The use of an unpleasant sound as an unconditional stimulus in a human aversive Pavlovian conditioning procedure

Ethical considerations can limit the use of traditional unconditional stimuli (US), such as electric shock and loud tones, when used in a human aversive Pavlovian conditioning procedure. The risk of the US causing pain or excessive anxiety is a particular concern when testing sensitive populations such as children, the elderly, and those with psychological or neurodevelopmental disorders. Two experiments used a differential conditioning procedure to determine whether an unpleasant sound (metal scraping on slate) could support the acquisition and extinction of conditioned responses to the same extent as either electric shock or a 100 dB(A) tone US. Experiment 1 (N=48) demonstrated equivalent or superior conditioning effects for the signal-based learning measures of US expectancy, skin conductance responses, and heart rate. Experiment 2 (N=57) yielded similar outcomes in the affective-based learning measures of startle blink modulation and pleasantness ratings. The results support the use of an unpleasant sound as a US in human Pavlovian conditioning experiments.     

The use of an unpleasant sound unconditional stimulus in an aversive conditioning procedure with 8- to 11-year-old children

The study of aversive Pavlovian conditioning in children can contribute to our understanding of how fears are acquired and extinguished during development. However, methodological issues hamper further research because of ethical and procedural concerns regarding the use of traditional aversive unconditional stimuli (USs) and no established method to measure trial-by-trial changes in the child's expectancy of the US. The present experiment used geometric shape conditional stimuli (CSs) and an unpleasant sound US with 8- to 11-year-old children. Reliable acquisition and extinction were observed with first, second, and third interval skin conductance responses, on-line expectancy judgments, and post-conditioning subjective ratings of pleasantness and arousal. The experiment confirms the novel use of an unpleasant sound of metal scraping on slate as a US in aversive conditioning with children. The methods have the potential to facilitate the ethical conduct of aversive conditioning research in children using psychophysiological, affective, and self-report expectancy measures.     

Evaluating feeding as unconditioned stimulus for conditioning of an endocrine effect in Nile tilapia

This study tested the adequacy of feeding as an unconditioned stimulus (US) to condition an endocrine response (plasma cortisol increase) in the cichlid fish Nile tilapia (Oreochromis niloticus). In a first study, conditioning was confirmed in grouped fish in the only experiment using single-held Nile tilapia. In this test a conditioned stimulus (CS - aeration off) was associated with a stressor (air emersion for 2 min- US). We then assessed whether several events of paired CS-US resulted in a conditioned endocrine response (CR), in this case an increase in plasma cortisol after presentation of the CS only. Before testing feeding as US, the postprandial or social holding condition for feeding effects on cortisol levels was tested. Nile tilapia showed increased cortisol after feeding associated to social context (grouped fish), but not to food only (single-held fish). In a third study, feeding was tested as US in an experiment similar to the first study but an increase in feeding-induced cortisol could not be conditioned. The absence of CR suggests that the stressor affects acquisition of this response, which may be a consequence of stimulus intensity or biological relevance. This study expands the recently reported Pavlovian conditioning paradigm for endocrine response in fish.     

Reaction to omission of reward in an operant conditioning situation in adult rats after undernutrition early in life

Rats were undernourished during the suckling and early post-weaning periods and were then fed a good quality diet ad lib from 43 to 100 days, prior to behavioural testing. Male, previously undernourished and control rats were exposed to a number of operant conditioning tasks involving partial or total omission of a food reward. In the first condition each lever press response was rewarded for five sessions, and then two sessions were given in which food was discontinued. Both groups showed an initial increase in response rate upon omission of reward, but did not behave differently. Following this, subjects were trained for 38 sessions on a fixed-interval 60 sec schedule. Under this schedule no differences were found between the groups in either post-reinforcement pause or response rate. After this, subjects received 10 sessions in which half the rewards at the end of the 60 sec intervals were randomly replaced by brief blackouts. Both groups of subjects paused for longer after food than after blackout but differed in that response rates of previously undernourished rats after both food and blackout increased markedly over sessions whereas those of the controls did not. Finally food was discontinued and both groups showed a rapid drop in response rate, as well as spontaneous recovery effects. The above results, in conjunction with those from other studies indicate that reward omission per se dose not produce higher than normal response rates in previously undernourished rats, but that unpredictable reward omission may do so.     

