2014
Diagnosing Depression
We developed a computational method called analysis of brain recurrence (ABR) to measure non-random brain electrical activity present in the electroencephalogram (EEG). The purpose of ABR is to uncover information concerning brain function that cannot be obtained using conventional methods. ABR was used to study a range of problems in basic and clinical neuroscience. One application involved the development of a new way to measure sleep depth and sleep variability. Employing markers of these variables obtained from the EEG recorded during sleep, we validated the concept that complex physiologic disorders leave an objectively discernible and specific footprint on brain electrical activity.
We became interested in whether the markers could be used to identify subjects with depression or other forms of psychological distress. Our objective in this study was to determine whether a combination of the markers could be employed to accurately diagnose subjects with psychological distress.
EEGs recorded during sleep were obtained from a national information repository of de-identified patient data. Psychological distress was assessed using the mental health inventory questionnaire. Subjects with a score less than 50 (the control group, regarded as free from distress) were matched for sex, body-mass index, age, and race with subjects who had scores greater than 50 (the group with distress). ABR markers derived from the EEG were analyzed using conventional statistical procedures to identify marker combinations that reliably classified individual subjects as either with or without distress.
We found that ABR of EEGs obtained during sleep successfully classified subjects with regard to the severity of mental health symptoms (sensitivity and specificity of 79% and 77%, respectively), indicating that mood symptoms were reflected in brain electrical activity.
The results mean that symptoms of psychological distress can be objectively detected in the EEG of an individual subject using ABR markers extracted from the EEG of that subject. Our results were a proof-of-concept, suggesting that ABR of the sleep-acquired EEG is a practical and incrementally valuable data source for identifying the presence of impaired mental health. Diagnostic and prognostic information about mental illness may be hiding in plain sight.
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2013
My Last EMF Experimental Study (Perhaps)
Under the leadership of my chief Robert Becker, I published my first paper dealing with the biological effects of environmental electromagnetic fields (EMFs) more than 40 years ago (read the paper). The work was aggravating to people who were certain in their hearts that EMF-induced bioeffects were no more than fantasy. I saw that reaction among the audience the day I presented my results. This discontent did not deter us from continuing our EMF studies, and ultimately integrating our results and those of many others into a coherent general picture of how EMFs produced biological effects (Fig. 1) (R.O. Becker and A.A. Marino. Electromagnetism & Life. Original Edition, State University of New York Press, 1982; Facsimile Edition, Cassandra Press, 2012).
Subsequently we each published books that described our life experiences with EMF studies (R.O. Becker and Gary Selden. The Body Electric. Morrow, 1985; A.A. Marino, Going Somewhere: Truth About a Life in Science. Cassandra Press, 2010).
I had the opportunity to persist in a long sequence of studies aimed at testing the model we described in Electromagnetism and Life (Fig. 1). The first series of studies in this sequence were designed to rebut arguments that the effects were necessarily artifactual because they contradicted physical law (Fig. 1, red→yellow). At the end of the day the studies showed that cause-effect relationships were real, which entailed the conclusion that the argument was certainly wrong. The next series of studies (Fig. 1, red→orange) dealt directly with the hypothesized intermediary processes that mediated EMF exposure and human disease. In many independent studies I showed that EMFs induced changes in brain electrical activity, which was the postulated physiological process that mediated the link between EMFs and biological effects. I then turned my attention to the biophysical processes involved in EMF signal transduction (Fig. 1, red→red), the physical gateway by which the body took cognizance of the existence of an external EMF. In a series of publications I showed how EMF signal transduction was to be expected under known physical law, given the existence of known biological structures. These experiments were particularly satisfying because they directly refuted the shibboleth with which I was confronted at the inception of my research career (link to PDFs for individual studies).
In the present paper I dealt with what is perhaps my final deduction from my proposed model. Given the biophysical and electrophysiological observations I had made previously, we predicted that glutamate receptors in the trigeminal nucleus mediated the afferent signal induced by EMF transduction. The paper presented the experimental evidence that supported our hypothesis. The evidence can be integrated with that from my earlier studies, leading to a model for EMF detection that is more detailed than the initial version of the model (Fig. 2).
Fig. 2. Detailed model proposed in 2013.
