Human Threshold Research Group - Electric and Magnetic Bioeffects

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Figure Caption: This experiment suggests that, after a 30 minute rest, less activation (middle panel, blue colour on functional MRI) is involved to produce a rhythmic thumb/index finger opposition task compared to control (top panel, yellow colour) and that exposure to a power- line frequency MF may cancel this effect (bottom panel, no change as compared to top panel).
Future Directions

The group continues to strengthen and extend its fundamental research effort, and new projects aiming to establish thresholds at which a systematic neurophysiological response is induced by a magnetic stimulus are being developed and initiated. Studies aiming to better understand the magnetophosphene mechanisms have been initiated. Also, a new original starting project is studying the possible threshold for a similar acute effect on the human vestibular system (controling for standing balance). Neurocomputational modeling is being promoted as a new promising window to understand the underlying electromagnetic interactions: this modelling approach offers for example a mechanistic hypothesis supporting reported effects on synaptic plasticity and in terms of threshold. Both these experimental and theoretical insights are integrated within an emerging research effort: potential translation to therapeutic strategies in neuromotor disorders (http://www.cihr-irsc.gc.ca/e/45375.html).

This group is supporting a facility also available on contract to test other stimuli and for patient/study diagnostic use as a wide-range test facility for human sensory/motor and neurocognitive testing.  The facility contains a wide assortment of testing capability all housed within an available hypoxia-controlled (monitored artificial hypoxic atmosphere to 4500m altitude) environment.  Equipment includes 32 channel ambulatory EEG, 64 and 128 channel fixed-lead EEG/EMG, 6 degrees of freedom force plate, 16 channel Polhemus, fingertip micro-tremor monitoring, HR, BOP, audio/video, PC-controlled psychometrics, hot/cold neurosensory stimulation.  Most of the above equipment, including a 128 channel EEG/EMG, is also available within our 3T mMR/PET/EEG/EMG hybrid imaging facility.

This scientific group has an international reputation and expertise regarding the biological effects of low frequency time-varying magnetic field (MF) exposures. This multidisciplinary team of scientists and fellows/students is working toward a common general objective: establishing thresholds for physiological responses to specific time-varying MF exposures. The studies currently conducted at 50 and 60 Hz are not only addressing a need for international regulatory agencies, they are also providing a new point of view regarding the potential mechanisms of action of magnetic field stimuli in the milliTesla range. 

Researchers
A. Legros
Group Director - BEMS, Kinesiology, Neurosciences, Modelling (external collaboration)
A.W. Thomas
BEMS, Neuromodulation
J. Modolo
Scientist - At-Large, Computational Neuroscience/Modelling
R.Z. Stodilka
Nuclear Medicine Physics, Theoretical Modelling
J. Théberge
MRI Physics
M. Corbacio
Research Assistant - Lab Manager
L. Keenliside
Manager Technical Services
A.N. Allen
MSc Candidate
S. Davarpanah Jazi
Research Assistant - PhD Candidate
Technologies
3T PET/MR
Bioelectromagnetics
Human Threshold Testing Facility
Prototype Facility

Collaborators
F.S. Prato
Lawson Imaging Program Leader, MR and Nuclear Medicine Phsyics
R.T. Thompson
MRI, Facility Director
S.P. Loughran
Academic Collaborator
A. Beuter
Academic Collaborator
Key Accomplishments

Using a multimodality experimental approach, we have suggested an effect of 1.8 and 3 mT 60 MF on neuroprocessing in humans (via synaptic plasticity). More recently, we have established a threshold at which a time-varying MF systematically triggers a neurophysiological response in humans through an acute perception called magnetophosphenes (transient perception of flickering lights due to the exposure, while with the eyes closed in the dark). These achievements are contributing to the enrichment of the scientific base used by international agencies such as ICNIRP (International Commission on Non-Ionizing Radiation Protection) and IEEE-ICES (Institute of Electrical and Electronics Engineers - International Committee on Electromagnetic Safety) to develop and support international guidelines regulating human exposure to electromagnetic fields.

In more details:

The question of the possible impact of power-line frequency magnetic fields (MF) or electric devices from our daily lives is often raised, but what do we really know? This is the question we are tackeling since 2005 with a research program experimentally testing, in humans, incremental 50 and 60 Hz MF until we reach the threshold at which a reliable systematic effect can be triggered. The objective of this work is to consolidate the basic knowledge used to support international recommendations from ICNIRP and IEEE. Indeed, these main international agencies in charge of publishing guidelines to limit public and workers to 50 and 60 Hz MF exposure agree to point out a major limitation in terms of available scientific data supporting their recommendations: A serious lack of experimental data acquired in humans regarding the exposure threshold triggering acute, reliable, systematic neurophysiological effects.

