Neurotoxic effects of home radon exposure on oscillatory dynamics serving attentional orienting in children and adolescents.

Radon is a naturally occurring gas that contributes significantly to radiation in the environment and is the second leading cause of lung cancer globally. Previous studies have shown that other environmental toxins have deleterious effects on brain development, though radon has not been studied as thoroughly in this context. This study examined the impact of home radon exposure on the neural oscillatory activity serving attention reorientation in youths. Fifty-six participants (ages 6-14 years) completed a classic Posner cuing task during magnetoencephalography (MEG), and home radon levels were measured for each participant. Time-frequency spectrograms indicated stronger theta (3-7 Hz, 300-800 ms), alpha (9-13 Hz, 400-900 ms), and beta responses (14-24 Hz, 400-900 ms) during the task relative to baseline. Source reconstruction of each significant oscillatory response was performed, and validity maps were computed by subtracting the task conditions (invalidly cued - validly cued). These validity maps were examined for associations with radon exposure, age, and their interaction in a linear regression design. Children with greater radon exposure showed aberrant oscillatory activity across distributed regions critical for attentional processing and attention reorientation (e.g., dorsolateral prefrontal cortex, and anterior cingulate cortex). Generally, youths with greater radon exposure exhibited a reverse neural validity effect in almost all regions and showed greater overall power relative to peers with lesser radon exposure. We also detected an interactive effect between radon exposure and age where youths with greater radon exposure exhibited divergent developmental trajectories in neural substrates implicated in attentional processing (e.g., bilateral prefrontal cortices, superior temporal gyri, and inferior parietal lobules). These data suggest aberrant, but potentially compensatory neural processing as a function of increasing home radon exposure in areas critical for attention and higher order cognition.

Monitorización electroencefalográfica en el paciente crítico: ¿qué información útil puede aportar? / Electroencephalographic monitoring in the critically ill patient: What useful information can it contribute?

La monitorización es crucial en el cuidado del paciente crítico. Detecta disfunciones orgánicas y provee orientación en el abordaje terapéutico. Los intensivistas monitorizan habitualmente la función de varios sistemas orgánicos y el cerebro no es la excepción. La monitorización EEG continuo es una vía no invasiva e ininterrumpida para valorar la actividad eléctrica cortical con aceptable resolución espacial y excelente resolución temporal. La efectividad diagnóstica del estado epiléptico no convulsivo como causa de compromiso de la consciencia no explicable por otras causas se ha incrementado con el empleo del EEG continuo; sin embargo, no es la única indicación para valorar la actividad eléctrica cortical cerebral. Este manuscrito intenta resumir las indicaciones, modos de empleo y metodología para el empleo del monitoreo electroencefalográfico continuo en la unidad de cuidados intensivos con la finalidad que el intensivista se familiarice con el mismo

Monitoring is a crucial part of the care of the critically ill patient. It detects organ dysfunction and provides guidance on the therapeutic approach. Intensivists closely monitor the function of various organ systems, and the brain is no exception. Continuous EEG monitoring is a noninvasive and uninterrupted way of assessing cerebral cortical activity with good spatial and excellent temporal resolution. The diagnostic effectiveness of non-convulsive status epilepticus as a cause of unexplained consciousness disorder has increased the use of continuous EEG monitoring in the neurocritical care setting. However, non-convulsive status epilepticus is not the only indication for the assessment of cerebral cortical activity. This study summarizes the indications, usage and methodology of continuous EEG monitoring in the intensive care unit, with the aim of allowing practitioners to become familiarized the technique

Does emergent implantation of a vagal nerve stimulator stop refractory status epilepticus in children?

