Inhibitory control in otherwise healthy overweight 10-year-old children.

BACKGROUND: Preventing obesity is a worldwide public health priority. In vulnerable children living in obesogenic environments, with easy access to high-caloric food, alterations in inhibitory control functions might favor excessive food intake and affect energy regulation. We hypothesized that overweight/obese children would present lower inhibitory control in comparison to normal weight children. METHODS: We measured inhibitory control functions in 93 otherwise healthy overweight/obese and 92 normal weight 10-year-old children using the Stroop test and the Go/No-Go task. Event-related potentials were recorded during the Go/No-Go task. RESULTS: Overweight/obese children showed slower reaction times (1248.6 ms (95% confidence interval (CI): 1182.9-1314.3) vs 1149.0 ms (95% CI: 1083.0-1215.1)) on the Stroop test, higher reaction time variability (0.25 (95% CI: 0.22-0.27) vs 0.21 (95% CI: 0.19-0.24)) on the Go/No-Go task and decreased P300 amplitude (4.1 µV (95% CI: 3.0-5.2) vs 6.4 µV (95% CI: 5.2-7.6)) on event-related potentials compared with normal weight children. CONCLUSIONS: Our results indicate altered inhibitory control functions in otherwise healthy overweight/obese children, which might contribute to their excessive food consumption.

Single trial P300 detection in children using expert knowledge and SOM.

Preliminary results of an automatic system for single trial P300 visual evoked potential events detection are presented. For each single trial P300, several candidate events were generated, and then filtered, using 3 wave features. The surviving candidate events were fed into a SOM-based classifier. A context filter was applied before the final output. No stationary condition of the P300 is involved in the algorithms. Recordings of 27 assessment sessions, each with 120 trials, were visually inspected by experts to identify and mark the P300 events, which was accomplished in about one third of the trials. The dataset was divided in training (18) and testing (9) subsets. The system identifies the initial and end times of the P300; it obtained a sensitivity of 53.9%, a specificity of 64.0% and an accuracy of 61.2% in the testing dataset.

A balanced sleep/wakefulness classification method based on actigraphic data in adolescents.

Several research groups have developed automated sleep-wakefulness classifiers for night wrist actigraphic (ACT) data. These classifiers tend to be unbalanced, with a tendency to overestimate the detection of sleep, at the expense of poorer detection of wakefulness. The reason for this is that the measure of success in previous works was the maximization of the overall accuracy, disregarding the balance between sensitivity and specificity. The databases were usually sleep recordings, hence the over-representation of sleep samples. In this work an Artificial Neural Network (ANN), sleep-wakefulness classifier is presented. ACT data was collected every minute. An 11-min moving window was used as observing frame for data analysis, as applied in previous sleep ACT studies. However, our feature set adds new variables such as the time of the day, the median and the median absolute deviation. Sleep and Wakefulness data were balanced to improve the system training. A comparison with previous studies can still be done, by choosing the point in the ROC curve associated with the corresponding data balance. Our results are compared with a polysomnogram-based hypnogram as golden standard, rendering an accuracy of 92.8%, a sensitivity of 97.6% and a specificity of 73.4%. Geometric mean between sensitivity and specificity is 84.9%.

Night time sleep macrostructure is altered in otherwise healthy 10-year-old overweight children.

OBJECTIVE: Epidemiological evidence shows an inverse relationship between sleep duration and overweight/obesity risk. However, there are few polysomnographic studies that relate the organization of sleep stages to pediatric overweight (OW). We compared sleep organization in otherwise healthy OW and normal-weight (NW) 10-year-old children. SUBJECTS: Polysomnographic assessments were performed in 37 NW and 59 OW children drawn from a longitudinal study beginning in infancy. Weight and height were used to evaluate body mass index (BMI) according to international criteria. Non-rapid eye movement (NREM) sleep (stages N1, N2 and N3), rapid eye movement (REM) sleep (stage R) and wakefulness (stage W) were visually scored. Sleep parameters were compared in NW and OW groups for the whole sleep period time (SPT) and for each successive third of it using independent Student's t-tests or nonparametric tests. The relationship between BMI and sleep variables was evaluated by correlation analyses controlling for relevant covariates. RESULTS: The groups were similar in timing of sleep onset and offset, and sleep period time. BMI was inversely related to total sleep time (TST) and sleep efficiency. OW children showed reduced TST, sleep efficiency and stage R amount, but higher stage W amount. In analysis by thirds of the SPT, the duration of stage N3 episodes was shorter in the first third and longer in the second third in OW children as compared with NW children. CONCLUSIONS: Our results show reduced sleep amount and quality in otherwise healthy OW children. The lower stage R amount and changes involving stage N3 throughout the night suggest that OW in childhood is associated with modifications not only in sleep duration, but also in the ongoing night time patterns of NREM sleep and REM sleep stages.

