A numerical study to compare stimulations by intraoperative microelectrodes and chronic macroelectrodes in the DBS technique.

Deep brain stimulation is a clinical technique for the treatment of parkinson's disease based on the electric stimulation, through an implanted electrode, of specific basal ganglia in the brain. To identify the correct target of stimulation and to choose the optimal parameters for the stimulating signal, intraoperative microelectrodes are generally used. However, when they are replaced with the chronic macroelectrode, the effect of the stimulation is often very different. Here, we used numerical simulations to predict the stimulation of neuronal fibers induced by microelectrodes and macroelectrodes placed in different positions with respect to each other. Results indicate that comparable stimulations can be obtained if the chronic macroelectrode is correctly positioned with the same electric center of the intraoperative microelectrode. Otherwise, some groups of fibers may experience a completely different electric stimulation.

Novel passive element circuits for microdosimetry of nanosecond pulsed electric fields.

Microdosimetric models for biological cells have assumed increasing significance in the development of nanosecond pulsed electric field technology for medical applications. In this paper, novel passive element circuits, able to take into account the dielectric dispersion of the cell, are provided. The circuital analyses are performed on a set of input pulses classified in accordance with the current literature. Accurate data in terms of transmembrane potential are obtained in both time and frequency domains for different cell models. In addition, a sensitivity study of the transfer function for the cell geometrical and dielectric parameters has been carried out. This analysis offers a new, simple, and efficient tool to characterize the nsPEFs' action at the cellular level.

Effects of nanosecond pulsed electric fields on the activity of a Hodgkin and Huxley neuron model.

The cell membrane poration is one of the main assessed biological effects of nanosecond pulsed electric fields (nsPEF). This structural change of the cell membrane appears soon after the pulse delivery and lasts for a time period long enough to modify the electrical activity of excitable membranes in neurons. Inserting such a phenomenon in a Hodgkin and Huxley neuron model by means of an enhanced time varying conductance resulted in the temporary inhibition of the action potential generation. The inhibition time is a function of the level of poration, the pore resealing time and the background stimulation level of the neuron. Such results suggest that the neuronal activity may be efficiently modulated by the delivery of repeated pulses. This opens the way to the use of nsPEFs as a stimulation technique alternative to the conventional direct electric stimulation for medical applications such as chronic pain treatment.

Signal transduction on enzymes: the effect of electromagnetic field stimuli on superoxide dismutase (SOD).

Protein functions and characteristics can highly differ from physiological conditions in presence of chemical, mechanical or electromagnetic stimuli. In this work we provide a rigorous picture of electric field effects on proteins behavior investigating, at atomistic details, the possible ways in which an external signal can be transduced into biochemical effects. Results from molecular dynamics (MD) simulations of a single superoxidismutase (SOD) enzyme in presence of high exogenous alternate electric fields will be discussed.

Micro vs macro electrode DBS stimulation: A dosimetric study.

Deep Brain Stimulation (DBS) is a clinically suitable technique for the treatment of the Parkinson's disease. Recently, also other neurological disorders such as Tourette syndrome, obsessive-compulsive disorder, epilepsy are being to be treated with DBS. However, the debate on its therapeutic mechanisms of action is still open. In order to a better understanding of such mechanisms, in this work the attention is focused on the DBS micro-stimulation. Indeed, a micro electrodes registration and stimulation is a fundamental step, during the surgical phase, to optimize the technique in terms of DBS lead positioning and DBS signal parameters. In this paper a dosimetric analysis with micro electrodes has been carried out, showing a more focused distribution of the electrical potential induced in the neuroanatomical tissues and changes of the excited/inhibited regions, respect to a macro electrodes stimulation.

Channel noise enhances signal detectability in a model of acoustic neuron through the stochastic resonance paradigm.