PURPOSE: Status Epilepticus can be a serious life threatening event in epileptic patients. The definition of refractory or super-refractory Status Epilepticus was based on the therapeutic response to anti-epileptic and anesthetic drugs. Vagal Nerve Stimulation showed efficacy in treating drug-resistant epilepsy but there are only few reports on emergentplacement of Vagal Nerve Stimulator for refractory or super-refractory Status Epilepticus. METHODS: Among 49 children implanted at our Institution with Vagal Nerve Stimulation for drug-resistant epilepsy, the authors retrospectively identified those implanted for refractory or super-refractory Status Epilepticus, according with the current definitions. RESULTS: 4 patients were operated upon at ages ranging 7 to 17 months and reached the programmed output current of 1 mA over a time ranging from 24 to 36 h (fast ramping-up). In 3 out of 4 patient we observed the abrupt of Status Epilepticus; one patient was refractory both to drugs and Vagal Nerve Stimulation and later died, without recovering from SE. At follow up, ranging from 24 to 45 months, the remaining 3 patients showed a decrease of the seizures frequency >80% without relapse of Status Epilepticus; in all the patients, output current and/or Duty Cycle were increased later. CONCLUSION: VNS can be effective in treating refractory or super-refractory Status Epilepticus.

Autophagy mediates the degradation of synaptic vesicles: A potential mechanism of synaptic plasticity injury induced by microwave exposure in rats.

To explore how autophagy changes and whether autophagy is involved in the pathophysiological process of synaptic plasticity injury caused by microwave radiation, we established a 30 mW/cm2 microwave-exposure in vivo model, which caused reversible injuries in rat neurons. Microwave radiation induced cognitive impairment in rats and synaptic plasticity injury in rat hippocampal neurons. Autophagy in rat hippocampal neurons was activated following microwave exposure. Additionally, we observed that synaptic vesicles were encapsulated by autophagosomes, a phenomenon more evident in the microwave-exposed group. Colocation of autophagosomes and synaptic vesicles in rat hippocampal neurons increased following microwave exposure. CONCLUSION: microwave exposure led to the activation of autophagy in rat hippocampal neurons, and excessive activation of autophagy might damage synaptic plasticity by mediating synaptic vesicle degradation.

Layer-specific optogenetic activation of pyramidal neurons causes beta-gamma entrainment of neonatal networks.

Coordinated activity patterns in the developing brain may contribute to the wiring of neuronal circuits underlying future behavioural requirements. However, causal evidence for this hypothesis has been difficult to obtain owing to the absence of tools for selective manipulation of oscillations during early development. We established a protocol that combines optogenetics with electrophysiological recordings from neonatal mice in vivo to elucidate the substrate of early network oscillations in the prefrontal cortex. We show that light-induced activation of layer II/III pyramidal neurons that are transfected by in utero electroporation with a high-efficiency channelrhodopsin drives frequency-specific spiking and boosts network oscillations within beta-gamma frequency range. By contrast, activation of layer V/VI pyramidal neurons causes nonspecific network activation. Thus, entrainment of neonatal prefrontal networks in fast rhythms relies on the activation of layer II/III pyramidal neurons. This approach used here may be useful for further interrogation of developing circuits, and their behavioural readout.

Optogenetically Blocking Sharp Wave Ripple Events in Sleep Does Not Interfere with the Formation of Stable Spatial Representation in the CA1 Area of the Hippocampus.

During hippocampal sharp wave/ripple (SWR) events, previously occurring, sensory input-driven neuronal firing patterns are replayed. Such replay is thought to be important for plasticity-related processes and consolidation of memory traces. It has previously been shown that the electrical stimulation-induced disruption of SWR events interferes with learning in rodents in different experimental paradigms. On the other hand, the cognitive map theory posits that the plastic changes of the firing of hippocampal place cells constitute the electrophysiological counterpart of the spatial learning, observable at the behavioral level. Therefore, we tested whether intact SWR events occurring during the sleep/rest session after the first exploration of a novel environment are needed for the stabilization of the CA1 code, which process requires plasticity. We found that the newly-formed representation in the CA1 has the same level of stability with optogenetic SWR blockade as with a control manipulation that delivered the same amount of light into the brain. Therefore our results suggest that at least in the case of passive exploratory behavior, SWR-related plasticity is dispensable for the stability of CA1 ensembles.

Spatial Heterogeneity of Cortical Excitability in Migraine Revealed by Multifrequency Neuromagnetic Signals.

