On-line action monitoring of response execution: An electrophysiological study.

In between-hand choice-RT-tasks, small incorrect EMG activations occurring before the correct response ("partial errors") are assumed to reflect the detection, inhibition and correction of erroneous hand selection, revealing the existence of an action monitoring system, acting "on-line". Now, EMG activations of the correctly selected hand muscles, too small to reach the response threshold, may also occur before these hand muscles produce an overt correct response ("partial corrects"). We hypothesized that partial corrects reflect incorrect execution of correctly selected responses. We found 1) that response force was smaller on trials preceding a partial correct trial and 2) that the Error Negativity, a performance sensitive ERP, assumed to reveal "on-line" action monitoring, was larger for partial corrects than for correct trials. This also suggests that the competence of the action monitoring system is not restricted to selection errors but also extends to execution errors.

Modulation by the Noble Gas Helium of Tissue Plasminogen Activator: Effects in a Rat Model of Thromboembolic Stroke.

INTERVENTIONS: Helium has been shown to provide neuroprotection in mechanical model of acute ischemic stroke by inducing hypothermia, a condition shown by itself to reduce the thrombolytic and proteolytic properties of tissue plasminogen activator. However, whether or not helium interacts with the thrombolytic drug tissue plasminogen activator, the only approved therapy of acute ischemic stroke still remains unknown. This point is not trivial since previous data have shown the critical importance of the time at which the neuroprotective noble gases xenon and argon should be administered, during or after ischemia, in order not to block tissue plasminogen activator-induced thrombolysis and to obtain neuroprotection and inhibition of tissue plasminogen activator-induced brain hemorrhages. MEASUREMENTS AND MAIN RESULTS: We show that helium of 25-75 vol% inhibits in a concentration-dependent fashion the catalytic and thrombolytic activity of tissue plasminogen activator in vitro and ex vivo. In vivo, in rats subjected to thromboembolic brain ischemia, we found that intraischemic helium at 75 vol% inhibits tissue plasminogen activator-induced thrombolysis and subsequent reduction of ischemic brain damage and that postischemic helium at 75 vol% reduces ischemic brain damage and brain hemorrhages. CONCLUSIONS: In a clinical perspective for the treatment of acute ischemic stroke, these data suggest that helium 1) should not be administered before or together with tissue plasminogen activator therapy due to the risk of inhibiting the benefit of tissue plasminogen activator-induced thrombolysis; and 2) could be an efficient neuroprotective agent if given after tissue plasminogen activator-induced reperfusion.

Xenon Blocks Neuronal Injury Associated with Decompression.

Despite state-of-the-art hyperbaric oxygen (HBO) treatment, about 30% of patients suffering neurologic decompression sickness (DCS) exhibit incomplete recovery. Since the mechanisms of neurologic DCS involve ischemic processes which result in excitotoxicity, it is likely that HBO in combination with an anti-excitotoxic treatment would improve the outcome in patients being treated for DCS. Therefore, in the present study, we investigated the effect of the noble gas xenon in an ex vivo model of neurologic DCS. Xenon has been shown to provide neuroprotection in multiple models of acute ischemic insults. Fast decompression compared to slow decompression induced an increase in lactate dehydrogenase (LDH), a well-known marker of sub-lethal cell injury. Post-decompression administration of xenon blocked the increase in LDH release induced by fast decompression. These data suggest that xenon could be an efficient additional treatment to HBO for the treatment of neurologic DCS.

Linking EEG signals, brain functions and mental operations: Advantages of the Laplacian transformation.