Psychophysiology of spider phobia in 8- to 12-year-old girls

The present investigation focused on late event-related potentials (ERPs) and facial electromyographic (EMG) activity in response to symptom provocation in 8- to 12-year-old spider phobic girls and compared results to those in non-fearful controls. Fourteen patients and 14 controls were presented with phobia-relevant, generally fear-inducing, disgust-inducing and affectively neutral pictures in an EEG/EMG session. ERPs were extracted in the time-windows 340-500 ms (P300) and 550-770 ms (late positive potential, LPP). Relative to controls, phobics showed enhanced amplitudes of P300 and LPP in response to spider pictures. This result is interpreted to reflect motivated attention to emotionally salient stimuli. Moreover, phobics showed enhanced average facial EMG activity of the levator labii and the corrugator supercilii in response to spider pictures, reflecting the negative valence and disgust relevance of spiders. Additionally, spider phobic girls relative to controls showed higher overall disgust proneness and heightened average facial EMG activity in both muscle regions in response to disgust stimuli, possibly revealing a disgust-based origin of spider phobia in children. These aspects should be considered in psychotherapeutic treatment of childhood spider phobia.     

Temporal prominence of auditory evoked potentials (N1 wave) in 4-8-year-old children

Cortical auditory evoked potentials (N1 wave) were studied in 24 adults (12 men, 12 women) and 20 children (12 boys, 8 girls; age: 4-8 years). In adults, this wave was recorded with maximal amplitude at frontocentral sites, peaking at about 100 ms poststimulation, whereas in children the auditory response displayed maximal amplitude at the midtemporal sites, with a positive wave at about 100 ms and a large negative wave at approximately 170 ms. Moreover, the modulatory effects of intensity on N1 amplitude were prominent at frontocentral sites in adults and at temporal sites in children. Frontocentral negative response was also recorded in children but was smaller in amplitude and longer in peak latency (around 140 ms) than in adults; responses were of greater amplitude at the frontal site than at the vertex before 6 years of age, whereas the reverse was more often found after this age. These data suggest great differences with age in the neural generators contributing to auditory evoked potentials recorded in the N1 latency range.     

Development of an ability to maintain verbally instructed central gaze fixation studied in 8- to 10-year-old children

Development of an ability to maintain verbally instructed central gaze fixation was studied in 8-, 9- and 10-year-old boys. The stability of central gaze fixation was tested by the sudden appearance of a novel, peripheral stimulus triggering reflexive saccade. In Experiment I, the ability to maintain verbally instructed central gaze fixation upon nonsense geometrical pattern was found to be equal in 8 and 9 years of life. This ability increased markedly between 9 and 10 years of age. Gaze fixation upon gradually appearing shapes during a TV-like game reducing volitional effort of subject was, however, equal in all age groups. Concentration of attention upon central stimulus as reflected by saccade latency (Experiment I) and P3-N3 amplitude of evoked potentials to peripheral flashes (Experiment II) was equal in both tasks in 8-year-olds. In contrast, higher concentration of attention upon meaningful central stimulus presented during the TV-like game was found in 9- as well as in 10-year-old boys. Developmental changes of the ability to maintain verbally instructed central gaze fixation might be related to the late structural maturation of frontal cortex.     

Validation of a pictorial rating scale for grip strength evaluation in 3- to 6-year-old children

The present study aimed to validate a pictorial rating scale to evaluate the child's ability to produce grip forces. Thirty-seven children aged 3 to 6 years participated as subjects in this investigation. We used a tailor-made pictorial scale and a hand grip strength meter, as well as a Piaget's clinical interview aimed to gather information on the child's understanding of the rating scale. The sensitivity of the rating scale was measured by testing a 4-intensity-level hand grip effort with 3- to 6-year-old children. In addition, the reproducibility of this pictorial rating scale was investigated by a test and randomised re-test procedure. Statistical analysis revealed that no significant main effect (P > 0.05) for test was observed in any child. In addition, no significant main effect (P > 0.05) for intensity was found in 3-year-old children. However, in the 4-year-old children and over, a significant main effect (P < 0.05) was found for intensity. The results also showed that 5- and 6-year-old children were able to produce four differentiated intensities of grip forces. These findings suggest that the pictorial rating scale for grip strength evaluation showed acceptable reproducibility and was sensitive to the age of the children tested. To conclude, this pictorial rating scale appears to be a valid tool to investigate accurately the child's ability to produce grip forces in young children from 5-year-old and over.     