UNLABELLED: To investigate the spatial heterogeneity of cortical excitability in adolescents with migraine, magnetoencephalography (MEG) recordings at a sampling rate of 6,000 Hz were obtained from 35 adolescents with an acute migraine and 35 age- and sex-matched healthy control participants during an auditory-motor task. Neuromagnetic activation from low- to high-frequency ranges (5-1,000 Hz) was measured at sensor and source levels. The heterogeneity of cortical excitability was quantified within each functional modality (auditory vs motor) and hemispherical lateralization. MEG data showed that high-frequency, not low-frequency neuromagnetic signals, showed heterogeneous cortical activation in migraine subjects compared with control participants (P < .001). The alteration of the heterogeneity of cortical excitability in migraine subjects was independent of age and sex. The degree of the neuromagnetic heterogeneity of cortical activation was significantly correlated with headache frequency (r = .71, P < .005). The alteration of cortical excitability in migraine subjects was spatially heterogeneous and frequency dependent, which previously has not been reported. The finding may be critical for developing spatially targeted therapeutic strategies for normalizing cortical excitability with the purpose of reducing headache attacks. PERSPECTIVE: This article presents a new approach to quantitatively measure the spatial heterogeneity of cortical excitability in adolescents with migraine using MEG signals in a frequency range of 5 to 1,000 Hz. The characteristics of the location and degree of cortical excitability may be critical for spatially targeted treatment for migraine.

Effect of noninvasive focused ultrasound stimulation on gamma oscillations in rat hippocampus.

In recent years, noninvasive focused ultrasound stimulation (FUS), with the advantage of high spatial resolution and high penetration depth, has developed rapidly for modulating neuron activities in the brain. Gamma oscillations serve to synchronize neurons and play important roles in cortical information processing and cognitive function. However, how FUS modulates gamma oscillations in the rat hippocampus is not well understood. In this work, we characterized the interactions between the gamma amplitude and phases of the delta, theta, and alpha bands during FUS. Our results show that FUS can significantly modulate the extent of phase-locked gamma amplitude and phase-amplitude coupling of brain oscillations. In summary, FUS can modulate gamma oscillations in the rat hippocampus, indicating its potential as a powerful noninvasive method to interfere with brain rhythms for diagnostic and therapeutic purposes.

Effects of concurrent caffeine and mobile phone exposure on local target probability processing in the human brain.

Millions of people use mobile phones (MP) while drinking coffee or other caffeine containing beverages. Little is known about the potential combined effects of MP irradiation and caffeine on cognitive functions. Here we investigated whether caffeine intake and concurrent exposure to Universal Mobile Telecommunications System (UMTS) MP-like irradiation may interactively influence neuro-cognitive function in an active visual oddball paradigm. In a full factorial experimental design, 25 participants performed a simple visual target detection task while reaction time (RT) and electroencephalogram (EEG) was recorded. Target trials were divided into Low and High probability sets based on target-to-target distance. We analyzed single trial RT and alpha-band power (amplitude) in the pre-target interval. We found that RT was shorter in High vs. Low local probability trials, and caffeine further shortened RT in High probability trials relative to the baseline condition suggesting that caffeine improves the efficiency of implicit short-term memory. Caffeine also decreased pre-target alpha amplitude resulting in higher arousal level. Furthermore, pre-target gamma power positively correlated with RT, which may have facilitated target detection. However, in the present pharmacologically validated study UMTS exposure either alone or in combination with caffeine did not alter RT or pre-stimulus oscillatory brain activity.

Clinical Correlates and Prognostic Significance of Lateralized Periodic Discharges in Patients Without Acute or Progressive Brain Injury: A Case-Control Study.

