Phasic modulation of corticomotor excitability during passive movement of the upper limb: effects of movement frequency and muscle specificity

Modulations in the excitability of spinal reflex pathways during passive rhythmic movements of the lower limb have been demonstrated by a number of previous studies [4]. Less emphasis has been placed on the role of supraspinal pathways during passive movement, and on tasks involving the upper limb. In the present study, transcranial magnetic stimulation (TMS) was delivered to subjects while undergoing passive flexion-extension movements of the contralateral wrist. Motor evoked potentials (MEPs) of flexor carpi radialis (FCR) and abductor pollicus brevis (APB) muscles were recorded. Stimuli were delivered in eight phases of the movement cycle during three different frequencies of movement. Evidence of marked modulations in pathway excitability was found in the MEP amplitudes of the FCR muscle, with responses inhibited and facilitated from static values in the extension and flexion phases, respectively. The results indicated that at higher frequencies of movement there was greater modulation in pathway excitability. Paired-pulse TMS (sub-threshold conditioning) at short interstimulus intervals revealed modulations in the extent of inhibition in MEP amplitude at high movement frequencies. In the APE muscle, there was some evidence of phasic modulations of response amplitude, although the effects were less marked than those observed in FCR. It is speculated that these modulatory effects are mediated via Ia afferent pathways and arise as a consequence of the induced forearm muscle shortening and lengthening. Although the level at which this input influences the corticomotoneuronal pathway is difficult to discern, a contribution from cortical regions is suggested. (C) 2001 Published by Elsevier Science B.V.

DNA and chromosomal damage in response to intermittent extremely low-frequency magnetic fields.

Considerable controversy still exists as to whether electric and magnetic fields (MF) at extremely low frequencies are genotoxic to humans. The aim of this study was to test the ability of alternating magnetic fields to induce DNA and chromosomal damage in primary human fibroblasts. Single- and double-strand breaks were quantified using the alkaline comet assay and the gammaH2AX-foci assay, respectively. Chromosomal damage was assayed for unstable aberrations, sister chromatid exchange and micronuclei. Cells were exposed to switching fields - 5min on, 10min off - for 15h over the range 50-1000microT. Exposure to ionizing radiation was used as a positive-effect calibration. In this study two separate MF exposure systems were used. One was based on a custom-built solenoid coil system and the other on a commercial system almost identical to that used in previous studies by the EU REFLEX programme. With neither system could DNA damage or chromosomal damage be detected as a result of exposure of fibroblasts to switching MF. The sensitive gammaH2AX assay could also not detect significant DNA damage in the MF-exposed fibroblasts, although the minimum threshold for this assay was equivalent to an X-ray dose of 0.025Gy. Therefore, with comparable MF parameters employed, this study could not confirm previous studies reporting significant effects for both the alkaline and neutral comet assays and chromosomal aberration induction.

Humour: Stylistic Approaches

An important focus in contemporary stylistics has been on the connections between style and verbal humor, and this article charts the ways in which stylisticians have used a variety of linguistic models to analyze humorous discourse. The idea of stylistic incongruity is identified as being especially important in triggering the humor reflex. The principle of incongruity applies to any level of language or discourse, as is illustrated here by examples of puns and related forms of humor as well as by incongruities that are more to do with mismatches between text and discourse context. The principle of incongruity is also aligned with the concept of irony, through which a number of points are made about the stylistic analysis of both parody and satire.

Nociception or pain in a decapod crustacean?

Nociception is the ability to perceive a noxious stimulus and react in a re flexive manner and occurs across a wide range of taxa. However, the ability to experience the associated aversive sensation and feeling, known as pain, is not widely accepted to occur in nonvertebrates. We examined the responses of a decapod crustacean, the prawn, Palaemon elegans, to different noxious stimuli applied to one antenna to assess reflex responses (nociception) and longer-term, specifically directed behavioural responses that might indicate pain. We also examined the effects of benzocaine, a local anaesthetic, on these responses. Noxious stimuli elicited an immediate reflex tail flick response, followed by two prolonged activities, grooming of the antenna and rubbing of the antenna against the side of the tank, with both activities directed specifically at the treated antenna. These responses were inhibited by benzocaine; however, benzocaine did not alter general swimming activity and thus the decline in grooming and rubbing is not due to general anaesthesia. Mechanical stimulation by pinching also resulted in prolonged rubbing, but this was not inhibited by benzocaine. These results indicate an awareness of the location of the noxious stimuli, and the prolonged complex responses indicate a central involvement in their organization. The inhibition by a local anaesthetic is similar to observations on vertebrates and is consistent with the idea that these crustaceans can experience pain.

