Working memory and processing speed abilities are related to habituation and change detection in school-aged children: An ERP study.

High cognitive performance is related to efficient brain processing while accomplishing complex cognitive tasks. This efficiency is observed through a rapid engagement of the brain regions and the cognitive processes required for task accomplishment. However, it is unclear if this efficiency is also present in basic sensory processes such as habituation and change detection. We recorded EEG with 85 healthy children (51 males) aged between 4 and 13 years old, while they listened to an auditory oddball paradigm. Cognitive functioning was evaluated using the Weschler Intelligence Scales for Children Fifth Edition and the Weschler Preschool & Primary School for Intelligence Fourth Edition. Auditory evoked potentials (AEPs) analyses and repeated measure analysis of covariance as well as regression models were performed. The analysis revealed that P1 and N1 repetition effects were observed across levels of cognitive functioning. Further, working memory abilities were related to repetition suppression on the auditory P2 component amplitude, while faster processing speed was related to repetition enhancement on the N2 component amplitude. Also, Late Discriminative Negativity (LDN) amplitude, a neural correlate of change detection, increased with working memory abilities. Our results confirm that efficient repetition suppression (i.e. greater reduction in amplitudes with greater levels of cognitive functioning) and more sensitive change detection (greater amplitude changes of the LDN) are related to the level of cognitive functioning in healthy children. More specifically, working memory and processing speed abilities are the cognitive domains related to efficient sensory habituation and change detection.

How to interpret high levels of distress when using the Distress Thermometer in the long-term follow-up clinic? A study with Acute Lymphoblastic Leukemia survivors.

OBJECTIVES: Recent guidelines recommend to assess emotional distress in pediatric oncology during treatment and in after care. One tool used to do this is the distress thermometer (DT), a simple tool which has almost exclusively been studied in its screening abilities. Given its increased used as a measure of distress per se, it is necessary to document its concurrent validity. The goal of this study was to identify clinical domains (eg, depression, anxiety) and individual symptoms associated with pediatric cancer survivors' rating on the DT. PARTICIPANTS: To do so we used data collected from 84 young (≤18 years old), and 120 older (>18 years old) survivors who were treated for pediatric leukemia. METHODS: Participants responded to self-report questionnaires as part of a research visit. RESULTS: Results from stepwise regressions show that in the younger group, high scores on the thermometer were associated with higher negative affectivity only. In adults, high scores were associated with higher anxiety, higher negative affectivity, and lower positive affectivity. When exploring associations with individual items, we found that the main emotional tone reflected by the thermometer score was anxiety. CONCLUSIONS: Interpreting ratings on the thermometer should probably focus on anxiety in childhood cancer survivors. This widely used tool also does not measure the same domains in young versus older survivors, so that age groups should be considered separately in future work.

Adverse neuropsychological effects associated with cumulative doses of corticosteroids to treat childhood acute lymphoblastic leukemia: A literature review.

Corticosteroids (CS) are an essential component of childhood acute lymphoblastic leukemia treatments (cALL). Although there is evidence that daily doses of CS can have neuropsychological effects, few studies have investigated the role of cumulative doses of CS in short- and long-term neuropsychological effects in cALL. The aims of this review were to identify the measures used for documenting adverse neuropsychological effects (ANEs) of CS treatment and to study the association between cumulative doses of CS and the presence of ANEs. Twenty-two articles met the inclusion criteria. A variety of measures were used to evaluate outcomes in the domains of emotion, behaviour, neurocognition, and fatigue/sleep. The results suggest that we cannot conclude in favour of an association between the cumulative dosage of CS and ANEs. Yet, several factors including the heterogeneity of measures used to evaluate outcomes and reporting biases may limit the scope of the results. We offer several recommendations that could help improve the future published evidence on ANEs in relation to CS treatment in cALL.

fMRI brain response during sentence reading comprehension in children with benign epilepsy with centro-temporal spikes.