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2012
Electromagnetic Hypersensitivity
Man-made electromagnetic fields (EMFs) such as those produced by cell phones, powerlines, and/or computers are ubiquitous in the general and workplace environments, and their presence is increasing exponentially. Chemically-triggered allergic reactions such as type-1 and type-4 hypersensitivities are well known, and the idea that environmental EMFs could serve as an initiating agent for an acute inflammatory response has been frequently suggested but never proved, at least not pursuant to the generally accepted method for establishing such facts.
During the last 35 years I met many people who complained of electromagnetic hypersensitivity (EHS), but the conditions were never appropriate for a scientific study devoted to establishing the existence of the syndrome. Public interest in the EHS issue increased enormously in that period, as did counter-pressure from the EMF industry.
Recently the necessary conditions occurred, and my colleagues and I were able to conduct a properly controlled study in which we demonstrated that EHS was a real neurological syndrome. The subject was a young female physician with multiple neurologic and somatic symptoms including headaches, hearing and visual disturbances, subjective sleep disturbances and non-restorative sleep, and musculoskeletal complaints, all of which she reported could be precipitated by exposure to environmental EMFS and abated by withdrawal from the fields. Among the environmental triggering devices she identified were cell phones, computers, powerlines, and various common electrical devices. During extensive pre-study interviews she credibly explained the reasons for her belief that EMFs from common environmental sources could provoke symptoms. Her ability to do so was an important consideration in our decision to commit resources to the study.
After she agreed to medical tests that were appropriate for evaluating her medical condition, she underwent a physical exam, a comprehensive neurologic exam, a clinical electroencephalogram, a non-contrast magnetic resonance imaging of the brain, an overnight sleep study with video and expanded EEG montage, a standard laboratory evaluation of serum electrolytes and blood chemistry, liver function tests, and serum fasting cortisol determination. In the judgments of her attending physicians, none of her signs and symptoms supported a diagnosis in terms of any generally recognized specific medical disorder.
When she was exposed to a controlled EMF under conditions designed to minimize unintentional sensory clues, she developed temporal pain, headache, muscle twitching, and skipped heartbeats. All these symptoms occurred within 100 sec after initiation of EMF exposure. The possibility of a psychosomatic basis for the reported symptoms was ruled out at the 5% level.
In response to our report a psychologist named James Rubin raised a series of objections. Rubin had previously explained his belief that EHS is a psychosomatic disorder that he named idiopathic environmental intolerance, and attributed to the desire on the part of some people to take refuge from modernity, a belief that is ludicrously inconsistent with the personality of the subject).
We replied to the real issue, and didn’t focus on Rubin’s voiced complaints. We had recognized the true dynamical complexity of EHS, and designed our study accordingly. He had failed to recognize the nature of EHS, and consequently employed a wrong experimental design, one that blinded him to the existence of EHS. Rubin simply averaged it away, like the man with his feet in a fire and his head in a block of ice who reported that his body temperature was normal, on average. That was the reason his many publications denied the existence of the EHS syndrome but our publication had verified its existence.
The determined Rubin objected again (discussion p. 404), which afforded me the opportunity to further highlight a key point for the clinical neuroscience community regarding symptomology—the reason why Rubin had averaged away reality in his well-funded studies. We had assumed that any symptoms triggered by the controlled field that we applied would be specific to the subject, rather than universal reactions that were similar in nature and intensity to the reactions of all true EHS sufferers. We further assumed that the reproducibility requirement of the scientific method applied to the existence of symptoms, not to the precise type of symptom. We had conducted preliminary studies to identify the subject’s symptoms, and we standardized the language that she would use to report them and identify their intensity. We then took steps to ensure that the EMF intensity was sufficiently low that they produced only reversible symptoms, which was a critical aspect of our statistical design (independent trials). These steps were taken prior to the data collection we reported because our goal was not to predict the subject’s specific symptoms, but rather to test the hypothesis that they were not explainable as psychosomatic effects. Rubin had done all of these things oppositely. He always demanded that true symptoms must be precisely reproducible in each subject, and in all subjects studied—a demand that was a perfect storm for failure to observe EHS. This was the key point for the clinician.
