Characterization of visual percepts evoked by noninvasive stimulation of the human posterior parietal cortex

Phosphenes are commonly evoked by transcranial magnetic stimulation (TMS) to study the functional organization, connectivity, and excitability of the human visual brain. For years, phosphenes have been documented only from stimulating early visual areas (V1-V3) and a handful of specialized visual regions (V4, V5/MT+) in occipital cortex. Recently, phosphenes were reported after applying TMS to a region of posterior parietal cortex involved in the top-down modulation of visuo-spatial processing. In the present study, we systematically characterized parietal phosphenes to determine if they are generated directly by local mechanisms or emerge through indirect activation of other visual areas. Using technology developed in-house to record the subjective features of phosphenes, we found no systematic differences in the size, shape, location, or frame-of-reference of parietal phosphenes when compared to their occipital counterparts. In a second experiment, discrete deactivation by 1 Hz repetitive TMS yielded a double dissociation: phosphene thresholds increased at the deactivated site without producing a corresponding change at the non-deactivated location. Overall, the commonalities of parietal and occipital phosphenes, and our ability to independently modulate their excitability thresholds, lead us to conclude that they share a common neural basis that is separate from either of the stimulated regions.     

Frequency Band-Specific Electrical Brain Stimulation Modulates Cognitive Control Processes

A large body of findings has tied midfrontal theta-band (4–8 Hz) oscillatory activity to adaptive control mechanisms during response conflict. Thus far, this evidence has been correlational. To evaluate whether theta oscillations are causally involved in conflict processing, we applied transcranial alternating current stimulation (tACS) in the theta band to a midfrontal scalp region, while human subjects performed a spatial response conflict task. Conflict was introduced by incongruency between the location of the target stimulus and the required response hand. As a control condition, we used alpha-band (8–12 Hz) tACS over the same location. The exact stimulation frequencies were determined empirically for each subject based on a pre-stimulation EEG session. Behavioral results showed general conflict effects of slower response times (RT) and lower accuracy for high conflict trials compared to low conflict trials. Importantly, this conflict effect was reduced specifically during theta tACS, which was driven by slower response times on low conflict trials. These results show how theta tACS can modulate adaptive cognitive control processes, which is in accordance with the view of midfrontal theta oscillations as an active mechanism for cognitive control.     

Characterization of Levels of Extremely Low Frequency Magnetic Fields Emitted From Portable Hand‐Held Fans

This study aims to assess the levels of extremely low frequency magnetic fields (ELF‐MF) emitted from portable hand‐held fans (HHFs) and their principal frequency and to identify factors influencing these levels. We collected a total of eleven models of HHF and monitored the ELF‐MF as a function of fan speed and distance from the fan. EMDEX II was used to monitor the ELF‐MF. An SMP2 EMF‐meter equipped with a P400 field probe was used to determine the levels of ELF‐MF and the frequency spectrum. Ten of the fans, excluding only one bladeless‐fan model, emitted a high level of ELF‐MF near the source of the HHF direct‐current motor. The maximum measured level of ELF‐MF ranged from 14.07 to 218.7 µT. All measurements of the ELF‐MF taken within 10 cm from the HHFs showed values higher than 1.0 µT. ELF‐MF levels were found to decrease markedly with distance, regardless of the HHF product. The level of ELF‐MF rose noticeably with increased fan speed. The speed of and distance from the HHF significantly influenced the level of ELF‐MF. All principal frequencies ranged from 1 to 300 Hz, which falls in the typical range of ELF. Bioelectromagnetics. 2019;40:569–577. © 2019 Bioelectromagnetics Society.     