INTRODUCTION: Children with benign epilepsy with centro-temporal spikes (BECTS) often have language problems. Abnormal epileptic activity is found in central and temporal brain regions, which are involved in reading and semantic and syntactic comprehension. Using functional magnetic resonance imaging (fMRI), we examined reading networks in BECTS children with a new sentence reading comprehension task involving semantic and syntactic processing. METHOD: Fifteen children with BECTS (age=11y 1m ± 16 m; 12 boys) and 18 healthy controls (age=11 y 8m ± 20 m; 11 boys) performed an fMRI reading comprehension task in which they read a pair of syntactically complex sentences and decided whether the target sentence (the second sentence in the pair) was true or false with respect to the first sentence. All children also underwent an exhaustive neuropsychological assessment. RESULTS: We demonstrated weaknesses in several cognitive domains in BECTS children. During the sentence reading fMRI task, left inferior frontal regions and bilateral temporal areas were activated in BECTS children and healthy controls. However, additional brain regions such as the left hippocampus and precuneus were activated in BECTS children. Moreover, specific activation was found in the left caudate and putamen in BECTS children but not in healthy controls. Cognitive results and accuracy during the fMRI task were associated with specific brain activation patterns. CONCLUSION: BECTS children recruited a wider network to perform the fMRI sentence reading comprehension task, with specific activation in the left dorsal striatum. BECTS cognitive performance differently predicted functional activation in frontal and temporal regions compared to controls, suggesting differences in brain network organisation that contribute to reading comprehension.

Enhanced EEG connectivity in children with febrile seizures.

BACKGROUND: Epilepsy is currently conceptualized as a disturbance of neuronal networks with altered connectivity that persists into the interictal phase. Febrile seizures are sometimes a precursor in childhood of lifelong epilepsy. We investigated whether studying functional connectivity in children with febrile seizures could help understand the mechanisms underlying their long-term seizure susceptibility. METHODS: EEG was recorded during rest and intermittent photic stimulation (IPS) in 12 FS patients, 5 siblings and 15 control children between 6 and 36 months of age. Original EEG data were transformed into source space using a multiple regional source model. Source coherence values were calculated for the interfrontal, interoccipital and occipito-frontal connections for the delta, theta, alpha, beta and gamma frequency bands. RESULTS: Our results suggest enhanced delta and theta frequency EEG source coherence in patients with FSs compared to siblings and control children, both under resting conditions and during IPS, more consistent for the theta band and the occipito-frontal connections. CONCLUSIONS: Enhanced connectivity in patients with FSs could indicate a seizure-prone state and interfere with the maturation of cerebral networks. Further prospective studies are needed to assess whether hyperconnectivity is a risk factor for epileptogenesis and neurodevelopmental disorders.

The neuropsychology of the Klüver-Bucy syndrome in children.

The Klüver-Bucy syndrome (KBS) is characterized by a number of peculiar behavioral symptoms. The syndrome was first observed in 1939 by Heinrich Klüver and Paul Bucy in the rhesus monkey following removal of the greater portion of the monkey's temporal lobes and rhinencephalon. The animal showed (a) visual agnosia (inability to recognize objects without general loss of visual discrimination), (b) excessive oral tendency (oral exploration of objects), (c) hypermetamorphosis (excessive visual attentiveness), (d) placidity with loss of normal fear and anger responses, (e) altered sexual behavior manifesting mainly as marked and indiscriminate hypersexuality, and (f) changes in eating behavior. In humans, KBS can be complete or incomplete. It occurs as a consequence of neurological disorders that essentially cause destruction or dysfunction of bilateral mesial temporal lobe structures (i.e., Pick disease, Alzheimer disease, cerebral trauma, cerebrovascular accidents, temporal lobe epilepsy, herpetic encephalopathy, heat stroke). As for epilepsy, complete and incomplete KBS are well documented in temporal lobe epilepsy, temporal lobectomy, and partial status epilepticus. KBS can occur at any age. Children seem to show similar symptoms to adults, although some differences in the manifestations of symptoms may be related to the fact that children have not yet learned certain behaviors.

Children with a history of atypical febrile seizures show abnormal steady state visual evoked potential brain responses.

Atypical febrile seizures (FSs) are considered a risk factor for the onset of epilepsy in later life as well as for potential cognitive impairment. However, distinctive characteristics defining the group of children at risk for negative outcomes are not well established. In the following study, children from 6 to 59 months with a history of atypical FSs were investigated using steady state visual evoked potentials (ssVEP), a brain response known to increase with age. Abnormally, low theta and alpha ssVEP brain responses were found in children with a history of atypical FSs.

The development of a noisy brain.

