Validation of mechanical, electrical and thermal nociceptive stimulation methods in horses

To validate a model for investigating the effects of analgesic drugs on mechanical, thermal and electrical stimulation testing. To investigate repeatability, sensitivity and specificity of nociceptive tests. Randomised experiment with 2 observers in 2 phases. Mechanical (M), thermal (TL) and electrical (E) stimuli were applied to the dorsal metacarpus (M-left and TL-right) and coronary band of the left thoracic limb (E) and a thoracic thermal stimulus (TT) was applied caudal to the withers in 8 horses (405 ± 43 kg). Stimuli intensities were increased until a clear avoidance response was detected without exceeding 20 N (M), 60°C (TL and TT) and 15 V (E). For each set of tests, 3 real stimuli and one sham stimulus were applied (32 per animal) using a blinded, randomised, crossover design repeated after 6 months. A distribution frequency and, for each stimulus, Chi-square and McNemar tests compared both the proportion of positive responses detected by 2 observers and the 2 study phases. The κ coefficients estimated interobserver agreement in determining endpoints. Sensitivity (384 tests) and specificity (128 tests) were evaluated for each nociceptive stimulus to assess the evaluators' accuracy in detecting real and sham stimuli. Nociceptive thresholds were 3.1 ± 2 N (M), 8.1 ± 3.8 V (E), 51.4 ± 5.5°C (TL) and 55.2 ± 5.3°C (TT). The level of agreement after all tests, M, E, TL and TT, was 90, 100, 84, 98 and 75%, respectively. Sensitivity was 89, 100, 89, 98 and 70% and specificity 92, 97, 88, 91 and 94%, respectively. The high interobserver agreement, sensitivity and specificity suggest that M, E and TL tests are valid for pain studies in horses and are suitable tools for investigating antinociceptive effects of analgesics in horses.

Effects of neuromuscular electrical stimulation on the masticatory muscles and physiologic sleep variables in adults with cerebral palsy: a novel therapeutic approach

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Activity of neurons in the preoptic area and their participation in reproductive senescence: preliminary findings

Alterations in the hypothalamic-pituitary-gonadal axis in females determine the transition from regular to irregular reproductive cycles, with loss of fertility. Stimulation of noradrenergic neurons of the anteroventral periventricular neurons (AVPV) is essential for regular reproductive cycles. Therefore, we examined the activity of neurons of the AVPV and measure the noradrenaline (NE) of acyclic rats, in constant estrus, and compared it with that of cyclic rats in estrus. Female cyclic (4-5months) and acyclic (17-18months) rats were euthanized at 10, 14, and 18h in estrus. Brains were processed for immunoreactivity to antigens related to Fos (FRA) in AVPV, and the NE was determined by HPLC-ED. Plasma concentrations of LH, FSH, E2 and P4 were determined. In the acyclic animals, plasma LH was higher but the FSH was lower. There was decreasing P4 at different times, while the E2 was constant and lower in acyclic rats. FRA-ir expression in AVPV neurons of acyclic rats as well as turnover of NE was higher when compared with cyclic group. The preliminary findings showed increased activity in AVPV neurons in aging contribute to changes in the temporal pattern of neuroendocrine signaling, compromising the accuracy of inhibitory and stimulatory effects, causing irregularity in the estrous cycle and determining reproductive senescence.

Atividade dos neurônios do núcleo anterovental periventricular e sua participação no envelhecimento reprodutivo de ratas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Observations on a Cyclic Decline of Lemmings (Lemmus) on the Arctic Coast of Alaska during the Spring of 1949

The importance to the biotic community of various species of lemmings in arctic and subarctic regions has long been recognized, but there is little known about the ecology of these mammals. of the two species that occur on the Arctic Slope of Alaska, namely, the collared lemming, Dicrostonyx groenlandicus rubricatus (Richardson), and the brown lemming, Lemmus trimucronatus alascensis Merriam, during the spring of 1949 the writer had the good fortune to observe a cyclic decline in the population of the brown lemming on the Arctic Coast of Alaska. Observations were made during the peak density preceding this decline and were continued for more than a year subsequent to it. It is the purpose of this paper to present the results of these studies.