Motivational trade-offs and potential pain experience in hermit crabs

One criterion of pain experience is that the emotional response to pain may be traded-off against other motivational requirements. This was tested in hermit crabs, housed in either preferred or unpreferred species of shells, by subjecting their abdomens to electric shocks of gradually increasing intensity. The first observable response was not affected by shell species but those in preferred shells evacuated at a higher shock level than those in poor quality shells. Thus, they seem to trade-off the requirement to retain a high quality shell with that of avoidance of the noxious stimulus. Some crabs returned to their shells and those that got back into the preferred species did so with less probing of the aperture before getting in and subsequently thrust their abdomen in and out less often in further investigation, thus confirming their shell species preference. Not all crabs returned to the vicinity of the shell and some attempted to climb the wall of the experimental chamber. Others engaged in shell rapping as if in a fight and grooming of the abdomen was noted. These findings are consistent with the idea of a pain experience rather than a nociceptive reflex. (C) 2009 Elsevier B.V. All rights reserved.

Line-profile tomography of exoplanet transits - II. A gas-giant planet transiting a rapidly rotating A5 star

Most of our knowledge of extrasolar planets rests on precise radial-velocity measurements, either for direct detection or for confirmation of the planetary origin of photometric transit signals. This has limited our exploration of the parameter space of exoplanet hosts to solar- and later-type, sharp-lined stars. Here we extend the realm of stars with known planetary companions to include hot, fast-rotating stars. Planet-like transits have previously been reported in the light curve obtained by the SuperWASP survey of the A5 star HD15082 (WASP-33 V = 8.3, v sini = 86 km s-1). Here we report further photometry and time-series spectroscopy through three separate transits, which we use to confirm the existence of a gas-giant planet with an orbital period of 1.22d in orbit around HD15082. From the photometry and the properties of the planet signal travelling through the spectral line profiles during the transit, we directly derive the size of the planet, the inclination and obliquity of its orbital plane and its retrograde orbital motion relative to the spin of the star. This kind of analysis opens the way to studying the formation of planets around a whole new class of young, early-type stars, hence under different physical conditions and generally in an earlier stage of formation than in sharp-lined late-type stars. The reflex orbital motion of the star caused by the transiting planet is small, yielding an upper mass limit of 4.1MJupiter on the planet. We also find evidence of a third body of substellar mass in the system, which may explain the unusual orbit of the transiting planet. In HD 15082, the stellar line profiles also show evidence of non-radial pulsations, clearly distinct from the planetary transit signal. This raises the intriguing possibility that tides raised by the close-in planet may excite or amplify the pulsations in such stars.

Future Directions in Treating Cough

Cough is a common and troublesome symptom that can be difficult to treat. New therapeutic options that are safe and more effective than those currently available are needed. In this article, the authors offer opinion on future directions in the treatment of cough, with a particular emphasis on the clinical syndrome associated with cough reflex hypersensitivity. In addition, the article provides an overview of some of the diagnostic technologies and promising drug targets likely to emerge from current clinical and scientific endeavor.

Pain and suffering in invertebrates?

All animals face hazards that cause tissue damage and most have nociceptive reflex responses that protect them from such damage. However, some taxa have also evolved the capacity for pain experience, presumably to enhance longterm protection through behavior modification based on memory of the unpleasant nature of pain. In this article I review various criteria that might distinguish nociception from pain. Because nociceptors are so taxonomically widespread, simply demonstrating their presence is not sufficient. Furthermore, investigation of the central nervous system provides limited clues about the potential to experience pain. Opioids and other analgesics might indicate a central modulation of responses but often peripheral effects could explain the analgesia; thus reduction of responses by analgesics and opioids does not allow clear discrimination between nociception and pain. Physiological changes in response to noxious stimuli or the threat of a noxious stimulus might prove useful but, to date, application to invertebrates is limited. Behavior of the organism provides the greatest insights. Rapid avoidance learning and prolonged memory indicate central processing rather than simple reflex and are consistent with the experience of pain. Complex, prolonged grooming or rubbing may demonstrate an awareness of the specific site of stimulus application. Tradeoffs with other motivational systems indicate central processing, and an ability to use complex information suggests sufficient cognitive ability for the animal to have a fitness benefit from a pain experience. Available data are consistent with the idea of pain in some invertebrates and go beyond the idea of just nociception but are not definitive. In the absence of conclusive data, more humane care for invertebrates is suggested.

