Motor intracortical inhibition in PD: L-DOPA modulation of high-frequency rTMS effects

Dopaminergic drugs and deep brain stimulation restore cortical inhibition in Parkinson disease (PD) patients. High-frequency rTMS was also found to increase cortical inhibition in PD but its therapeutic effect is still controversial. Here we hypothesize that, if dopaminergic drugs reverse to normal cortical excitability in M1, the effect of high-frequency (hf)-rTMS in PD patients could depend on whether they are in a medicated or unmedicated state. The present study aims to explore the lasting effects of sub-threshold hf rTMS trains over M1 on cortical inhibition in patients with “on” and without “off” L-DOPA treatment. Fourteen PD patients were examined twice while “on” and “off” medication. In both conditions, a paired-pulse paradigm was used to evaluate short intracortical inhibition (SICI) and long intracortical inhibition (LICI) that were evaluated before and after hf rTMS trains applied on the motor cortex. The results were compared with those obtained from normal controls. In baseline condition, SICI and LICI were significantly reduced in “off” compared to “on” patients and controls. hf-rTMS over the motor cortex significantly increased SICI and LICI in “off” medication PD patients. Magnetic stimulation proved to be ineffective when the same patients were in “on” state. The results showed that hf-rTMS affected intracortical inhibition (ICI) only in unmedicated patients. By restoring cortical inhibitory circuits dopaminergic drugs, normalize the excitability changes in M1 subsequent to motor rTMS. Whether patients are in a medicated or an unmedicated state would therefore appear to be critical for rTMS effects in PD patients. If a positive correlation exists between increased cortical inhibition and clinical improvement, hf-rTMS during the “off” state could be regarded as a potential add-on treatment to reduce the need of L-dopa and thus delay the adverse effects of its chronic use.     

Sarcomere length-dependent Ca<Superscript>2+</Superscript> activation in skinned rabbit psoas muscle fibers: coordinated regulation of thin filament cooperative activation and passive force

In skeletal muscle, active force production varies as a function of sarcomere length (SL). It has been considered that this SL dependence results simply from a change in the overlap length between the thick and thin filaments. The purpose of this study was to provide a systematic understanding of the SL-dependent increase in Ca²⁺ sensitivity in skeletal muscle, by investigating how thin filament “on–off” switching and passive force are involved in the regulation. Rabbit psoas muscles were skinned, and active force measurements were taken at various Ca²⁺ concentrations with single fibers, in the short (2.0 and 2.4 μm) and long (2.4 and 2.8 μm) SL ranges. Despite the same magnitude of SL elongation, the SL-dependent increase in Ca²⁺ sensitivity was more pronounced in the long SL range. MgADP (3 mM) increased the rate of rise of active force and attenuated SL-dependent Ca²⁺ activation in both SL ranges. Conversely, inorganic phosphate (Pi, 20 mM) decreased the rate of rise of active force and enhanced SL-dependent Ca²⁺ activation in both SL ranges. Our analyses revealed that, in the absence and presence of MgADP or Pi, the magnitude of SL-dependent Ca²⁺ activation was (1) inversely correlated with the rate of rise of active force, and (2) in proportion to passive force. These findings suggest that the SL dependence of active force in skeletal muscle is regulated via thin filament “on–off” switching and titin (connectin)-based interfilament lattice spacing modulation in a coordinated fashion, in addition to the regulation via the filament overlap.     

Effects of attention on inhibitory and facilitatory phenomena elicited by paired-pulse transcranial magnetic stimulation in healthy subjects

We investigated whether human attentional processes influence the activity of intracortical inhibitory and excitatory circuits—short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and the intracortical facilitation (ICF)—elicited by paired-pulse transcranial magnetic stimulation (TMS) in healthy subjects. In eight healthy subjects we tested SICI, LICI and ICF under different attention-demanding conditions: “relaxed”, “target hand” and “non-target hand”. To compare the effects of attentional levels on SICI, LICI and ICF with those produced on the MEPs elicited by repetitive TMS (rTMS), in the same subjects we also delivered supra-threshold 5-Hz rTMS under the same three experimental conditions. To disclose whether attentional processes act selectively on circuits engaged by TMS delivered at 5 Hz frequency and at an interstimulus interval (ISI) of 200 ms, we also investigated the effects of different attention levels on paired-pulse TMS delivered at the 200 ms ISI and on the MEP size during 1-Hz rTMS. Attentional levels had no influence on SICI, ICF and LICI activated by paired-pulse TMS, but increased the MEP facilitation elicited by 5-Hz rTMS. Varying the attention level left the findings from 1-Hz rTMS unchanged. The finding that attention leaves the activity of intracortical inhibitory and excitatory circuits elicited by paired-pulse TMS unchanged but influences the MEP facilitation elicited by 5-Hz rTMS suggests that attention operates only when the stimulation entrains neural circuits made up of a large number of cortical cells with plasticity properties.     