Motor activity and intra-individual variability according to sleep-wake states in preschool-aged children with iron-deficiency anemia in infancy.

BACKGROUND: A chronic or acute insult may affect the regulatory processes that guide motor and behavioral performance, leading to increased intra-individual variability (IIV). Increased variability is often interpreted as an indication of regulatory dysfunction. Iron plays an important role in the regulatory processes of the nervous system and affects motor activity. To our knowledge, no study has examined the long-lasting patterns and IIV of motor activity following iron-deficiency anemia in human infants. AIMS: This study compared 48-h motor activity and variability in preschool-aged children with or without iron-deficiency anemia (IDA) in infancy. METHODS: Motor activity was recorded through actigraphs during two week-days in 47 4-year-old Chilean children (23 former IDA and 24 non-anemic in infancy). All were given oral iron as infants. Sleep-wake states were identified by means of automated software. The frequency of movement units per minute was determined for each waking/sleep state during the individual day and night periods; data were examined in blocks of 15 min. Analyses of mean frequency and duration and intra-individual variability were conducted using multivariate mixed models. RESULTS: For daytime sleep, former IDA children were more active without a difference in the total duration. They also spent less time awake throughout the individual day period. Motor activity intra-individual variability was higher in former IDA children. CONCLUSIONS: The findings suggest that IDA in infancy sets the stage for long lasting dysfunction in the neural processes regulating sleep-wake states and spontaneous motor activity patterns.

Twenty-four-hour motor activity in human infants with and without iron deficiency anemia.

Iron deficiency anemia (IDA) is a very common nutritional problem that alters motor activity. The aim of this study was to compare 24-h motor activity in the home in healthy 6-month-old infants with and without IDA. Activity was assessed via actigraphs on the leg during 24 continuous hours in 17 Chilean infants with IDA and 18 with normal hemoglobin levels. All infants were given oral iron, and activity was reassessed at 12 and 18 months. The frequency of movement units per minute was determined for each waking/sleep state during the day and night, and the duration of each state was computed. At 6 months of age, there were no differences between anemic and nonanemic infants in time per state. However, infants with IDA showed an overall increase in motor activity compared to controls. These differences were no longer observed at 12 and 18 months of age. Increased activity during the period of IDA raises the issue of a shared underlying mechanism with restless legs syndrome, a sensorimotor dysfunction where iron deficiency increases the severity of the symptoms and iron supplementation ameliorates them. Due to previous findings of decreased motor activity in the laboratory at 12 months during the waking time surrounding an afternoon nap, we also compared those data to a nap in the home. Infants with IDA were less active in the laboratory than in the home. The home versus laboratory results suggest that contextual factors affect the motor activity of IDA infants to a larger extent than controls.

Polysomnographic pattern recognition for automated classification of sleep-waking states in infants.

A robust, automated pattern recognition system for polysomnography data targeted to the sleep-waking state and stage identification is presented. Five patterns were searched for: slow-delta and theta wave predominance in the background electro-encephalogram (EEG) activity; presence of sleep spindles in the EEG; presence of rapid eye movements in an electro-oculogram; and presence of muscle tone in an electromyogram. The performance of the automated system was measured indirectly by evaluating sleep staging, based on the experts' accepted methodology, to relate the detected patterns in infants over four months of post-term age. The set of sleep-waking classes included wakefulness, REM sleep and non-REM sleep stages I, II, and III-IV. Several noise and artifact rejection methods were implemented, including filters, fuzzy quality indices, windows of variable sizes and detectors of limb movements and wakefulness. Eleven polysomnographic recordings of healthy infants were studied. The ages of the subjects ranged from 6 to 13 months old. Six recordings counting 2665 epochs were included in the training set. Results on a test set (2,369 epochs from five recordings) show an overall agreement of 87.7% (kappa 0.840) between the automated system and the human expert. These results show significant improvements compared with previous work.

Spontaneous motor activity in human infants with iron-deficiency anemia.

This study compared spontaneous motor activity in 6-month-old Chilean infants with or without iron-deficiency anemia (IDA) who were otherwise healthy. Activity was assessed in conjunction with polysomnographic recording during an afternoon nap in 11 infants with IDA and 15 with normal hemoglobin levels. All infants were given oral iron, and activity was reassessed at 12 and 18 months. Using actigraphs placed on the ankle, the frequency of movement units per minute was determined for each waking/sleep state. The total amount of time infants were in an alert-active state before and after the nap was used to calculate the proportion of movements/minute of waking. There were no differences between anemic and nonanemic infants in total recording time, duration of sleep, or motor activity during sleep. However, infants with IDA showed reduced motor activity during waking at all ages. The magnitude of the differences increased at 12 and 18 months. Thus, IDA was associated with reduced motor activity in infants even after iron treatment. It will be important to confirm these results in a larger sample and to determine the 24-h pattern of motor activity, since reduced motor activity may limit infants' opportunities to explore and learn from the social and physical environment.