A Novel Approach for Documenting Phosphenes Induced by Transcranial Magnetic Stimulation

Stimulation of the human visual cortex produces a transient perception of light, known as a phosphene. Phosphenes are induced by invasive electrical stimulation of the occipital cortex, but also by non-invasive Transcranial Magnetic Stimulation (TMS)¹ of the same cortical regions. The intensity at which a phosphene is induced (phosphene threshold) is a well established measure of visual cortical excitability and is used to study cortico-cortical interactions, functional organization ², susceptibility to pathology ^3,4 and visual processing ^5-7. Phosphenes are typically defined by three characteristics: they are observed in the visual hemifield contralateral to stimulation; they are induced when the subject s eyes are open or closed, and their spatial location changes with the direction of gaze ². Various methods have been used to document phosphenes, but a standardized methodology is lacking. We demonstrate a reliable procedure to obtain phosphene threshold values and introduce a novel system for the documentation and analysis of phosphenes. We developed the Laser Tracking and Painting system (LTaP), a low cost, easily built and operated system that records the location and size of perceived phosphenes in real-time. The LTaP system provides a stable and customizable environment for quantification and analysis of phosphenes.Download video file.^{(84M, mp4)}     

Morphological Changes Induced By Extremely Low‐Frequency Electric Fields

In this paper, morphological effects of electric fields on avian erythrocytes (nucleated red blood cells) have been studied in detail. Morphological changes include rounding and cytoplasm transparency. It has been shown that the effect is non‐thermal. Careful imaging and image analyses have been carried out to show that the degree of this effect is frequency‐dependent, and has a higher conversion rate at higher temperatures. Furthermore, to better understand the mechanisms behind the morphological changes, we investigated the dedifferentiation hypothesis and performed a series of tests on avian erythrocytes including fluorescence spectroscopy for hemoglobin, and tests on human umbilical cord blood, mesenchymal stem cells, and bone marrow mesenchymal stem cells including flow‐cytometry analysis for expression of certain markers and calcium staining. Bioelectromagnetics. 2019;40:375–390. © 2019 Bioelectromagnetics Society.     

A Vascular Thrombus Therapy Method Based on Magnetic‐Induced Vibration

A vascular thrombus therapy method based on magnetic‐induced vibration is presented. It is a mechanicalway of removing vascular thrombus that adopts the combined use of two concepts, namely (i) magnetic‐induced vibration of magnetostrictive materials and (ii) changes in physical form of thrombus under high‐frequency impact and vibration. This method has many advantages that (i) eliminate the side effects of drug treatment, (ii) reduce the complexity of traditional mechanical method, and (iii) improve the reliability of treatment. Practical results obtained from the simulations and experiments are included. They verify the proposed system and indicate that this method can effectively treat vascular thrombus and reduce patient's suffering and costs. Bioelectromagnetics. 2019;40:391–401. © 2019 Bioelectromagnetics Society.     

From Oscillatory Transcranial Current Stimulation to Scalp EEG Changes: A Biophysical and Physiological Modeling Study

Both biophysical and neurophysiological aspects need to be considered to assess the impact of electric fields induced by transcranial current stimulation (tCS) on the cerebral cortex and the subsequent effects occurring on scalp EEG. The objective of this work was to elaborate a global model allowing for the simulation of scalp EEG signals under tCS. In our integrated modeling approach, realistic meshes of the head tissues and of the stimulation electrodes were first built to map the generated electric field distribution on the cortical surface. Secondly, source activities at various cortical macro-regions were generated by means of a computational model of neuronal populations. The model parameters were adjusted so that populations generated an oscillating activity around 10 Hz resembling typical EEG alpha activity. In order to account for tCS effects and following current biophysical models, the calculated component of the electric field normal to the cortex was used to locally influence the activity of neuronal populations. Lastly, EEG under both spontaneous and tACS-stimulated (transcranial sinunoidal tCS from 4 to 16 Hz) brain activity was simulated at the level of scalp electrodes by solving the forward problem in the aforementioned realistic head model. Under the 10 Hz-tACS condition, a significant increase in alpha power occurred in simulated scalp EEG signals as compared to the no-stimulation condition. This increase involved most channels bilaterally, was more pronounced on posterior electrodes and was only significant for tACS frequencies from 8 to 12 Hz. The immediate effects of tACS in the model agreed with the post-tACS results previously reported in real subjects. Moreover, additional information was also brought by the model at other electrode positions or stimulation frequency. This suggests that our modeling approach can be used to compare, interpret and predict changes occurring on EEG with respect to parameters used in specific stimulation configurations.     