Feature versus gestalt representation of stimuli in the mismatch negativity system of 7- to 9-year-old children

We examined preattentive auditory change detection in 7- to 9-year-old children. The question of interest was whether the preattentive comparison of stimuli indexed by the scalp-recorded mismatch negativity (MMN) was performed on representations of individual stimulus features or on gestalt representations of their combined attributes. The design of the study, based on a work by D. Deacon, J. Nousak, M. Pilotti, W. Ritter, and C. Yang (Psychophysiology, 1998), was such that both feature and gestalt representations could have been available to the comparator mechanism generating the MMN. The data indicated that for the majority of the children-those that exhibited an inverse relationship between the amplitude of the MMN and the probability of the deviant-the MMN was based on feature-specific information. This study also provides a method to obtain MMNs to deviants in three different features in the time usually required to obtain an MMN to a single acoustic feature.     

Successful use of intralesional and intravenous cidofovir in association with indole-3-carbinol in an 8-year-old girl with pulmonary papillomatosis

We report the history of an 8-year-old girl who was treated for suspected lung lesions of respiratory papillomatosis with Indole-3-Carbinol, local and intravenous injections of Cidofovir for 27 months. This is the first report where a complete cure of the lung lesions occurred in a child, and was sustained for at least 24 months.     

The perceptual response to exercise of progressively increasing intensity in children aged 7–8 years: Validation of a pictorial curvilinear ratings of perceived exertion scale

This study assessed the validity of the Eston-Parfitt (E-P) curvilinear Ratings of Perceived Exertion (RPE) Scale and a novel marble quantity task to provide estimates of perceived exertion during cycle ergometry. Fifteen children aged 7–8 years performed a discontinuous incremental graded-exercise test, and reported exertional ratings at the end of each minute. Significant increases in physiological and perceptual data were observed with increasing work rate. The relationship between work rate and marbles was curvilinear (mean R ²=.94), supporting the theoretical justification for the E-P Scale. Strong linear ( R ²=.93) and curvilinear ( R ²=.94) relationships between RPE from the E-P Scale and work rate confirmed the robustness of the E-P Scale. Valid exertional ratings may be obtained using the E-P Scale with young children. The novel marble quantity task offers an alternative method of deriving perceived exertion responses in children.     

The association between maternal cocaine use during pregnancy and physiological regulation in 4- to 8-week-old infants: an examination of possible mediators and moderators

OBJECTIVE: To examine the association between maternal cocaine use during pregnancy and physiological measures of regulation, which included heart rate (HR) and respiratory sinus arrhythmia (RSA). METHODS: Potential mediators and moderators of this association were explored. Participants were 141 mother-infant dyads (77 cocaine exposed and 64 nonexposed) recruited at birth. Average infant HR and RSA was assessed at 4-8 weeks of age during a 15 minute period of sleep. RESULTS: Results indicated a dose-dependent effect of prenatal exposure to cocaine on RSA. There was no evidence that fetal growth or other prenatal exposure to substances mediated this association or that fetal growth or maternal age moderated this association. Regression analyses also indicated that birth weight (BW), but not birthlength (BL), head circumference (HC) or other substance use, mediated the association between prenatal exposure to cocaine and heart rate. CONCLUSIONS: These results suggest that cocaine exposure is associated with physiological regulation at 4-8 weeks of age and highlight the importance of considering level of exposure when assessing infant outcomes.     

The cortisol awakening response (CAR) in 2- to 4-year-old children: effects of acute nighttime sleep restriction, wake time, and daytime napping

The cortisol awakening response (CAR) is presumed critically important for healthy adaptation. The current literature, however, is hampered by systematic measurement difficulties relative to awakening, especially with young children. While reports suggest the CAR is smaller in children than adults, well‐controlled research in early childhood is scarce. We examined whether robust CARs exist in 2‐ to 4‐year‐old children and if sleep restriction, wake timing, and napping influence the CAR (n = 7). During a 25‐day in‐home protocol, researchers collected four salivary cortisol samples (0, 15, 30, 45 min post‐wake) following five polysomnographic sleep recordings on nonconsecutive days after 4 hr (morning nap), 7 hr (afternoon nap), 10 hr (evening nap), 13 hr (baseline night), and 16 hr (sleep restriction night) of wakefulness (20 samples/child). The CAR was robust after nighttime sleep, diminished after sleep restriction, and smaller but distinct after morning and afternoon (not evening) naps. Cortisol remained elevated 45 min after morning and afternoon naps. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 54:412–422, 2012.     