Rubin’s persistence had the further salutary effect of allowing me to place EHS in perspective regarding the entire EMF health-hazard issue, regarding which the EHS is only one part. The biophysical mechanism for detecting EMFs is reasonably well understood (Bioelectromagnetics 2007, Int. J. Radiat. Biol. 2009) and the existence of human sensibility for EMFs was shown. The direct effects on brain were demonstrated (Neurosci. Res. 2008, Synapse 2009), and analytical methods for examining the electroencephalogram to demonstrate these effects were described (Neurosci. Meth. 2006, J. Neurosci. Meth. 2008, J. Neurosci. Meth. 2012). These methods will permit objective characterization of the differences in the immediate early processing of information by the brain following transduction that occurs in EHS sufferers but not in those without the disorder. It would then be possible to create case-definition/case-selection tools that could be used by clinicians in determining diagnoses of subjects with EHS.
The psychological disorder involved in this story is not psychosomatic, but rather something equally old and human, as in the story of Procrustes, the ancient innkeeper who offered a bed to travelers in Attica. If the traveler’s legs were too long, Procrustes cut them off. If they were too short he stretched them to fit the bed. After several years, Procrustes wrote a book entitled “On the Uniformity of Stature of Travelers in Attica.” This metaphor fits Rubin’s experiments well.
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2011
Magnetic Fields Affect Brain Metabolism
It is difficult to appreciate that the EMFs so ubiquitously present in the environment have never been seriously evaluated for potential health risks. The issue has been considered by numerous blue-ribbon committees, but without exception they were organized and administered by pro-EMF special interests. Pro forma evaluations have been made by various government agencies, but almost always the only meaningful voices heard were those of the special interests. The NIH RAPID program is an outstanding example. Some court cases have resulted in compensation for the creation of EMF risks or for causing cancer and other diseases, but each was a private-law matter with one plaintiff and one defendant.
Increased fluorodeoxyglucose uptake in the rat hindbrain produced by a weak pulsed magnetic field. The activated voxels (shown in color) were located in the mid-sagittal region and occurred in three consecutive slices (locations shown in the inserts). First column, coronal magnetic resonance (MR) sections of the rat brain; slice thickness, 1.2 mm. Second column, average difference image (10 rats) (superimposed outlines from MR atlas). Third column, locations in the image plane of the voxels activated by the magnetic field. Color bar for the difference image is expressed as a percent difference between the average exposure and sham-exposure PET images. Voxel dimension 0.845 × 0.845 mm. Caudal view. Field applied orthogonal to the plane of the section.
Perhaps the special interests do not deserve criticism for failing to conscientiously look for scientific evidence suggesting that the EMFs they produce could cause disease. The ethical implications of that strategy might be questioned but most would probably agree that the decision rests on a firm financial footing. But what if the ante were raised? Suppose that there was reliable evidence that EMFs affected the brain, for example evidence that every second of cell-phone use results in the induction of approximately 216 evoked potentials per second in the user’s brain, which I showed was the case (see CV #160). That evidence didn’t prove that cell phones caused cancer or other disease, but nevertheless was important because it crossed a threshold and established that energy from cell phones produced physiological effects in the body’s most critical organ. Although the position of the special interests wasn’t breached by the new evidence, their position was at least dented because people who do not have a dog in the hunt can now reasonably suspect that the finding at least suggests the possibility of health-related consequences, and therefore that unbiased evaluation and follow-up is merited.
I turned my attention to an objection to the study results voiced by the special interests, namely that the techniques I used were novel, and have not been used by other investigators. The gist of their argument is that, even though their experts can’t find any defect, it could still be there and could obviate the results of the study. The conclusion of the argument is that it would be premature to conclude that cell-phone fields affected the brain. I took this objection into account by examining the effects of EMFs using a completely different methodology from that used previously. We injected rats with a metabolic surrogate of glucose (fluorodeoxyglucose) which is radioactive and spontaneously decays into a particle termed a positron that can be detected by standard instrumentation. The instrumentation produces cross-sectional views of the rat’s head, similar to those produced in computed tomography (CT) or magnetic resonance imaging (MRI). Unlike CT and MRI, however, imaging of positrons produces a direct measure of functional activity in the brain, rather than simply mirroring structural changes.
