This site provides Dr. Marino’s scientific publications and presentations dealing with electromagnetic fields, neurophysiology, the musculoskeletal system, and sleep research.

Presentations

Classification of Sleep States

Sleep is a dynamic state of the brain characterized by shifting levels of electrical activity. Key to this give-and-take is the complex interaction among hundreds of organized networks, each containing billions of brain cells. The interaction produces about twenty statistically distinct brain-wide functional states that can be algorithmically detected in the EEG recorded during sleep. It is reasonable to expect that specific clinical disorders produce characteristic changes in the brain states, suggesting that knowledge of the states occurring in a patient might assist in clinical diagnosis.
View Abstract.
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Recurrence Analysis of the Sleep EEG

Recurrence analysis (RA) is a new method for quantifying non-randomness in the EEG. Applied to the sleep-staged EEG (SS-EEG), RA yields 16 markers for stage-dependent sleep depth and fragmentation. We postulated that RA could accurately identify the presence of temporal information (“signature”) in the SS-EEG specifically associated with OSA, as assessed by RA’s capability to reliably identify the subjects in a cohort consisting of those who did and did not have OSA.

OSA subjects (AHI ≥ 5) were identified by RA, using only a single EEG lead. The SS-EEG contained a signature detectable by RA that allowed a reliable binary classification of the individual subjects in a cohort that included a group with no OSA and an equally-sized group of subjects who exhibited a wide range of disorder severity.
View Abstract.
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The EEG Fingerprint of REM

REM sleep is a prime example of the connectivity model of cognition. Analysis of brain recurrence (ABR) is a method for quantifying brain connectivity that is particularly useful when used in connection with the sleep EEG. In the present study we examined whether REM could be disambiguated from the other stages of sleep using a statistically determined combination of ABR markers for sleep depth and variability.

When the principal components of the ABR markers were computed and used in 3-class support vector machines, the results matched ground truth as determined by expert staging, indicating that REM sleep could be reliably identified using a single EEG channel. REM sleep can be disambiguated from the other stages of sleep by means of ABR.
View Abstract.
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The EEG During Sleep is a Window to the Mind

Analysis of brain recurrence (ABR) is a novel method of algorithmically quantifying the degree of non-randomness (complexity) in an EEG signal. We showed that ABR accurately identified a signature in the sleep EEG that was specific for the presence of mental health symptoms, as assessed using the MHI-5 questionnaire.
View Abstract.
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Brain-Related Biomarkers: Past, Present, and a Possible Future

My goal is to coherently describe the work we have been doing here during the past 10 years involving the development of novel methods for extracting useful and important information from the EEG. What We’re really after is clinically important information regarding neurological disorders, and secondarily in information related to basic neurophysiology. First I discuss the concept of a biomarker. Then I describe and evaluate work that’s been done in the area of brain-related biomarkers. Lastly I discuss the work we have been doing, and where we intend to take this project.
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Concussions, Chronic Traumatic Encephalopathy, and Informed Consent

RPFootball-related concussions are a mild form of traumatic brain injury, and a rapidly increasing level of public concern has developed regarding their short-term and long-term health risks. The traditional view that concussions were brief reversible injuries having no long-term significance regardless of the total number of concussions experienced has been significantly eroded by reports of serious neurological and psychiatric consequences in professional football players, and by the discovery of chronic encephalopathy in their brains at autopsy. Recent developments in the biophysics of impact forces delivered to the head established that rotational acceleration of the brain was a previously unrecognized and potentially important mechanism by which the forces resulted in brain injury. The physiological consequences of the injuries include the recently recognized phenomenon of axonal shearing in the gray-matter/white-matter region, which is now thought to be an important mechanism of traumatic brain injury both in the presence and absence of neurological symptoms. Legal responsibility for football-related brain injuries is a hotly contested issue in the context of professional football. But both the health risks and legal consequences are far greater and more complex in the case of football players who play for sport, not principally for money. A perfect storm may be developing in the context of more than 4 million youth football players whose brains are still undergoing development, who lack the ability to give meaningful informed consent, and who undergo a significant number of concussive and sub-concussive blows to the head during practice and games in a typical football season. The popularity of professional football has continued to increase despite the mounting evidence that the brains in many of the players will exhibit the pathology previously seen only in prize fighters. The popularity of youth football may not be so robust.
View announcement.
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Clinical Validation of New Sleep-Depth Marker