Brain activity during ankle proprioceptive stimulation predicts balance performance in young and older adults

Proprioceptive information from the foot/ankle provides important information regarding body sway for balance control, especially in situations where visual information is degraded or absent. Given known increases in catastrophic injury due to falls with older age, understanding the neural basis of proprioceptive processing for balance control is particularly important for older adults. In the present study, we linked neural activity in response to stimulation of key foot proprioceptors (i.e., muscle spindles) with balance ability across the lifespan. Twenty young and 20 older human adults underwent proprioceptive mapping; foot tendon vibration was compared with vibration of a nearby bone in an fMRI environment to determine regions of the brain that were active in response to muscle spindle stimulation. Several body sway metrics were also calculated for the same participants on an eyes-closed balance task. Based on regression analyses, multiple clusters of voxels were identified showing a significant relationship between muscle spindle stimulation-induced neural activity and maximum center of pressure excursion in the anterior-posterior direction. In this case, increased activation was associated with greater balance performance in parietal, frontal, and insular cortical areas, as well as structures within the basal ganglia. These correlated regions were age- and foot-stimulation side-independent and largely localized to right-sided areas of the brain thought to be involved in monitoring stimulus-driven shifts of attention. These findings support the notion that, beyond fundamental peripheral reflex mechanisms, central processing of proprioceptive signals from the foot is critical for balance control.

Clinical cough II:therapeutic treatments and management of chronic cough

Chronic cough is a common and frequently disruptive symptom which can be difficult to treat with currently available medicines. Asthma/eosinophilic airway disease and gastro-oesophageal reflux disease are most commonly associated with chronic cough but it may also trouble patients with chronic obstructive pulmonary disease, pulmonary fibrosis and lung cancer. Over the last three decades there have been a number of key advances in the clinical approach to cough and a number of international guidelines on the management of cough have been developed. Despite the undoubted benefit of such initiatives, more effective treatments for cough are urgently needed. The precise pathophysiological mechanisms of chronic cough are unknown but central to the process is sensitization (upregulation) of the cough reflex. One well-recognized clinical consequence of this hypersensitive state is bouts of coughing triggered by apparently trivial provocation such as scents and odours and changes in air temperature. The main objective of new treatments for cough would be to identify ways to downregulate this heightened cough reflex but yet preserve its crucial role in protecting the airway. The combined efforts of clinicians, scientists and the pharmaceutical industry offer most hope for such a treatment breakthrough. The aim of this chapter is to provide some rationale for the current treatment recommendations and to offer some reflections on the management of patients with chronic cough.

Does idiopathic cough exist?

Despite a meticulous protocol involving diagnostic testing and trials of empirical therapy, there may be no obvious cause for a chronic cough in up to 42% of cases referred for specialist evaluation. In some cases, failure to consider causes that include the asthma/eosinophilic airway syndromes such as eosinophilic bronchitis and atopic cough, or nonacid gastroesophageal reflux disease may explain diagnostic failure. However, a distinct group of patients may be considered to have true idiopathic cough. Current published evidence suggests a certain patient phenotype, namely, middle-aged females with prolonged nonproductive cough and cough reflex hypersensitivity. Almost nothing else is known about this clinical entity and currently no specific therapy exists.

Shock avoidance by discrimination learning in the shore crab (Carcinus maenas) is consistent with a key criterion for pain

Nociception allows for immediate reflex withdrawal whereas pain allows for longer-term protection via rapid learning. We examine here whether shore crabs placed within a brightly lit chamber learn to avoid one of two dark shelters when that shelter consistently results in shock. Crabs were randomly selected to receive shock or not prior to making their first choice and were tested again over 10 trials. Those that received shock in trial 2, irrespective of shock in trial 1, were more likely to switch shelter choice in the next trial and thus showed rapid discrimination. During trial 1, many crabs emerged from the shock shelter and an increasing proportion emerged in later trials, thus avoiding shock by entering a normally avoided light area. In a final test we switched distinctive visual stimuli positioned above each shelter and/or changed the orientation of the crab when placed in the chamber for the test. The visual stimuli had no effect on choice, but crabs with altered orientation now selected the shock shelter, indicating that they had discriminated between the two shelters on the basis of movement direction. These data, and those of other recent experiments, are consistent with key criteria for pain experience and are broadly similar to those from vertebrate studies. © 2013. Published by The Company of Biologists Ltd.