Extremely low frequency (ELF) electric and magnetic field exposure limits: rationale for basic restrictions used in the development of an Australian standard

There are large disparities between basic restrictions for exposure to extremely low-frequency (0-3 kHz) Electric and Magnetic Fields set by two major international bodies. Both bodies agree that these basic restrictions should prevent neuro-stimulatory effects: the retinal phosphene at frequencies up to a few hundred Hertz and peripheral nervous stimulation (PNS) at higher frequencies. The disparity arises from differences in estimated thresholds and frequency dependence, and whether restrictions should be of tissue induced current density or electric field. This paper argues that the latter metric more directly relates to neurostimulatory processes. By analysing available literature, a threshold for retinal phosphenes occurrence is found to be 56 mV/m (95% Confidence Interval 2-1330 mV/m), with a characteristic frequency of 20 Hz. Similarly, the smallest PNS sensation threshold is identified at 2 V/m (characteristic frequency above 3 kHz). In the case of the former, the large range of uncertainty suggests a 'power of ten' value of 100 mV/m. For the latter, because of the small margin between sensation and pain threshold, and because of the large individual variation, the smallest estimate of sensation threshold (2 V/m) represents a basic restriction with precaution incorporated.     

Spatial attention changes excitability of human visual cortex to direct stimulation

Conscious perception depends not only on sensory input, but also on attention [1, 2]. Recent studies in monkeys [3-6] and humans [7-12] suggest that influences of spatial attention on visual awareness may reflect top-down influences on excitability of visual cortex. Here we tested this specifically, by providing direct input into human visual cortex via cortical transcranial magnetic stimulation (TMS) to produce illusory visual percepts, called phosphenes. We found that a lower TMS intensity was needed to elicit a conscious phosphene when its apparent spatial location was attended, rather than unattended. Our results indicate that spatial attention can enhance visual-cortex excitability, and visual awareness, even when sensory signals from the eye via the thalamic pathway are bypassed.     

Intermittent pulsed electromagnetic field stimulation activates the mTOR pathway and stimulates the proliferation of osteoblast‐like cells

Pulsed electromagnetic fields (PEMFs) have been shown to be a noninvasive physical stimulant for bone fracture healing. However, PEMF stimulation requires a relatively long period of time and its mechanism of action has not yet been fully clarified. Recently, the mammalian target of rapamycin (mTOR) pathway has been shown to be involved in bone formation. This study aimed to investigate the effects of PEMFs on osteoblastic MC3T3‐E1 cells by examining various cellular responses including changes in the mTOR pathway. Continuous PEMF stimulation induced a transient phosphorylation of the mTOR pathway, whereas intermittent PEMF stimulation (1 cycle of 10 min stimulation followed by 20 min of stimulation pause) revitalized the reduced phosphorylation. Moreover, PEMF stimulation stimulated cell proliferation (bromodeoxyuridine incorporation) rather than differentiation (alkaline phosphatase activity), with a more notable effect in the intermittently stimulated cells. These results suggest that intermittent PEMF stimulation may be effective in promoting bone fracture healing by accelerating cell proliferation, and in shortening stimulation time. Bioelectromagnetics. 2019;40:412–421. © 2019 Bioelectromagnetics Society.     

Novel ETV6‐RUNX1 Mouse Model to Study the Role of ELF‐MF in Childhood B‐Acute Lymphoblastic Leukemia: a Pilot Study

