Aversive, positive prediction error (+PE) provides a mechanism to update and increase future fear to uncertain threat predictors. The ventrolateral periaqueductal grey (vlPAG) has been offered as a neural locus for +PE computation. Yet, a causal demonstration of vlPAG +PE activity to update fear remains elusive. We devised a fear discrimination procedure in which a danger cue predicts shock deterministically and an uncertainty cue predicts shock probabilistically, requiring prediction errors to achieve an appropriate fear response. Recording vlPAG single‐unit activity during fear discrimination in Long‐Evans rats, we reveal activity related to shock is consistent with +PE and updates subsequent fear to uncertainty at the trial level. We further demonstrate that vlPAG inhibition during shock selectively decreases future fear to uncertainty, but not danger, and temporal emergence of this effect is consistent with single‐unit activity. These findings provide causal evidence that vlPAG +PE is necessary for fear updating. 相似文献
Ricin is a potential bioweapon that could be used against civilian and military personnel. Aerosol exposure is the most likely route of contact to ricin toxin that will result in the most severe toxicity. Early recognition of ricin exposure is essential if specific antidotes are to be applied. Initial diagnosis will most likely be syndromic, i.e., fitting clinical and laboratory signs into a pattern which then will guide the choice of more specific diagnostic assays and therapeutic interventions. We have studied the pathology of ricin toxin in rhesus macaques exposed to lethal and sublethal ricin aerosols. Animals exposed to lethal ricin aerosols were followed clinically using telemetry, by clinical laboratory analyses and by post-mortem examination. Animals exposed to lethal aerosolized ricin developed fever associated with thermal instability, tachycardia, and dyspnea. In the peripheral blood a marked neutrophilia (without immature bands) developed at 24 h. This was accompanied by an increase in monocytes, but depletion of lymphocytes. Red cell indices indicated hemoconcentration, as did serum chemistries, with modest increases in sodium and blood urea nitrogen (BUN). Serum albumin was strikingly decreased. These observations are consistent with the pathological observations of fluid shifts to the lungs, in the form of hemorrhages, inflammatory exudates, and tissue edema. In macaques exposed to sublethal aerosols of ricin, late pathologic consequences included chronic pulmonary fibrosis, likely mediated by M2 macrophages. Early administration of supportive therapy, specific antidotes after exposure or vaccines prior to exposure have the potential to favorably alter this outcome. 相似文献
Objective: To evaluate the utility of vacuum-pressed, BruxChecker® sheets for the diagnosis of sleep bruxism.
Methods: Twenty subjects participated in this study. Tooth contact during sleep was recorded using a 0.1 mm-thick polyvinyl chloride sheet called BruxChecker®. The area of the BruxChecker® in which the red dye was removed was measured. In addition, the EMG activity of the masseter muscle during sleep was recorded. The numbers of bruxism bursts and episodes were counted, and their correlations with the peeled area of the red dye on the BruxChecker® were evaluated.
Results: The number of bruxism bursts and episodes/hr significantly correlated with the peeled area at all cut-off values. The peeled area significantly correlated with the number of phasic type bruxism episodes but not with tonic or mixed type bruxism episodes.
Discussion: Since the BruxChecker® peeled area reflected phasic type sleep bruxism, the sheets may be useful in sleep bruxism screening. 相似文献
Vincristine, a widely used chemotherapeutic agent for treating different cancer, often induces severe peripheral neuropathic pain. A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia. However, mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood. In the present study, we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity. Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting (RA) mechanically-activated (MA) currents in rat dorsal root ganglion (DRG) neurons. We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension (SPMT) of these cells following vincristine treatment. Reducing SPMT of DRG neurons by cytochalasin D (CD), a disruptor of the actin filament, abolishes vincristine-induced potentiation of PIEZO2 MA currents, and suppresses vincristine-induced mechanical hypersensitivity in rats. Collectively, enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristine-induced mechanical allodynia and hyperalgesia in rats. Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity. 相似文献
Segregating streams of sounds from sources in complex acoustic scenes is crucial for perception in real world situations. We analyzed an objective psychophysical measure of stream segregation obtained while simultaneously recording forebrain neurons in the European starlings to investigate neural correlates of segregating a stream of A tones from a stream of B tones presented at one-half the rate. The objective measure, sensitivity for time shift detection of the B tone, was higher when the A and B tones were of the same frequency (one stream) compared with when there was a 6- or 12-semitone difference between them (two streams). The sensitivity for representing time shifts in spiking patterns was correlated with the behavioral sensitivity. The spiking patterns reflected the stimulus characteristics but not the behavioral response, indicating that the birds’ primary cortical field represents the segregated streams, but not the decision process.In the natural environment, sounds produced by multiple sources must be segregated to retrieve the information that they convey. At the