Essential fatty acids in visual and brain development.

Essential fatty acids are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LC-PUFA). These fatty acids serve as specific precursors for eicosanoids, which regulate numerous cell and organ functions. Recent human studies support the essential nature of n-3 fatty acids in addition to the well-established role of n-6 essential fatty acids in humans, particularly in early life. The main findings are that light sensitivity of retinal rod photoreceptors is significantly reduced in newborns with n-3 fatty acid deficiency, and that docosahexaenoic acid (DHA) significantly enhances visual acuity maturation and cognitive functions. DHA is a conditionally essential nutrient for adequate neurodevelopment in humans. Comprehensive clinical studies have shown that dietary supplementation with marine oil or single-cell oil sources of LC-PUFA results in increased blood levels of DHA and arachidonic acid, as well as an associated improvement in visual function in formula-fed infants matching that of human breast-fed infants. The effect is mediated not only by the known effects on membrane biophysical properties, neurotransmitter content, and the corresponding electrophysiological correlates but also by a modulating gene expression of the developing retina and brain. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation and retinal and nervous system development. Regulation of gene expression by LC-PUFA occurs at the transcriptional level and may be mediated by nuclear transcription factors activated by fatty acids. These nuclear receptors are part of the family of steroid hormone receptors. DHA also has significant effects on photoreceptor membranes and neurotransmitters involved in the signal transduction process; rhodopsin activation, rod and cone development, neuronal dendritic connectivity, and functional maturation of the central nervous system.

Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovarian syndrome: endocrine aspects.

BACKGROUND: The aim of this study was to evaluate the changes in gonadotrophin concentrations and the dynamics of the episodic fluctuations of circulating LH during night-time, in fully breastfeeding normal women and in those with polycystic ovarian syndrome (PCOS) during lactational amenorrhoea and after weaning, in order to provide insights into the onset of this syndrome. Additionally, ovarian activity was evaluated by ultrasound examination and steroid concentrations. METHODS: Twelve lactating PCOS (LPCOS) women and six normal lactating (NL) women of similar age were selected. On the 4th and 8th week postpartum (PP) and eight weeks after weaning, blood samples were collected every 10 min (10.00--20.00h). Gonadotrophin concentrations were determined in all samples. Steroid hormones were measured in one fasting sample and ovarian morphology was assessed by ultrasound. RESULTS: On the 8th week PP, LH pulse frequency was higher and FSH concentrations were lower in LPCOS women compared with NL women, and steroid hormone concentrations remained low, except for androstenedione which was higher in LPCOS patients. After weaning, similar differences were observed between both groups. PCOS patients also showed enlarged ovaries with a PCOS pattern in the three study periods. CONCLUSIONS: The enlarged ovaries associated with higher androstenedione concentrations suggest that PCOS is a primary ovarian defect, making it difficult to establish if the abnormal LH pattern observed in these women is primary or secondary to the ovarian dysfunction.

The effect of sleep state on electroretinographic (ERG) activity during early human development.

To assess the effects of sleep state on human retinal electric responses, full-field electroretinograms were obtained in a cross-sectional study from 123 preterm infants at 36, 40 and 56 weeks of post-gestational age. At each age, electroretinographic recordings were assigned to one of two groups according to whether the infants were in active sleep or quiet sleep. Both sleep states were determined behaviorally. Pure rod, maximal, 30 Hz flicker and light adapted single cone responses were evaluated when a sleep state was clearly established. Peak-to-peak amplitudes of most electroretinographic responses were significantly larger in active sleep relative to quiet sleep at 36 and 40 weeks of post-gestational age. We speculate that larger amplitudes during active sleep may play a role in the maturation of the visual system.

Expert-system classification of sleep/waking states in infants.

This work is part of a project to develop an expert system for automated classification of the sleep/waking states in human infants; i.e. active or rapid-eye-movement sleep (REM), quiet or non-REM sleep (NREM), including its four stages, indeterminate sleep (IS) and wakefulness (WA). A model to identify these states, introducing an objective formalisation in terms of the state variables characterising the recorded patterns, is presented. The following digitally recorded physiological events are taken into account to classify the sleep/waking states: predominant background activity and the existence of sleep spindles in the electro-encephalogram; existence of rapid eye movements in the electro-oculogram; and chin muscle tone in the electromyogram. Methods to detect several of these parameters are described. An expert system based on artificial ganglionar lattices is used to classify the sleep/waking states, on an off-line minute-by-minute basis. Algorithms to detect patterns automatically and an expert system to recognise sleep/waking states are introduced, and several adjustments and tests using various real patients are carried out. Results show an overall performance of 96.4% agreement with the expert on validation data without artefacts, and 84.9% agreement on validation data with artefacts. Moreover, results show a significant improvement in the classification agreement due to the application of the expert system, and a discussion is carried out to justify the difficulties of matching the expert's criteria for the interpretation of characterising patterns.