Electroencephalography (EEG) is a very popular technique for investigating brain functions and/or mental processes. To this aim, EEG activities must be interpreted in terms of brain and/or mental processes. EEG signals being a direct manifestation of neuronal activity it is often assumed that such interpretations are quite obvious or, at least, straightforward. However, they often rely on (explicit or even implicit) assumptions regarding the structures supposed to generate the EEG activities of interest. For these assumptions to be used appropriately, reliable links between EEG activities and the underlying brain structures must be established. Because of volume conduction effects and the mixture of activities they induce, these links are difficult to establish with scalp potential recordings. We present different examples showing how the Laplacian transformation, acting as an efficient source separation method, allowed to establish more reliable links between EEG activities and brain generators and, ultimately, with mental operations. The nature of those links depends on the depth of inferences that can vary from weak to strong. Along this continuum, we show that 1) while the effects of experimental manipulation can appear widely distributed with scalp potentials, Laplacian transformation allows to reveal several generators contributing (in different manners) to these modulations, 2) amplitude variations within the same set of generators can generate spurious differences in scalp potential topographies, often interpreted as reflecting different source configurations. In such a case, Laplacian transformation provides much more similar topographies, evidencing the same generator(s) set, and 3) using the LRP as an index of response activation most often produces ambiguous results, Laplacian-transformed response-locked ERPs obtained over motor areas allow resolving these ambiguities.

Basics for sensorimotor information processing: some implications for learning.

In sensorimotor activities, learning requires efficient information processing, whether in car driving, sport activities or human-machine interactions. Several factors may affect the efficiency of such processing: they may be extrinsic (i.e., task-related) or intrinsic (i.e., subjects-related). The effects of these factors are intimately related to the structure of human information processing. In the present article we will focus on some of them, which are poorly taken into account, even when minimizing errors or their consequences is an essential issue at stake. Among the extrinsic factors, we will discuss, first, the effects of the quantity and quality of information, secondly, the effects of instruction and thirdly motor program learning. Among the intrinsic factors, we will discuss first the influence of prior information, secondly how individual strategies affect performance and, thirdly, we will stress the fact that although the human brain is not structured to function errorless (which is not new) humans are able to detect their errors very quickly and (in most of the cases), fast enough to correct them before they result in an overt failure. Extrinsic and intrinsic factors are important to take into account for learning because (1) they strongly affect performance, either in terms of speed or accuracy, which facilitates or impairs learning, (2) the effect of certain extrinsic factors may be strongly modified by learning and (3) certain intrinsic factors might be exploited for learning strategies.

Cost-efficient method and device for the study of stationary tissular gas bubble formation in the mechanisms of decompression sickness.

BACKGROUND: Current in vivo methods cannot distinguish between the roles of vascular and stationary tissular gas bubbles in the mechanisms of decompression sickness (DCS). NEW METHOD: To answer this question, we designed a normobaric-hyperbaric chamber for studying specifically the contribution of stationary tissular gas bubbles in the mechanisms of DCS in individually-superfused tissue samples. For validating our method, we investigated in rat brain slices exposed to 0.4MPa air absolute pressure whether fast decompression rate - the most important cause of cerebral DCS - may induce an increase of lactate dehydrogenase (LDH), a marker of cell injury, compared to slow decompression rate. RESULTS: We provide a technical description of our pressure chamber and show that fast decompression rate of 0.3MPamin(-1) induced a rapid and sustained increase of LDH release compared to slow compression rate of 0.01MPamin(-1) (P<0.0001). COMPARISON WITH EXISTING METHODS: There is no current method for studying stationary tissular gas bubbles. CONCLUSIONS: This report describes the first method for studying specifically in tissue samples the role of stationary tissular gas bubbles in the mechanisms of DCS. Advantageously, according to this method (i) biological markers other than LDH could be easily studied; (ii) tissue samples could be taken not only from the brain but also from any part of the animal's body known of interest in DCS research, allowing performing tissue compartment research, a major question in the physics and theory of decompression research; and (iii) histological studies could be performed from the tissue samples.

Effects of hyperbaric nitrogen-induced narcosis on response-selection processes.

Certain underwater circumstances carry risk of inert gas narcosis. Impairment of sensorimotor information processing due to narcosis, induced by normobaric nitrous oxide or high partial nitrogen pressure, has been broadly evidenced, by a lengthening of the reaction time (RT). However, the locus of this effect remains a matter of debate. We examined whether inert gas narcosis affects the response-selection stage of sensorimotor information processing. We compared an air normobaric condition with a hyperbaric condition in which 10 subjects were subjected to 6 absolute atmospheres of 8.33% O2 Nitrox. In both conditions, subjects performed a between-hand choice-RT task in which we explicitly manipulated the stimulus-response association rule. The effect of this manipulation (which is supposed to affect response-selection processes) was modified by inert gas narcosis. It is concluded, therefore, that response selection processes are among the loci involved in the effect of inert gas narcosis on information processing.