Evidence for pain in decapod crustaceans

Vast numbers of decapods are used in human food and currently subject to extreme treatments and there is concern that they might experience pain. If pain is indicated then a positive change in the care afforded to this group has the potential to produce a major advance in animal welfare. However, it is difficult to determine pain in animals. The vast majority of animal phyla have a nociceptive ability that enables them to detect potential or actual tissue damage and move away by a reflex response. In these cases there is no need to assume an unpleasant feeling that we call pain. However, various criteria have been proposed that might indicate pain rather than simple nociception. Here, with respect to decapod crustaceans, four such criteria are discussed: avoidance learning, physiological responses, protective motor reactions and motivational trade-offs. The evidence from various experiments indicates that all four criteria are fulfilled and the data are thus consistent with the idea of pain. The responses cannot be explained by nociception alone but, it is still difficult to state categorically that pain is experienced by decapods. However, the evidence is as strong for this group as it is for fish but the idea that fish experience pain has broader acceptance than does the idea of decapod pain. A taxonomic bias is evident in the evaluation of experimental data. © 2012 Universities Federation for Animal Welfare.

The sympathetic release test: a test used to assess thermoregulation and autonomic control of blood flow

When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the subject is gently heated by placing the feet and calves in a commercially available foot warming pouch or immersing the feet and calves in warm water and wrapping the subject in blankets. Skin blood flow is estimated from measurements of skin temperature in the fingers. Normally skin temperature of the fingers is 65-75 degrees F in cool conditions (environmental temperature: 59-68 degrees F) and rises to 85-95 degrees F during body heating. Deviations in this pattern may mean that there is abnormal sympathetic vasoconstrictor control of skin blood flow. Abnormal skin blood flow can substantially impair an individual's ability to thermoregulate and has important clinical implications. During whole body heating, the skin temperature from three different skin sites is monitored and oral temperature is monitored as an index of core temperature. Students determine the fingertip temperature at which the reflex release of sympathetic activity occurs and its maximal attainment, which reflects the vasodilating capacity of this cutaneous vascular bed. Students should interpret typical sample data for certain clinical conditions (Raynaud's disease, peripheral vascular disease, and postsympathectomy) and explain why there may be altered skin blood flow in these disorders.

Pharmacological studies of 8-OH-DPAT-induced pupillary dilation in anesthetized rats

Serotonin (5-HT) receptor agonists have been reported to produce mydriasis in mice, and miosis in rabbits and humans. However, the underlying mechanisms for this action are unclear. This study was undertaken in an attempt to explore the mechanism by which 5-HT receptors are involved in the modulation of pupillary size in pentobarbital-anesthetized rats. Intravenous administration of the 5-HT receptor agonist, (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.003-3 mg/kg), elicited dose-dependent pupillary dilation, which was not affected by section of the preganglionic cervical sympathetic nerve. 8-OH-DPAT-elicited mydriatic responses were attenuated by the selective 5-HT receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2- pyridinylcyclohexanecarboxamide maleate (WAY 100635; 0.3-1 mg/kg, i.v.), as well as by the selective a -adrenoceptor antagonist, (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13,13a-dechydro-3-methoxy-12- (ethylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridine hydrochloride (RS 79948; 0.3 mg/kg, i.v.), but not by the selective a -adrenoceptor antagonist, prazosin (0.3 mg/kg, i.v.). Mydriatic responses elicited by the a -adrenoceptor agonist, guanabenz (0.003-0.3 mg/kg, i.v.), were not antagonized by WAY 100635 (0.3-1 mg/kg, i.v.). To determine whether central nervous system (CNS) 5-HT receptors, like a -adrenoceptors, are involved in reflex mydriasis, voltage response curves of pupillary dilation were constructed by stimulation of the sciatic nerve in anesthetized rats. WAY 100635 (1 mg/kg, i.v.) did not antagonize the evoked reflex mydriasis, which, however, was blocked by RS 79948 (0.3 mg/kg, i.v.). Taken together, these results suggest that 8-OH-DPAT produces pupillary dilation in anesthetized rats by stimulating CNS 5-HT receptors, which in turn trigger the release of norepinephrine, presumably from the locus coeruleus. The latter reduces parasympathetic neuronal tone to the iris sphincter muscle by stimulation of postsynaptic a - adrenoceptors within the Edinger-Westphal nucleus. Unlike a - adrenoceptors, 5-HT receptors in the CNS do not mediate reflex mydriasis evoked by sciatic nerve stimulation. © 2004 Elsevier B.V. All rights reserved.