Evidence of altered central nervous system development in infants with iron deficiency anemia at 6 mo: delayed maturation of auditory brainstem responses.

Iron deficiency anemia has long been thought to have effects on the central nervous system (CNS). Finding direct evidence of this in human infants, however, has been challenging. Auditory brainstem responses (ABRs) provide a noninvasive means of examining an aspect of the CNS that is rapidly maturing during the age period when iron deficiency is most common. ABRs represent the progressive activation of the auditory pathway from the acoustic nerve (wave I) to the lateral lemniscus (wave V). The central conduction time (CCT, or wave I-V interpeak latency) is considered an index of CNS development because myelination of nerve fibers and maturation of synaptic relays lead to an exponential reduction in the CCT from birth to 24 mo. In 55 otherwise healthy, 6-mo-old Chilean infants (29 with iron deficiency anemia and 26 nonanemic control infants), the CCT was longer in those who had been anemic at 6 mo, with differences becoming more pronounced at 12- and 18-mo follow-ups despite effective iron therapy. The pattern of results--differences in latencies but not amplitudes, more effects on the late ABR components (waves III and V), and longer CCTs (as an overall measure of nerve conduction velocity)--suggested altered myelination as a promising explanation, consistent with recent laboratory work documenting iron's essential role in myelin formation and maintenance. This study shows that iron deficiency anemia in 6-mo-old infants is associated with adverse effects on at least one aspect of CNS development and suggests the fruitfulness of studying other processes that are rapidly myelinating during the first 2 y of life.

Respiratory characteristics during sleep in healthy small-for- gestational age newborns.

OBJECTIVE: Small-for-gestational age (SGA) infants born with intrauterine growth retardation (IUGR) differ from appropriate-for-gestational age (AGA) infants by: a) alterations in a number of neurologic and neurophysiologic characteristics; b) modified heart rate variability during the neonatal period; and c) increased morbidity rates during the first months of life. However, there are no data on the impact of IUGR on respiratory function at birth. METHODS: We studied newborns who were 35 to 36, 37 to 38, and 39 to 41 weeks' conceptional age (CA): 31 were AGA and 26 were SGA. All were clinically and neurologically normal at birth and none exhibited abnormal events during the first year of life. Polygraphic recordings were performed between two meals during the normal postnatal stay in the maternity ward. RESULTS: During both active sleep (AS) and quiet sleep (QS), SGA infants in all CA groups had significantly higher values for the incidence of 2 to 4.9 seconds and 5 to 9.9 seconds central respiratory pauses (RP), the apnea index (AI) [AI=% of nonbreathing time], and the time spent with periodic breathing (PB), as compared with AGA infants. Respiratory frequency was usually similar in SGA and AGA infants. In addition, the trend of age-related respiratory modifications was disturbed in SGA infants, as compared with AGA infants: at 39 to 41 weeks CA, SGA infants had no significant decreases in RP, AI, or PB, and no increase in respiratory frequency. However, between-state differences were similar in both groups. In all AGA and SGA infant groups respiratory frequency seemed to be an individual characteristic: infants who breathed faster during AS breathed faster during QS, and vice-versa. CONCLUSION: Our data demonstrate significant modifications in the establishment of respiratory rhythm control in SGA infants, whereas the patterns of state-related and subject-dependent breathing characteristics were similar in SGA and AGA infants. We speculate that the dysregulation of respiratory function control maturation observed in healthy SGA infants may be related to subtle brainstem modifications attributable to the decreased blood supply and chronic hypoxia associated with IUGR.

Role of essential fatty acids in the function of the developing nervous system.

The basis for n-3 fatty acid essentially in humans includes not only biochemical evidence but functional measures associated with n-3 deficiency in human and nonhuman primates. Functional development of the retina and the occipital cortex are affected by alpha-linolenic acid deficiency and by a lack of docosahexaenoic acid (DHA) in preterm infant formulas and, as reported more recently, in term diets. Functional effects of n-3 supply on sleep-wake cycles and heart rate rhythms support the need for dietary n-3 fatty acids during early development. Our results indicate that n-3 long-chain polyunsaturated fatty acids should be considered provisionally essential for infant nutrition. DHA may also be required by individuals with inherited metabolic defects in elongation and desaturation activity, such as patients with peroxisomal disorders and some forms of retinitis pigmentosa.