Argon prevents the development of locomotor sensitization to amphetamine and amphetamine-induced changes in mu opioid receptor in the nucleus accumbens.

Systemic administration of γ-amino-butyric acid type A (GABA-A) and benzodiazepine receptor agonists has been reported to block the development of locomotor sensitization to amphetamine. Here, we investigated whether the non-anesthetic noble gas argon, shown to possess agonistic properties at these receptors, may block the acquisition of amphetamine-induced locomotor sensitization and mu opioid receptor activation in the nucleus accumbens. Rats were pretreated with saline solution or amphetamine (1 mg/kg) from day 1 to day 3 and then exposed, immediately after injection of amphetamine, to medicinal air or argon at 75 vol% (with the remainder being oxygen). After a 3-day period of withdrawal, rats were challenged with amphetamine on day 7. Rats pretreated with amphetamine and argon had lower locomotor activity (U = 5, P < 0.005) and mu opioid receptor activity in the nucleus accumbens (U = 0, P < 0.001) than rats pretreated with amphetamine and air. In contrast, argon had effect on locomotor and mu receptor activity neither in rats pretreated with saline and challenged with amphetamine (acute amphetamine) nor in rats pretreated and challenged with saline solution (controls). These results indicate that argon inhibits the development of both locomotor sensitization and mu opioid receptor activation induced by repeated administration of amphetamine.

Submarine rescue decompression procedure from hyperbaric exposures up to 6 bar of absolute pressure in man: effects on bubble formation and pulmonary function.

Recent advances in submarine rescue systems have allowed a transfer under pressure of crew members being rescued from a disabled submarine. The choice of a safe decompression procedure for pressurised rescuees has been previously discussed, but no schedule has been validated when the internal submarine pressure is significantly increased i.e. exceeding 2.8 bar absolute pressure. This study tested a saturation decompression procedure from hyperbaric exposures up to 6 bar, the maximum operating pressure of the NATO submarine rescue system. The objective was to investigate the incidence of decompression sickness (DCS) and clinical and spirometric indices of pulmonary oxygen toxicity. Two groups were exposed to a Nitrogen-Oxygen atmosphere (pO2 = 0.5 bar) at either 5 bar (N = 14) or 6 bar (N = 12) for 12 h followed by 56 h 40 min resp. 60 h of decompression. When chamber pressure reached 2.5 bar, the subjects breathed oxygen intermittently, otherwise compressed air. Repeated clinical examinations, ultrasound monitoring of venous gas embolism and spirometry were performed during decompression. During exposures to 5 bar, 3 subjects had minor subjective symptoms i.e. sensation of joint discomfort, regressing spontaneously, and after surfacing 2 subjects also experienced joint discomfort disappearing without treatment. Only 3 subjects had detectable intravascular bubbles during decompression (low grades). No bubbles were detected after surfacing. About 40% of subjects felt chest tightness when inspiring deeply during the initial phase of decompression. Precordial burning sensations were reported during oxygen periods. During decompression, vital capacity decreased by about 8% and forced expiratory flow rates decreased significantly. After surfacing, changes in the peripheral airways were still noticed; Lung Diffusion for carbon monoxide was slightly reduced by 1% while vital capacity was normalized. The procedure did not result in serious symptoms of DCS or pulmonary oxygen toxicity and may be considered for use when the internal submarine pressure is significantly increased.

The N-40: an electrophysiological marker of response selection.

A frontocentral electrophysiological wave occurring before the response, the N-40, has been reported in response choice situations compared to no-choice situations. This was interpreted as reflecting response selection. The gradual sensitivity of the N-40 to the demands put on response choice was tested by manipulating stimulus-response (S-R) congruence so as to influence response selection processes. After Laplacian transformation, an N-40 clearly emerged and was larger for incongruent (more demanding) than for congruent (less demanding) S-R associations. The N-40, which possibly reflects SMA activation, thus provides information about the implementation of response selection in the brain.

To err or to guess: an ERP study on the source of errors.

