A comparison of the antidotal effects of three oximes against an organophosphate on chick skeletal muscle

Background: One of the most toxic effects of organophosphorus poisoning (OP) is the paralysis of skeletal muscles. The oximes are a group of available antidotes. This study investigated the effects of different concentrations of paraoxon on the function of skeletal muscle and reversal or prevention of these effects by three different oximes (i.e., pralidoxime, obidoxime, and HI-6). Materials and Methods: This study was conducted based on the chicken biventer cervices (CBC) nerve-muscle preparation and the use of twitch tension recording technique. The twitches of the CBC were evoked by stimulating the motor nerve at 0.1 Hz with pulses of 0.2 msec duration and a voltage greater than that required to produce the maximum response. Moreover, twitches and contractures were recorded isotonically using Grass Biosystems. Results: Paraoxon at 0.1 µM induced a significant increase (more than 100%) in the twitch amplitude, while higher concentrations (0.3 and 1µM) induced partial or total contracture. Therefore, paraoxon at a concentration of 0.1 µ M was used to examine the capability of oximes to prevent or reverse its effects. Pralidoxime, obidoxime, and HI-6 dose-dependently prevented (when it was used as pre-treatment, 20 min before or at the same time of administration of the toxin) and reversed (when it was used as post-treatment, 20 min after the administration of the toxin) the effect of paraoxon. Conclusion: In conclusion, these results revealed that oximes were very useful in the prevention and reversal of the OP toxic effects on the skeletal muscle. Moreover, it was suggested that oximes were more effective when used as pre-treatment. Pralidoxime was more potent than obidoxime and HI-6. The HI-6, which is a newer oxime, was unexpectedly less effective than the other two.

Consolidation of Reward Memory during Sleep Does Not Require Dopaminergic Activation

Sleep enhances memories, especially if they are related to future rewards. Although dopamine has been shown to be a key determinant during reward learning, the role of dopaminergic neurotransmission for amplifying reward-related memories during sleep remains unclear. In this study, we scrutinize the idea that dopamine is needed for the preferential consolidation of rewarded information. We impaired dopaminergic neurotransmission, thereby aiming to wipe out preferential sleep-dependent consolidation of high- over low-rewarded memories during sleep. Following a double-blind, balanced, crossover design, 17 young healthy men received the dopamine d2-like receptor blocker sulpiride (800 mg) or placebo, after learning a motivated learning task. The task required participants to memorize 80 highly and 80 lowly rewarded pictures. Half of them were presented for a short (750 msec) and a long (1500 msec) duration, respectively, which permitted dissociation of the effects of reward on sleep-associated consolidation from those of mere encoding depth. Retrieval was tested after a retention interval of approximately 22 hr that included 8 hr of nocturnal sleep. As expected, at retrieval, highly rewarded memories were remembered better than lowly rewarded memories, under placebo. However, there was no evidence for an effect of reducing dopaminergic neurotransmission with sulpiride during sleep on this differential retention of rewarded information. This result indicates that dopaminergic activation likely is not required for the preferential consolidation of reward-associated memory. Rather, it appears that dopaminergic activation only tags such memories at encoding for intensified reprocessing during sleep.

Uncoupling Sensation and Perception in Human Time Processing

Timing emerges from a hierarchy of computations ranging from early encoding of physical duration (time sensation) to abstract time representations (time perception) suitable for storage and decisional processes. However, the neural basis of the perceptual experience of time remains elusive. To address this, we dissociate brain activity uniquely related to lower-level sensory and higher-order perceptual timing operations, using event-related fMRI. Participants compared subsecond (500 msec) sinusoidal gratings drifting with constant velocity (standard) against two probe stimuli: (1) control gratings drifting at constant velocity or (2) accelerating gratings, which induced illusory shortening of time. We tested two probe intervals: a 500-msec duration (Short) and a longer duration required for an accelerating probe to be perceived as long as the standard (Long—individually determined). On each trial, participants classified the probe as shorter or longer than the standard. This allowed for comparison of trials with an “Objective” (physical) or “Subjective” (perceived) difference in duration, based on participant classifications. Objective duration revealed responses in bilateral early extrastriate areas, extending to higher visual areas in the fusiform gyrus (at more lenient thresholds). By contrast, Subjective duration was reflected by distributed responses in a cortical/subcortical areas. This comprised the left superior frontal gyrus and the left cerebellum, and a wider set of common timing areas including the BG, parietal cortex, and posterior cingulate cortex. These results suggest two functionally independent timing stages: early extraction of duration information in sensory cortices and Subjective experience of duration in a higher-order cortical–subcortical timing areas.

