A Comparison of Quantitative R1 and Cortical Thickness in Identifying Age, Lifespan Dynamics, and Disease States of the Human Cortex.

Brain development and aging are complex processes that unfold in multiple brain regions simultaneously. Recently, models of brain age prediction have aroused great interest, as these models can potentially help to understand neurological diseases and elucidate basic neurobiological mechanisms. We test whether quantitative magnetic resonance imaging can contribute to such age prediction models. Using R1, the longitudinal rate of relaxation, we explore lifespan dynamics in cortical gray matter. We compare R1 with cortical thickness, a well-established biomarker of brain development and aging. Using 160 healthy individuals (6-81 years old), we found that R1 and cortical thickness predicted age similarly, but the regions contributing to the prediction differed. Next, we characterized R1 development and aging dynamics. Compared with anterior regions, in posterior regions we found an earlier R1 peak but a steeper postpeak decline. We replicate these findings: firstly, we tested a subset (N = 10) of the original dataset for whom we had additional scans at a lower resolution; and second, we verified the results on an independent dataset (N = 34). Finally, we compared the age prediction models on a subset of 10 patients with multiple sclerosis. The patients are predicted older than their chronological age using R1 but not with cortical thickness.

Effect of early or delayed insertion of tympanostomy tubes for persistent otitis media on developmental outcomes at the age of three years.

BACKGROUND: A main indication for the insertion of tympanostomy tubes in infants and young children is persistent otitis media with effusion, reflecting concern that this condition may cause lasting impairments of speech, language, cognitive, and psychosocial development. However, evidence of such relations is inconclusive, and evidence is lacking that the insertion of tympanostomy tubes prevents developmental impairment. METHODS: We enrolled 6350 healthy infants from 2 to 61 days of age and evaluated them regularly for middle-ear effusion. Before the age of three years 429 children with persistent effusion were randomly assigned to have tympanostomy tubes inserted either as soon as possible or up to nine months later if effusion persisted. In 402 of these children we assessed speech, language, cognition, and psychosocial development at the age of three years. RESULTS: By the age of three years, 169 children in the early-treatment group (82 percent) and 66 children in the late-treatment group (34 percent) had received tympanostomy tubes. There were no significant differences between the early-treatment group and the late-treatment group at the age of three years in the mean (+/-SD) scores on the Number of Different Words test, a measure of word diversity (124+/-32 and 126+/-30, respectively); the Percentage of Consonants Correct-Revised test, a measure of speech-sound production (85+/-7 vs. 86+/-7); the General Cognitive Index of McCarthy Scales of Children's Abilities (99+/-14 vs. 101+/-13); or on measures of receptive language, sentence length, grammatical complexity, parent-child stress, and behavior. CONCLUSIONS: In children younger than three years of age who have persistent otitis media, prompt insertion of tympanostomy tubes does not measurably improve developmental outcomes at the age of three years.

Prevalence and assessment of attention-deficit/hyperactivity disorder in primary care settings.

Research literature relating to the prevalence of attention-deficit/hyperactivity disorder (ADHD) and co-occurring conditions in children from primary care settings and the general population is reviewed as the basis of the American Academy of Pediatrics clinical practice guideline for the assessment and diagnosis of ADHD. Epidemiologic studies revealed prevalence rates generally ranging from 4% to 12% in the general population of 6 to 12 year olds. Similar or slightly lower rates of ADHD were revealed in pediatric primary care settings. Other behavioral, emotional, and learning problems significantly co-occurred with ADHD. Also reviewed were rating scales and medical tests that could be employed in evaluating ADHD. The utility of using both parent- and teacher-completed rating scales that specifically assess symptoms of ADHD in the diagnostic process was supported. Recommendations were made regarding the assessment of children with suspected ADHD in the pediatric primary care setting.

Measurement properties of the MacArthur communicative development inventories at ages one and two years.