Patients with severe obstructive sleep apnea sometimes exhibit a marked increase in the amount of rapid eye movement sleep when they begin using a positive airway pressure device. That increase is normally interpreted clinically to indicate an increase in sleep depth resulting from a reduction in the stress caused by the apnea. We therefore expected that a new marker for sleep depth which we developed would be significantly increased in such patients, and the predicted result was observed.
View Abstract.
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Sleepiness in Apnea Patients: It’s Not Just Low Oxygen

The use of positive airway pressure devices reduces cardiovascular risk in patients with obstructive sleep apnea, nevertheless they often remain feeling unwell and suffering from daytime sleepiness. A possible explanation was that the devices were less effective in these patients with regard to increasing their blood oxygen levels, and consequently they remained sleepy. We found that oxygen levels were lower in the sleepy patients, but not by an amount that could fully account for the extent of the clinical problem, indicating that other factors must be involved. One possibility was that the patients who remained sleepy waited too long before seeking treatment, resulting in permanent changes in the brain.
View Abstract.
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Depth of Human Sleep

The distinction between light and heavy sleep has long been recognized, and serves as the basis for the clinical classification of sleep stages. Nevertheless there had been no quantitative measure of sleep depth that would permit it to be compared between different times during overnight sleep in a particular subject, or between different subjects. Based on the analysis of signals routinely obtained during overnight sleep studies, we developed a practical, quantitative method for continuously measuring sleep depth. The method may lead to new insights into normal and abnormal human sleep.
View Abstract.
View poster.

Blast from the Past

1988 Politics

A Gordon Research Conference on Bioelectrochemistry was held in rural New Hampshire August 15–19, 1988. The idea behind the conference was to give experts a chance to exchange ideas, off the record, in an environment designed to promote intense interactions and to exclude distracting external influences. There were 23 invited speakers, including me. We were well fed, given spartan rooms, and encouraged to think deeply about EMFs. In her letter to the speakers, the conference chairperson Betty Sisken wrote, “Speakers should minimize the presentation of review data and emphasize creative thinking in the form of speculation and controversial interpretations. Remember that none of the material presented is published in any form and may not even be cited.” We all signed a written pledge. “The recording of lectures by tapes, etc. and the photography of slide material are prohibited. Printed references to Gordon Research papers and discussion is not permitted. Authors are requested to omit reference to the Conference in any publication. Each member of the Conference agrees to these regulations when registration is accepted.” But 25 years have elapsed, and the statute of limitations on my promise has expired. Consequently I decided to publish my presentation.

I told the audience that only nerve cells directly detected fields, that linear dose–effect relationships were not to be expected, that fields were present in the detecting tissue but not in the tissue that manifested the effect, that explaining results by resorting to Adey-type windowing violated the law of parsimony, and that EMFs were stressors that caused effects by means of chronic activation of the HPA axis. I also said that the approach favored by almost all the other speakers was misguided, and I explained why.

Despite these wide deviations from the average view at the conference, the response embodied in the questions at the end of my talk was muted. One possible explanation was that the audience considered my position so inconsistent with facts and theory that any effort to educate me by pointing out my errors simply wasn’t worthwhile. But if so, there were people in the audience who would have taken great delight in highlighting my errors. I decided that the better view was that my presentation had no obvious weaknesses, at least that could be seen by those who heard me. The experience reinforced my belief that I was on the right track, and that the thing for me to do was to continue in the same direction, trying to make progress in establishing the correctness of my approach.

To a significant extent, my talk at the 1988 Gordon Conference on Bioelectrochemistry was the blueprint I followed for the rest of my career.
Click here for Powerpoint presentation.

Neuroenhancers and Other Legal/Ethical Issues in Neurology

Neuroenhancers

Because neurologists treat diseases of the brain, which is the seat of the mind, they deal with an increasingly broad range of complex legal/ethical issues. Three of these issues were discussed from a legal perspective in this presentation. They included the professional disciplinary system of the American Academy of Neurology, neurologic malpractice, and potential legal liability associated with prescribing neuroenhancers.
View Announcement.
View Presentation.

