Individualized developmental care for a large sample of very preterm infants: health, neurobehaviour and neurophysiology.

AIM: To assess medical and neurodevelopmental effects of Newborn Individualized Developmental Care and Assessment Program (NIDCAP) for a large sample of very early-born infants. METHODS: One hundred and seven singleton inborn preterm infants, <29 weeks gestational age (GA), <1250 g birth weight, enrolled in three consecutive phases, were randomized within phase to NIDCAP (treatment, E) or standard care (C). Treatment extended from admission to the Newborn Intensive Care Unit to 2 weeks corrected age (wCA). Outcome included medical, neurobehavioural and neurophysiological status at 2 wCA, and growth and neurobehavioural status at 9 months (m) CA. RESULTS: The C- and E-group within each of the three consecutive phases and across the three phases were comparable in terms of all background measures; they therefore were treated as one sample. The results indicated for the E-group significant reduction in major medical morbidities of prematurity as well as significantly improved neurodevelopmental (behaviour and electrophysiology) functioning at 2 wCA; significantly better neurobehavioural functioning was also found at 9 mCA. CONCLUSION: The NIDCAP is an effective treatment for very early-born infants. It reduces health morbidities and enhances neurodevelopment, functional competence and life quality for preterm infants at 2 w and 9 mCA.

Structure and function: brain electrical activity mapping and computed tomography in schizophrenia.

A computerized topographic technique that maps brain electrical activity is applied to the investigation of neurophysiological abnormalities in medicated and drug-free schizophrenic patients. This topographic approach uses EEG and evoked potentials to provide functional measures of electrophysiological abnormalities. Neurophysiological differences between schizophrenic patients and controls are delineated which add further evidence that frontal lobe dysfunction may be relevant to our understanding of schizophrenia. An initial investigation employs computed tomography to examine the relationship of structural anatomical pathology in schizophrenia with the functional abnormalities that may be defined using brain electrical activity mapping. When schizophrenic patients with and without frontal cortical atrophy were compared, electrophysiological differences were delineated that overlay frontal cortical regions. This preliminary work suggests that in schizophrenia, abnormal electrophysiological function is associated with definable gross morphological abnormalities of the brain.

Abnormal flash visual evoked response in melancholia: a replication study.

Grand mean flash visual evoked responses (FVER) were measured in two new groups of depressed patients with melancholia to replicate findings of an abnormal FVER in a previously reported pilot study (Vasile et al 1989). These different, independently collected groups of melancholic patients demonstrated a statistically significant negative deviation of the FVER 224-300 msec poststimulus maximal in the midline centroparietal region when compared with appropriate normative age-matched control groups (n = 56) in each group). We utilized the identical computer-based quantified neurophysiological technique with mapping to analyze the data in all three melancholic patient groups--the pilot group (n = 9) with mean age 73.1 years, an older replication group (n = 14) with mean age 75.5 years, and a younger replication group (n = 15) with mean age 63.8 years. We also studied a group of depressed patients without melancholia (n = 11) with mean age 65.2 years, and found a similar, but less pronounced, alteration of the FVER. Lastly, we studied a group of nondepressed neuropsychiatric patients (n = 10) with mean age 61.9 years and found no abnormality of the FVER. Our data suggest that a gradient of FVER abnormality exists in depressed patients, most prominent, but not limited to elderly melancholic patients.

Effects of age upon interhemispheric EEG coherence in normal adults.

Age-related differences in quantified electrophysiological measures of interhemispheric EEG coherence were studied in 371 subjects (171 males and 200 females), ages 20-80, all of whom were judged to be optimally healthy. Principal components analysis (PCA) was performed on interhemispheric coherence of Laplacian referenced data from eight homologous left-right electrode pairs, from 0.5 to 32 Hz. Regression procedures, using signals from artifact monitoring channels, were used to minimize effects of eye movement and muscle artifact. Forty-six factors described 80% of the total variance, with electrode location the primary source of communality in factor formation. Within 350 right-handed subjects, results indicated a broad trend for decreased interhemispheric coherence with advancing age. Using canonical correlation, the coherence-based factors also successfully predicted spectral variables, previously found to maximally illustrate age-related EEG desynchronization. We speculate that age-related reduction of interhemispheric coherence may in part explain age-related EEG desynchrony and stems from age-related reduction of cortical connectivity. Gender differences of interhemispheric coherence were also evident. Females demonstrated higher interhemispheric coherence than males. Within a smaller subpopulation of 63 subjects (21 left and 42 right handed), there was a gender-by-handedness interaction, with higher interhemispheric coherence in right-handed females than right-handed males and the reverse in left-handed male and female subjects.