PURPOSE: Lateralized periodic discharges (LPDs, also known as periodic lateralized epileptiform discharges) in conjunction with acute brain injuries are known to be associated with worse prognosis but little is known about their importance in absence of such acute injuries. We studied the clinical correlates and outcome of patients with LPDs in the absence of acute or progressive brain injury. METHODS: This is a case-control study of 74 patients with no acute brain injury undergoing continuous EEG monitoring, half with LPDs and half without, matched for age and etiology of remote brain injury, if any, or history of epilepsy. RESULTS: Lateralized periodic discharges were found in 145/1785 (8.1%) of subjects; 37/145 (26%) had no radiologic evidence of acute or progressive brain injury. Those with LPDs were more likely to have abnormal consciousness (86% vs. 57%; P = 0.005), seizures (70% vs. 24%; P = 0.0002), and functional decline (62% vs. 27%; P = 0.005), and were less likely to be discharged home (24% vs. 62%; P = 0.002). On multivariate analysis, LPDs and status epilepticus were associated with abnormal consciousness (P = 0.009; odds ratio = 5.2, 95% CI = 1.60-20.00 and P = 0.017; odds ratio = 5.0, 95% CI = 1.4-21.4); and LPDs were independently associated with functional decline (P = 0.001; odds ratio = 4.8, 95% CI = 1.6-15.4) and lower likelihood of being discharged home (P = 0.009; odds ratio = 0.2, 95% CI = 0.04-0.6). CONCLUSIONS: Despite absence of acute or progressive brain injury, LPDs were independently associated with abnormal consciousness and worse outcome at hospital discharge.

Inter-individual and intra-individual variation of the effects of pulsed RF EMF exposure on the human sleep EEG.

Pulse-modulated radiofrequency electromagnetic fields (RF EMF) can alter brain activity during sleep; increases of electroencephalographic (EEG) power in the sleep spindle (13.75-15.25 Hz) and delta-theta (1.25-9 Hz) frequency range have been reported. These field effects show striking inter-individual differences. However, it is still unknown whether individual subjects react in a similar way when repeatedly exposed. Thus, our study aimed to investigate inter-individual variation and intra-individual stability of field effects. To do so, we exposed 20 young male subjects twice for 30 min prior to sleep to the same amplitude modulated 900 MHz (2 Hz pulse, 20 Hz Gaussian low-pass filter and a ratio of peak-to-average of 4) RF EMF (spatial peak absorption of 2 W/kg averaged over 10 g) 2 weeks apart. The topographical analysis of EEG power during all-night non-rapid eye movement sleep revealed: (1) exposure-related increases in delta-theta frequency range in several fronto-central electrodes; and (2) no differences in spindle frequency range. We did not observe reproducible within-subject RF EMF effects on sleep spindle and delta-theta activity in the sleep EEG and it remains unclear whether a biological trait of how the subjects' brains react to RF EMF exists.

Brain Topography of Emf-Induced Eeg-Changes in Restful Wakefulness: Tracing Current Effects, Targeting Future Prospects.

INTRODUCTION: Covering a handful of decades but spanning across two centuries, mobile phones announced the dawn of the technological revolution, standing at the forefront as its' most prominent symbol. Over the course of their sovereign dominance, human generations born with the birth of the mobile phone reached the age of maturity, while scientific community started reaching for experience-based perceptivity. AIM: The following review serves as a short-cut across a half-decade old research gap, and a clear-cut analysis on the cutting-edge knowledge of the EMF induced EEG changes. MATERIAL AND METHODS: The selection covers 28 articles about mobile phone effects on resting wakeful EEG in humans conducted over the last two decades, across three continents and 12 countries, of which 75% had positive findings. CONCLUSIONS: At present, the general protocol of a typical study includes investigations on adults (20-60 yrs) grouped in smaller samples and exposed to shorter intervals of GSM-like pulse-modulated signal (10-30 subjects/minutes). The assessment usually involves linear methods for quantitative analysis, while the results mostly revolve around posterior increase in alpha and beta frequency range. The qualitative variations, however, remain open to interpretation. Future research may benefit from multiplication of sub-specific studies leading to replication of more consistent results. The long-term and large-size epidemiologic studies, stratified by age and gender, may also improve the expected outcomes. Regarding the interpretation, non-linear methods could be employed for assessment of individual variations. The emphasis should be placed on theories/measures for better understanding of the subtle interplay between the spectral individualities and mobile phone radiation specifics.

Alterations of cognitive function and 5-HT system in rats after long term microwave exposure.