Brain Activity During Sleep

Brainwaves

The brain is a complex hierarchical system governed by nonlinear spatio-temporal interactions between local neuronal networks that themselves are governed by nonlinear laws. During wakefulness the electrical activity of the brain, as sampled by a voltage measurement at any point on the scalp, reflects the myriad simultaneous functions regulated and controlled by the brain including awareness, sensation, thought, and autonomic regulation of the body. During sleep the brain cycles through clinically recognizable states in which the measured signal is relatively stable and recognizable. The N1 state corresponds to light sleep, and states N2 and N3 to progressively deeper sleep. The present practice is to classify each 30-second epoch during sleep into one of these three stages based on the observed pattern of change in the EEG. Additionally, epochs during which dreaming occurs (in principle, in any of the three sleep stages) are identified by means of non-EEG physiological measurements. We addressed the need for a continuous measure of brain activity during sleep to supplement and extend the present discrete sleep classification system. We recognized that the progression from wakefulness to deep sleep was associated with a decrease in complexity of the EEG or, expressed in other words, an increase in the amount of lawful determinism contained in the signal. We quantified the determinism by means of the variable termed percent recurrence (for descriptions of the technical details of the calculation see “Detection of Nonlinear Event-related Potentials” (2006) and “Method for Detection of Changes in the EEG Induced by the Presence of Sensory Stimuli” (2008)). As we expected, percent recurrence varied continuously throughout the night, with the lowest values occurring during wakefulness, and the highest values during N3 sleep. Also as expected the recurrence values during REM sleep overlapped those of all three sleep states, and the extent of overlapping varied from patient to patient.
View Abstract.
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Waves Through Gap Junctions

Gap Junctions

A major factor in the progression of osteoarthritis is the breakdown of joint cartilage by MMP enzymes produced by synovial cells in response to tiny changes in the level of the chemical signalling agent IL-1. We were interested in determining how such tiny changes occurring anywhere in the joint could trigger increases in MMP large enough to destroy joint cartilage. We previously discovered that all synovial cells in the joint were connected by gap junctions, tiny pores between cells that permitted direct communication between the interiors of adjacent cells. In the present study we showed that a signal delivered to a single synovial cell by IL-1 could pass instantaneously through the gap junctions to all other synovial cells thereby activating them to produce MMPs as if they had reacted directly with IL-1. Such a signal-transmission process may mediate other diseases besides osteoarthritis.
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Dying Too Young

Too Young

Death is the most certain fact of our experience. In cases involving trauma we are confident we understand why death occurred. We commonly think that old age is responsible for death in the aged, like an automobile driven too many miles, although we wonder why the apparent natural term of life varies from person to person. We just don’t think much about what causes non-traumatic deaths among younger people. Disease is not an answer. That would be like saying the bumper of the car that hit a pedestrian was the cause of death. We tend to concentrate on enjoying life as best we can and to hide in a psychological sense from the questions of why and when our lives will end in the particular manner decreed by fate or God’s will. We behave this way even though death is a physical process and, under the founding assumption of science, has a lawful or at least rational physical explanation.

Perhaps one of the reasons the physical conditions that predispose toward death at a young age remain essentially unexplored is fear of the implications of what we might learn if we studied the matter. If you had good evidence of what would cause your death sometime in the future, would you modify your behavior in the present to delay death or at least lessen its accompanying pain? Would a decision not to do so in favor of the pleasure the behavior confers here and now be irrational, or merely a thoughtful choice between competing values?

If you choose to pursue the issue, you might consider thinking about EMFs, which probably have the highest probability of promoting the most premature deaths. In the following series of four interviews I discussed the scientific and sociological background of the issue of the causal role of EMFs in human disease.

View Part 1: Studying EMFs
View Part 2: EMFs and the Brain
View Part 3: Hazards of EMFs
View Part 4: Controlling EMF Research

Brain Recurrence Analysis: Not Your Father’s EEG

Hans Berger

The electroencephalogram (EEG) was once an important tool for studying brain behavior and diagnosing brain disorders. MRI and CT have largely replaced diagnostic use of the EEG, but its use in functional studies is expanding. The assumption had long been that important information about brain function was buried in the complex electrical pattern encoded by the EEG. Unfortunately the traditional methods for analyzing EEGs, signal averaging and spectral analysis, were ineffective in uncovering the putative hidden information. Within the last several decades, however, advances in unrelated areas including the thermodynamics of irreversible systems and the mathematical analysis of time series data from nonlinear systems led to the development of analytical techniques capable of extracting meaning from data that was previously unobtainable. Use of these techniques for analyzing the EEG hold the promise of providing new and important information regarding brain function. There is now a reasonable hope that important diagnostic and physiological information can be safely and economically obtained from EEG analysis.
View Abstract.
View Powerpoint presentation.

