activated region in the brain. In response to a 2.5-G, 60-Hz stimulus, onset- and offset-evoked potentials were detected (P < 0.05 in each of the 10 animals studied); the evoked potentials had the same magnitude, latency, and nonlinear relationship to the field seen in previous studies on rabbits and human subjects. The neuroanatomical region of activation associated with the electrophysiological effect was identified by positron emission tomography using fluorodeoxyglucose. Paired emission scans (the same animal with and without field treatment) from 10 additional rats were differenced and averaged to produce a t-statistic image using the pooled variance; the t value of each voxel was compared with a calculated critical t value to identify the activated voxels (P < 0.05). A brain volume of 13 mm(3) (15 voxels) located in the posterior, central cerebellum was found to have been activated by exposure to the field. Taken together, the results indicated that magnetosensory evoked potentials in the rats were associated with increased glucose utilization in the cerebellum, thereby supporting earlier evidence that EMF transduction occurred in the brain.

Method for detection of changes in the EEG induced by the presence of sensory stimuli.

The onset and offset of sensory stimuli evoke transient changes in the electroencephalogram (EEG) that can be detected by linear and/or nonlinear analysis. However, there is presently no systematic procedure to quantify the brain-electrical-activity correlate of the presence of a stimulus (as opposed to its onset evoked potential). We describe a method for detecting a stimulus-related change in brain electrical activity that persists while the stimulus is present (presence effect). The method, which is based on phase-space embedding of the EEG time series followed by quantitative analysis of the recurrence plot of the embedded signal, was used to demonstrate the occurrence of a presence effect in separate groups of human subjects exposed to sound, a magnetic field, and light. Any form of law-governed dynamical activity induced in the EEG can be detected, particularly activity that is nonlinearly related to the stimulus. Salient mathematical features of the method were reproduced in a model EEG system containing known nonlinear determinism.

The effects of low-frequency environmental-strength electromagnetic fields on brain electrical activity: a critical review of the literature.

Reports dealing with the stimulus-response relationship between low-level, low-frequency electromagnetic fields (EMFs) and changes in brain electrical activity permit assessment of the hypothesis that EMFs are detected by the body via the process of sensory transduction. These reports, as well as those involving effects on brain activity observed after a fixed time of exposure, are critically reviewed here. A consistent stimulus-response relationship between EMFs and changes in brain activity has been demonstrated in animal and human subjects. The effects, which consisted of onset and offset evoked potentials, were observed under conditions permitting the inference that the fields were transduced like ordinary stimuli such as light and sound. However, unlike the changes in brain activity induced by these stimuli, the changes induced by EMFs were governed by nonlinear laws. The studies involving attempts to determine whether a period of EMF exposure caused a metabolic effect reflected in pre-exposure/post-exposure differences in brain activity were generally inconclusive.

Magnetosensory evoked potentials: consistent nonlinear phenomena.

Electromagnetic fields (EMFs) having strengths typically found in the general environment can alter brain activity, but the reported effects have been inconsistent. We theorized that the problem arose from the use of linear methods for analyzing what were actually nonlinear phenomena, and therefore studied whether the nonlinear signal-processing technique known as recurrence quantification analysis (RQA) could be employed as the basis of a reliable method for demonstrating consistent changes in brain activity. Our primary purpose was to develop such a method for observing the occurrence of evoked potentials in individual subjects exposed to magnetic fields (2G, 30 and 60 Hz). After all conditions that affected the analysis of the EEG were specified in advance, we detected magnetosensory evoked potentials (MEPs) in all 15 subjects (P<0.05 in each experiment). The MEPs, which occurred within the predicted latency interval of 109-504 ms, were independent of the frequency and the direction of the field, and were not detected using the traditional linear method of analysis, time averaging. When the results obtained within subjects were averaged across subjects, the evoked potentials could not be detected, indicating how real nonlinear phenomena can be averaged away when the incorrect method of analysis is used. Recurrence quantification analysis, but not linear analysis, permitted consistent demonstration of MEPs. The use of nonlinear analysis might also resolve apparent inconsistencies in other kinds of brain studies.

Nonlinear EEG activation evoked by low-strength low-frequency magnetic fields.

Recent electrophysiological evidence suggested the existence of a human magnetic sense, but the kind of dynamical law that governed the stimulus-response relationship was not established. We tested the hypothesis that brain potentials evoked by the onset of a weak, low-frequency magnetic field were nonlinearly related to the stimulus. A field of 1G, 60 Hz was applied for 2s, with a 5s inter-stimulus period, and brain potentials were recorded from occipital electrodes in eight subjects, each of whom were measured twice, with at least 1 week between measurements. The recorded signals were subjected to nonlinear (recurrence analysis) and linear (time averaging) analyses. Using recurrence analysis, magnetosensory evoked potentials (MEPs) were detected in each subject in both the initial and replicate studies, with one exception. All MEPs exhibited the expected latency but differed in dynamical characteristics, indicating that they were nonlinearly related to the stimulus. MEPs were not detected using time averaging, thereby further confirming their nonlinearity. Evolutionarily conditioned structures that help mediate linear field-transduction in lower life forms may be expressed and functionally utilized in humans, but in a role where they facilitate vulnerability to man-made environmental fields.

Detection of nonlinear event-related potentials.

The methods used to evaluate event-related potentials (ERPs) are generally insensitive to nonlinear responses. Our goal was to show that nonlinear ERPs could be detected using recurrence analysis (RA). When fixed-phase sine signals were added to baseline electroencephalograms (EEGs), the added linear determinism was detected by signal averaging, as expected, and by RA. However, when nonlinear determinism was simulated by adding either random-phase sine or Lorenz signals, the added signals were detected only by RA. Auditory evoked potentials (AEPs) were studied in five subjects using RA. We detected not only the characteristic linear effects caused by onset and offset of the sound, but also nonlinear AEPs not previously reported; they occurred at 473-661 ms after onset, and 282-602 ms after offset, depending on the subject. In five other subjects we found nonlinear magnetosensory evoked potentials; they occurred at 209-354 ms after field onset, depending on the subject. RA was less sensitive than time averaging for detecting linear ERPs, but had the advantage of being able to detect nonlinear ERPs.