Yaghmazadeh O. (2024). Pulsed High-Power Radio Frequency Energy Can Cause Non-Thermal Harmful Effects on the BRAIN. IEEE open journal of engineering in medicine and biology, 5, 50–53. https://doi.org/10.1109/OJEMB.2024.3355301 Abstract High-power microwave applications are growing for both military and civil purposes, yet they can induce brain-related risks and raise important public health concerns. High-power sub-millisecond radio frequency energy pulses have been demonstrated to be able to induce neurological and neuropathological changes in the brain while being compliant with current regulatory guidelines’ limits, highlighting the necessity of revising them. Keywords: Brain damage, high power microwave, non-thermal effects, radio frequency, RF pulse I. Introduction Ever since the primary applications of Radio Frequency (RF) energy waves, their interactions with the biological tissue have been of immense interest for potential health concerns making them an important topic in public health [1], [2], [3]. Novel advances in the development of high power microwave (HPM) applications, providing the possibility of producing very short time-scale extremely high-power RF pulses, has brought new insights in this subject and raised novel concerns regarding RF energy radiation exposure [4], [5], [6], [7]. Some recent studies have shown that application of short high power RF pulses can lead to brain damage with potential severe impact [8], [9]. This raises an important concern in environmental health as there is a growing trend for HPM applications [10]. Such health effects should, therefore, be studied more carefully, and regulatory guidelines should be updated to avoid their impact on the society. II. Non-Thermal Effects From the Biophysical vs. the Biological Perspectives The brain, due to its electrical nature, has long been considered the most vulnerable organ to exposure to RF energy waves [11], [12], [13], [14]. It is well known that RF energy can cause heating of the biological tissue, such as the brain [15], and consequently affect its function (as it is established that local increase in brain temperature can affect the ongoing neural activity [16]). There has been, however, a long-lasting question that whether RF energy is able to affect neuronal activity and brain function in a non-thermal manner. This question has been at the center of a controversial debate where theories and experiments both in favor and against such possibility have been reported over several decades [17]. The non-thermal effects of RF energy on the biological parameters can be considered from two different angles: 1) form the “biophysical” point of view, non-thermal effects of RF energy are such effects whose mechanisms are not thermal (nor thermally-mediated); 2) from the “biological” point of view, non-thermal effects of RF energy are any effects that do not increase the tissue temperature in a biologically meaningful timescale. These concepts are illustrated by the drawings in Fig. 1. As shown in Fig. 1(a), a thermal effect, from the biophysical point of view, on a given neuron is caused or mediated by a thermal change in the surrounding medium. A biophysically non-thermal effect, is thus, an effect that occurs either in the absence of such thermal change or by a cause not related to it. On the other hand, Fig. 1(b) illustrates situations to highlight thermal and non-thermal effects from the biological point of view, where a mouse head is exposed to an RF source and its brain temperature is recorded. When RF with higher power is applied, brain temperature rises significantly which is not the case for the low power scenario. Now, any potential observed effect on the local neurons is biologically thermal for the first case, and biologically non-thermal for the latter. A good example for further clarification of these concepts is the case of the ‘RF/Microwave auditory effect’, where RF pulses (of moderate strength (∼5watt/cm2 incident power density) and shorter than 50 μs) can be perceived as sound [18], [19], [20]. This effect was well studied in the 60’s and 70’s and it is established that the cause of the perceived sound is the mechanical effect of thermos-elastic waves, caused by the RF-induced temperature rises, on the cochlea. While the nature of the induced effect, i.e., hearing of sounds, is thermally mediated, the temperature rises are estimated to be at the order of ([19]. In this context, this effect is non-thermal from the biological point of view but not from the biophysical point of view. Open in a new tab Thermal or Non-thermal categorization of effects can be done from the ‘Biophysical’ or the ‘Biological’ point of view. From the ‘Biophysical’ point of view, thermal effects are those whose mechanisms are thermal or thermally-mediated (a; a temperature gradient in the vacancy of the neuron can induce changes in its neural activity). Biophysically non-thermal effects are those effects