 

The Cellular Basis of EMF Sensitivity

Dallas 2010

Many articles argued that weak low-frequency EMFs cannot be detected by the body because their interaction energy is too small compared with the energy inherent in thermal motion of atoms. It has long been known, however, that many animals including the catfish, shark, and platypus have specialized electroreceptor cells that are evolutionarily conditioned to detect such EMFs by means of sensory transduction. We showed that detection can be prevented in catfish by means of blocking antibodies. The possibility therefore exists that human EMF sensitivity can be treated using antibodies against one or more of the proteins involved in the transduction process.
View Abstract.
View Powerpoint presentation.

 

Overview of Brain Nonlinear Activity

Mt. Etna

Published reports dealing with effects of man-made environmental electromagnetic fields (EMFs) on human brain electrical activity have been inconsistent. We hypothesized that the problem arose from widespread use of linear methods such as time averaging and spectral analysis to analyze what were essentially nonlinear stimulus-response relationships. We developed a nonlinear analytical method to detect EMF effects on the brain and used the method to consistently demonstrate the occurrence of such effects.
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View poster.

 

Sense and Sensibility

In one way or another, the body’s sensory systems undergird all human knowledge. Some forms of knowledge, such as what we see or hear, are present to consciousness. Other forms such as information coded in afferent signals in the autonomic nervous systems, exist below the level of awareness. Identification of the range of sensory capabilities of the body permits an identification of the number and nature of input channels to the central nervous system. We identified a previously unrecognized human sensory system that is capable of detecting low-frequency magnetic fields.
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The Gears and Pulleys Behind the Effects of Low-Frequency EMFs

gears

The question of how low-frequency EMFs affect the body, the actual mechanism of gears and pulleys that mediate the effect, has been of great interest since the inception of the hazards issue in the 1970s. The question has been of interest because of the fundamental insight into the way our bodies work that would be provided by the answer, and also because of the quirky argument first advanced by Herman Schwan that the absence of established biophysical principles of interaction that govern EMF effects is evidence that such effects do not exist. In the tabula rasa approach to the question one begins with Maxwell’s equations and knowledge of the randomizing energy present in the body, namely kT, and intuits a model by which a living system could detect a low-frequency EMF. No one succeeded, which had the unfortunate effect of crediting Schwan’s hubristically illogical argument. We approached the question by beginning with an example in nature of an animal that actually detects a low-frequency EMF and employed our knowledge of the structure of the electroreceptor to deduce a model of the gears and pulleys consistent with physical law that could be responsible.
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View poster.

Electrical Stimulation of Bone

Bone

Use of electromagnetic fields (EMFs) for treating bone diseases began in the early 1960s and had a meteoric rise in popularity that peaked around 1982, which was the year that EBI, the first EMF-bone company, was judged to be the most successful small business in the U.S. Nevertheless clinical use of EMF devices declined, and by about 2005 was essentially nil. My presentation describes the EMF techniques that developed and the factors that largely accounted for the boom–bust cycle. The presentation is a compilation of slides from various lectures that I gave between 1995–2005.
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Biological Nonlinearity: Can Physics Help?

Physics-Biology

Physics is an intellectual system that attempts to explain everything with certainty, that is, it seeks deductive conclusions based on mathematical laws. Essentially, there are only three things that physics can’t do. It can’t explain where the laws come from, it can’t answer a small set of insignificant questions concerning subatomic particles that move very fast, and it can’t explain life. A hundred Einsteins working together couldn’t even show deductively that there was such a thing as mankind, or any other animal. That’s why if you went to a Harvard or a Yale to study for a Ph.D. in biology you would not study physics. But the Harvards and Yales have gone too far. The laws of physics are mostly irrelevant to biology, but not the physics mindset and method. Physics can help.
View Abstract.
View Powerpoint presentation.
View book chapter.