Pre-dive normobaric oxygen reduces bubble formation in scuba divers

Oxygen pre-breathing is routinely employed as a protective measure to reduce the incidence of altitude decompression sickness in aviators and astronauts, but the effectiveness of normobaric oxygen before hyperbaric exposure has not been well explored. The objective of this study was to evaluate the effect of 30-min normobaric oxygen (O₂) breathing before diving upon bubble formation in recreational divers. Twenty-one subjects (13 men and 8 women, mean age (SD) 33 ± 8 years) performed random repetitive open-sea dives (surface interval of 100 min) to 30 msw for 30 min with a 6-min stop at 3 msw under four experimental protocols: “air–air” (control), “O₂–O₂”, “O₂–air” and “air–O₂” where “O₂” corresponds to a dive with oxygen pre-breathing and “air” a dive without oxygen administration. Post-dive venous gas emboli were examined by means of a precordial Doppler ultrasound. The results showed decreased bubble scores in all dives where preoxygenation had taken place (p < 0.01). Oxygen pre-breathing before each dive (“O₂–O₂” condition) resulted in the highest reduction in bubble scores measured after the second dive compared to the control condition (–66%, p < 0.05). The “O₂–air” and “air–O₂ “conditions produced fewer circulating bubbles after the second dive than “air–air” condition (–47.3% and –52.2%, respectively, p < 0.05) but less bubbles were detected in “air–O₂ “condition compared to “O₂–air” (p < 0.05). Our findings provide evidence that normobaric oxygen pre-breathing decreases venous gas emboli formation with a prolonged protective effect over time. This procedure could therefore be beneficial for multi-day repetitive diving.     

Salivary estradiol, interleukin-6 production, and the relationship to substrate metabolism during exercise in females

Estradiol (E₂) has been documented to have anti-inflammatory effects on the immune system. Interleukin-6 (IL-6), is classified as a “myokine”, and has known metabolic consequences. Thus, the purpose of this study was to determine the effects of menstrual phase and exercise on the interaction of E₂ and IL-6, and the role of IL-6 in substrate metabolism. Ten female subjects completed three separate testing sessions: baseline evaluation, and 1 h of treadmill exercise at 65% of peak [(V)\dot] \textO₂ \dot V {\text{O}}_{2} during both the midfollicular (MF) and midluteal (ML) menstrual phases. Saliva was collected prior to, during, and post-exercise for determination of E₂ and IL-6. Expired gases and an additional saliva sample were collected 30 min post-exercise. No significant differences were observed in any of the measured variables across menstrual phase. Exercise resulted in an acute rise in estradiol and IL-6; however, E₂ was not related to IL-6 at baseline or in response to exercise. IL-6 remained elevated at the end of exercise and was found to be related to energy expenditure from fat, and to total energy expenditure at 60 min, and 30 min post-exercise. No relationships were found between the anti-inflammatory estrogen E₂ and the cytokine IL-6. However, relationships were found between IL-6 and indices of substrate metabolism. Based on the data from the current research, IL-6 likely plays a metabolic role in healthy individuals during exercise when released from the muscle as a result of reduced energy availability, acting as a “myokine”, in comparison to inflammation-induced IL-6 release.     