A number of experimental investigations have evidenced the extraordinary sensitivity of neuronal cells to weak input stimulations, including electromagnetic (EM) fields. Moreover, it has been shown that biological noise, due to random channels gating, acts as a tuning factor in neuronal processing, according to the stochastic resonant (SR) paradigm. In this work the attention is focused on noise arising from the stochastic gating of ionic channels in a model of Ranvier node of acoustic fibers. The small number of channels gives rise to a high noise level, which is able to cause a spike train generation even in the absence of stimulations. A SR behavior has been observed in the model for the detection of sinusoidal signals at frequencies typical of the speech.

Fundamental electrical quantities in deep brain stimulation: influence of domain dimensions and boundary conditions.

Deep Brain Stimulation (DBS) has revealed a convincing clinical efficacy in Parkinson's diseases and essential tremor. Unfortunately, to date no clear understanding of the therapeutic mechanisms has been achieved. Characterization of the distribution of the electrical quantities inside the target areas of the central nervous system is one fundamental step ahead. Starting from the studies that so far addressed this issue, aim of this work is to quantify the role of some parameters, such as dimensions of the conducting domain and of boundary conditions, on the distribution of the fundamental electric quantities inside the brain target area.

Effects of an exogenous noise on a realistic network model: encoding of an EM signal.

Endogenous noise has been shown to play a central role in the detection of an electromagnetic signal in the nervous system. In this work, following a biomedical perspective, an exogenous noise applied to a realistic feedforward network model has been considered. It will be shown that, if the exogenous noise is properly filtered and its level is adjusted, a clear optimization of network encoding of an electromagnetic signal, representative of an external stimulation, is obtained through the stochastic resonance paradigm.

Comparison between low-level 50 Hz and 900 MHz electromagnetic stimulation on single channel ionic currents and on firing frequency in dorsal root ganglion isolated neurons.

Alteration of membrane surface charges represents one of the most interesting effects of the electromagnetic exposure on biological structures. Some evidence exists in the case of extremely low frequency whereas the same effect in the radiofrequency range has not been detected. Changes in transmembrane voltages are probably responsible for the mobilization of intracellular calcium described in some previous studies but not confirmed in others. These controversial results may be due to the cell type under examination and/or to the permeability properties of the membranes. According to such a hypothesis, calcium oscillations would be a secondary effect due to the induced change in the membrane voltage and thus dependent on the characteristics of ionic channels present in a particular preparation. Calcium increases could suggest more than one mechanism to explain the biological effects of exposure due to the fact that all the cellular pathways using calcium ions as a second messenger could be, in theory, disturbed by the electromagnetic field exposure. In the present work, we investigate the early phase of the signal transmission in the peripheral nervous system. We present evidence that the firing rate of rat sensory neurons can be modified by 50/60 Hz magnetic field but not by low level 900 MHz fields. The action of the 50/60 Hz magnetic field is biphasic. At first, the number of action potentials increases in time. Following this early phase, the firing rate decreases more rapidly than in control conditions. The explanation can be found at the single-channel level. Dynamic action current recordings in dorsal root ganglion neurons acutely exposed to the electromagnetic field show increased functionality of calcium channels. In parallel, a calcium-activated potassium channel is able to increase its mean open time.

Effects of exogenous noise in a silent neuron model: firing induction and em signal detection.

Neuronal intrinsic noise has already shown to play a constructive role in stimuli detection. Here, an exogenous noise, applied to the neuron model as a random membrane voltage perturbation, has been considered. Properly choosing its frequency band, such a noise is able to induce firing activity in a silent neuron and to enhance the detectability of an exogenous signal, representative of an electromagnetic stimulation, through the phenomenon known as stochastic resonance.

Is the brain influenced by a phone call? An EEG study of resting wakefulness.

We recorded the resting electroencephalogram of 20 healthy subjects in order to investigate the effect of electromagnetic field (EMF) exposure on EEG waking activity and its temporal development. The subjects were randomly assigned to two groups and exposed, in double-blind conditions, to a typical mobile phone signal (902.40 MHz, modulated at 217 Hz, with an average power of 0.25 W) before or during the EEG recording session. The results show that, under real exposure as compared to baseline and sham conditions, EEG spectral power was influenced in some bins of the alpha band. This effect was greater when the EMF was on during the EEG recording session than before it. The present data lend further support to the idea that pulsed high-frequency electromagnetic fields can affect normal brain functioning, also if no conclusions can be drawn about the possible health effects.