Variability of intraoperative electrostimulation parameters in conscious individuals: language cortex

OBJECTIVEElectrostimulation in awake brain mapping is widely used to guide tumor removal, but methodologies can differ substantially across institutions. The authors studied electrostimulation brain mapping data to characterize the variability of the current intensity threshold across patients and the effect of its variations on the number, type, and surface area of the essential language areas detected.METHODSOver 7 years, the authors prospectively studied 100 adult patients who were undergoing intraoperative brain mapping during resection of left hemisphere tumors. In all 100 cases, the same protocol of electrostimulation brain mapping (a controlled naming task—bipolar stimulation with biphasic square wave pulses of 1-msec duration and 60-Hz trains, maximum train duration 6 sec) and electrocorticography was used to detect essential language areas.RESULTSThe minimum positive thresholds of stimulation varied from patient to patient; the mean minimum intensity required to detect interference was 4.46 mA (range 1.5–9 mA), and in a substantial proportion of sites (13.5%) interference was detected only at intensities above 6 mA. The threshold varied within a given patient for different naming areas in 22% of cases. Stimulation of the same naming area with greater intensities led to slight changes in the type of response in 19% of cases and different types of responses in 4.5%. Naming sites detected were located in subcentimeter cortical areas (50% were less than 20 mm2), but their extent varied with the intensity of stimulation. During a brain mapping session, the same intensity of stimulation reproduced the same type of interference in 94% of the cases. There was no statistically significant difference between the mean stimulation intensities required to produce interfereince in the left inferior frontal lobe (Broca's area), the supramarginal gyri, and the posterior temporal region.CONCLUSIONSIntrasubject and intersubject variations of the minimum thresholds of positive naming areas and changes in the type of response and in the size of these areas according to the intensity used may limit the interpretation of data from electrostimulation in awake brain mapping. To optimize the identification of language areas during electrostimulation brain mapping, it is important to use different intensities of stimulation at the maximum possible currents, avoiding afterdischarges. This could refine the clinical results and scientific data derived from these mapping sessions.

The Functional and Structural Changes in the Basilar Artery Due to Overpressure Blast Injury

Overpressure blast-wave induced brain injury (OBI) leads to progressive pathophysiologic changes resulting in a reduction in brain blood flow, blood brain barrier breakdown, edema, and cerebral ischemia. The aim of this study was to evaluate cerebral vascular function after single and repeated OBI. Male Sprague-Dawley rats were divided into three groups: Control (Naive), single OBI (30 psi peak pressure, 1 to 2 msec duration), and repeated (days 1, 4, and 7) OBI (r-OBI). Rats were killed 24 hours after injury and the basilar artery was isolated, cannulated, and pressurized (90 cm H2O). Vascular responses to potassium chloride (KCl) (30 to 100 mmol/L), endothelin-1 (10−12 to 10−7 mol/L), acetylcholine (ACh) (10−10 to 10−4 mol/L) and diethylamine-NONO-ate (DEA-NONO-ate) (10−10 to 10−4 mol/L) were evaluated. The OBI resulted in an increase in the contractile responses to endothelin and a decrease in the relaxant responses to ACh in both single and r-OBI groups. However, impaired DEA-NONO-ate-induced vasodilation and increased wall thickness to lumen ratio were observed only in the r-OBI group. The endothelin-1 type A (ETA) receptor and endothelial nitric oxide synthase (eNOS) immunoreactivity were significantly enhanced by OBI. These findings indicate that both single and r-OBI impairs cerebral vascular endothelium-dependent dilation, potentially a consequence of endothelial dysfunction and/or vascular remodelling in basilar arteries after OBI.

Double Dissociation of Dopamine Genes and Timing in Humans

A number of lines of evidence implicate dopamine in timing [Rammsayer, T. H. Neuropharmacological approaches to human timing. In S. Grondin (Ed.), Psychology of time (pp. 295–320). Bingley, UK: Emerald, 2008; Meck, W. H. Neuropharmacology of timing and time perception. Brain Research, Cognitive Brain Research, 3, 227–242, 1996]. Two human genetic polymorphisms are known to modulate dopaminergic activity. DRD2/ANKK1-Taq1a is a D2 receptor polymorphism associated with decreased D2 density in the striatum [Jönsson, E. G., Nothen, M. M., Grunhage, F., Farde, L., Nakashima, Y., Propping, P., et al. Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Molecular Psychiatry, 4, 290–296, 1999]; COMT Val158Met is a functional polymorphism associated with increased activity of the COMT enzyme such that catabolism of synaptic dopamine is greater in pFC [Meyer-Lindenberg, A., Kohn, P. D., Kolachana, B., Kippenhan, S., McInerney-Leo, A., Nussbaum, R., et al. Midbrain dopamine and prefrontal function in humans: Interaction and modulation by COMT genotype. Nature Neuroscience, 8, 594–596, 2005]. To investigate the role of dopamine in timing, we genotyped 65 individuals for DRD2/ANKK1-Taq1a, COMT Val158Met, and a third polymorphism, BDNF Val66Met, a functional polymorphism affecting the expression of brain-derived neurotrophic factor [Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell, 112, 257–269, 2003]. Subjects were tested on a temporal discrimination task with sub- and supra-second intervals (500- and 2000-msec standards) as well as a spontaneous motor tempo task. We found a double dissociation for temporal discrimination: the DRD2/ANKK1-Taq1a polymorphism (A1+ allele) was associated with significantly greater variability for the 500-msec duration only, whereas the COMT Val158Met polymorphism (Val/Val homozygotes) was associated with significantly greater variability for the 2000-msec duration only. No differences were detected for the BDNF Vall66Met variant. Additionally, the DRD2/ANKK1-Taq1a polymorphism was associated with a significantly slower preferred motor tempo. These data provide a potential biological basis for the distinctions between sub- and supra-second timing and suggest that BG are integral for the former whereas pFC is implicated in the latter.