Influence of exercise on the circulating levels and macrophage production of IL-1β and IFNγ affected by metabolic syndrome: an obese Zucker rat experimental animal model

Regular physical activity is recognized as a non-pharmacological treatment of genetic obesity and type-II diabetes, and based on the “anti-inflammatory” effects of exercise, it has been also proposed for improving the “chronic low-grade inflammation” in metabolic syndrome (MS). The aim of the present work was to evaluate the effects of an habitual exercise program (running, 5 days/week for 35 min at 35 cm/s for 14 weeks) and of a bout of acute exercise (running, for 35 min at 35 cm/s) on MS-associated disorders in the pro-inflammatory cytokines IL-1β and IFNγ. The study was carried out on obese Zucker rats (fa/fa). The obese rats presented higher circulating concentrations and constitutive macrophage production (in the absence of antigenic stimulus) of IL-1β (but not of IFNγ). But their production of both IL-1β and IFNγ by lipopolysaccharide (LPS)-stimulated macrophages was lower than that of the control lean rats. Our protocol of exercise training did not modify the circulating concentration and constitutive macrophage release of either IL-1β or IFNγ in the obese rats, but increased the production of both cytokines by LPS-stimulated macrophages. The single bout of acute exercise only increased the release of IL-1β by the LPS-stimulated macrophages from obese rats, in both sedentary and trained animals. The results indicated that: (1) circulating levels and constitutive production of IL-1β by macrophages are deregulated in rats with MS, and (2) IL-1β and IFNγ production by macrophages in response to antigenic stimulus (LPS) is impaired in the obese animals, and this MS-associated disorder is improved by the program of habitual exercise training.     

Chronic low frequency/low volume resistance training reduces pro-inflammatory cytokine protein levels and TLR4 mRNA in rat skeletal muscle

Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin 6 (IL-6), a cytokine that exerts inhibitory effects on several pro-inflammatory cytokines. Although dynamic chronic resistance training has been shown to produce the known “repeated bout effect”, which abolishes the acute muscle damage, performing of high-intensity resistance training has been regarded highly advisable, at least from the hypertrophy perspective. On the other hand, a more therapeutic, “non-damaging” resistance training program, mainly composed of concentric forces, low frequency/low volume of training, and the same exercise, could theoretically benefit the muscle when the main issue is to avoid muscle inflammation (as in the treatment of several “low-grade” inflammatory diseases) because the acute effect of each resistance exercise session could be diminished/avoided, at the same time that the muscle is still being overloaded in a concentric manner. However, the benefits of such “less demanding” resistance training schedule on the muscle inflammatory profile have never been investigated. Therefore, we assessed the protein expression of IL-6, TNF-α, IL-10, IL-10/TNF-α ratio, and HSP70 levels and mRNA expression of SCF^β-TrCP, IL-15, and TLR-4 in the skeletal muscle of rats submitted to resistance training. Briefly, animals were randomly assigned to either a control group (S, n = 8) or a resistance-trained group (T, n = 7). Trained rats were exercised over a duration of 12 weeks (two times per day, two times per week). Detection of IL-6, TNF-α, IL-10, and HSP70 protein expression was carried out by western blotting and SCF^β-TrCP (SKP Cullin F-Box Protein Ligases), a class of enzymes involved in the ubiquitination of protein substrates to proteasomal degradation, IL-15, and TLR-4 by RT-PCR. Our results show a decreased expression of TNF-α and TLR4 mRNA (40 and 60%, respectively; p < 0.05) in the plantar muscle from trained, when compared with control rats. In conclusion, exercise training induced decreased TNF-α and TLR-4 expressions, resulting in a modified IL-10/TNF-α ratio in the skeletal muscle. These data show that, in healthy rats, 12-week resistance training, predominantly composed of concentric stimuli and low frequency/low volume schedule, down regulates skeletal muscle production of cytokines involved in the onset, maintenance, and regulation of inflammation.     

Use of the new levodopa agent Stalevo (levodopa/carbidopa/entacapone) in the treatment of Parkinson's disease in out-patient clinical practice (the START-M open trial)

Despite the significant symptomatic effects of levodopa, stable 24-h treatment responses are in the vast majority of patients replaced 2–3 years from the start of treatment by oscillations in motor symptoms (fluctuation, dyskinesia), amelioration of which requires addition of constant (physiological) stimulation of postsynaptic dopamine receptors. To some extent this is provided by Stalevo, which contains levodopa and two enzyme inhibitors: the DDC inhibitor carbidopa and the COMT inhibitor entacapone. The results obtained in the present study demonstrated the advantages of Stalevo over traditional agents in patients with the “wearing off” and “on-off” phenomena. __________ Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 107, No. 12, pp. 21–24, December, 2007.     