Exposure to extremely low‐frequency magnetic fields (ELF‐MFs) has been classified by the International Agency for Research on Cancer (IARC) as “possibly carcinogenic to humans,” based on limited scientific evidence concerning childhood leukemia. This assessment emphasized the lack of appropriate animal models recapitulating the natural history of this disease. Childhood B‐cell acute lymphoblastic leukemia (B‐ALL) is the result of complex interactions between genetic susceptibility and exposure to exogenous agents. The most common chromosomal alteration is the ETV6‐RUNX1 fusion gene, which confers a low risk of developing the malignancy by originating a preleukemic clone requiring secondary hits for full‐blown disease to appear. To develop potential prophylactic interventions, we need to identify the environmental triggers of the second hit. Recently, we generated a B‐ALL mouse model of the human ETV6‐RUNX1⁺ preleukemic state. Here, we present the results from the ARIMMORA pilot study, obtained by exposing 34 Sca1‐ETV6‐RUNX1 mice (vs. 27 unexposed) to a 50 Hz magnetic field of 1.5 mT with both fundamental and harmonic content, with an on/off cycle of 10 min/5 min, for 20 h/day, from conception until 3 months of age. Mice were monitored until 2 years of age and peripheral blood was periodically analyzed by flow cytometry. One of the exposed mice developed B‐ALL while none of the non‐exposed did. Although the results are statistically non‐significant due to the limited number of mice used in this pilot experiment, overall, the results show that the newly developed Sca1‐ETV6‐RUNX1 mouse can be successfully used for ELF‐MF exposure studies about the etiology of childhood B‐ALL. Bioelectromagnetics. 2019;40:343–353. © 2019 Bioelectromagnetics Society.     

The Short‐Term Effect of Occupational Levels of 50 Hz Electromagnetic Field on Human Heart Rate Variability

Previous studies have indicated that there is no consensus on the effects of extremely low‐frequency electromagnetic (ELF‐EMF) exposure on the cardiovascular system. This study aimed to explore the short‐term effect of ELF‐EMF exposure on heart rate (HR) and HR variability (HRV). The sample consisted of 34 healthy males aged 18–27 years. The participants were randomly assigned to the EMF (n = 17) or the Sham group (n = 17). We employed a double‐blind repeated‐measures design consisting of three 5 min experimental periods. The chest region of each individual in the EMF group was exposed to 50 Hz, 28 μT, linear polarized, continuous EMF during the EMF exposure period. HR and HRV data were recorded continuously by using a photoplethysmography sensor. Within‐subject statistical analysis indicated a significant HR deceleration in both the EMF and Sham groups. However, the standard deviation of the NN intervals (SDNN), root mean square of successive differences (RMSSD), low‐frequency (LF), and high‐frequency (HF) powers increased only in the EMF group and remained stable in the Sham group. We also compared the same HRV indices measured during the EMF and Sham periods between the two experimental groups. The between‐subject analysis results demonstrated significantly higher SDNN, RMSSD, LF, and HF values in the EMF group than in the Sham group. The LF/HF ratio did not change significantly within and between groups. On the basis of these results, we concluded that short‐term exposure of the chest region to ELF‐EMF could potentially enhance parasympathetic predominance during the resting condition. Bioelectromagnetics. 2021;42:60–75. © 2020 Bioelectromagnetics Society.     

Theoretical evaluation of magnetoreception of power‐frequency fields

Several effects of power‐frequency (50/60 Hz) magnetic fields (PF‐MF) of weak intensity have been hypothesized in animals and humans. No valid mechanism, however, has been proposed for an interaction between PF‐MF and biological tissues and living beings at intensities relevant to animal and human exposure. Here we proposed to consider PF‐MF as disrupters of the natural magnetic signal. Under exposure to these fields, an oscillating field exists that results from the vectorial summation of both the PF‐MF and the geomagnetic field. At a PF‐MF intensity (rms) of 0.5 µT, the peak‐to‐peak amplitude of the axis and/or intensity variations of this resulting field exceeds the related discrimination threshold of magnetoreception (MR) in migrating animals. From our evaluation of the 50/60 Hz responsiveness of the putative mechanisms of MR, single domain particles (Kirschvink's model) appear unable to transduce that oscillating signal. On the contrary, radical pair reactions are able to, as well as interacting multidomain iron–mineral platelets and clusters of superparamagnetic particles (Fleissner/Solov'yov's model). It is, however, not yet known whether the reception of 50/60 Hz oscillations of the natural magnetic signal might be of consequence or not. Bioelectromagnetics 31:371–379, 2010. © 2010 Wiley‐Liss, Inc.     