The Neural Substrates of Visual Perceptual Learning of Words: Implications for the Visual Word Form Area Hypothesis

It remains under debate whether the fusiform visual word form area (VWFA) is specific to visual word form and whether visual expertise increases its sensitivity (Xue et al., 2006; Cohen et al., 2002). The present study examined three related issues: (1) whether the VWFA is also involved in processing foreign writing that significantly differs from the native one, (2) the effect of visual word form training on VWFA activation after controlling the task difficulty, and (3) the transfer of visual word form learning. Eleven native English speakers were trained, during five sessions, to judge whether two subsequently flashed (100-msec duration with 200-msec interval) foreign characters (i.e., Korean Hangul) were identical or not. Visual noise was added to the stimuli to manipulate task difficulty. In functional magnetic resonance imaging scans before and after training, subjects performed the task once with the same noise level (i.e., parameter-matched scan) and once with noise level changed to match performance from pretraining to posttraining (i.e., performance-matched scan). Results indicated that training increased the accuracy in parameter-matched condition but remained constant in performance-matched condition (because of increasing task difficulty). Pretraining scans revealed stronger activation for English words than for Korean characters in the left inferior temporal gyrus and the left inferior frontal cortex, but not in the VWFA. Visual word form training significantly decreased the activation in the bilateral middle and left posterior fusiform when either parameters or performance were matched and for both trained and new items. These results confirm our conjecture that the VWFA is not dedicated to words, and visual expertise acquired with training reduces rather than increases its activity.

Information on Location in Visual Persistence: Effects of Temporal Delay and Duration of Exposure on Report of Dot Location

This study of location information involved in information persistence used the partial-report paradigm. Six subjects were asked on 144 trials to recall positions of dots presented in a display. The subjects were instructed to maintain only information on location (but not on identity information) of the presented dots until a partial-report cue was introduced. The effects of display duration (50, 200, and 350 msec.) and cue delay (interval between the display offset and the onset of the partial-report cue: 50, 250, and 500 msec.) were examined. Analysis showed effect of cue delay on partial-report performance decreased as the duration of display increased so performance was negatively affected by the cue delay only when the subject was exposed to the presented dots for 50 msec. Contrarily, partial-report performance did not decline much for a 200-msec. duration and showed little variation in a 350-msec. duration, even though the cue delay increased. Consequently, the decay of the information on location mediating partial-report performance about dots varies with duration of display.

Transcutaneous Electrical Stimulation of the Recurrent Laryngeal Nerve: A Method of Controlling Vocal Cord Position

This study was designed to examine the feasibility of transcutaneous stimulation of the recurrent laryngeal nerve. Electrical activation of the recurrent laryngeal nerve was achieved by applying a blunt electrode to the intact neck skin at specific points along the tracheoesophageal groove in anesthetized adult dogs. The stimulus consisted of 10 mA cathodal pulses, each of 1 msec duration, delivered at a frequency of 10 Hz and increased by 10 Hz increments up to 100 Hz. Vocal cord excursion was directly related to the frequency of applied current. In all six dogs studies, stimulation at 30 Hz resulted in maximal ipsilateral vocal cord adduction, while stimulation at frequencies greater than 40 Hz resulted in ipsilateral vocal cord adduction up to or across the midline. Vocal cord movement was immediate and persisted for the duration of the stimulus train. Surrounding neck muscles were not visibly activated. We propose that the observed frequency-dependent movement of the vocal cords occurred because of the difference between the contraction times of the intrinsic abductor and adductor muscles of the larynx. Transcutaneous recurrent laryngeal nerve stimulation appears promising, both as a diagnostic aid in laryngoscopy and as a therapeutic tool in controlling the glottiC aperture.

An Analysis of Vocal Communication in the Adult Brown Noddy (Anous stolidus)

I analyzed vocal signals of marked adult Brown Noddies (Anous stolidus) throughout their nesting season in the Dry Tortugas, Florida from 1979 to 1982. The basic unit of the adult repertoire is a wide-band click, less than 4 msec duration, ranging in frequency from 200 to 3,300 Hz. I identified nine temporal arrangements of these clicks, which form the notes of the calls. These calls differ little in frequency range, but they differ in the mean frequency of the most intense sound energy band, in note duration, in the number of clicks per note, and in internote interval. These calls are used in different contexts, which sometimes overlap. Frequency, note duration, and internote interval do not differ between sexes. Mean frequency and note length varied among individuals for some calls. No tonal elements characteristic of calls of Brown Noddy nestlings remain in the adult repertoire.