Proinflammatory Cytokine Gene Polymorphisms among Iranian Patients with Asthma

Introduction  Asthma is one of the most common respiratory diseases caused by acute and chronic inflammation of airways. Proinflammatory cytokines could contribute to this inflammatory process. This study was performed in order to analyze the genetic profile of proinflammatory cytokines in Iranian asthmatic patients. Patients and Methods  The allele and genotype frequencies of a number polymorphic genes coding for tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-1 receptor (IL-1R), IL-1RA, and IL-6 were investigated in 60 patients with asthma in comparison with 140 controls using polymerase chain reaction with sequence-specific primers. Results  The most frequent genotypes in our patients were TNF-α GA at position −308 (P = 0.001), TNF-α AA at position −238 (P = 0.01), IL-1α TC at position −889 (P = 0.0001), IL-1β TC at position −511 (P = 0.0001), and IL-1RA TC at position Mspa-I 11100 (P = 0.001). In contrast, the frequencies of the genotypes TNF-α GG at position −308 (P = 0.001), IL-1α CC at position −889 (P = 0.005), IL-1β CC at position −511 (P = 0.0001), and IL-1RA TT at position Mspa-I 11100 (P = 0.0001) in the patient group were significantly lower than controls. The most frequent haplotypes for TNF-α (positions 308, −238) was A/A in the patient group in comparison with controls (P = 0.0001). Conclusion  While environmental factors are important in the development of asthma, genetic factors could have a critical role in the expression of the disease. Considering the high frequency of presence of TNF-α AG genotype (−308), it seems that the production of TNF-α in the asthmatic patients could be higher than normal subjects.     

Attention influences the excitability of cortical motor areas in healthy humans

We investigated whether human attentional processes influence the size of the motor evoked potentials (MEP) facilitation and the duration of the cortical silent period (CSP) elicited by high-frequency repetitive transcranial magnetic stimulation (rTMS). In healthy subjects we assessed the effects of 5 Hz-rTMS, delivered in trains of 10 stimuli at suprathreshold intensity over the hand motor area, on the MEP size and CSP duration in different attention-demanding conditions: “relaxed,” “target hand,” and “non-target hand” condition. We also investigated the inhibitory effects of 1 Hz-rTMS conditioning to the premotor cortex on the 5 Hz-rTMS induced MEP facilitation. F-waves evoked by ulnar nerve stimulation were also recorded. rTMS trains elicited a larger MEP size facilitation when the subjects looked at the target hand whereas the increase in CSP duration during rTMS remained unchanged during the three attention-demanding conditions. The conditioning inhibitory stimulation delivered to the premotor cortex decreased the MEP facilitation during the “target hand” condition, leaving the MEP facilitation during the other conditions unchanged. None of the attentional conditions elicited changes in the F wave. In healthy subjects attentional processes influence the size of the MEP facilitation elicited by high-frequency rTMS and do so through premotor-to-motor connections.     

Motor learning in the “podokinetic” system and its role in spatial orientation during locomotion

The present study characterizes a previously reported adaptive phenomenon in a somatosensory-motor system involved in directional control of locomotor trajectory through foot contact with the floor. We call this the “podokinetic” (PK) system. Podokinetic adaptation was induced in six subjects by stepping in-place over the axis of a horizontally rotating disc over a range of disc angular velocities (11.25–90°/s) and durations (7.5–60 min). After adaptation, subjects were blindfolded and attempted to step in-place on the floor without turning. Instead they all rotated relative to space. The rate of the “podokinetic afterrotation” (PKAR) was linearly related to stimulus amplitude up to 45°/s, and the ratio of initial PKAR velocity to that of the adaptive stimulus was approximately 1:3. PKAR exhibited exponential decay, which was composed of “short-” and “long-term” components with “discharging” time constants on the order of 6–12 min and 1–2 h, respectively. The effect of stimulus duration on PKAR revealed a “charging” time constant that approximated that of the short-term component. A significant suppression of PKAR occurred during the 1st min of the postadaptive response, suggesting functional interaction between the PK and vestibular systems during the period of vestibular stimulation. During PKAR subjects perceived no self-rotation, indicating that perception as well as locomotor control of spatial orientation were remodeled by adaptation of the PK system. Received: 4 August 1997 / Accepted: 19 November 1997     

Image-to-sound conversion: experience-induced plasticity in auditory cortex of blindfolded adults