Combination of noninvasive brain stimulation with pharmacotherapy

Noninvasive brain stimulation (NIBS) techniques are being increasingly investigated as a therapeutic approach for neuropsychiatric disorders. One method is to combine NIBS with pharmacotherapy to enhance the clinical effects or avoid an increase in drug dosages to decrease the incidence of side effects. However, few studies to date have investigated the relative and combined efficacy of NIBS with pharmacotherapy. Based on a literature review of previous studies and meta-analyses for major depression, we identified four randomized, controlled trials that tested the combination of NIBS with a new drug and two trials that directly compared NIBS versus pharmacotherapy. There was no study designed to address the relative efficacy of each intervention against placebo and against combined therapy. We discuss the methods and rationale of NIBS-pharmacotherapy trials, addressing some methodological aspects, including factorial design, recruitment, blinding, blinding assessment, placebo effect and quantitative aspects, such as power analysis, statistics and interaction effects. Our review of the methodology underlying NIBS-drug trials provides insights for the further clinical research development of NIBS in major depression.

Clinical Predictors Associated With Duration of Repetitive Transcranial Magnetic Stimulation Treatment for Remission in Bipolar Depression A Naturalistic Study

Repetitive transcranial magnetic stimulation (rTMS) has been widely tested and shown to be effective for unipolar depression. Although it has also been investigated for bipolar depression (BD), there are only few rTMS studies with BD. Here, we investigated 56 patients with BD who received rTMS treatment until remission (defined as Hamilton Depression Rating Scores <= 7). We used simple and multiple logistic regressions to identify clinical and demographic predictors associated with duration of treatment (defined as <15 vs. >15 rTMS sessions). Age, refractoriness, number of prior depressive episodes, and severe depression at baseline were associated with a longer rTMS treatment. In the multivariate analysis, refractoriness (likelihood ratio (LR) = 4.33; p < 0.01) and baseline severity (LR = 0.18, p < 0.01) remained significant predictors. Our preliminary study showed that, in remitted patients, refractoriness and severity of index episode are associated with the need of a longer rTMS treatment; providing preliminary evidence of important factors associated with rTMS parameters adjustment.

Transcranial DC Stimulation Coupled With TENS for the Treatment of Chronic Pain A Preliminary Study

Objective: Based on evidence showing that electrical stimulation of the nervous system is an effective method to decrease chronic neurogenic pain, we aimed to investigate whether the combination of 2 methods of electrical stimulation-a method of peripheral stimulation [transcutaneous electrical nerve stimulation (TENS)] and a method of noninvasive brain stimulation (transcranial direct current stimulation (tDCS)]-induces greater pain reduction as compared with tDCS alone and sham stimulation. Methods: We performed a preliminary, randomized, sham-controlled, crossover, clinical study in which 8 patients were randomized to receive active tDCS/active TENS (""tDCS/TENS"" group), active tDCS/sham TENS (""tDCS"" group), and sham tDCS/sham TENS (""sham"" group) stimulation. Assessments were performed immediately before and after each condition by a blinded rater. Results: The results showed that there was a significant difference in pain reduction across the conditions Of stimulation (P = 0.006). Post hoc tests showed significant pain reduction as compared with baseline after the tDCS/TENS condition [reduction by 36.5% (+/- 10.7), P = 0.004] and the tDCS condition [reduction by 15.5% (+/- 4.9), P = 0.014], but not after sham stimulation (P = 0.35). In addition, tDCS/TENS induced greater pain reduction than tDCS (P = 0.02). Conclusions: The results of this pilot study suggest that the combination of TENS with tDCS has a superior effect compared with tDCS alone.

Cumulative priming effects of cortical stimulation on smoking cue-induced craving