Gap Junctions in Osteoarthritis

GJ

Synovial cells are electrically and metabolically coupled through gap junctions, but their specific role in synovial tissue is unknown. The question is important because synovial tissue lines the inside of all joints, and metabolic changes in synovial cells are ulitmately responsible for osteoarthritis. We suspected that synovial gap junctions were involved in the development and progression of osteoarthritis, and we examined the question by comparing synovial tissue between patients who did or did not suffer from the disease. Using electron microscopy, we found more gap junctions in the patients with osteoarthritis, and using biochemical analysis we found that the osteoarthritic patients had higher levels of gap-junction protein. Thus the results established an association between gap junctions and the presence of the disease.
View Abstract.
View poster.

Assessing Health Risks of EMFs from Cell Towers

Cell Tower

People who live in the vicinity of cell-phone towers commonly wonder whether doing so is safe. Not surprisingly the cell-phone companies maintain that even long-term exposure to the EMFs from the towers has no impact whatever on human health and is completely non-hazardous. Just as unsurprisingly at least some of the people who are exposed to the tower EMFs are skeptical of the companies’ opinions concerning EMF safety. But the people who are exposed also have other reactions and attitudes. They think, for example, that the company experts are educated scientists who are highly knowledgeable about EMFs, and this perception results in a kind of intimidation that makes those who are exposed to the EMFs more or less accepting of their fate. Added to this pressure to remain silent is the notion that if cell-tower EMFs really were hazardous, the federal government would never allow the exposure to occur, at least not involuntarily. If you were interested in escaping from the subservient position that results from adoption of this perspective, then the first thing that you must do is to recognize the kind of a problem that is presented by cell-tower EMFs. In reality, it is not a scientific problem but rather one involving choices between competing values. The simple fact is that the values of the cell-phone companies are different than yours. The government’s position is more complex because it has a responsibility to balance competing values when it makes laws and rules. Protecting human health is one of its values, but so is protecting economic development, and the balance that is struck in a particular case such as that involving a cell-tower next to your house might not be the balance that you would strike. The point is that the EMF health-risk issue is more fundamental than the arcane area of EMF science. The next most important point is that you are absolutely as qualified as the most erudite expert working for the cell-phone companies or the government. I think that leading an authentic life involves the responsibility of making your own value judgments rather than allowing the experts to do it for you. These were the points that I made in the presentation I delivered in Connecticut, in 2000.
View Abstract.
View book chapter.
View presentation.

Mechanistic Basis of Osteoarthritis

knee

Something causes osteoarthritis, which is the erosion of the specialized cartilage that covers the ends of bones inside joints. We developed a detailed mechanistic hypothesis to explain how the disease process is mediated. Our idea was that the inflammatory cytokine IL-1β depolarized the membranes of synovial cells by means of a process that involved activation of protein kinase C and the passage of calcium ions into the cell through a sodium-channel subtype, resulting in overproduction of enzymes that destroy cartilage. In a presentation for graduate students, I described the experiments we performed to test the hypothesis. The principal aim of my talk was to illustrate the relation between a hypothesis and the evidence adduced to test it.
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Chaos and Fractals in Medicine and Biology

Lava Lamps

Despite the successes of modern science, many important problems remain. As examples, we do not know what causes cancer or other diseases, we cannot predict when heart attacks or strokes will occur, and we do not know how information is stored in the brain. Solutions to these and other problems require a reformulation of our world view to include the existence of nonlinearity and, in particular, the occurrence of deterministic chaos. My purpose is to describe the inherent limitations of the present scientific paradigm, and to indicate how some important scientific problems might be satisfactorily resolved by looking at the world in a nonlinear way. In my view, one such problem involves an understanding of the mechanistic basis by which environmental electromagnetic fields can give rise to health hazards. Resolution of the EMF hazards issue was used as a particular example of the power of biological nonlinearity to explain the meaning of bona fide data.
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Electromagnetic Fields are Transduced Like Other Stimuli