The increased use of microwaves raises concerns about its impact on health including cognitive function in which neurotransmitter system plays an important role. In this study, we focused on the serotonin system and evaluated the long term effects of chronic microwave radiation on cognition and correlated items. Wistar rats were exposed or sham exposed to 2.856GHz microwaves with the average power density of 5, 10, 20 or 30mW/cm(2) respectively for 6min three times a week up to 6weeks. At different time points after the last exposure, spatial learning and memory function, morphology structure of the hippocampus, electroencephalogram (EEG) and neurotransmitter content (amino acid and monoamine) of rats were tested. Above results raised our interest in serotonin system. Tryptophan hydroxylase 1 (TPH1) and monoamine oxidase (MAO), two important rate-limiting enzymes in serotonin synthesis and metabolic process respectively, were detected. Expressions of serotonin receptors including 5-HT1A, 2A, 2C receptors were measured. We demonstrated that chronic exposure to microwave (2.856GHz, with the average power density of 5, 10, 20 and 30mW/cm(2)) could induce dose-dependent deficit of spatial learning and memory in rats accompanied with inhibition of brain electrical activity, the degeneration of hippocampus neurons, and the disturbance of neurotransmitters, among which the increase of 5-HT occurred as the main long-term change that the decrease of its metabolism partly contributed to. Besides, the variations of 5-HT1AR and 5-HT2CR expressions were also indicated. The results suggested that in the long-term way, chronic microwave exposure could induce cognitive deficit and 5-HT system may be involved in it.

Daytime light exposure: effects on biomarkers, measures of alertness, and performance.

Light can elicit an alerting response in humans, independent from acute melatonin suppression. Recent studies have shown that red light significantly increases daytime and nighttime alertness. The main goal of the present study was to further investigate the effects of daytime light exposure on performance, biomarkers and measures of alertness. It was hypothesized that, compared to remaining in dim light, daytime exposure to narrowband long-wavelength (red) light or polychromatic (2568K) light would induce greater alertness and shorter response times. Thirteen subjects experienced three lighting conditions: dim light (<5lux), red light (λmax=631nm, 213lux, 1.1W/m(2)), and white light (2568K, 361lux, 1.1W/m(2)). The presentation order of the lighting conditions was counterbalanced across the participants and each participant saw a different lighting condition each week. Our results demonstrate, for the first time, that red light can increase short-term performance as shown by the significant (p<0.05) reduced response time and higher throughput in performance tests during the daytime. There was a significant decrease (p<0.05) in alpha power and alpha-theta power after exposure to the white light, but this alerting effect did not translate to better performance. Alpha power was significantly reduced after red light exposure in the middle of the afternoon. There was no significant effect of light on cortisol and alpha amylase. The present results suggest that red light can be used to increase daytime performance.

Occipital seizures induced by intermittent photic stimulation in Dravet syndrome.

PURPOSE: Dravet syndrome (DS) is a rare disorder with seizure onset in the first year of life, typically beginning with prolonged febrile hemiclonic seizures or generalized tonic-clonic seizures. Photosensitivity is reported in more than 40% of patients. We present two cases of DS in which we had the chance to record occipital seizures induced by Intermittent Photic Stimulation (IPS). METHOD: We retrospectively reviewed the medical records of 32 children affected by DS. All clinical notes were reviewed in order to evaluate the occurrence of seizures induced by IPS. RESULTS: Among the 32 reviewed clinical records, two patients with IPS-induced seizures were found. In both patients seizures originated from the occipital-temporal region. Clinical history was characterized by generalized tonic-clonic seizures, and myoclonia. At the age respectively of 11 months and 20 months they presented a prolonged focal seizure induced by IPS at a frequency of 10 Hz. During the follow-up they additionally presented with hypomotor seizures, also induced by IPS during laboratory EEG examinations. The semiology of hypomotor seizures resembled what is described as "complex partial status", a type of non-convulsive status with ictal discharges arising unilaterally from the occipito-temporal region. CONCLUSION: Based on available literature, IPS induced occipital seizures have not been reported during the first year of life. Although pathophysiological features are not yet completely understood, both photosensitivity and occipital seizures should be considered in the diagnostic evaluation in DS. The documentation of IPS induced occipital seizures might contribute to widen the clinical and neurophysiological spectra of DS.