Features of anti‐inflammatory effects of modulated extremely high‐frequency electromagnetic radiation

Using a model of acute zymosan‐induced paw edema in NMRI mice, we test the hypothesis that anti‐inflammatory effects of extremely high‐frequency electromagnetic radiation (EHF EMR) can be essentially modified by application of pulse modulation with certain frequencies. It has been revealed that a single exposure of animals to continuous EHF EMR for 20 min reduced the exudative edema of inflamed paw on average by 19% at intensities of 0.1–0.7 mW/cm² and frequencies from the range of 42.2–42.6 GHz. At fixed effective carrier frequency of 42.2 GHz, the anti‐inflammatory effect of EHF EMR did not depend on modulation frequencies, that is, application of different modulation frequencies from the range of 0.03–100 Hz did not lead to considerable changes in the effect level. On the contrary, at “ineffective” carrier frequencies of 43.0 and 61.22 GHz, the use of modulation frequencies of 0.07–0.1 and 20–30 Hz has allowed us to restore the effect up to a maximal level. The results obtained show the critical dependence of anti‐inflammatory action of low‐intensity EHF EMR on carrier and modulation frequencies. Within the framework of this study, the possibility of changing the level of expected biological effect of modulated EMR by a special selection of combination of carrier and modulation frequencies is confirmed. Bioelectromagnetics 30:454–461, 2009. © 2009 Wiley‐Liss, Inc.     

fMRI of Retina-Originated Phosphenes Experienced by Patients with Leber Congenital Amaurosis

A phenomenon characterized by the experience of seeing light without any light actually entering the eye is called phosphenes or photopsias. Phosphenes can occur spontaneously or via induction by external stimuli. Previous reports regarding phosphenes have primarily focused on externally induced phosphenes such as by applying alternating or direct current to the cortex. A few of these reports used functional magnetic resonance (fMRI) to study activations induced by cortical phosphenes. However, there are no fMRI reports on spontaneous phosphenes originating from the retina and the resulting pattern of cortical activations. We performed fMRI during a reversing checkerboard paradigm in three LCA patients who underwent unilateral gene therapy and reported experiencing frequent phosphene on a daily basis. We observed bilateral cortical activation covering the entire visual cortices when patients reported experiencing phosphenes. In contrast, in the absence of phosphenes, activation was regulated by patient''s visual ability and demonstrated improved cortical activation due to gene therapy. These fMRI results illustrate the potential impact of phosphene perception on visual function and they may explain some of the variability that clinicians find in visual function testing in retinal degeneration. Although we did not perform correlations between visual function and phosphenes, we hope data presented here raises awareness of this phenomenon and its potential effect on visual function and the implications for clinical testing. We recommend a thorough history for phosphene experiences be taken in patients with retinal disease who are candidates for gene or molecular therapy. Lastly, these data illustrate the potential power of fMRI as an outcome measure of gene therapy and the negative impact phosphenes may have on vision testing. fMRI has proven to be a sensitive, non-invasive, and reproducible test paradigm for these purposes and can complement standard visual function testing.     

Proprioceptive alignment of visual and somatosensory maps in the posterior parietal cortex

A touch on one hand can enhance the response to a visual stimulus delivered at a nearby location [1, 2], improving our interactions with the external world. In order to keep such visual-tactile spatial interactions effective, the brain updates the continuous postural changes, like those typically accompanying hand actions, through proprioception, thus maintaining the somatosensory and visual maps in spatial register [2, 3]. The posterior parietal cortex (PPC) might be critical for such a spatial remapping [4]; nevertheless, a direct causal demonstration of its involvement is lacking. Here, we found that unattended touches to one hand enhanced visual sensitivity for phosphenes induced by occipital trancranial magnetic stimulation (TMS) [5] when the touched hand was spatially coincident to the reported location of the phosphenes in external space. Notably, this spatially specific crossmodal facilitation was maintained after hand crossing, suggesting an efficient visual-tactile remapping. Critically, after 1 Hz repetitive TMS interference [6] over the PPC, but not over the primary somatosensory cortex, phosphene detection was still enhanced by spatially coincident touches with uncrossed hands, but it was enhanced by spatially noncoincident touches after hand crossing. This is the first causal evidence in humans that the PPC constantly updates the representation of the body in space in order to facilitate crossmodal interactions.     