Time-course of electromagnetic field effects on human performance and tympanic temperature.

The study aimed to investigate the time-course of electromagnetic field (EMF)-induced effects on human cognitive and behavioral performance and on tympanic temperature. Subjects were randomly assigned to two groups, exposed to a 902.40 MHz EMF before the testing session, or to the same signal during the data collecting session. Following a double-blind paradigm, subjects were tested on four performance tasks: an acoustic simple-reaction time task, a visual search task, an arithmetic descending subtraction task and an acoustic choice-reaction time task. Moreover, tympanic temperature was collected five times during each session. Results indicated an improvement of both simple- and choice-reaction times and an increase of local temperature on the exposed region under the active exposure. There was a clear time-course of the reaction time and temperature data, indicating that performance and physiological measures need a minimum of 25 min of EMF exposure to show appreciable changes.

A possible mechanism explaining variation in membrane permeability under exposure to weak magnetic fields.

The problem of the interaction between electromagnetic fields and a biological system can be properly faced at cell membrane level. Specifically, in this work, the target of the interaction has been located in the charged lipid group emerging from the membrane surface. A possible mechanism based on the Larmor precession theory is here proposed. The results evidence the possibility of specific exposure conditions that enhance the membrane permeability.

Definition and development of an automatic procedure for narrowband measurements.

Measurements in the real environment, i.e. with several different electromagnetic field (EMF) sources and scattering problems, require an accurate analysis of problems concerning narrowband measurements. The aim of the present work was the development of an automatic procedure for narrowband electric field measurements in open sites with multiple sources, in order to perform accurate and reproducible measurements. Results regarding measurements carried out in a suburban site are reported.

Effect of low frequency, low amplitude magnetic fields on the permeability of cationic liposomes entrapping carbonic anhydrase: I. Evidence for charged lipid involvement.

The influence of low frequency (4-16 Hz), low amplitude (25-75 mu T) magnetic fields on the diffusion processes in enzyme-loaded unilamellar liposomes as bioreactors was studied. Cationic liposomes containing dipalmitoylphosphatidylcholine, cholesterol, and charged lipid stearylamine (SA) at different molar ratios (6:3:1 or 5:3:2) were used. Previous kinetic experiments showed a very low self-diffusion rate of the substrate p-nitrophenyl acetate (p-NPA) across intact liposome bilayer. After 60 min of exposure to 7 Hz sinusoidal (50 mu T peak) and parallel static (50 mu T) magnetic fields the enzyme activity, as a function of increased diffusion rate of p-NPA, rose from 17 +/- 3% to 80 +/- 9% (P < .0005, n = 15) in the 5:3:2 liposomes. This effect was dependent on the SA concentration in the liposomes. Only the presence of combined sinusoidal (AC) and static (DC) magnetic fields affected the p-NPA diffusion rates. No enzyme leakage was observed. Such studies suggest a plausible link between the action of extremely low frequency magnetic field on charged lipids and a change of membrane permeability.

Effect of low frequency, low amplitude magnetic fields on the permeability of cationic liposomes entrapping carbonic anhydrase: II. No evidence for surface enzyme involvement.