The pattern of age-related differences in electrophysiological activity of healthy males and females.

Age-related differences in quantified electrophysiological measures were examined in 202 subjects (109 females; 93 males) ages 30-80 all of whom were judged to be optimally healthy on a wide variety of criteria. The study utilized both absolute and relative measures from EEG spectral analysis as well as additional measures from long latency-evoked potentials. The same findings were noted for the 109 newly studied females as were reported for 63 previously studied male subjects. Results indicate that there is a broad trend for decreased EEG slow and increased fast activity with age, however, some of the measures change linearly and others are best represented by nonlinear functions. There is no decade where activities remain stable. Overall the pattern of change for males and females is similar, however, gender differences in both the EEG and EP data were present. The females had higher magnitudes for almost all absolute spectral and fast relative spectral measures. However, females demonstrated lower absolute alpha amplitude, lower relative slow activity, and lower late-latency EP data. Moreover, the absolute slow activity measure showed a gender X age interaction, indicating that the females had a different change in pattern of activity with increasing age than the males. Thus, gender-related findings were complex and could not be expressed as simple differences in overall amplitude. Age-related change is not a simple linear process but differs for differing EEG spectral bands, relative, and absolute spectral measures and for males and females. The overall findings contradict the common wisdom that EEG and alpha slow with age and that age related EEG change is on a continuum with findings in Alzheimer's disease where increased slowing predominates.

Electrophysiologic comparisons between two groups of patients with Alzheimer's disease.

Two groups of patients with Alzheimer's disease were compared using brain electrical activity mapping. The patients were selected on the basis of their cognitive history. The initial symptom of disease of the patients in group 1 was a significant and profound memory deficit, whereas the patients in group 2 initially presented with a gradually progressive spatial impairment. Fourteen topographic features distinguished the groups. Eleven of the 14 features pertained to electrical activity differences in parietal regions, and 9 were bilateral. These features were highly correlated with cognitive measures that are also useful in distinguishing the groups.

Lecithin: absence of neurophysiologic effect in Alzheimer's disease by EEG topography.

Ten patients with Alzheimer's disease participated in a 26-week double-blind trial of lecithin. EEG data were recorded at baseline, after administration of the placebo, and after administration of the drug. Topographic maps of EEG spectra were compared when patients were on and off drugs. A direct comparison of drug and nondrug data was not significant. A second approach, comparing differences between drug and nondrug with differences between the two nondrug conditions, also produced no evidence of a drug treatment effect. The data confirm other reports that lecithin has no effect upon spectrally analyzed EEG activity in Alzheimer's disease.

Neurophysiological heterogeneity and the definition of dyslexia: preliminary evidence for plasticity.

Developments in the field of quantified electroencephalography have enhanced visualization of brain function in the learning disabilities. Optimal utilization of these techniques requires that populations under study be unambiguously defined. Evidence from the literature demonstrates that brain electrical activity of children with reading disability is more extensive and differs from that seen in children with "dyslexia-pure". Preliminary data are presented demonstrating that electrophysiological change seen in children with dyslexia-plus (dyslexia and attentional deficit disorder) could not be predicted by knowledge of electrophysiologic change in children with dyslexia-pure alone and attentional deficit disorder alone. Data from our laboratory are summarized to show that within dyslexia-pure the anomic, dysphonemic and global Denckla subtypes differ electrophysiologically from one another. Of particular interest is the demonstration that regions of electrophysiological difference among these subtypes may reflect compensatory mechanisms rather than pathological change. Finally, a case study is presented demonstrating advantageous effects of remediation upon brain electrical function. As both spontaneous and environmentally induced change in brain function can be documented, developmental dyslexia in its broadest terms appears to represent a more dynamic or plastic process than previously appreciated.

Individualized behavioral and environmental care for the very low birth weight preterm infant at high risk for bronchopulmonary dysplasia: neonatal intensive care unit and developmental outcome.

