Alexandre Legros

A Methodological Note on Nonlinear Time Series Analysis: Is the Open-and Closed-Loop Model of Collins and De Luca (1993) a Statistical Artifact?

Abstract The authors reexamined, theoretically and empirically, the method proposed by J. J. Collins and C. D. De Luca (1993) for the analysis of center-of-pressure trajectories. The main argument in this article is that Collins and De Lucas approach is not adapted to the analysis of bounded time series and leads to statistical artifacts such as underestimation of the diffusion process for long-term intervals. The open- and closed-loop model developed by Collins and De Luca is a direct consequence of those statistical problems. Applying more classical methods, such as rescaled range analysis or detrended fluctuation analysis, the authors show that center-of-pressure trajectories can be modeled as continuous, antipersistent fractional Brownian motion. More specifically, those trajectories behave like 1/f noise, a ubiquitous feature in adaptive biological systems.

A literature review: the cardiovascular effects of exposure to extremely low frequency electromagnetic fields

The effects of exposure to extremely low frequency (ELF) electromagnetic fields (EMFs) on human cardiovascular parameters remain undetermined. Epidemiological studies have utilized dosimetry estimations of employee workplace exposure using altered heart rate variability (HRV) as predictive of certain cardiovascular pathologies. Laboratory studies have focused on macrocirculatory indicators including heart rate, HRV and blood pressure. Few studies have been conducted on the response of the microcirculatory system to EMF exposure. Attempts to replicate both epidemiological and laboratory studies have been mostly unsuccessful as study design, small sample populations and confounding variables have hampered progress to date. Identification of these problems, in the current context of international exposure guideline re-evaluation, is essential for future EMF studies. These studies should address the possible deleterious health effects of EMFs as well as the detection and characterization of subtle physiological changes they may induce. Recommendations for future work include investigating the macro- and microcirculatory relationship and the use of laboratory geomagnetic shielding.

Using a virtual cortical module implementing a neural field model to modulate brain rhythms in Parkinson's disease.

We propose a new method for selective modulation of cortical rhythms based on neural field theory, in which the activity of a cortical area is extensively monitored using a two-dimensional microelectrode array. The example of Parkinsons disease illustrates the proposed method, in which a neural field model is assumed to accurately describe experimentally recorded activity. In addition, we propose a new closed-loop stimulation signal that is both space- and time- dependent. This method is especially designed to specifically modulate a targeted brain rhythm, without interfering with other rhythms. A new class of neuroprosthetic devices is also proposed, in which the multielectrode array is seen as an artificial neural network interacting with biological tissue. Such a bio-inspired approach may provide a solution to optimize interactions between the stimulation device and the cortex aiming to attenuate or augment specific cortical rhythms. The next step will be to validate this new approach experimentally in patients with Parkinsons disease.

Pulsed magnetic field exposure induces lasting changes in neural network dynamics

How extremely low frequency (ELF) electromagnetic fields (such as power line exposure) impacts brain activity is today an intense area of research. One challenge is to unveil transduction mechanisms allowing ELF to interact with brain tissue. Thus, we present a cortical network model receiving internal and external stimuli. Using frequency analysis, we study how these stimuli durably modulate network dynamics depending on exposure duration, stimuli properties and transduction mechanisms. Our results indicate that these stimuli induce different responses in the frequency domain. Ultimately, such models might be useful in evaluating power line exposure thresholds, and in developing innovative brain stimulation methods.

Model-driven therapeutic treatment of neurological disorders: reshaping brain rhythms with neuromodulation

Electric stimulation has been investigated for several decades to treat, with various degrees of success, a broad spectrum of neurological disorders. Historically, the development of these methods has been largely empirical but has led to a remarkably efficient, yet invasive treatment: deep brain stimulation (DBS). However, the efficiency of DBS is limited by our lack of understanding of the underlying physiological mechanisms and by the complex relationship existing between brain processing and behaviour. Biophysical modelling of brain activity, describing multi-scale spatio-temporal patterns of neuronal activity using a mathematical model and taking into account the physical properties of brain tissue, represents one way to fill this gap. In this review, we illustrate how biophysical modelling is beginning to emerge as a driving force orienting the development of innovative brain stimulation methods that may move DBS forward. We present examples of modelling works that have provided fruitful insights in regards to DBS underlying mechanisms, and others that also suggest potential improvements for this neurosurgical procedure. The reviewed literature emphasizes that biophysical modelling is a valuable tool to assist a rational development of electrical and/or magnetic brain stimulation methods tailored to both the disease and the patients characteristics.

Using “Smart Stimulators” to Treat Parkinson’s Disease: Re-Engineering Neurostimulation Devices

Let’s imagine the cruise control of your car locked at 120 km/h on any road in any condition (city, country, highway, sunny or rainy weather), or your car air conditioner set on maximum cold in any temperature condition (even during a snowy winter): would you find it efficient? That would probably not be the most optimal strategy for a proper and comfortable driving experience. As surprising as this may seem, this is a pretty accurate illustration of how deep brain stimulation is used today to treat Parkinson’s disease motor symptoms and other neurological disorders such as essential tremor, obsessive-compulsive disorder, or epilepsy.

Possible mechanisms of synaptic plasticity modulation by extremely low-frequency magnetic fields.