Early in life, brain development carries with it a large number of structural changes that impact the functional interactions of distributed neuronal networks. Such changes enhance information processing capacity, moving the brain from a deterministic system to one that is more stochastic. The evidence from empirical studies with EEG and functional MRI suggests that this stochastic property is a result of an increased number of possible functional network configurations for a given situation. This is captured in the variability of endogenous and evoked responses or "brain noise ". In empirical data from infants and children, brain noise increases with maturation and correlates positively with stable behavior and accuracy. The noise increase is best explained through increased noise from network level interactions with a concomitant decrease of local noise. In old adults, brain noise continues to change, although the pattern of changes is not as global as in early development. The relation between high brain noise and stable behavior is maintained, but the relationships differ by region, suggesting changes in local dynamics that then impact potential network configurations. These data, when considered in concert with our extant modeling work, suggest that maturational changes in brain noise represent the enhancement offunctional network potential--the brain's dynamic repertoire.

Electrophysiological study of auditory development.

Cortical auditory evoked potential (CAEP) testing, a non-invasive technique, is widely employed to study auditory brain development. The aim of this study was to investigate the development of the auditory electrophysiological signal without addressing specific abilities such as speech or music discrimination. We were interested in the temporal and spectral domains of conventional auditory evoked potentials. We analyzed cerebral responses to auditory stimulation (broadband noises) in 40 infants and children (1 month to 5 years 6 months) and 10 adults using high-density electrophysiological recording. We hypothesized that the adult auditory response has precursors that can be identified in infant and child responses. Results confirm that complex adult CAEP responses and spectral activity patterns appear after 5 years, showing decreased involvement of lower frequencies and increased involvement of higher frequencies. In addition, time-locked response to stimulus and event-related spectral pertubation across frequencies revealed alpha and beta band contributions to the CAEP of infants and toddlers before mutation to the beta and gamma band activity of the adult response. A detailed analysis of electrophysiological responses to a perceptual stimulation revealed general development patterns and developmental precursors of the adult response.

Electrophysiological markers of visuocortical development.

The development of noninvasive techniques for the assessment of functional brain maturation is critical. The present study analyzed 63 babies' and children's (27 days to 5.5 years) cerebral responses to a pattern-reversal visual stimulation using high-density (128 electrodes) electrophysiological recordings. Developmental data were further compared with those of young adults (n = 16). Tremendous changes in pattern visual evoked potentials (pVEPs) morphology were observed between 7 and 24 months characterized by the emergence of negative components labeled "N70" and "N145" and the reduction of the P100 amplitude. The adult pattern of response appears from 24 months onward. Spectral density values show an increase of higher frequencies with age. Coherence values show a reduction between 3 and 23 months of age as well as a further increase toward adulthood between areas implicated in visual processing. These results are discussed in light of developmental features such as synaptogenesis, myelination, and neuronal networks refinement.

[Neuropsychological profile of intractable partial epilepsies]. / Le bilan d'une épilepsie partielle pharmaco-résistante: explorations neuropsychologiques.

The neuropsychological assessment is an essential part of the clinical work-up of patients suffering from pharmaco-resistant epilepsy. The aim of the present article is to give an overview of the assessment with regard to the functions tested, the techniques employed and the factors influencing the interpretation of the results. In the first part of the article, the role of the neuropsychological evaluation is discussed in relation to other methods of clinical investigation, such as EEG, brain imaging techniques and sodium amytal exploration, all of which intend to identify the localization (region and laterality) of the epileptogenic focus. This is particularly important for patients slated for epilepsy surgery. In addition, the neuropsychological exam aims to determine the extent of the deficits in various cognitive and sensori-motor domains by taking into account the structural and/or functional reorganization that may have taken place and the compensatory mechanisms that are available to the patient. In this context, the effect of various factors influencing the mental and emotional functioning of the patient, such as the age at onset and duration of the epilepsy, the presence of a structural lesion, the type and number of anticonvulsant drugs, the personality and the adaptability of the patient must be considered. In children, the effect of recurrent seizures may be more devastating since these risk to interfere with normal brain development. On the other hand, the greater plasticity of the immature brain provides a larger window in which compensation can take place. Evidence suggests that attentional processes are affected in all types of epilepsy. Furthermore, the antiepileptic medication may have a deleterious effect on the cognitive and emotional status of the patient, particularly in patients with pharmaco-resistant epilepsy who are usually taking a combination of anticonvulsant drugs. The second part of the article presents localization-specific neuropsychological impairments and the tests most suited to reveal these deficits. Thus, in temporal lobe epilepsy, memory functions are more affected than in other types of partial epilepsy, whereas intellectual functions are usually preserved. However, recent studies cast some doubt on the prevailing view that left-hemisphere foci are associated with verbal memory deficits only and that right-hemisphere foci solely affect visuo-spatial memory. The dichotomy appears to be more subtle, especially in patients with a long-standing seizure history. Frontal foci produce deficits in motor coordination, attention, working memory and executive functions. These deficits appear to be more pronounced in children than in adults. Few studies have explored the neuropsychological consequences of parieto-occipital foci given that this type of epilepsy is relatively rare. The neuropsychological profile of the patient should guide healthcare providers to implement the necessary remedial measures to facilitate the patient's social integration and to improve his quality of life.