The ability to adapt to environmental changes is based on the impressive capacity of the central nervous system for plasticity changes. A better understanding of the requirements of neuroplasticity will help to apprehend and predict the success of sensory prostheses. To investigate neuroplastic changes associated with (1) blindfolding and (2) the use of a mobile visual–auditory substitution system, five normally sighted adults underwent weekly measurements of neuromagnetic activity using a 122-channel whole head neuromagnetometer. The substitution device converted visual images into sound patterns. During measurements subjects listened to “geometric sounds” converted from images of geometric shapes, “natural sounds” representing photographs of everyday objects, as well as to original “environmental sounds”. To assess the role of visual deprivation, three individuals were blindfolded throughout a 3-week testing period. To assess the effect of extended exposure to “visual sounds”, three subjects—two blindfolded, one sighted—had free use of the substitution device. Neuromagnetic responses were restricted to the auditory cortex across all measurements. Activity at 100 ms after presentation of “natural sounds”, but not other auditory stimuli, showed a significant enhancement over time only in blindfolded subjects using the substitution system, indicating that the combination of visual deprivation and practice facilitated intra-modal plasticity. The fact that changes occurred only in response to “natural sounds” probably reflects the increased behavioural relevance of this category evident only for blindfolded subjects using the substitution device.     

EEG inter/intra-hemispheric coherence and asymmetric responses to visual stimulations

In the past, many studies have claimed that extremely low frequency (ELF) magnetic field (MF) exposures could alter the human electroencephalographic (EEG) activity. This study aims at extending our ELF pilot study to investigate whether MF exposures at ELF in series from 50, 16.66, 13, 10, 8.33 to 4 Hz could alter relative power within the corresponding EEG bands. 33 human subjects were tested under a double-blind and counter-balanced conditions. The multiple repeated three-way analysis of variance (ANOVA) mixed design (within and between-subject) analysis was employed followed by post-hoc t-tests and Bonferroni alpha-correction. The results from this study have shown that narrow alpha1 (7.5–9.5 Hz) and alpha2 (9–11 Hz) bands, associated with 8.33 and 10 Hz MF exposures, were significantly (p < 0.0005) lower than control over the temporal and parietal regions within the 10–16 min of first MF exposure session and the MF exposures were significantly higher than control of the second session MF exposure (60–65 min from the commencement of testing). Also, it was found that the beta1 (12–14 Hz) band exhibited a significant increase from before to after 13-Hz first MF exposure session at frontal region. The final outcome of our result has shown that it is possible to alter the human EEG activity of alpha and beta bands when exposed to MF at frequencies corresponding to those same bands, depending on the order and period of MF conditions. This type of EEG synchronisation of driving alpha and beta EEG by alpha and beta sinusoidal MF stimulation, demonstrated in this study, could possibly be applied as therapeutic treatment(s) of particular neurophysiological abnormalities such as sleep and psychiatric disorders.     

The Transport Profile of Cytokines in Epidermal Equivalents Subjected to Mechanical Loading

Pressure ulcer risk assessment might be optimized by incorporating the soft tissue reaction to mechanical loading in the currently used risk assessment scales. Cytokines, like IL-1α, IL-1RA, IL-8, and TNF-α, might be used to determine this tissue reaction, since they are released after 24 h of mechanical loading of epidermal equivalents. In the current study, the release and transport of these cytokines with time was evaluated. Epidermal equivalents were subjected to 20 kPa for different time periods (1, 2, 4, 6, 8, 16, and 24 h). Compared to the unloaded control group, a significant increase was found for IL-1α (4.7-fold), IL-1RA (4.8-fold), and IL-8 (3.6-fold) release after 1 h loading. For TNF-α, the release was significantly increased after 4 h of loading (5.1-fold compared to the unloaded situation), coinciding with the first signs of gross structural tissue damage. These cytokine values were determined in the surrounding medium and a transport model was developed to evaluate the distribution of cytokines inside the culture. These simulations revealed that all IL-8 and TNF-α was released from the keratinocytes, whereas most of the IL-1α and IL-1RA remained inside the keratinocytes during the 24 h loading period. In conclusion, IL-1α, IL-1RA, and IL-8 appear promising biochemical markers for pressure ulcer risk assessment, since their release is increased after 1 h of epidermal loading and before the onset of structural tissue damage.     