Smoking cue-provoked craving is an intricate behavior associated with strong changes in neural networks. Craving is one of the main reasons subjects continue to smoke; therefore interventions that can modify activity in neural networks associated with craving can be useful tools in future research investigating novel treatments for smoking cessation. The goal of this study was to use a neuromodulatory technique associated with a powerful effect on spontaneous neuronal firing - transcranial direct current stimulation (tDCS) - to modify cue-provoked smoking craving. Based on preliminary data showing that craving can be modified after a single tDCS session, here we investigated the effects of repeated tDCS sessions on craving behavior. Twenty-seven subjects were randomized to receive sham or active tDCS (anodal tDCS of the left DLPFC). Our results show a significant cumulative effect of tDCS on modifying smoking cue-provoked craving. In fact, in the group of active stimulation, smoking cues had an opposite effect on craving after stimulation - it decreased craving - as compared to sham stimulation in which there was a small decrease or increase on craving. In addition, during these 5 days of stimulation there was a small but significant decrease in the number of cigarettes smoked in the active as compared to sham tDCS group. Our findings extend the results of our previous study as they confirm the notion that tDCS has a specific effect on craving behavior and that the effects of several sessions can increase the magnitude of its effect. These results open avenues for the exploration of this method as a therapeutic alternative for smoking cessation and also as a mean to change stimulus-induced behavior. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Non-invasive brain stimulation for the management of arterial hypertension

The neural control of the cardiovascular system is a complex process that involves many structures at different levels of nervous system. Several cortical areas are involved in the control of systemic blood pressure, such as the sensorimotor cortex, the medial prefrontal cortex and the insular cortex. Non-invasive brain stimulation techniques - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) - induce sustained and prolonged functional changes of the human cerebral cortex. rTMS and tDCS has led to positive results in the treatment of some neurological and psychiatric disorders. Because experiments in animals show that cortical modulation can be an effective method to regulate the cardiovascular system, non-invasive brain stimulation might be a novel tool in the therapeutics of human arterial hypertension. We here review the experimental evidence that non-invasive brain stimulation can influence the autonomic nervous system and discuss the hypothesis that focal modulation of cortical excitability by rTMS or tDCS can influence sympathetic outflow and, eventually, blood pressure, thus providing a novel therapeutic tool for human arterial hypertension. (C) 2009 Published by Elsevier Ltd.

Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: A double-blind, sham-controlled study

Background: Functional neuroimaging studies have shown that specific brain areas are associated with alcohol craving including the dorsolateral prefrontal cortex (DLPFC). We tested whether modulation of DLPFC using transcranial direct current stimulation (tDCS) could alter alcohol craving in patients with alcohol dependence while being exposed to alcohol cues. Methods: We performed a randomized sham-controlled study in which 13 subjects received sham and active bilateral tDCS delivered to DLPFC (anodal left/cathodal right and anodal right/cathodal left). For sham stimulation, the electrodes were placed at the same positions as in active stimulation; however, the stimulator was turned off after 30 s of stimulation. Subjects were presented videos depicting alcohol consumption to increase alcohol craving. Results: Our results showed that both anodal left/cathodal right and anodal right/cathodal left significantly decreased alcohol craving compared to sham stimulation (p < 0.0001). In addition, we found that following treatment, craving could not be further increased by alcohol cues. Conclusions: Our findings showed that tDCS treatment to DLPFC can reduce alcohol craving. These findings extend the results of previous studies using noninvasive brain stimulation to reduce craving in humans. Given the relatively rapid suppressive effect of tDCS and the highly fluctuating nature of alcohol craving, this technique may prove to be a valuable treatment strategy within the clinical setting. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Clinical trial design in non-invasive brain stimulation psychiatric research

Major depressive disorder (MDD) trials - investigating either non-pharmacological or pharmacological interventions - have shown mixed results. Many reasons explain this heterogeneity, but one that stands out is the trial design due to specific challenges in the field. We aimed therefore to review the methodology of non-invasive brain stimulation (NIBS) trials and provide a framework to improve clinical trial design. We performed a systematic review for randomized, controlled MDD trials whose intervention was transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in MEDLINE and other databases from April 2002 to April 2008. We created an unstructured checklist based on CONSORT guidelines to extract items such as power analysis, sham method, blinding assessment, allocation concealment, operational criteria used for MDD, definition of refractory depression and primary study hypotheses. Thirty-one studies were included. We found that the main methodological issues can be divided in to three groups: (1) issues related to phase II/small trials, (2) issues related to MDD trials and, (3) specific issues of NIBS studies. Taken together, they can threaten study validity and lead to inconclusive results. Feasible solutions include: estimating the sample size a priori; measuring the degree of refractoriness of the subjects; specifying the primary hypothesis and statistical tests; controlling predictor variables through stratification randomization methods or using strict eligibility criteria; adjusting the study design to the target population; using adaptive designs and exploring NIBS efficacy employing biological markers. In conclusion, our study summarizes the main methodological issues of NIBS trials and proposes a number of alternatives to manage them. Copyright (C) 2011 John Wiley & Sons, Ltd.