Effects of extremely low‐frequency magnetic fields on the oviposition of Drosophila melanogaster over three generations

The aim of this study was to determine the effects of an extremely low‐frequency 50 Hz magnetic field (ELFMF) on the oviposition and development of Drosophila melanogaster. The results show that exposure of D. melanogaster females of generation P and all the development stages of generation F1 to an ELFMF weakened the oviposition of these insects in their subsequent generations. Bioelectromagnetics 30:687–689, 2009. © 2009 Wiley‐Liss, Inc.     

Sleep after mobile phone exposure in subjects with mobile phone‐related symptoms

Several studies show increases in activity for certain frequency bands (10–14 Hz) and visually scored parameters during sleep after exposure to radiofrequency electromagnetic fields. A shortened REM latency has also been reported. We investigated the effects of a double‐blind radiofrequency exposure (884 MHz, GSM signaling standard including non‐DTX and DTX mode, time‐averaged 10 g psSAR of 1.4 W/kg) on self‐evaluated sleepiness and objective EEG measures during sleep. Forty‐eight subjects (mean age 28 years) underwent 3 h of controlled exposure (7:30–10:30 PM; active or sham) prior to sleep, followed by a full‐night polysomnographic recording in a sleep laboratory. The results demonstrated that following exposure, time in Stages 3 and 4 sleep (SWS, slow‐wave sleep) decreased by 9.5 min (12%) out of a total of 78.6 min, and time in Stage 2 sleep increased by 8.3 min (4%) out of a total of 196.3 min compared to sham. The latency to Stage 3 sleep was also prolonged by 4.8 min after exposure. Power density analysis indicated an enhanced activation in the frequency ranges 0.5–1.5 and 5.75–10.5 Hz during the first 30 min of Stage 2 sleep, with 7.5–11.75 Hz being elevated within the first hour of Stage 2 sleep, and bands 4.75–8.25 Hz elevated during the second hour of Stage 2 sleep. No pronounced power changes were observed in SWS or for the third hour of scored Stage 2 sleep. No differences were found between controls and subjects with prior complaints of mobile phone‐related symptoms. The results confirm previous findings that RF exposure increased the EEG alpha range in the sleep EEG, and indicated moderate impairment of SWS. Furthermore, reported differences in sensitivity to mobile phone use were not reflected in sleep parameters. Bioelectromagnetics 32:4–14, 2011. © 2010 Wiley‐Liss, Inc.     

900 MHz modulated electromagnetic fields accelerate the clathrin‐mediated endocytosis pathway

We report new data regarding the molecular mechanisms of GSM‐induced increase of cell endocytosis rate. Even though endocytosis represents an important physical and biological event for cell physiology, studies on modulated electromagnetic fields (EMF) effects on this process are scarce. In a previous article, we showed that fluid phase endocytosis rate increases when cultured cells are exposed to 900 MHz EMF similar to mobile phones' modulated GSM signals (217 Hz repetition frequency, 576 µs pulse width) and to electric pulses similar to the GSM electrical component. Trying to distinguish the mechanisms sustaining this endocytosis stimulation, we exposed murine melanoma cells to Lucifer Yellow (LY) or to GSM–EMF/electric pulses in the presence of drugs inhibiting the clathrin‐ or the caveolin‐dependent endocytosis. Experiments were performed at a specific absorption rate (SAR) of 3.2 W/kg in a wire patch cell under homogeneously distributed EMF field and controlled temperature (in the range of 28.5–29.5 °C). Thus, the observed increase in LY uptake was not a thermal effect. Chlorpromazine and ethanol, but not Filipin, inhibited this increase. Therefore, the clathrin‐dependent endocytosis is stimulated by the GSM–EMF, suggesting that the cellular mechanism affected by the modulated EMF involves vesicles that detach from the cell membrane, mainly clathrin‐coated vesicles. Bioelectromagnetics 30:222–230, 2009. © 2008 Wiley‐Liss, Inc.