Approach for Fabricating Tissue Engineered Vascular Grafts with Stable Endothelialization

A major roadblock in the development of tissue engineered vascular grafts (TEVGs) is achieving construct endothelialization that is stable under physiological stresses. The aim of the current study was to validate an approach for generating a mechanically stable layer of endothelial cells (ECs) in the lumen of TEVGs. To accomplish this goal, a unique method was developed to fabricate a thin EC layer using poly(ethylene glycol) diacrylate (PEGDA) as an intercellular “cementing” agent. This EC layer was subsequently bonded to the lumen of a tubular scaffold to generate a bi-layered construct. The viability of bovine aortic endothelial cells (BAECs) through the “cementing” process was assessed. “Cemented” EC layer expression of desired phenotypic markers (AcLDL uptake, VE-cadherin, eNOS, PECAM-1) as well as of injury-associated markers (E-selectin, SM22α) was also examined. These studies indicated that the “cementing” process allowed ECs to maintain high viability and expression of mature EC markers while not significantly stimulating primary injury pathways. Finally, the stability of the “cemented” EC layers under abrupt application of high shear pulsatile flow (~11 dyn/cm², P _avg ~ 95 mmHg, ΔP ~ 20 mmHg) was evaluated and compared to that of conventionally “seeded” EC layers. Whereas the “cemented” ECs remained fully intact following 48 h of pulsatile flow, the “seeded” EC layers delaminated after less than 1 h of flow. Furthermore, the ability to extend this approach to degradable PEGDA “cements” permissive of cell elongation was demonstrated. Combined, these results validate an approach for fabricating bi-layered TEVGs with stable endothelialization.     

Cortical processing of tactile stimuli applied in quick succession across the fingertips: temporal evolution of dipole sources revealed by magnetoencephalography

We used magnetoencephalography (MEG) in 10 healthy human subjects to study cortical responses to tactile stimuli applied to the fingertips of digits 2–5 of the right hand. Each stimulus lasted 50 ms and was produced by air-driven elastic membranes. Four-hundred stimuli were delivered on each finger in three temporal patterns (conditions). In the “Discrete” condition, stimuli were applied to each finger repetitively with an interstimulus interval (ISI) of 1–2 s. In the “Continuous” condition, stimuli were applied to the fingers sequentially as four-stimulus trains with zero ISI and 1–2 s intervening between trains. Finally, in the “Gap” condition, stimuli were applied as in the Continuous condition but with an ISI of 50 ms. A sensation of tactile motion across fingers (digit 2 → digit 5) was reported by all subjects in the Continuous and Gap conditions. Cortical responses were extracted as single equivalent current dipoles over a period of 1 s following stimulus onset. In all three conditions, initial responses in left primary somatosensory cortex (SI) were observed ~20 to 50 ms after stimulus onset and were followed by additional left SI responses and bilateral responses in the secondary somatosensory cortex (SII). In addition, in the Continuous and Gap conditions, there was an activation of the precentral gyrus, the temporal aspects of which depended on the temporal relation of the administered stimuli, as follows. An ISI of 0 ms led to activation of the precentral gyrus shortly after the second stimulation, whereas an ISI of 50 ms led to activation of the precentral gyrus after the third stimulation. The current findings support results from previous studies on temporal activity patterns in SI and SII, verify the participation of the precentral gyrus during tactile motion perception and, in addition, reveal aspects of integration of sequential sensory stimulations over nonadjacent areas as well as temporal activity patterns in the postcentral and precentral gyri.     

Using EEG to Explore How rTMS Produces Its Effects on Behavior

A commonly held view is that, when delivered during the performance of a task, repetitive TMS (rTMS) influences behavior by producing transient “virtual lesions” in targeted tissue. However, findings of rTMS-related improvements in performance are difficult to reconcile with this assumption. With regard to the mechanism whereby rTMS influences concurrent task performance, a combined rTMS/EEG study conducted in our lab has revealed a complex set of relations between rTMS, EEG activity, and behavioral performance, with the effects of rTMS on power in the alpha band and on alpha:gamma phase synchrony each predicting its effect on behavior. These findings suggest that rTMS influences performance by biasing endogenous task-related oscillatory dynamics, rather than creating a “virtual lesion”. To further differentiate these two alternatives, in the present study we compared the effects of 10 Hz rTMS on neural activity with the results of an experiment in which rTMS was replaced with 10 Hz luminance flicker. We reasoned that 10 Hz flicker would produce widespread entrainment of neural activity to the flicker frequency, and comparison of these EEG results with those from the rTMS study would shed light on whether the latter also reflected entrainment to an exogenous stimulus. Results revealed pronounced evidence for “entrainment noise” produced by 10 Hz flicker—increased oscillatory power and inter-trial coherence (ITC) at the driving frequency, and increased alpha:gamma phase synchronization—that were nonetheless largely uncorrelated with behavior. This contrasts markedly with 10-Hz rTMS, for which the only evidence for stimulation-induced noise, elevated ITC at 30 Hz, differed qualitatively from the flicker results. Simultaneous recording of the EEG thus offers an important means of directly testing assumptions about how rTMS exerts its effects on behavior.     