Based on this fact, the Human Threshold Research Group began in 2005 a first experimental phase testing for the effect of a 1 800 µT MF at 60 Hz in humans, using a first exposure system developed for that purpose. Phase 1 involved 73 healthy volunteers in which selected physiological parameters were evaluated before, during and after one hour of exposure to the MF: cardiac rhythm (measured by electrocardiogram, ECG), electrical activity of the brain (measured by electroencephalography, EEG), voluntary movements of the hand (measured using a 3D movement tracking system), postural sway (measured using a force plate), and physiological tremor (measured with a laser at the level of the fingertip). No effect of the exposure was observed on cardiovascular parameters, voluntary movements of the hand, or resting EEG activity. However, results showed small modulations of physiological tremor and postural sway (i.e. vestibular system) that need to be replicated and explored further. These effects are not acute or systematic, but subtle and appear after 45 minutes of exposure, during a continuous exposure. Phase 1 also included a pilot study (9 volunteers) using for the very first time functional magnetic resonance imaging (fMRI) to identify potential effects of MF exposure on brain activity while using for the first time the MRI scanner itself to generate the 60 Hz MF exposure, still at 1 800 μT. Pilot results showed a relative increase in the functional activation of the motor cortex (brain region controlling movement) during a repetitive hand movement after 30 minutes of exposure (see Figure).

Phase 2 of this research program began in 2008. It involved a total of 119 volunteers in 2 distinct experiments. The level of MF exposure at 60 Hz was increased to 3 000 μT (new exposure system developed), with the same exposure duration of 1 hour. The first experiment tested the performance of 99 volunteers in 10 psychometric tests before, during and after exposure. Results indicate a possible effect of the MF exposure on short-term memory, but no effect on the 9 other psychometric tests studied. These effects are not acute or systematic, but subtle and appear after one hour of exposure. The second experiment took place in an MRI scanner, where 20 volunteers had to perform a motor task (repetitive hand movement) and a cognitive task (« mental rotations » test) before and after MF exposure. Results showed that brain activation associated with the execution of these tasks was increased in volunteers who had been exposed to the MF, without any change in the performance in these tasks. Similarly to the first experiment, these effects were detected after one hour of exposure, suggesting taken together a possible effect on the neurophysiological processes underlying learning, called synaptic plasticity.

If the results of Phase 1 and 2 led to suggesting the existence of cumulative effects of MF exposure of 45 minutes or more, at 1 800 µT and above, they still did not identify acute and systematic effects linked with the exposure. Therefore, on the basis on the knowledge from Phase 1 and 2, and on results showing the safety of exposure on the order of tens of milliTesla, we initiated the Phase 3 of this research program with the goal of identifying this threshold effect using exposure levels reaching 50 000 µT: Phase 3 began in 2011 with experiments involving a total of 90 volunteers. The first experiment tested 30 volunteers in an MRI scanner generating short head exposures at 50 and 60 Hz: 7 600 μT (2 seconds, 100 repetitions), 3 000 μT (10 seconds, 12 repetitions), 5 000 μT  (10 minutes). Different modalities of brain activity at rest were measured during and/or between exposure periods using independently or simultaneously fMRI and EEG. No significant effect of the exposure or fMRI was found in any of the tested conditions, suggesting that 7 600 µT at 50 and 60 Hz is not sufficient to trigger an acute effect on electrical or metabolic activity of the brain at rest.

The second experiment went even further and tested the magnetophosphene perception threshold in 60 volunteers exposed to up to 50 000 µT at 50 and 60 Hz. Magnetophosphenes are a perception of flickering lights observed in darkness, eyes closed, as a consequence of a sufficiently strong time-varying MF exposure. They are the consequence of induced electric fields and currents at the level of specific cells of the retina. The magnetophosphene perception threshold, although not well understood, is at the core of exposure limits published by ICNIRP and IEEE. New exposure systems have again been developed and used to expose volunteers to 11 levels of MF between 0 and 50 000 µT (increments of 5 000 µT), each repeated 5 times. This protocol was repeated 3 times using 3 different exposure locations (eye, visual cortex, whole head). Volunteers had to report magnetophosphene perception using a button-press, and the electrical activity of their brain was continuously collected  (EEG). Results of this study not only show a perception threshold at 50 and 60 Hz of 15 000 µT at last measured in humans (Figure 5), it also shows a significant reduction of associated EEG activity above this perception threshold, which represents the first objective measure of an acute neurophysiological effect at this field level. Results also show a differential response at 50 and 60 Hz. This preliminary threshold for acute effects on retinal neurons is therefore established at 15 000 µT, but fluctuates depending on the MF frequency, of the MF orientation, and time of adaptation to darkness. New studies have already been initiated in a Phase 4 of this program, aiming at improving the understanding of these effect fluctuations. Furthermore, the clear identification of this retinal threshold allows formulating new hypotheses on possible effects on the human vestibular system, which controls postural sway.

Overall, these results obtained since 2005 allow to better understand the effects of 50 and 60 Hz MF, and also to suggest possible mechanisms of interaction between the MF and different physiological processes in humans. In addition to establishing these thresholds for neurophysiological effects due to extremely low-frequency MF in humans, critical from a sanitary and international regulatory perspective; these projects also allow to acquire new knowledge in terms of mechanisms of action, which enable translational research projects towards potential novel therapeutic applications.

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