Brave New World

The nervous system is the pathway by which environmental-strength EMFs produce normal and abnormal physiological effects (see Electromagnetism & Life). Much of the manufactured controversy regarding the health hazards of EMFs falls away when the connection between external energy and internal change is recognized, because then it becomes clear that post-EMF-detection changes caused by EMFs are indirect, and consequently nonlinear. In this presentation I summarized the evidence and reasoning that led to the hypothesized link between EMFs and biological changes, and presented supporting experimental evidence. The nature of biological EMF detection entails the need to change the way we design experiments intended to generate knowledge of EMF-induced bioeffects. It’s a new world.
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EMF Debate Results from Paradigmatic Shift

APS-biology

I admit to deep amazement at the chutzpah of the APS. Their press release said “Physicists are frequently asked to comment on the potential danger of cancer from electromagnetic fields that emanate from common powerlines and electrical appliances.” I suppose it’s also true that physicists are frequently asked to comment on whether O.J. is guilty or Dole would have made a better president than Clinton. The frequency with which physicsts may be asked questions seems to me to be an exceedingly poor basis for the APS to attempt to influence public opinion.
View Abstract.
View slides.

Health Risks from Electric Power Facilities

Toronto

I gave an invited talk at the symposium which was sponsored by the Electric Power Research Institute, the Canadian Electrical Association, the Edison Electric Institute, the National Rural Electric Cooperative Association, Bonneville Power Administration, and Ontario Hydro. Details regarding events at the symposium are provided in Going Somewhere. Click here for an audio file of the presentation.

The oily character who begins talking after my presentation is H.B. Graves, who was the face of the power-industry effort in the 1980s aimed at convincing the public that powerline EMFs were not health risks. He began as a major contractor for the Electric Power Research Institute in the 1970s, and was recruited to replace the team of Morton Miller, Solomon Michaelson, and Herman Schwan after they had become discredited.

Graves moved through the EMF issue in the 1980s like shit through a goose. He was the chairman of an EMF literature review that was carried out by the American Institute of Biological Sciences, chairman of the Florida EMF Science Commission, and chairman of a commission that examined EMF issues for the Australian Department of Health. He went to work for Tom Watson, as Watson’s chief of staff, and was largely responsible for organizing the team of NIH experts that successfully defended the power industry in a famous case in Goshen, New York.

At the Toronto meeting Graves was at the apex of his career as an apologist for the power industry. It was therefore his responsibility to respond to the challenge posed by my presentation.

Click here for a PDF of my written presentation.

Analysis of Battelle 60-Hz Studies

Battelle

Investigators at Battelle conducted numerous studies of potential EMF-induced health hazards from powerlines, using funds provided by the Electric Power Research Institute and the U.S. Department of Energy. The Battelle EMF research was rigged in multiple dimensions to guarantee that it would not yield data whose implications were adverse to the companies’ interests. These dimensions included experimental hypothesis, study design, statistical design, and falsification of data. Surprisingly, despite the multiple strategies employed to control the appearance and implications of the data, the Battelle studies were a failure even when assessed against their stated goals, because the studies did not produce the expected and predicted results.
View Abstract.
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Environmental EMFs and Stress: An Inconvenient Truth

Stress

Consideration of the role of electrical forces in biological systems began with a move away from a purely chemical view of life and toward one which emphasized electron dynamics and the physical properties of biological tissue. Studies of the physiological role of the body’s intrinsic electrical signals then began, and they led to experiments on the therapeutic effects of artificial electrical signals. But during this forty-year developmental period, electricity became firmly established in society. There was a proliferation of transmitter towers, high-voltage lines, and the innumerable devices they serve, and it resulted in environmental levels of electromagnetic energy comparable to those being studied in the laboratory and applied clinically. I spoke about the side-effects of environmental electromagnetic energy, and concluded that present exposure patterns were a significant public-health risk.
View Abstract.
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High Voltage Tension

60 Minutes

In the early 1970s two major EMF-related issues combined to produce a major impact on the public consciousness. The governor of New York struck a deal with Canadian power producers and ordered construction of a 750,000-volt powerline to bring electrical power to New York City, which was paying the highest rates in the world for electricity. At about the same time the U.S. Navy decided to build the world’s largest antenna, which would stretch over 26 counties in northern Wisconsin. In both cases, the potential health impacts of the EMFs that would be produced by the construction projects were unstudied and essentially unconsidered. 60 Minutes did a piece on the antenna construction project in which Dan Rather interviewed Dr. Becker. They did a second piece in which Mike Wallace interviewed me.
To see this interview, click here.

 

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