Alerting effects of short-wavelength (blue) and long-wavelength (red) lights in the afternoon.

Light has an acute effect on neuroendocrine responses, performance, and alertness. Most studies to date have linked the alerting effects of light to its ability to suppress melatonin, which is maximally sensitive to short-wavelength light. Recent studies, however, have shown alerting effects of white or narrowband short-wavelength lights during daytime, when melatonin levels are low. While the use of light at night to promote alertness is well understood, it is important to develop an understanding of how light impacts alertness during the daytime, especially during the post-lunch hours. The aim of the current study was to investigate how 48-minute exposures to short-wavelength (blue) light (40 lux, 18.9 microWatts/cm(2) λ(max) = 470 nanometers [nm]) or long-wavelength (red) light (40 lux, 18.9 microWatts/cm(2) λ(max) = 630 nm) close to the post-lunch dip hours affect electroencephalogram measures in participants with regular sleep schedules. Power in the alpha, alpha theta, and theta ranges was significantly lower (p<0.05) after participants were exposed to red light than after they remained in darkness. Exposure to blue light reduced alpha and alpha theta power compared to darkness, but these differences did not reach statistical significance (p>0.05). The present results extend those performed during the nighttime, and demonstrate that light can be used to increase alertness in the afternoon, close to the post-lunch dip hours. These results also suggest that acute melatonin suppression is not needed to elicit an alerting effect in humans.

[Desynchronization/synchronization of lateral EEG rhythms during habituation to photostimulation in adults]. / [Desincronización/sincronización de ritmos EEG laterales en la habituación a la fotoestimulación en adultos].

BACKGROUND: Berger related the EEG with cognition; we are attempting to identify which rhythms and circuits participate in habituation, a learning that decreases responses to meaningless stimuli which, changed the absolute power (AP) of EEG oscillations. OBJECTIVE: To characterize habituation, analyzing the AP of four rhythms in lateral regions of both hemispheres (BH), proposing that their diminution, desynchronization (D), means activation whereas their increase, synchronization (S), means inhibition. MATERIAL AND METHODS: qEEG analysis in 83 college students, in waking state with closed eyes, and photostimulated (RPh). The used UAMI/Yáñez software identifies RPh signals and takes 2-s samples before (Pre) and during RPh; the Welch periodogram integrates the AP of the four rhythms. We calculated the average AP (AAP) in Pre and RPh per frequency in bipolar lateral leads per hemisphere. AAP differences were evaluated with the Wilcoxon tests correcting with Bonferroni for repeated samples. Applying the linear regression model, we plotted the AAP distribution slopes during Pre and RPh. RESULTS: We established the differences of the AP of the four rhythms within each hemisphere and between both hemispheres (BH). During PRE, AAP of δ and θ increased whereas α and ß decreased. RPh increased the AAP (p = 0.01) of the four rhythms in fronto-frontal (FF) leads; the increase in δ persisted in fronto-temporal (FT) and temporo-occipital (TO), whereas ß's increase persisted in all leads. The AAP of α decreased with the first RPh (D) increasing with the following ones; its slope starts with desynchronization and ends with synchronization. Theta followed a D/S pattern in temporal leads. Beta followed and ascending (S) slope in all leads. CONCLUSIONS: Habituation results from the D/S of a in all cortical regions, of θ in temporal, of δ in frontal regions and ß in all regions. Synchronization reflects hyperpolarization of neuronal membranes, decreasing their activity.

Electrophysiological differences between high and low frequency rTMS protocols in depression treatment.