In a prospective study of child development in relation to early-life otitis media, we administered the MacArthur Communicative Development Inventories (CDI) to a large (N = 2,156), sociodemographically diverse sample of 1- and 2-year-old children. As a prerequisite for interpreting the CDI scores, we studied selected measurement properties of the inventories. Scores on the CDI/Words and Gestures (CDI-WG), designed for children 8 to 16 months old, and on the CDI/Words and Sentences (CDI-WS), designed for children 16 to 30 months old, increased significantly with months of age. On several scales of both CDI-WG and CDI-WS, standard deviations approximated or exceeded mean values, reflecting wide variability in results. Statistically significant differences in mean scores were found according to race, maternal education, and health insurance status as an indirect measure of income, but the directionality of differences was not consistent across inventories or across scales of the CDI-WS. Correlations between CDI-WG and CDI-WS ranged from .18 to .39. Our findings suggest that the CDI reflects the progress of language development within the age range 10 to 27 months. However, researchers and clinicians should exercise caution in using results of the CDI to identify individual children at risk for language deficits, to compare groups of children with different sociodemographic profiles, or to evaluate the effects of interventions.

Language, speech sound production, and cognition in three-year-old children in relation to otitis media in their first three years of life.

OBJECTIVE: As part of a prospective study of possible effects of early-life otitis media on speech, language, cognitive, and psychosocial development, we tested relationships between children's cumulative duration of middle ear effusion (MEE) in their first 3 years of life and their scores on measures of language, speech sound production, and cognition at 3 years of age. METHODS: We enrolled 6350 healthy infants by 2 months of age who presented for primary care at 1 of 2 urban hospitals or 1 of 2 small town/rural and 4 suburban private pediatric practices. We intensively monitored the children's middle ear status by pneumatic otoscopy, supplemented by tympanometry, throughout their first 3 years of life; we monitored the validity of the otoscopic observations on an ongoing basis; and we treated children for otitis media according to specified guidelines. Children who met specified minimum criteria regarding the persistence of MEE became eligible for a clinical trial in which they were assigned randomly to undergo tympanostomy tube placement either promptly or after a defined extended period if MEE remained present. From among those remaining, we selected randomly, within sociodemographic strata, a sample of 241 children who represented a spectrum of MEE experience from having no MEE to having MEE whose cumulative duration fell just short of meeting randomization criteria. In subjects so selected, the estimated duration of MEE ranged from none to 65.6% of the first year of life and 44.8% of the first 3 years of life. In these 241 children we assessed language development, speech sound production, and cognition at 3 years of age, using both formal tests and conversational samples. RESULTS: We found weak to moderate, statistically significant negative correlations between children's cumulative durations of MEE in their first year of life or in age periods that included their first year of life, and their scores on formal tests of receptive vocabulary and verbal aspects of cognition at 3 years of age. However, the percent of variance in these scores explained by time with MEE in the first year of life beyond that explained by sociodemographic variables ranged only from 1.2% to 2.9%, and the negative correlations were concentrated in the subgroup of children whose families had private health insurance (rather than Medicaid). We found no significant correlations in the study population as a whole or in any subgroup between time with MEE during antecedent periods and children's scores on measures of spontaneous expressive language, speech sound production, or other measured aspects of cognition. In contrast, by wide margins, scores on all measures were consistently highest among the most socioeconomically advantaged children and lowest among the most socioeconomically disadvantaged children. CONCLUSIONS: Our findings suggest either that persistent early-life MEE actually causes later small, circumscribed impairments of receptive language and verbal aspects of cognition in certain groups of children or that unidentified, confounding factors predispose children both to early-life otitis media and to certain types of developmental impairment. Findings in the randomized clinical trial component of the larger study should help distinguish between causality and confounding as explanations for our findings.language, speech, cognition, development, otitis media, middle ear effusion.

Developmental and lesion effects in brain activation during sentence comprehension and mental rotation.