Observations recently reported by our group indicate that combined 7 Hz sinusoidal (B(acpeak) = 50 mu T) and parallel static (B(dc) = 50 mu T) magnetic fields can induce a significant increase in diffusion rate of substrate across carbonic anhydrase (CA)-loaded liposomes (DPPC:Chol:SA). A direct involvement of charges of stearylamine (SA) on the lipid membrane surface was also demonstrated. Kinetic studies showed that CA was mainly entrapped in liposomes at 5:3:2 molar ratio, although a small amount (17%) of enzyme was also located on the external surface of these cationic liposomes. In this paper we report steady state kinetic studies on this latter CA after ELF-EMFs exposure. No difference in the apparent K(m) between exposed and sham samples was observed. On the contrary the apparent V(max) was increased by approximately a factor of 2 after field exposure. In spite of the proteolytic digestion of this external CA, a significant increase of enzymatic activity, as a function of increase in the diffusion rate of substrate across the lipid bilayer, was observed in the exposed samples. Based on these results, a conformational change induced by the field on the CA located on the external surface of 5:3:2 liposomes is excluded as an explanation for our previous observations, supporting the primary role of bilayer SA in the interaction with ELF. A model of ELF interaction, based on the Larmor precession theory, explaining the physical phenomenon induced on the dipole of SA has been developed.

A generalized ionic model of the neuronal membrane electrical activity.

A new ionic model of the neuronal-membrane electrical activity has been developed. The proposed model generalizes those usually quoted in the literature, taking into account the significant ionic currents, the temperature dependence of the electrical parameters, and the stochastic synaptic inputs. The model allows us to simulate both the membrane firing activity, as a function of the temperature, and the membrane resistance behavior, as a function of temperature and of intracellular calcium concentration. The I-V nonlinear characteristic, together with histograms and correlograms of the time intervals between spikes, have been numerically reproduced. Various comparisons we have carried out with available experimental data show a good theoretical-experimental agreement.

Effect of microwave radiation on the permeability of carbonic anhydrase loaded unilamellar liposomes.

The influence of 2.45 GHz microwave exposure (6 mW/g) on the diffusion processes in enzyme-loaded unilamellar liposomes as bioreactors was studied. The enzyme carbonic anhydrase (CA) was entrapped into cationic unilamellar vesicles. Previous kinetic experiments showed a very low self-diffusion rate of the substrate p-nitrophenyl acetate (PNPA) across intact liposome bilayer. A twofold increase in the diffusion rate of PNPA through the lipid bilayer was observed after 120 min of microwave radiation compared to temperature control samples. The microwave effect was time dependent. The enzyme activity, as a function of increased diffusion of PNPA, rises over 120 min from 22.3% to 80%. The increase in stearylamine concentration reduces the enzyme activity from 80% to 65% at 120 min. No enzyme leakage was observed.

Matching between theoretical and experimental data for ELF ion transport effects.

In recent years, several studies have been focused on the problem of nonthermal interaction between extremely low-frequency (ELF) electromagnetic fields and cell environment at membrane level. In the paper, to analyse the dynamic effects of weak static and harmonic fields on charged particles, some new considerations have been developed, based on the Lorentz model. The authors have reached a suitable formulation so that the data processing has led expressly to the evaluation of ionic-velocity components against magnetic-field amplitudes and frequencies, as well as a viscosity parameter. Even through a direct and rough comparison, the results of the authors' investigation have demonstrated an interesting agreement with some experimental data relative to ionic fluxes through cell membranes. Indeed, by means of an algorithm based on the techniques of the inversion theory, the author's have found definite values of the viscosity parameter for which the expected resonant behaviours (amplitude and frequency windows) fit existing experiments well. It seems worthy of interest that such viscosity values fall within a consistent, narrow range of low amplitude.

Microwave effects on acetylcholine-induced channels in cultured chick myotubes.

The behavior of cultured myotubes from chick embryos exposed to microwaves has been experimentally analyzed. Recordings of acetylcholine-induced currents have been obtained via patch-clamp techniques using both cell-attached (single-channel current recording) and whole-cell (total current recording) configurations. During the exposure to low-power microwaves the frequency of the ACh-activated single channel openings decreased, while the ACh-induced total current showed a faster falling phase. Channel open time and conductance were not affected by microwave irradiation. It is concluded that the exposure to microwaves increases the rate of desensitization and decreases the channel opening probability. The nonthermal origin and the molecular interaction mechanisms governing these electromagnetic-induced effects are discussed.