Repetitive transcranial magnetic stimulation (rTMS) is a rapidly expanding mean in drug resistant depression treatment. Yet, despite vast research in this field, exact neurophysiological mechanism of rTMS therapy still remains unclear. This results in difficulties choosing suitable rTMS parameters in advance and compromises thorough evaluation of efficacy after the treatment. In order to obtain more explicit assessment of rTMS therapy in the psychiatric field, we evaluated and compared the influence of two most widely used antidepressive rTMS protocols on EEG band power spectrum and relation to clinical test scores (MADRS, BDI, HAM-D17). Forty-five patients (12 male, 33 female, mean age 52.16 years) participated in the study. Twenty-three patients received high frequency (10 Hz) stimulation, the rest 22 were stimulated using low frequency (1 Hz) protocol. Both groups received 10 to 15 daily rTMS sessions. EEG recordings and clinical tests were obtained the day before rTMS course and same day after the last session. Majority (57.78%) of patients showed considerable improvement after the treatment. There were no notable differences in clinical test score drop between the two rTMS protocols. However, we found that different protocols resulted in significantly different electrophysiological changes. High frequency (10 Hz) rTMS resulted in widespread changes off EEG band power, including delta power increase on the left hemisphere and alpha power growth on the right. Theta power increase was also obtained in parietal-occipital areas. Low frequency (1 Hz) rTMS showed to have no major effect on basic EEG band power, however, we found a notable shift of frontal alpha power asymmetry towards the right hemisphere, which correlated with the clinical outcome. Our study results suggest that two widely used rTMS protocols strongly differ in their electrophysiological mechanisms. Low frequency stimulation finesse on frontal alpha power asymmetry shift, whereas high frequency protocol acts on wider electrophysiological changes in the brain.

Evaluating aftereffects of short-duration transcranial random noise stimulation on cortical excitability.

A 10-minute application of highfrequency (100-640 Hz) transcranial random noise stimulation (tRNS) over the primary motor cortex (M1) increases baseline levels of cortical excitability, lasting around 1 hr poststimulation Terney et al. (2008). We have extended previous work demonstrating this effect by decreasing the stimulation duration to 4, 5, and 6 minutes to assess whether a shorter duration of tRNS can also induce a change in cortical excitability. Single-pulse monophasic transcranial magnetic stimulation (TMS) was used to measure baseline levels of cortical excitability before and after tRNS. A 5- and 6-minute tRNS application induced a significant facilitation. 4-minute tRNS produced no significant aftereffects on corticospinal excitability. Plastic after effects after tRNS on corticospinal excitability require a minimal stimulation duration of 5 minutes. However, the duration of the aftereffect of 5-min tRNS is very short compared to previous studies using tRNS. Developing different transcranial stimulation techniques may be fundamental in understanding how excitatory and inhibitory networks in the human brain can be modulated and how each technique can be optimised for a controlled and effective application.

Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity.

BACKGROUND: Epilepsy is a common neurological disorder, which is attributed to uncontrollable abnormal hyper-excitability of neurons. We investigated the feasibility of using low-intensity, pulsed radiation of focused ultrasound (FUS) to non-invasively suppress epileptic activity in an animal model (rat), which was induced by the intraperitonial injection of pentylenetetrazol (PTZ). RESULTS: After the onset of induced seizures, FUS was transcranially administered to the brain twice for three minutes each while undergoing electroencephalographic (EEG) monitoring. An air-backed, spherical segment ultrasound transducer (diameter: 6 cm; radius-of-curvature: 7 cm) operating at a fundamental frequency of 690 KHz was used to deliver a train of 0.5 msec-long pulses of sonication at a repetitive rate of 100 Hz to the thalamic areas of the brain. The acoustic intensity (130 mW/cm2) used in the experiment was sufficiently within the range of safety guidelines for the clinical ultrasound imaging. The occurrence of epileptic EEG bursts from epilepsy-induced rats significantly decreased after sonication when it was compared to the pre-sonication epileptic state. The PTZ-induced control group that did not receive any sonication showed a sustained number of epileptic EEG signal bursts. The animals that underwent sonication also showed less severe epileptic behavior, as assessed by the Racine score. Histological analysis confirmed that the sonication did not cause any damage to the brain tissue. CONCLUSIONS: These results revealed that low-intensity, pulsed FUS sonication suppressed the number of epileptic signal bursts using acute epilepsy model in animal. Due to its non-invasiveness and spatial selectivity, FUS may offer new perspectives for a possible non-invasive treatment of epilepsy.