The development of neurocognitive networks was examined in 2 cognitive paradigms: auditory sentence comprehension and mental rotation of alphanumeric stimuli. Patterns of brain activation were measured with whole brain echoplanar functional magnetic resonance imaging at 3 Tesla in 5 adults (20-28 years old), 7 children (9-12 years old), and 6 pediatric patients (9-12 years old) with perinatal strokes or periventricular hemorrhages. Healthy children and adults activated similar neurocognitive networks, but there were developmental differences in the distribution of activity across these networks. In the sentence task, children showed more activation in the inferior visual area suggesting an imagery strategy rather than a linguistic strategy for sentence processing. Furthermore, consistent use of a sentence comprehension strategy, whether correct or incorrect as compared to chance performance, was associated with greater activation in the inferior frontal area (Broca's) in both children and pediatric patients. In the mental rotation task, healthy adults showed more activation in the superior parietal and middle frontal areas and less activation in the supramarginal gyrus, suggesting adults were primarily engaged in visual-spatial manipulation and less engaged in the recognition of noncanonical views of stimuli. The pediatric patients showed patterns of activation consistent with organization of cognitive processing into homologous areas of the contralateral hemisphere.

Maternal education and measures of early speech and language.

The present study was designed to determine whether 4 measures of children's spontaneous speech and language differed according to the educational level of the children's mothers. Spontaneous language samples from 240 three-year-old children were analyzed to determine mean length of utterance in morphemes (MLUm), number of different words (NDW), total number of words (TNW), and percentage of consonants correct (PCC). A norm-referenced, knowledge-dependent measure of language comprehension, the Peabody Picture Vocabulary Test-Revised (PPVT-R), was also included for purposes of comparison with the spontaneous measures. Three levels of maternal education were compared: less than high school graduate, high school graduate, and college graduate. Trend analyses showed statistically significant linear trends across educational levels for MLUm, NDW, TNW, and PPVT-R; the trend for PCC was not significant. The relationship of maternal education and other sociodemographic variables to measures of children's language should be examined before using such measures to identify children with language disorders.

Parental stress and parent-rated child behavior in relation to otitis media in the first three years of life.

OBJECTIVE: As part of a long-term study of possible effects of early-life otitis media on speech, language, cognitive, and psychosocial development, we tested relationships between parents' ratings of parent-child stress at ages 1, 2, and 3 years, and of their children's behavior problems at ages 2 and 3 years, and the children's cumulative duration of middle-ear effusion (MEE) in their first 3 years of life. METHODS: We enrolled healthy infants by age 2 months who presented for primary care at 1 of 2 urban hospitals or 1 of 2 small-town/rural and 4 suburban private pediatric practices. We obtained standardized baseline measures of parental stress; we intensively monitored the children's middle-ear status by pneumatic otoscopy, supplemented by tympanometry, throughout their first 3 years of life; we monitored the validity of the otoscopic observations on an ongoing basis; and we treated children for otitis media according to specified guidelines. We obtained parent ratings of parental stress using the Parenting Stress Index/Short Form when the children reached ages 1, 2, and 3 years, and parent ratings of children's behavior using the Child Behavior Checklist when the children reached ages 2 and 3 years. RESULTS: In 2278 children we found no substantial relationships between parents' ratings of parent-child stress when the children reached ages 1, 2, and 3 years, or of their children's behavior problems at ages 2 and 3 years, and the cumulative duration of the children's MEE during antecedent periods. On the other hand, ratings both of parent-child stress and of behavior problems were consistently highest among the most socioeconomically disadvantaged children and lowest among the most socioeconomically advantaged children. Ratings also tended to be highest among children whose parents' baseline stress scores were highest. CONCLUSIONS: Parent-child stress and children's behavior problems in the first 3 years of life, as rated by parents, bear little or no relationship to the children's previous cumulative duration of MEE.

American Academy of Pediatrics. Committee on Psychosocial Aspects of Child and Family Health. The child in court: a subject review.

When children come to court as witnesses, or when their needs are decided in a courtroom, they face unique stressors from the legal proceeding and from the social predicament that resulted in court action. Effective pediatric support and intervention requires an understanding of the situations that bring children to court and the issues that will confront children and child advocates in different court settings.