The outcome of targeted NGS screening in patients with syndromic forms of sagittal and pansynostosis - IL11RA is an emerging core-gene for pansynostosis

Here, we have studied the prevalence and spectrum of genetic alterations in syndromic forms of sagittal and pansynostosis. Eighteen patients with sagittal synostosis (isolated or combined with other synostoses, except coronal) or pansynostosis were phenotypically assessed by retrospective analysis of medical records, three-dimensional computed tomography skull reconstructions, and registered photos. Patient DNAs were analyzed using a targeted next-generation sequencing (NGS) panel including 63 craniosynostosis (CS) related genes. Pathogenic and likely pathogenic variants were found in 72% of the cases, mainly affecting FGFR2, TWIST1, IL11RA, and SKI. Two patients that were negative at NGS screening – one with a supernumerary marker chromosome with duplication of 15q25.2q26.3 and one with a pathogenic PHEX variant – were identified using microarray and single gene analysis, respectively. The overall diagnostic rate in the cohort was thus 83%. We identified two novel likely pathogenic variants in FGFR2 (NM_022970.3: c.811_812delGGinsCC, p.Gly271Pro) and TWIST1 (NM_000474.3: c.476T > A, p.Leu159His), and a novel variant of unclear phenotypic significance in RUNX2 (NM_001024630.3: c.340G > A, p.Val114Ile) which could suggest a modulatory effect. Notably, we also identified three new patients with pansynostosis and a Crouzon-like phenotype with IL11RA mutation. Targeted NGS using a broad panel of CS-related genes is a simple and powerful tool for detecting pathogenic mutations in patients with syndromic forms of CS and multiple suture involvement, in particular pansynostosis. Our results provide additional evidence of an association between pansynostosis and IL11RA, an emerging core gene for autosomal recessive CS.     

The use of exhaled nitric oxide concentration to identify eosinophilic airway inflammation: an observational study in adults with asthma

BACKGROUND: Assessment of eosinophilic airway inflammation may be helpful in the management of asthma. Nitric oxide (NO) has potential advantages as a tool to monitor airway inflammation although little is known about the relationship between NO and eosinophilic airway inflammation and the factors which influence it. METHODS: We set out to define the relationship between exhaled NO and the sputum eosinophil count, identify the exhaled NO concentration that best identified a sputum eosinophil count >3% and investigate the impact of several potential confounding factors in 566 consecutive patients with varying severity of asthma. Finally we examined the ability of exhaled NO concentrations measured at differing exhalation flows to identify the presence of a sputum eosinophilia. RESULTS: We found a significant positive relationship between exhaled NO and sputum eosinophil count (R(2)=0.26, P<0.001) which was best described using a non-linear model. There were no clinically important confounding factors to this model. In non-smokers an exhaled NO concentration of >8.3 p.p.b. at 250 mL/s gave 71% sensitivity and 72% specificity for identifying a sputum eosinophil count of >3%. CONCLUSIONS: This value of exhaled NO would seem to be the best for identifying significant eosinophilic airway inflammation. It is applicable to a wide range of non-smoking patients with asthma; exhalation flow does not alter the ability of exhaled NO concentration to detect a sputum eosinophilia.     

The immune response to (T,G)-A-L and GAT in man: an association of nonresponsiveness to (T,G)-A-L with HLA-DRw8

The response of human lymphocytes to synthetic polypeptides has been measured by sensitizing cells in vitro followed by restimulation with the sensitizing antigen or with cross-reacting antigens. It was found that there was considerable individual heterogeneity in the specific response and the cross-reaction obtained with the antigens (T,G)-A-L, GAT, GT, and GA. In spite of this heterogeneity, it is possible to define three different response patterns using nonresponsiveness to (T,G)-A-L and the failure of (T,G)-A-L to cross-restimulate GAT sensitized cells as discriminating criteria. The nonresponders to (T,G)-A-L show a significant association with HLA-DRw8 and it is suggested that this might represent a dominant HLA associated immune response gene involved in the regulation of the response to (T,G)-A-L. We further show that the individuals whose cells respond to (T,G)-A-L form a heterogeneous group which may explain the conflicting results previously published on the genetic control of the immune response to (T,G)-A-L in man.