Rotavirus alters paracellular permeability and energy metabolism in Caco-2 cells.

Rotaviruses infect epithelial cells of the small intestine, but the pathophysiology of the resulting severe diarrhea is incompletely understood. Histological damage to intestinal epithelium is not a consistent feature, and in vitro studies showed that intestinal cells did not undergo rapid death and lysis during viral replication. We show that rotavirus infection of Caco-2 cells caused disruption of tight junctions and loss of transepithelial resistance (TER) in the absence of cell death. TER declined from 300 to 22 Omega. cm(2) between 8 and 24 h after infection and was accompanied by increased transepithelial permeability to macromolecules of 478 and 4,000 Da. Distribution of tight junction proteins claudin-1, occludin, and ZO-1 was significantly altered during infection. Claudin-1 redistribution was notably apparent at the onset of the decline in TER. Infection was associated with increased production of lactate, decreased mitochondrial oxygen consumption, and reduced cellular ATP (60% of control at 24 h after infection), conditions known to reduce the integrity of epithelial tight junctions. In conclusion, these data show that rotavirus infection of Caco-2 intestinal cells altered tight junction structure and function, which may be a response to metabolic dysfunction.

Cholestyramine ointment to treat buttocks rash and anal excoriation in an infant.

OBJECTIVE: To describe a novel treatment for perianal excoriation in an infant receiving a promotility agent. CASE SUMMARY: A 2-month-old boy with reflux, and regurgitation was treated with cisapride. Shortly after cisapride therapy he developed a rash on his buttocks and anal irritation that progressed in severity despite the use of numerous topical products and extended diaper-free periods. A topical cholestyramine ointment compound was prepared and administered, resulting in complete resolution within 3 days. DISCUSSION: Cisapride can decrease the gastrointestinal transit time, which can lead to less time for bile acid reabsorption in the distal ileum. If high concentrations of bile acids are contained in the stool, they can irritate the anus and buttocks in a manner similar to the skin irritation experienced by patients with ostomies. Cholestyramine, a bile acid sequestrant, can irreversibly bind the bile when applied topically and bring relief to the patient. CONCLUSIONS: Topical cholestyramine ointment may be a safe and efficacious treatment option for perianal irritation due to bile acids.

Evidence for cellular heterogeneity in primary cultures of human orbital fibroblasts.

Orbital fibroblasts in culture display phenotypic attributes that distinguish them from fibroblasts derived from other anatomical regions. The current studies were conducted to define potential cellular heterogeneity among orbital fibroblasts with regard to 1) differential expression of Thy-1, a 25-kilodalton glycoprotein associated with cell signaling; 2) cells undergoing a change in shape in response to prostaglandin E2 (PGE2); and 3) differences in morphology and Thy-1 expression between single cell-derived clonal fibroblast strains. On the basis of flow cytometric analysis using an anti-Thy-1 monoclonal antibody, 65% of intact orbital fibroblasts expressed surface Thy-1 (n = 5; range, 54-71%). In contrast, greater than 95% of the fibroblasts present in the five dermal strains tested were Thy-1 positive. A total of six strains of orbital fibroblasts were assessed for their shape change response to a 4-h treatment with PGE2 (100 nmol/L). A mean of 37% of the fibroblasts present in each culture responded to PGE2 (range, 22-50%). In contrast, only 1% of dermal fibroblasts exhibited any change in morphology. Three separate clones were generated from a single parent strain of Graves' orbital fibroblasts. These clones consisted of homogeneous appearing cells; however, substantial clone to clone differences in morphology were stably expressed for several population doublings. Thy-1 was expressed uniformly in cells of two clones, whereas the third was Thy-1 negative. Factor VIII and smooth muscle-specific alpha-actin were undetectable in any of the orbital or dermal cultures examined. Thus, Thy-1 expression is uniform in fibroblasts from certain anatomical regions such as the skin and heterogeneous in cells derived from human lung and orbit. These findings suggest that human orbital connective tissue may have a complexity not previously appreciated.