Parent-reported language and communication skills at one and two years of age in relation to otitis media in the first two years of life.

OBJECTIVE: As part of a study of possible effects of early life otitis media on children's development, we attempted to determine whether levels of language and communication skills at 1 and 2 years of age are associated with the cumulative duration of middle ear effusion (MEE) in the first 2 years of life. METHODS: Subjects (N = 2156) were followed at one of eight study sites in the Pittsburgh area. Middle ear status was monitored closely throughout the first 2 years of life. For each child, the cumulative percentage of days with MEE was estimated based on diagnoses at visits and interpolations for intervals between visits. For each child also, 1 or both parents completed the MacArthur Communicative Development Inventory-Words and Gestures (CDI-WG) when the child was 1 year of age and the MacArthur Communicative Development Inventory-Words and Sentences (CDI-WS) when the child was 2 years of age. RESULTS: Unadjusted correlations between scores on the CDI-WG and percentage of days with MEE in the first year of life were close to zero, and there were no statistically significant negative correlations. Unadjusted correlations between scores on the CDI-WS and the cumulative percentage of days with MEE in year 2 and in years 1 and 2 combined were generally negative and statistically significant, but the magnitudes of those correlations were no higher than 0.09. After adjustment for sociodemographic variables, only the Vocabulary Production Scale of the CDI-WS remained correlated significantly with the percentage of days with MEE, and the percentage of days with MEE accounted for only a negligible percentage of the variance in scores on this scale. CONCLUSIONS: In this diverse sample of children, parent-reported levels of language skills at 1 and 2 years of age were correlated negligibly with the cumulative percentage of days with MEE in the children's first and second years of life. otitis media, otitis media with effusion, language, communication.

Efficacy of methylphenidate among preschool children with developmental disabilities and ADHD.

OBJECTIVE: This was a double-blind, placebo-controlled, crossover design study of the safety and efficacy of methylphenidate (MPH) in 11 preschool children (aged 4.0-5.11 years) with developmental disabilities and attention-deficit hyperactivity disorder (ADHD). METHOD: MPH doses of 0.3 and 0.6 mg/kg per dose and a placebo were given. Drug response was evaluated via teacher-completed behavior checklists and clinic-based observations of activity level, attention, and compliance to adult requests. A side effects checklist was also completed by teachers and parents. RESULTS: Significant improvement on teacher ratings of hyperactivity and inattention as well as clinic-based observations of activity level and compliance were associated with MPH. Eight of 11 preschool children were medication responders (based on a minimum 40% decrease between placebo and one drug condition on either the teacher-rated Conners Hyperactivity Index or the Hyperactive-Distractible subscale of the Preschool Behavior Questionnaire). Five children exhibited significant adverse drug side effects such as severe social withdrawal, increased crying, and irritability, especially at the higher dose (0.6 mg/kg). CONCLUSIONS: Results suggest that preschool children with developmental disabilities and ADHD respond to MPH at rates similar to those of school-age children with mental retardation and ADHD. However, this population appears to be especially susceptible to adverse drug side effects.

A fork in the road: decision time for behavioral pediatrics.

The rapid growth of managed care, and especially that of managed behavioral healthcare organizations (MBHOs), is likely to diminish the role of developmental-behavioral pediatrics and separate care for medical and behavioral problems. Thus, a rethinking of the practice of developmental-behavioral pediatrics is required. This study reviews the structure of MBHOs, identifies barriers to the provision of services by developmental-behavioral pediatricians, describes alternative practice models for consideration, and makes recommendations. The aims of the recommendations are to stimulate an active discussion about these issues, spark an advocacy effort, and ensure the continued participation of developmental-behavioral pediatricians in the care of children with special needs. The study concludes that managed care will push developmental-behavioral pediatricians into integration with primary care group practices or into specialty mental health networks. Immediate discussion, action, and advocacy will be required to ensure a presence in these decisions for developmental-behavioral pediatricians.