First we conducted a study showing that EMFs affected the amount of positron emission which occurred (a direct measure of glucose uptake, which is a biomarker for metabolism (see CV #155)). In the present study we examined whether EMFs applied as a series of pulses, as in a cell phone, was particularly effective in altering brain metabolism (reflected as increased positron emission in the measurements). As hypothesized, we found that a pulsed EMF produced a greater effect on the brain compared with a continuous EMF.
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2010
Power-Frequency EMFs Produce Brain Activity Changes Having Unexamined Public-Health Significance
Good progress has been made recently towards understanding how the interaction process between environmental EMFs and the human body can best be conceptualized. The evidence indicates that the canonical type of interaction is sensory transduction, and that the transition in field strength from either off-to-on or on-to-off is the principal aspect of the field to which the electrosensory cells respond. In the present study we addressed the question of how small a change in 60-Hz EMF intensity could be detected by human subjects. In each of 22 subjects, under conditions designed to facilitate detection of a sensory response, altered brain electrical activity occurred in response to changes in EMF intensity between levels known to be ubiquitously present in modern urban environments. The straightforward implication of the study results is that the brain activity of essentially everyone is constantly affected by power-frequency EMFs. The significance of this implication, that is the public-health consequences occasioned by chronic 60-Hz stimulation of the brain, is unknown because the consequences are essentially unstudied, as if we didn’t want to see.
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2010
Cell-Phone EMFs Alter Brain Electrical Activity
If cell-phone electromagnetic fields (EMFs) are hazardous, there must be a process by which the body detects the fields. We hypothesized that pulses produced by cell phones were detected in the same way the body detects ordinary environmental stimuli. We planned to accept as evidence of this theory the observation that cell-phone pulses produced a specific kind of change in brain electrical activity termed the evoked potential (EP). We reasoned that since only typical environmental stimuli are known to produce EPs, evidence that cell-phone EMFs also did so would be evidence that they were detected like the ordinary stimuli. We found that a simulated cell-phone pulse produced EPs, as predicted.
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2010
Conclusions of Some Functional MR Studies May Be Affected by the MR Magnetic Fields
Functional magnetic resonance imaging (fMRI) is commonly used to infer the areas of the brain that mediate specific behavioral or cognitive functions. A fundamental assumption in fMRI is that changes in the measured signal are caused solely by the task being studied, and are unaffected by the strong magnetic field used to produce the images. We simulated one component of the fMRI environment and found that it produced changes in brain electrical activity in 21 of 22 subjects. The effect was nonlinearly related to the presence of the field, indicating that it would not be averaged away during the statistical analyses commonly used to evaluate fMRI images. At least in some cases, the effect of the fMRI magnetic field on brain electrical activity may be confounded with the effect produced by the task being studied.
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2010
Multiple Sclerosis Impairs Ability to Detect Weak EMFs
The appearance of plaques in the brain MRI are part of the diagnosis of multiple sclerosis (MS). With the aim of developing a functional test to help diagnose MS and follow its rate of progression, we studied the ability of patients with MS to respond to the onset of a weak EMF, as assessed by measuring changes in the electroencephalogram (EEG) caused by the onset. An onset response occurred in only 27% of the patients with MS, compared with 85% in the control groups; when the patients with MS did respond to the EMF, the timing of the response was abnormal. The results suggested that nonlinear analysis of EEGs recorded during sudden presentation of a stimulus could serve as the basis of a functional test for MS.
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2009
On the Basis of a Treatment for Osteoarthritis Pain
Injection of hyaluronan (under various trade names including Synvisc, Hyalgan, Orthovisc, Euflexxa, Supartz) into the knee as a treatment for pain due to osteoarthritis (OA) was approved by the FDA under the theory that hyaluronan works by acting as a lubricant within the joint. But hyaluronan is also a signalling molecule, and we suspected that its effectiveness was related to its biological rather than physical properties. Under this hypothesis we expected that the receptor proteins for hyaluronan in the joint would differ from normal in patients with OA. We found that the amount of CD44 and RHAMM, the two principal receptors for hyaluronan, were each significantly increased in synovial tissue from patients with OA, thereby supporting the idea that the mode of action of hyaluronan is more complicated than previously thought.