Cognitive, Mood, and Electroencephalographic Effects of Noninvasive Cortical Stimulation With Weak Electrical Currents

Objectives: The use of noninvasive cortical electrical stimulation with weak currents has significantly increased in basic and clinical human studies. Initial, preliminary studies with this technique have shown encouraging results; however, the safety and tolerability of this method of brain stimulation have not been sufficiently explored yet. The purpose of our study was to assess the effects of direct current (DC) and alternating current (AC) stimulation at different intensities in order to measure their effects on cognition, mood, and electroencephalogram. Methods: Eighty-two healthy, right-handed subjects received active and sham stimulation in a randomized order. We conducted 164 ninety-minute sessions of electrical stimulation in 4 different protocols to assess safety of (1) anodal DC of the dorsolateral prefrontal cortex (DLPFC); (2) cathodal DC of the DLPFC; (3) intermittent anodal DC of the DLPFC and; (4) AC on the zygomatic process. We used weak currents of 1 to 2 mA (for DC experiments) or 0.1 to 0.2 mA (for AC experiment). Results: We found no significant changes in electroencephalogram, cognition, mood, and pain between groups and a low prevalence of mild adverse effects (0.11% and 0.08% in the active and sham stimulation groups, respectively), mainly, sleepiness and mild headache that were equally distributed between groups. Conclusions: Here, we show no neurophysiological or behavioral signs that transcranial DC stimulation or AC stimulation with weak currents induce deleterious changes when comparing active and sham groups. This study provides therefore additional information for researchers and ethics committees, adding important results to the safety pool of studies assessing the effects of cortical stimulation using weak electrical currents. Further studies in patients with neuropsychiatric disorders are warranted.

A cyclic bipolar wind in the interacting binary V 393 Scorpii

V393 Scorpii is a double periodic variable characterized by a relatively stable non-orbital photometric cycle of 253 d. Mennickent et al. argue for the presence of a massive optically thick disc around the more massive B-type component and describe the evolutionary stage of the system. In this paper, we analyse the behaviour of the main spectroscopic optical lines during the long non-orbital photometric cycle. We study the radial velocity of the donor determining its orbital elements and find a small but significant orbital eccentricity (e = 0.04). The donor spectral features are modelled and removed from the spectrum at every observing epoch using the light-curve model given by Mennickent et al. We find that the line emission is larger during eclipses and mostly comes from a bipolar wind. We also find that the long cycle is explained in terms of a modulation of the wind strength; the wind has a larger line and continuum emissivity at the high state. We report the discovery of highly variable chromospheric emission in the donor, as revealed by the Doppler maps of the emission lines Mg II 4481 and C I 6588. We discuss notable and some novel spectroscopic features like discrete absorption components, especially visible at blue depressed O I 7773 absorption wings during the second half-cycle, Balmer double emission with V/R curves showing 'Z-type' and 'S-type' excursions around secondary and main eclipses, respectively, and H beta emission wings extending up to +/- 2000 km s(-1). We also discuss possible causes for these phenomena and for their modulations with the long cycle.

Into the Island: A new technique of non-invasive cortical stimulation of the insula

Study aim. - We describe a new neuronavigation-guided technique to target the posterior-superior insula (PSI) using a cooled-double-cone coil for deep cortical stimulation. Introduction. - Despite the analgesic effects brought about by repetitive transcranial magnetic stimulation (TMS) to the primary motor and prefrontal cortices, a significant proportion of patients remain symptomatic. This encouraged the search for new targets that may provide stronger pain relief. There is growing evidence that the posterior insula is implicated in the integration of painful stimuli in different pain syndromes and in homeostatic thermal integration. Methods. - The primary motor cortex representation of the lower leg was used to calculate the motor threshold and thus, estimate the intensity of PSI stimulation. Results. - Seven healthy volunteers were stimulated at 10 Hz to the right PSI and showed subjective changes in cold perception. The technique was safe and well tolerated. Conclusions. - The right posterior-superior insula is worth being considered in future studies as a possible target for rTMS stimulation in chronic pain patients. (c) 2012 Elsevier Masson SAS. All rights reserved.