Functional organization of activation patterns in children: whole brain fMRI imaging during three different cognitive tasks.

1. Patterns of brain activation were measured with whole brain echo-planar functional magnetic resonance imaging (fMRI) at 3.0 Tesla in healthy children (N = 6) and in one child with a left-hemisphere encephalomalacic lesion as sequellae from early stroke. 2. Three cognitive tasks were used: auditory sentence comprehension, verb generation to line drawings, and mental rotation of alphanumeric stimuli. 3. There was evidence for significant bilateral activation in all three cognitive tasks for the healthy children. Their patterns of activation were consistent with previous functional imaging studies with adults. 4. The child with a left-hemisphere stroke showed evidence of homologous organization in the non-damaged hemisphere.

Naltrexone and communication skills in young children with autism.

OBJECTIVE: To evaluate the effect of naltrexone on communication skills of young children with autism. METHOD: Twenty-four children with autism, 3.0 to 8.3 years old (mean 5.1) who were living at home and attending appropriate school programs, participated in a randomized, double-blind, placebo-controlled, crossover trial. Naltrexone, 1.0 mg/kg, or placebo was administered daily for 2 weeks. Communication was evaluated from videotaped samples of seminaturalistic parent-child interaction. Child and parent language were assessed using similar measures. RESULTS: In this heterogeneous sample, the median number of words the child produced on placebo was 9.5 (range 0-124). The median proportion of utterances with echolalia was 0.16. No differences were found between the naltrexone and placebo conditions in any of the measures of children or parents' communication. Significant correlations were found between the child's number of words and developmental quotient (Spearman rho = 0.58, p = .003) and between the child's and parent's number of words (rho = 0.55, p = .005). CONCLUSIONS: Previous studies showed that naltrexone was associated with modest reduction in hyperactivity and restlessness in this group of children with autism. In this short-term study, the medication did not lead to improvement in communication, a core deficit of autism.

Physician-family partnerships: the adaptive practice model.

In the traditional medical model, the physician, acting in the best interests of the patient, assumes full responsibility for delivering information, making decisions about treatment, and providing care. This model is not suitable for chronic care or preventive health maintenance. Recent alternatives to this model include participatory decision-making and family-centered care, clinical approaches in which the patient and family share the responsibility for decision-making with the physician. Research has demonstrated that patients and families vary in their willingness to make decisions about care. The Adaptive Practice model describes how compassionate and effective medical practice ranges from traditional hierarchical relationships to full patient or family control, depending on the situation. Four different clinical approaches--directing, teaching, collaborating, and supporting--result from variations in the direction of leadership and in the degree of interaction in the situation. Each approach is suitable for specific situations. For example, directing is appropriate in emergencies or crises. Supporting is appropriate when families are both knowledgeable and motivated to make decisions that affect their quality of life. Sensitive physicians assess the situation, negotiate an approach suitable to the family's and patient's needs at the time, and adjust their approach as the partnership evolves. The Adaptive Practice model provides a structure for analyzing clinical situations, choosing clinical approaches, and understanding problems in physician-family relationships when they arise.

How pediatricians can respond to the psychosocial implications of disasters. American Academy of Pediatrics. Committee on Psychosocial Aspects of Child and Family Health, 1998-1999.

Natural and human-caused disasters, violence with weapons, and terrorist acts have touched directly the lives of thousands of families with children in the United States.1 Media coverage of disasters has brought images of floods, hurricanes, and airplane crashes into the living rooms of most American families, with limited censorship for vulnerable young children. Therefore, children may be exposed to disastrous events in ways that previous generations never or rarely experienced. Pediatricians should serve as important resources to the community in preparing for disasters, as well as acting in its behalf during and after such events.

Naltrexone in young autistic children: replication study and learning measures.