Experimental Study of Relationship between Biological Hazards of Low-Dose Radiofrequency Exposure and Energy Flow Density in <Emphasis Type="Italic">Spirostomum Ambiguum</Emphasis> Infusoria Exposed at a Mobile Connection Frequency (1 GHz)

Radiofrequency exposure at the mobile connection frequency (1 GHz) at different energy flow densities, 5 μW/cm² (2-fold below the maximum permissible level) and 50 μW/cm² (5-fold surpassing this level), caused a reduction of motor activity in unicellular hydrobionts Spirostomum ambiguum Ehrbg infusoria. In all cases, the effect was similar by the intensity and developed in a jump-wise manner after exposure of a certain duration, after which did not increase with prolongation of the exposure. The duration of radiofrequency exposure safe for the object varied signifi cantly: 8–9 h and 10 min at 5 and 50 μW, respectively. These innovation data on harmful biological effects of very low radiofrequency exposure (5 μW/cm²), the threshold form of biological reaction, presence of “safe” periods of exposure, and the data demonstrating a clear-cut relationship between these periods and energy flow density are interesting from theoretical viewpoint and in connection with the problem of evaluating permissible levels of radiofrequency exposure of biological objects.     

Suppression of experimental allergic encephalomyelitis in rats by 50-nT, 7-Hz amplitude-modulated nocturnal magnetic fields depends on when after inoculation the fields are applied

Female Lewis rats (n= 88) were inoculated with an emulsion of spinal cord and complete Freund's adjuvant. They were then exposed in 11 separate blocks of experiments over a year period for approximately 6 min every hour between midnight and 08:00 h during post-inoculation nights 1–7, 8–16, 1–16, or 9 and 10 to 50-nT, 7-Hz, amplitude-modulated magnetic fields or to sham field (control) conditions. Compared to the control rats those exposed to the magnetic fields for nights 1–7 and nights 9–10 displayed more severe clinical symptoms while those exposed for nights 1–16 or 8–16 showed less severe symptoms. There was a strong correlation between the severity of the clinical symptoms in the control groups and the global geomagnetic activity 9 and 10 days after inoculation. These results suggest that the immunosuppressive effects of weak nocturnal magnetic fields may depend upon when they are applied during various stages in the development of a disease.     

Screening for recombinant human erythropoietin using [Hb], reticulocytes, the OFFhr score, OFF z score and Hb z score: status of the Blood Passport

Haemoglobin concentration ([Hb]), reticulocyte percentage (retic%) and OFF_hr score are well-implemented screening tools to determine potential recombinant human erythropoietin (rHuEpo) abuse in athletes. Recently, the International Cycling Union implemented the OFF _z score and the Hb _z score in their anti-doping testing programme. The aim of this study is to evaluate the sensitivity of these indirect screening methods. Twenty-four human subjects divided into three groups with eight subjects each (G1; G2 and G3) were injected with rHuEpo. G1 and G2 received rHuEpo for a 4-week period with 2 weeks of “boosting” followed by 2 weeks of “maintenance” and a wash-out period of 3 weeks. G3 received rHuEpo for a 10-week period (boost = 3 weeks; maintenance = 7 weeks; wash out = 1 week). Three, seven and eight of the 24 volunteers exceeded the cut-off limits for OFF_hr score, [Hb] and retic%, respectively. One subject from G1, nobody from G2, and seven subjects from G3 exceeded the cut-off limit for Hb _z score. In total, ten subjects exceeded the cut-off limit for the OFF _z score; two subjects from G1, two subjects from G2 and six subjects from G3. In total, indirect screening methods were able to indicate rHuEpo injections in 58% of subjects. However, 42% of our rHuEpo-injected subjects were not detected. It should be emphasised that the test frequency in real world anti-doping is far less than the present study, and hence the detection rate will be lower.