We hypothesize that the respiratory and functional states of the very low birth weight infant with bronchopulmonary dysplasia can be improved in the neonatal intensive care unit by prevention of inappropriate sensory input. To test this hypothesis, we developed for preterm newborns a behavior observation method that catalogues specific reaction patterns according to putative stress and relaxation behaviors. We then collected behavioral information and heart rate, respiratory rate, and transcutaneous PO2 readings before, during, and after routine care-giving interventions. Eight control and eight experimental infants were selected for study based on the following criteria: birth weight less than 1,250 g, gestational age less than 28 weeks, on the respirator greater than 24 hours in first 48 hours of life at greater than or equal to 0.60 FiO2 for more than two hours during first 48 hours of life. Additionally, the two groups were comparable on other medical and demographic variables, including severity of respiratory status for the first ten days and incidence of intraventricular hemorrhage, patent ductus arteriosus, and socioeconomic status. Systematic observations were conducted on days 10, 20, and 30 after birth and at 36 and 40 weeks postconception. For the intervention infants, our observations were discussed with the infants' primary nurses, and individualized modifications for each infant's care plan were implemented based on these observations. Experimental infants showed significantly briefer stays on the respirator (P less than .01) and in increased FiO2 (P less than .05). Their feeding behavior was normalized significantly earlier (P less than .01). Experimental infants also showed significantly better behavioral regulation scores at 1 month after their mothers' estimated dates of confinement (post-EDC), as measured with the Assessment of Preterm Infants' Behavior, significantly better Mental and Psychomotor Developmental Indices at 3, 6, and 9 months post-EDC, as measured with the Bayley Scales of Infant Development, and significantly better behavioral regulation scores at 9 months post-EDC, as measured in a videotaped play observation. Measurements of weight, height, and head circumference at 3, 6, and 9 months post-EDC showed no differences. All assessments were performed by one of two trained testers not familiar with the goals of the study or the group status of the infant. These results support the hypothesis that very low birth weight preterm babies profit significantly both medically and developmentally from individualized behavioral care in the neonatal intensive care unit.

Effectiveness of individualized developmental care for low-risk preterm infants: behavioral and electrophysiologic evidence.

OBJECTIVE: We assessed the effectiveness of individualized developmental support in the special care nursery for low-risk preterm infants. SETTING: A university-affiliated teaching hospital. PARTICIPANTS: Twelve healthy full-term infants, and 24 low-risk preterm infants randomly assigned to a control or an experimental group. DESIGN: The preterm control group received standard care and the preterm experimental group received individualized developmental care at the same special care nursery. OUTCOME MEASURES: Medical, behavioral (Assessment of Preterm Infants' Behavior and Prechtl's Neurological Examination of the Full-Term Newborn Infant), and electrophysiologic outcome (using quantitative electroencephalography with topographic mapping) of all three groups was assessed 2 weeks after the expected due date. RESULTS: No between- or among-group medical differences were seen for this low-risk, healthy sample. The preterm experimental group showed behavioral and electrophysiologic performances comparable to those of the full-term group, whereas the preterm control group performed significantly less well. Behavioral measures suggested significantly poorer attentional functioning for the preterm control group. Electrophysiologic results implicated the frontal lobe. CONCLUSIONS: Individualized developmental intervention supports neurobehavioral functioning as measured at 2 weeks post-term. It appears to prevent frontal lobe and attentional difficulties in the newborn period, the possible causes of behavioral and scholastic disabilities often seen in low-risk preterm infants at later ages.

Nonsteroidal anti-inflammatory drugs in perisurgical pain management. Mechanisms of action and rationale for optimum use.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of agents with similar actions but diverse chemical structures. Aspirin (acetylsalicylic acid) and sodium salicylate were the first drugs of this type to be used clinically. However, over the past 3 decades there has been a dramatic increase in the number of NSAIDs available for the treatment of postoperative pain. Tissue injury, such as occurs with surgical intervention, is associated with the release of numerous inflammatory mediators including prostaglandins. Prostaglandins derived from the arachidonic acid cascade are implicated in the production of inflammatory pain, and in sensitising nociceptors to the actions of other mediators. They are synthesised from arachidonic acid via the endoperoxide biosynthesis pathway, the initial step of which is catalysed by the enzyme cyclo-oxygenase. Two forms of the cyclo-oxygenase enzyme (COX-1 and COX-2) have been characterised. COX-1 is important in circumstances where prostaglandins have a protective effect such as gastric mucus production and renal blood flow maintenance. NSAIDs inhibit the synthesis of prostaglandins at 1 or more points in the endoperoxide pathway. Three mechanisms of inhibition of the biosynthetic enzymes have been proposed: (i) rapid, reversible competitive inhibition; (ii) irreversible, time-dependent inhibition; and (iii) rapid, reversible noncompetitive (free radical trapping) inhibition. In addition, there is evidence that NSAIDs have a central antinociceptive mechanism of action that augments the peripheral effect. This may involve inhibition of central nervous system prostaglandins or inhibition of excitatory amino acids or bradykinins. There is considerable variability in the pain relief obtained from NSAIDs. Such variability in drug response may be explained in terms of differences between agents with respect to either pharmacodynamic actions or pharmacokinetic parameters or a combination of both. Stereoisomerism, where preparations exist as racemic mixtures and where only 1 enantiomer is active, may also be important. However, chiral inversion from inactive to active enantiomer may occur and may be rapid or slow. NSAIDs have numerous adverse effects. Gastrointestinal disturbances including ulceration are the commonest adverse responses to NSAIDs and carry the greatest risk of death. Also significant are renal impairment and an increased risk of postoperative haemorrhage. Asthma and allergic reactions are uncommon.(ABSTRACT TRUNCATED AT 400 WORDS)

Auditory evoked response data reduction by PCA: development of variables sensitive to reading disability.