OBJECTIVE: This study expanded upon previous work on naltrexone efficacy and safety in young autistic children and assessed performance on learning measures. METHOD: Eleven children with autistic disorder, aged 3.0 to 8.3 years, were studied in home, school, and outpatient laboratory, bringing to 24 the combined study sample. Naltrexone, 1.0 mg/kg, was given daily in a randomized, double-blind, crossover design. Dependent measures were parent and teacher Clinical Global Impressions (CGI) and Naltrexone Side Effects Rating Scale (SE), Conners Parent Impulsivity/Hyperactivity Factor, Teacher Hyperactivity Factor, laboratory CGI, and analysis of videotaped behavior. Learning measures were the Early Intervention Developmental Profile-Language and paired-associate learning. RESULTS: Comparisons between naltrexone and baseline, but not naltrexone and placebo, on parent and teacher ratings showed statistical significance. Three of 11 subjects improved in two or more settings. Side effects were mild. Administering naltrexone was a challenge. The combined study sample showed improvement on all parent measures and on Teacher CGI and SE-Restlessness compared with baseline and placebo. Eleven of the 24 children improved in two or more settings. Scores on learning measures did not change across conditions. CONCLUSIONS: Naltrexone was associated with modest improvement of behavior in 11 of 24 children, but learning did not improve.

Naltrexone in young autistic children: a double-blind, placebo-controlled crossover study.

OBJECTIVE: This study evaluated the efficacy and safety of naltrexone, an opiate blocker, in the treatment of autism. METHOD: Thirteen children with autistic disorder, aged 3.4 to 8.3 years (mean 5.4), were studied in home, school, and outpatient laboratory. Naltrexone, 1.0 mg/kg, was given daily in a randomized, double-blind, placebo-controlled crossover design. Dependent measures included parent and teacher Clinical Global Impressions (CGI), Conners Rating Scales, and Naltrexone Side-Effects (SE) Rating Scale; laboratory CGI, movement actometer readings, and a 10-second interval recording system analysis of on-task, communication initiations, disruptive behavior, and self-stimulation. RESULTS: Eight of 13 subjects improved in two or more settings. Changes in parent measures (CGI, Conners Impulsivity-Hyperactivity Factor, and SE-Restlessness) and Teacher CGI achieved statistical significance. Teacher SE-Restlessness and initiation of communication in the clinic showed a trend toward improvement. Actometer readings improved in two children who were very active at baseline. Adverse side effects were behavioral, mild, and transient. Administering the bitter tablet was a challenge. CONCLUSIONS: Naltrexone offers promise as an agent for modest improvement of behavior and social communication in young children with autism. Parent and teacher measures can be useful in outpatient trials to evaluate change.

Parent and professional perceptions about stress and coping strategies during a child's lengthy hospitalization.

The two goals of this study were (1) to describe the stressors and coping strategies of families whose children with chronic illness require lengthy hospitalizations and (2) to compare family reports of stress and coping strategies to professionals perceptions of the same. A non-randomized sample of 13 families (13 mothers and 5 fathers) whose child with chronic illness was hospitalized for a minimum of 30 days and 11 professionals who worked with such children were interviewed in a semi-structured survey using open-ended questions. Key phrases from family interviews were organized into categories of family-reported stressors and coping strategies. Key phrases from professional interviews were categorized into family stressors and descriptions of challenging families. Families and professionals reported that personal emotions and communication problems were the most predominant stressors.

Developmental changes in narrative and non-narrative discourse in children with and without brain injury.

This study presents a set of narrative and non-narrative tasks and analytic procedures for examining the discourse development of children with perinatal brain injury and typically developing children. Three oral discourse genres were collected at ages 5, 6, and 7: script, picture description, and replica play narration. Genre performances were assessed for the presence of hypothesized genre features. Results suggest these tasks and procedures are able to characterize development in discourse abilities for both a normative group and for children with perinatal brain injury. The group of children with brain injury produced shorter discourse performance with more off-task talk. This group also showed difficulty in fully differentiating the various genre types and in creating integrated discourse performances. However, most of these children demonstrated considerable growth in control of genre features over this time period. The possible utility of these tasks and procedures for clinical assessment is discussed.