Given the large contribution of human error in the failure of complex systems, understanding the source of errors is an important issue. It has been proposed that, in speeded situations, responses biases induce subjects to guess which response will be required. When the guess turns out to be wrong, a fast guess error occurs. In unbiased conditions the possible contribution of fast guess errors remains an open question. We used a response-locked event-related potential (N-40), assumed to reveal the presence of a response selection process during the reaction time, to probe the presence of a response selection in biased and unbiased situations. The N-40 was present without response bias but absent in biased situations. This lends physiological support to the idea that, in a priming paradigm as used here, most errors in biased conditions are fast guesses whereas most errors result from inappropriate response selections in unbiased conditions. This reveals different sources of errors.

Sleep deprivation affects the sensitivity of proactive and reactive action monitoring: a behavioural and ERP analysis.

We studied the impact of sleep deprivation on action monitoring. Each participant performed a Simon task after a normal night of sleep and after 26 h of awakening. Reaction time (RT) distributions were analyzed and the sensitivity of the error negativity (Ne/Ne like) to response correctness was examined. Results showed that (1) the Simon effect persisted for the longest RTs only after sleep deprivation and (2) the sensitivity of the Ne/Ne like to correctness decreased after sleep deprivation, especially on incongruent trials. This suggests that after sleep deprivation (1) the ability to inhibit prepotent response tendencies is impaired and (2) the sensitivity of a response monitoring system as revealed by the error negativity is less sensitive to performance. In conclusion, action monitoring was affected by sleep deprivation as revealed by distributional analyses and the sensitivity of the Ne/Ne like to performance, which may be attributed to the fragility of prefrontal structures to sleep deprivation.

Neuroprotective role of the TREK-1 channel in decompression sickness.

Nitrogen supersaturation and bubble formation can occur in the vascular system after diving, leading to death and nervous disorders from decompression sickness (DCS). Bubbles alter the vascular endothelium, activate platelets, and lead to focal ischemia with neurological damage mediated by the mechanosensitive TREK-1 neuronal potassium ion channel that sets pre- and postsynaptic resting membrane potentials. We report a neuroprotective effect associated with TREK-1. C57Bl6 mice were subjected to decompression from a simulated 90 msw dive. Of 143 mice that were wild type (WT) for TREK-1, 51.7% showed no DCS, 27.3% failed a grip test, and 21.0% died. Of 88 TREK-1 knockouts (KO), 26.1% showed no DCS, 42.0% failed a grip test, and 31.8% died. Mice that did not express TREK-1 had lower DCS resistance and were more likely to develop neurological symptoms. We conclude that the TREK-1 potassium channel was neuroprotective for DCS.

Executive control and response expectancy: a Laplacian ERP study.

The event-related potential called "Error Negativity" (Ne, ERN), which appears when subjects commit errors in choice reaction time tasks, is a marker of response monitoring. By introducing a response probability bias, we show that the Ne is sensitive to response expectancy. We further show that the small negativity evoked by correct responses (Ne-like, CRN) is also sensitive to response expectancy: On unexpected responses, the former decreases while the latter increases to such an extent that the amplitudes of the two components are in the same range of magnitude. Although the sensitivity of the Ne to response expectancy is compatible with the current models accounting for the Ne, the common sensitivity of the Ne and the Ne-like supports the idea that they reflect functionally similar monitoring processes.

Motor inhibition and response expectancy: a Laplacian ERP study.

In between-hand choice reaction time tasks, the motor cortex involved in the required response (contralateral) has been shown to be activated while the motor cortex involved in the non-required response (ipsilateral) has been shown to be inhibited. The aim of the present study was to test the hypothesis that ipsilateral inhibition reflects an active mechanism aimed at preventing errors. To this end, the risk of committing errors in between-hand choice reaction time tasks was manipulated by introducing a response probability bias. The surface Laplacian transforms of electroencephalographic waves recorded over the motor cortices, contralateral and ipsilateral to the responding hand were compared. Results showed that contralateral activation was not modulated by the risk of committing errors while ipsilateral inhibition was sensitive to this risk in a gradual manner: the higher the risk, the stronger the inhibition.