Long latency auditory evoked responses (AER) were formed on 232 healthy normal and learning impaired subjects to tone pairs of 50 msec inter-stimulus interval (TALAER) and also to the words "tight" and "tyke" (TTAER). Both evoked potential (EP) type have been used to demonstrate differences between good readers (WIAT Basic Reading score > 115, N = 42) and poor readers (Reading score < 85, N = 42). A largely automated, hands off approach was used to reduce artifact contamination, to develop canonical measures for discriminating good from poor readers, and to predict reading scores across the entire population including intermediate (average) readers. Eye and muscle artifact were diminished by multiple regression. Substantial EP data reduction was enabled by an unrestricted use of Principal Components Analysis (PCA). For each EP type, 40 factors encompassed 70-80% of initial variance, a meaningful data reduction of about 90:1. Factor interpretation was enhanced by mapping of the factor loadings. By discriminant analysis, resulting factors predicted reading group membership with over 80% jackknifed and also split--half replication accuracy. By multiple regression, they produced a canonical variate correlating significantly (p < 0.001) with the Basic Reading score (r = 0.39). The TTAER factors were more useful than the TALAER factors. The relevance of rapid auditory processing and phonemic discrimination measurements to dyslexia is discussed.

Auditory evoked responses to similar words with phonemic difference: comparison between children with good and poor reading scores.

Our previous study demonstrated a physiologic deficit in two-tone discrimination in poor readers. This was specific to the left parietal area suggesting that poor readers handled rapid tones differently. The current paper extends this finding in the same population, demonstrating that poor readers also have difficulty with phonemic discrimination. Long latency auditory evoked potentials (AEP) were formed using a phonemic discrimination task in a group of children with reading disabilities and controls. Measuring peak-to-peak amplitude of the waveforms, we found reduced N1-P2 amplitude in the Poor Reader group. Using the t-statistic significance probability map (SPM) technique, we also found a group difference, maximal over the mid-parietal area, from 584 msec to 626 msec after the stimulus onset. This difference was due to a lower amplitude on the Poor Reader group. We hypothesized that this late difference constitutes a P3 response and that the Poor Reader group generated smaller P3 waves. These auditory evoked response (AER) data support a discrimination deficit for close phonemes in the Poor Reader group as they had smaller N1-P2 absolute amplitude and developed smaller P3 waves. Based on these data we should be able to differentiate between Good and Poor readers based on long latency potentials created from phonemic stimuli.

Auditory evoked responses to single tones and closely spaced tone pairs in children grouped by reading or matrices abilities.

Long latency auditory evoked responses (AER) were formed to single tones and rapid tone pairs. Using the t-statistic SPM technique, children with poorer WIAT reading scores demonstrated group difference overlying the left parietal and frontal language regions but just for AER to tone pair stimuli. Variables derived from these regions were not significantly different when the same subjects were grouped by K-BIT Matrices scores. When the same children were regrouped by Matrices scores and compared using the SPM technique, differences were now seen over the right hemisphere, especially in the parietal and frontotemporal regions, for both single and two-tone derived AERs. Variables derived from these regions were not significantly different for children when grouped by reading score. AER data support a specific deficit in two-tone stimulation for poorer reading children over the left hemisphere and also a deficit to both single and two-tone stimulation over the right hemisphere for children with poorer Matrices scores.

Spectral coherence in normal adults: unrestricted principal components analysis; relation of factors to age, gender, and neuropsychologic data.