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2009
Towards an Understanding of the Brain’s Complexity
Hodgkin and Huxley’s explanation of the mechanism of the nerve impulse was a great achievement and a great setback for mankind. The greatness lay in how they blended mathematical exactness, physical reasoning, and brilliant experimental technique. Unfortunately their work was regarded as perfect and complete, a perception that had the effect of restricting subsequent neurophysiological inquiry to the realm of biochemistry, which cannot provide a satisfactory explanation of brain function. The study of memory, learning, and behavior is only now emerging from the almost total eclipse of Hodgkin and Huxley. The future seems brighter because work is now moving in the direction of nonlinear functionality.
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2009
A Biological Mechanism for Detecting EMFs
When magnetic fields are applied to the body they invariably produce electric fields, but electric fields can be applied essentially in the absence of magnetic fields. In earlier studies we showed that magnetic fields altered brain electrical activity. In this study we addressed the questions of which field the body recognized, and how it did so. We applied electric fields and duplicated the results obtained when magnetic fields had been used, thereby showing that electric fields were sufficient to explain the effects on brain electrical activity produced when magnetic fields were applied. Our proposed transduction mechanism consisted of a force exerted by the electric field on charged molecules attached to the gate of an ion channel, resulting in a biologically meaningful change in the mean open time of the channel gate. The model described is known to exist in animals. We showed that it could detect electric fields ubiquitously present in the body due to environmental EMFs despite the inherent random motion of the channel gate due to thermal fluctuations.
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2009
Where EMFs are Detected
Unlike the case for ordinary stimuli (light, sound, as examples), the location of the cells that actually detect EMFs in mammals is unknown. We knew from our earlier experiments with humans that the detection occurred within about a tenth of a second following the presentation of the EMF, but based on our knowledge of how fast impulses travel in nerves, our observations were consistent with the EMF receptor cells being located almost anyplace in the body. From rabbit studies, however, we knew that the receptor cells were located somewhere in the head. We used the method of positron emission tomography and showed that rats that had been exposed to EMFs for 45 minutes exhibited significantly elevated levels of activity in the hindbrain, either the cerebellum or the medulla, raising the possibility that the receptor cells may be located in the hindbrain.
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2009
“I Would Prefer Not To”
If weak EMFs alter human brain electrical activity, as we have reported, why hasn’t that fact clearly emerged from the published research sponsored by the cell-phone industry? We analyzed essentially all published English-language studies and found their likelihood of producing reliable information was nil because they were poorly designed. The negative studies had no value because anybody can find nothing, and the positive studies were hardly any better because their design and methods were sub-par. The cell-phone industry supported 87% of the published studies and was a major sponsor of the Bioelectromagnetics Society, whose journal published most of the negative studies. The industry probably chose not to fund meaningful studies for the same reason that motivated Bartleby the Scrivener in Melville’s novella, the industry preferred not to.
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2008
Recognizing that the Brain Response is Nonlinear Was Key
When ordinary stimuli such as light or sound are applied abruptly, they trigger brief changes in brain electrical activity known as evoked potentials. Evoked potentials are weaker than baseline EEG activity and therefore not normally seen in a typical EEG. But by repeatedly stimulating the subject and time-averaging the EEG, the evoked potentials can be detected because the baseline EEG signal is averaged away but the evoked potential, which is time locked to the stimulus, becomes progressively stronger. Time averaging works, however, only if the evoked potential always changes in the same direction at the same time after each stimulus (called a linear response); otherwise the evoked potential would also be averaged away. We recognized that the evoked potentials produced by EMFs were nonlinear, and hence could not be seen using time-averaging because it detects only linear phenomena. We devised a nonlinear method for analyzing the EEG, and discovered that evoked potentials occurred in essentially every subject tested.
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2008
Teaching Medical Students about the Musculoskeletal System
Approximately 35% of the patient population of a typical physician practicing family medicine, internal medicine, or pediatrics consists of patients with musculoskeletal complaints. It is now generally recognized that the amount of time devoted in medical school to training students to recognize and treat musculoskeletal complaints (less than 3% of the curriculum) is grossly inadequate. A necessary step in remedying the problem was the design of a curriculum capable of providing the minimum knowledge of musculoskeletal medicine necessary for a physician in general practice. We developed a philosophy to guide the development of such a course of instruction, designed its content, procedures for instruction, and tools for evaluating student progress, and then implemented the course for first-year medical students and evaluated the progress achieved using a validated method for determining musculoskeletal competence of physicians.
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