Understanding the biological mechanisms by which extremely low-frequency (ELF, < 300 Hz) magnetic fields (MFs) interact with human brain activity is an active field of research. Such knowledge is required by international agencies providing guidelines for general public and workers exposure to ELF MFs (such as ICNIRP, the International Commission on Non-Ionizing Radiation Protection). The identification of these interaction mechanisms is extremely challenging, since the effects of ELF MF exposure need to be monitored and understood at very different spatial (from micrometers to centimeters) and temporal (from milliseconds to minutes) scales. One possibility to overcome these issues is to develop biophysical models, based on the systems of mathematical equations describing the electric or metabolic activity of the brain tissue. Biophysical models of the brain activity offer the possibility to simulate how the brain tissue interacts with ELF MFs, in order to gain new insights into experimental data, and to test novel hypotheses regarding interaction mechanisms. This paper presents novel hypotheses regarding the effects of power line (60 Hz in North America) MFs on human brain activity, with arguments from biophysical models. We suggest a hypothetic chain of events that could bridge MF exposure with detectable effects on human neurophysiology. We also suggest novel directions of research in order to reach a convergence of biophysical models of brain activity and corresponding experimental data to identify interaction mechanisms.

Modulation of neuronal activity with extremely low-frequency magnetic fields: Insights from biophysical modeling

Time-varying magnetic stimulation of the central nervous system is nowadays a promising therapeutic approach already used to alleviate the symptoms in a variety of neurological disorders. Transcranial Magnetic Stimulation (TMS) is an example of a successful application involving specific patterns of magnetic field (MF) for therapeutic use, which provides clinical improvement in movement disorders or depression. Other neuromodulation strategies consist in proposing several orders of magnitude lower magnetic stimuli that are more flexible in terms of shape and frequency of the signal. However, the refinement of both of these techniques is limited due to the lack of understanding of the underlying mechanisms supporting the interaction between the magnetic stimulus and brain tissue. To provide insights into the modulation of neuronal activity by extremely low-frequency (ELF) MF, we present biophysical modeling results regarding 1) single neuron exposure to an ELF MF, and 2) neuronal network exposure to an ELF MF. These results shed light on the effect of ELF MFs on neuronal activity from the single cell to the network level, and illustrate the importance of a number of factors both in ELF MF characteristics and brain tissue properties in determining the outcome of the exposure. These principles may guide future therapeutic developments.

A comparison of MR-based attenuation correction in PET versus SPECT

Attenuation correction (AC) is a critical step in the reconstruction of quantitatively accurate positron emission tomography (PET) and single photon emission computed tomography (SPECT) images. Several groups have proposed magnetic resonance (MR)-based AC algorithms for application in hybrid PET/MR systems. However, none of these approaches have been tested on SPECT data. Since SPECT/MR systems are under active development, it is important to ascertain whether MR-based AC algorithms validated for PET can be applied to SPECT. To investigate this issue, two imaging experiments were performed: one with an anthropomorphic chest phantom and one with two groups of canines. Both groups of canines were imaged from neck to abdomen, one with PET/CT and MR (n = 4) and the other with SPECT/CT and MR (n = 4), while the phantom was imaged with all modalities. The quality of the nuclear medicine reconstructions using MR-based attenuation maps was compared between PET and SPECT on global and local scales. In addition, the sensitivity of these reconstructions to variations in the attenuation map was ascertained. On both scales, it was found that the SPECT reconstructions were of higher fidelity than the PET reconstructions. Further, they were less sensitive to changes to the MR-based attenuation map. Thus, MR-based AC algorithms that have been designed for PET/MR can be expected to demonstrate improved performance when used for SPECT/MR.

Effects of a 60 Hz Magnetic Field Exposure Up to 3000 μT on Human Brain Activation as Measured by Functional Magnetic Resonance Imaging.

Several aspects of the human nervous system and associated motor and cognitive processes have been reported to be modulated by extremely low-frequency (ELF, < 300 Hz) time-varying Magnetic Fields (MF). Due do their worldwide prevalence; power-line frequencies (60 Hz in North America) are of particular interest. Despite intense research efforts over the last few decades, the potential effects of 60 Hz MF still need to be elucidated, and the underlying mechanisms to be understood. In this study, we have used functional Magnetic Resonance Imaging (fMRI) to characterize potential changes in functional brain activation following human exposure to a 60 Hz MF through motor and cognitive tasks. First, pilot results acquired in a first set of subjects (N=9) were used to demonstrate the technical feasibility of using fMRI to detect subtle changes in functional brain activation with 60 Hz MF exposure at 1800 μT. Second, a full study involving a larger cohort of subjects tested brain activation during 1) a finger tapping task (N=20), and 2) a mental rotation task (N=21); before and after a one-hour, 60 Hz, 3000 μT MF exposure. The results indicate significant changes in task-induced functional brain activation as a consequence of MF exposure. However, no impact on task performance was found. These results illustrate the potential of using fMRI to identify MF-induced changes in functional brain activation, suggesting that a one-hour 60 Hz, 3000 μT MF exposure can modulate activity in specific brain regions after the end of the exposure period (i.e., residual effects). We discuss the possibility that MF exposure at 60 Hz, 3000 μT may be capable of modulating cortical excitability via a modulation of synaptic plasticity processes.