This paper demonstrates, by means of Principal Components Analysis (PCA), an objective approach to the reduction of large data sets produced by multichannel spectral coherence analyses. Coherence data, gathered from 371 normal healthy adults using Hjorth/Laplacian referencing during waking eyes-open and eyes-closed states, were analyzed by "unrestricted" PCA where neither spatial nor temporal variance was folded into among subject variance. There was substantial data reduction with our 4416 initial coherence variables for each state reduced to just 150 factors containing approximately 80% of the variance reflecting a 30 fold concentration of information content. Varimax rotation of the first 40 factors, encompassing 50% of the total variance for both states, revealed loading patterns primarily bilateral with no hemispheric bias, relationships primarily between distant single electrode pairs, (although a single electrode to multiple electrode pattern was also observed), and involvement of all spectral bands. Elemental left to right and anterior to posterior coherence patterns, often used on an a priori basis for coherence studies, were not evident among the rotated factor loading patterns. On the basis of high loadings upon extra bipolar artifact channels, 32 factors accounting for approximately 40% of the variance were identified as reflecting artifactual coherence relationships. By multiple regression the 48 non-artifactual factor scores successfully predicted subject age. In general, coherence diminished with age, which may partly explain age-related EEG desynchronization in healthy adults. Coherence factors also predicted 6 of 10 neuropsychologic variables. Gender was successfully predicted by discriminant analysis. No global interpretations about coherence and gender or neuropsychologic function were possible, i.e., almost equal numbers of factors increased as decreased in males as females. PCA derived coherence factor scores are useful for subsequent statistical analyses, but their factor loading plots of cortical coupling may require more experience to fully interpret.

Prediction of dyslexia in kindergarten boys.

This study followed 163 boys from kindergarten through fourth grade. A battery of neurospychological and preacademic tests and electrophysiological measures (BEAM) were administered in kindergarten, and reading tests at grade 4, in an attempt to delineate precursors of dyslexia. Three of the kindergarten tasks (giving sounds associated with letters, rapid naming of numbers, and finger localization) differentiated dyslexics from normal readers with 98 percent correct classification. The tasks primarily involve grapheme-phoneme associations, storage and retrieval of phonological information in long-term memory, and verbal labeling. Results are interpreted as confirming the role played by phonological processing tasks in the prediction of dyslexia. Preliminary BEAM results for visual evoked potential topography suggest a significant increment in the distribution of this potential in the left parietal and frontal region, and, for auditory evoked potential topography, a significant difference between the two groups in the right posterior hemisphere.

Linguistic profiles of dyslexic and good readers.

Linguistic profiles of 60 boys with average intelligence were examined at kindergarten, grade 2, and grade 4. The subjects were 7 dyslexic, 7 mildly dyslexic, 30 average, and 16 good readers, defined in terms of the discrepancy between standardized reading and intelligence scores. Across the three ages, reader groups did not differ in language comprehension, but did differ in confrontation and rapid automatized naming (RAN), three syntactic measures, and verbal memory. Group strengths and weaknesses were, with few exceptions apparent in kindergarten and maintained throughout. The kindergarten tasks which most effectively predicted reading group membership at grade 4 were giving letter sounds, and rapid naming; these predicted 4th grade reading group at close to 100 percent accuracy. The study, together with a further comparison of average and high IQ good readers, provides an interesting contrast between the role of RAN and Confrontation naming in reading.

Tracheal granulation tissue after percutaneous tracheostomy treated with Nd:Yag laser: three cases.

Three adult patients who received percutaneous serial dilatational tracheostomy post-cardiac surgery developed histologically confirmed tracheal granulation tissue superior to the point of entry of the tracheostomy tube into the trachea. This tissue significantly occluded the trachea in all patients and, in two, led to serious haemorrhage. Each patient had serial dilatational percutaneous tracheostomy using the Cook/Ciaglia technique. On each patient fibre-optic bronchoscopy confirmed satisfactory position of the guidewire and tracheostomy tube. Nd:Yag laser therapy was applied to areas of tracheal granulation tissue and was also employed to secure haemostasis. In each patient endobronchial Nd:YAG laser therapy successfully cleared the granulation tissue and secured haemostasis. Follow-up bronchoscopy showed no recurrence. Fibre-optic bronchoscopy at the time of tracheal decannulation may identify granulation tissue requiring appropriate referral and intervention.

Effectiveness of individualized neurodevelopmental care in the newborn intensive care unit (NICU).

The individual infant's neurodevelopmental process provides an integrative framework for the delivery of medical care needed to assure the infant's survival and quality of outcome. The infant's neurobehavioral functioning and expression provides an opportunity for caregivers to estimate the individual infant's current strengths, vulnerabilities and threshold to disorganization, as well as to identify the infant's strategies in collaborating in his or her best progression. This perspective supports caregivers in seeing themselves in a relationship with the infant, and in considering opportunities to enhance the infant's strengths and reduce apparent stressors in collaboration with the infant and the family. The results of several randomized studies supporting the effectiveness of such a neurodevelopment approach to NICU care will be presented, and suggest implications for staff education and nursery-wide implementation.