same time, sequential sound signals from an individual source must be integrated to perform the analysis. The auditory system of humans, as well as that of many vertebrate species, is able to parse signals from multiple sources into separate sets of “auditory streams” based on the signals’ spectral and/or temporal profiles (1–5). Attention affects auditory streaming, and imaging studies have shown that it modulates brain activity during the analysis of segregated streams of signals (6–13). Although to date most psychophysical and imaging studies on auditory streaming have investigated attentive, actively listening human subjects, animal studies have only investigated passively listening subjects not involved in a specific task requiring stream segregation (14–18). Better insight into the cellular mechanisms underlying auditory streaming can be gained by investigating neuronal responses in an actively listening animal.Here we present neuronal response data obtained from an actively listening bird, the European starling (Sturnus vulgaris), performing a task that has been shown in human subjects to be more easily mastered if signals are integrated into a single auditory stream rather than separated into two different streams (19–21). Behavioral performance in such tasks can serve as an objective measure for stream segregation, and correlated neuronal response measures can serve to elucidate the mechanisms underlying the perceptual effects. Behavioral responses indicating auditory stream segregation of pure tone sequences in the European starling have been reported previously (22). Because larger frequency differences lead to better stream segregation both in the physiological response and in perception in a similar way as in humans (16, 22), the European starling is a suitable animal model for studying the central processes involved in auditory scene analysis.We investigated the detection of irregular timing in a sequence of signals for which the auditory system is more sensitive if the signals are perceived as forming a single stream rather than being perceptually segregated into different streams (20, 21, 23, 24). We recorded multiunit activity in the songbird forebrain in an area (field L complex) that is homologous to the mammalian primary auditory cortex while presenting sequences of pure tone ABA- triplet stimuli (i.e., ABA-ABA-..., ref. 1). Neural responses were recorded while the bird behaviorally reported a shift in the temporal position of the B tone in the triplet. Based on psychophysical studies in humans, we expected shift detection thresholds to be smaller if the A and B tones were perceived as belonging to one stream rather than to two separate streams. Parallel measurements of neuronal responses and the bird’s perception, as reflected in behavioral responses, allowed us to correlate the sensitivity of the neuronal representation with behavioral sensitivity on a trial-by-trial basis. We applied a similar metric to perception and neuronal representation using signal detection theory and receiver operating characteristic (ROC) analysis. By comparing neuronal responses when the animal detected versus failed to detect a given time shift, we evaluated whether neural activity in the starling’s primary cortical area reflects the stimulus characteristics or whether it also indicates the bird’s perception, as evidenced by its behavioral decisions. 相似文献
Continuous ECG recording has been carried out for at least 24 h in 27 patients suffering from cluster headache. During the study a total of 84 attacks occurred in 25 of the 27 patients who took part. A computerized analysis of the heart rate changes accompanying attacks showed the following: (i) an increase in heart rate at the onset of attacks; the degree of this increase being dependent on the heart rate before attacks, (ii) a relative decrease in heart rate and increased variations in heart rate during attacks, (iii) a relative increase in heart rate at the end of attacks, and (iv) a relative decrease in heart rate after attacks. Five patients (18.5%) showed ECG rhythm disturbances: two frequent premature ventricular beats, one transient attacks of atrial fibrillation, one first degree atrio-ventricular block, and one patient sino-atrial block. 相似文献
Objective. To develop an algorithm that corrects pulmonary artery pressure signals of ventilated patients for the respiration artifact. The algorithm should test the validity of the pulmonary pressure signal and differentiate between the cyclic respiration artifact and true measurement artifacts.Methods. The shape of each pulmonary pressure beat is described by eight characteristic features, including mean pressure value and the systolic and diastolic timing and pressure values. The features are corrected for the respiration artifact by fitting them in a least-squares sense on the first and second harmonica of the ventilator frequency. The corrected features are used by a signal validation algorithm, which adds a validity flag to each pressure beat. The validation algorithm rejects pressure beats with sudden changes in their shape but adapts itself when the changes persist.Results. The performance of the correction and validation technique was evaluated using pulmonary artery pressure signals of 30 patients who were scheduled for open heart surgery. The algorithm correctly recognized as invalid data those pressure signals disturbed by coagulation, surgical manipulations, or flushes of the pressure line. The algorithm marked on average 77 ± 11 % of the pulmonary pressure beats as valid.Conclusions. The validation algorithm marked sufficient pressure beats as valid to update a trend display every 5 sec. The correction algorithm enabled the validation algorithm to differentiate between true measurement artifacts and the respiration artifact. 相似文献