whose causes are not from a thermal origin. From the ‘Biological’ point of view, thermal effects are those that are accompanied with a temperature change in biologically meaningful timescales. Biologically non-thermal effects are those effects who do not occur in company of a significant temperature rise in a biologically meaningful timescale, regardless of the thermal/non-thermal nature of their causes (b; here when an RF source with sufficient power is used a temperature change in the animal’s brain and/or body is observed, while a low-power source would not induce significant temperature changes (biologically non-thermal)). III. RF Exposure Can Affect (and Damage) the Brain in a Biologically ‘Non-Thermal’ Manner Recently, Hao et al. reported an experimental demonstration of biologically non-thermal effects of RF energy on the brain of freely behaving mice that disturbed their brain cognitive functions related to learning and memory [9]. They used RF energy at 2.856 GHz, pulsed at 80 Hz with 0.5ms pulse width and a power density of 200 mW/cm2. This exposure didn’t induce changes in the mice rectal temperature beyond the biological range (In another recent study, Dagro et al. studied the thermos-elastic effects of short duration high-power RF pulses on the human brain using a computational approach [8]. Their results demonstrated that short-timescale high-power single RF pulses are able to induce transient and fast thermal expansion in the brain that can cause mechanical stress leading to neurological effects. Particularly, they showed that for very short (few μs) and extremely high-power (with an incident power density of 1x107 mW/cm2) single RF pulses, the induced mechanical stress could exceed injury threshold and cause permanent neuropathological damage, while the applied RF exposure was biologically non-thermal and compliant with regulatory limits [8]. Although the required field strength to induce injuries as studied in Drago et al.’s report is extremely high (yet still accessible with current HPM developments for military, civil or research applications), their simulations also demonstrated the induction of a high level of mechanical stress inside the brain even for lower power levels and longer pulses. In addition, application of repeated pulses, which is not studied in their report, could have accumulating effects on the brain. This is indeed demonstrated in Hao et al.’s study where application of a repeated pulse sequence with larger duration (500 μs) and much lower power density (200 mW/cm2) lead to neurological effects that lasted over, at least, several days. Although their histological evaluation did not show any lesion, they reported some structural deformation related to the dopamine-related mechanisms. This indicates that repetitive sub-millisecond pulses at relatively (but not extremely) high power levels can induce brain damage and cognitive deficits in a biologically non-thermal manner. Lastly, in a third study, Yaghmazadeh et al. examined effects of continuous-wave (CW) RF energy exposure on the neural activity in a head-fixed mouse set-up in-vivo [21]. Using 1-photon Ca2+ imaging in mice brain, they reported that RF energy radiation, up to power levels that induce a local point SAR value of 28.8 W/Kg, does not alter the neuronal activity with statistical significance (measured by RF interference-free 1-photon Ca2+ imaging using head-mount Miniscope in n=5 head-fixed mice). Their study confirmed that for a relatively high level of CW RF energy radiation (several fold higher than what is permitted by the regulatory limits [21]) neuronal activity is not affected in a non-thermal manner (from both biophysical and biological points of view). IV. Different Effects of Pulsed vs. CW RF Energy on Neural Activity Hao et al. compared their findings with the results in Yaghmazadeh et al.’s report and stated a contradiction in the outcomes: while the latter report stated absence of non-thermal effects of RF energy exposure on neuronal activity, their results demonstrated a RF exposure paradigm that led to significant non-thermal effects. They attributed the contrariety of these findings to the difference in the applied frequency (2856 Hz in their study against 950 MHz in the other). However, there is no demonstrated mechanism that could explain why neurons would respond differently to distinct frequencies at the GHz range. It is important to highlight that, besides the applied frequencies, the major difference in the experimental paradigms that were used in these two studies lies under the fact that Hao et al. used sub-millisecond pulsed RF energy (with several fold higher power density) while Yaghmazadeh et al. used continuous-wave stimuli, which can explain the different observed outcomes. Hao et al.’s results demonstrated a ‘biologically’ non-thermal paradigm for affecting the brain by pulsed RF (with a thermally-mediated ‘biophysical’ mechanism as thermo-e
