Longitudinal Predictors of Neurodevelopmental Outcomes in Children with Down Syndrome.

This study examined longitudinal predictors of neurodevelopmental outcomes in children with Down syndrome (DS). Participants were assessed at Wave 1 during infancy on measures of looking behavior and caregivers provided infant sensory ratings. At Wave 2, child-age participants completed a developmental assessment and caregivers provided ratings of executive function, ADHD symptoms, and autism symptoms. Longer looking durations and greater sensory dysregulation during infancy were predictive of higher ADHD symptom ratings and other neurodevelopmental outcomes during childhood. The findings suggest that early indicators of neurodevelopmental dysregulation may be detectable during infancy in DS.

Expressive language sampling and outcome measures for treatment trials in fragile X and down syndromes: composite scores and psychometric properties.

The lack of psychometrically sound outcome measures has been a barrier to evaluating the efficacy of treatments proposed for core symptoms of intellectual disability (ID). Research on Expressive Language Sampling (ELS) procedures suggest it is a promising approach to measuring treatment efficacy. ELS entails collecting samples of a participant's talk in interactions with an examiner that are naturalistic but sufficiently structured to ensure consistency and limit examiner effects on the language produced. In this study, we extended previous research on ELS by analyzing an existing dataset to determine whether psychometrically adequate composite scores reflecting multiple dimensions of language can be derived from ELS procedures administered to 6- to 23-year-olds with fragile X syndrome (n = 80) or Down syndrome (n = 78). Data came from ELS conversation and narration procedures administered twice in a 4-week test-retest interval. We found that several composites emerged from variables indexing syntax, vocabulary, planning processes, speech articulation, and talkativeness, although there were some differences in the composites for the two syndromes. Evidence of strong test-retest reliability and construct validity of two of three composites were obtained for each syndrome. Situations in which the composite scores would be useful in evaluating treatment efficacy are outlined.

Dreams share phenomenological similarities with task-unrelated thoughts and relate to variation in trait rumination and COVID-19 concern.

While recent neurocognitive theories have proposed links between dreams and waking life, it remains unclear what kinds of waking thoughts are most similar in their phenomenological characteristics to those of dreams. To investigate this question and examine relevance of dreams to significant personal concerns and dispositional mental health traits, we employed ecological momentary assessment and trait questionnaires across 719 young adults who completed the study during the COVID-19 pandemic, a time marked by considerable societal concern. Across the group and at the level of individual differences, dreams showed the highest correspondence with task-unrelated thoughts. Participants who self-reported greater COVID-19 concern rated their dreams as more negative and unconstructive, a relationship which was moderated by trait rumination. Furthermore, dreams perceived as more negative unconstructive and immersive in nature associated with increased trait rumination beyond variation in rumination explained by waking task-unrelated thoughts alone. Together, these results point to similarities between perceived characteristics of dreams and task-unrelated thoughts, and support a relationship between dreams, current concerns, and mental health.

Profiles of Caregiver-Reported Executive Function in Children with Down Syndrome.

Children with Down syndrome (DS) are at risk for challenges with aspects of executive function (EF). The current study explores whether heterogeneity in EF profiles can be detected within a sample of children with DS. Participants were 69 children with DS, ages 3-10 years (M = 6.23, SD = 1.91). T-scores from a caregiver-report measure of executive function were modeled using latent profile analysis, and auxiliary analyses examined the association between demographic and biomedical factors and probability of profile membership. The two-profile solution was the best fit for the sample, with a profile that involved elevated scores in working memory only ("Working Memory Only" profile; 43% of sample) and a "Multi-Domain" profile that involved elevated scores in planning, inhibition, and working memory (57%). The presence of congenital heart defects was associated with a higher probability of assignment to the Multi-Domain profile. Findings from this study contribute to the characterization of heterogeneous outcomes associated with DS.

Analysis of a Repetitive Language Coding System: Comparisons between Fragile X Syndrome, Autism, and Down Syndrome.

Expressive language sampling (ELS) is a frequently used tool for language analysis, as it can be used across widely ranging cognitive and language abilities. ELS can also evaluate pragmatic language, including excessive self-repetition, which is challenging to assess with traditional standardized assessments. This study explored how a well-established ELS protocol can assess three types of linguistic self-repetition in three neurodevelopmental disabilities: fragile X syndrome (FXS), autism spectrum disorder (ASD), and Down syndrome (DS). We examined its ability to differentiate between these disorders, the relationships between repetitive language and other participant characteristics, and initial construct validity. We found that the groups with FXS and ASD differed significantly on each of the three repetitive language measure, and that the group with DS differed from either ASD or FXS on two. Cognitive ability was significantly related to phrase repetition in the group with ASD. When the groups were combined, there was evidence of convergent and divergent validity. This study extends previous research on ELS and supports its use as a means to characterize pragmatic language. It also provides information about the relationships between repetitive language and other phenotypic characteristics.

Spoken language outcome measures for treatment studies in Down syndrome: feasibility, practice effects, test-retest reliability, and construct validity of variables generated from expressive language sampling.

BACKGROUND: The purpose of this study was to evaluate expressive language sampling (ELS) as a procedure for generating spoken language outcome measures for treatment research in Down syndrome (DS). We addressed (a) feasibility, (b) practice effects across two short-term administrations, (c) test-retest reliability across two short-term administrations, (d) convergent and discriminant construct validity, and (e) considered comparisons across the conversation and narration contexts. METHOD: Participants were 107 individuals with DS between 6 and 23 years of age who presented with intellectual disability (IQ < 70). The utility of ELS procedures designed to collect samples of spoken language in conversation and narration were evaluated separately. Variables of talkativeness, vocabulary, syntax, utterance planning, and articulation quality, derived from transcripts segmented into C-units (i.e., an independent clause and its modifiers), were considered. A 4-week interval was used to assess practice effects and test-retest reliability. Standardized direct assessments and informant report measures were collected to evaluate construct validity of the ELS variables. RESULTS: Low rates of noncompliance were observed; youth who were under 12 years of age, had phrase-level speech or less, and had a 4-year-old developmental level or less were at particular risk for experiencing difficulty completing the ELS procedures. Minimal practice effects and strong test-retest reliability across the 4-week test-retest interval was observed. The vocabulary, syntax, and speech intelligibility variables demonstrated strong convergent and discriminant validity. Although significant correlations were found between the variables derived from both the conversation and narration contexts, some differences were noted. CONCLUSION: The ELS procedures considered were feasible and yielded variables with adequate psychometric properties for most individuals with DS between 6 and 23 years old. That said, studies of outcome measures appropriate for individuals with DS with more limited spoken language skills are needed. Context differences were observed in ELS variables suggest that comprehensive evaluation of expressive language is likely best obtained when utilizing both contexts.

Dreaming with hippocampal damage.

The hippocampus is linked with both sleep and memory, but there is debate about whether a salient aspect of sleep - dreaming - requires its input. To address this question, we investigated if human patients with focal bilateral hippocampal damage and amnesia engaged in dreaming. We employed a provoked awakening protocol where participants were woken up at various points throughout the night, including during non-rapid eye movement and rapid eye movement sleep, to report their thoughts in that moment. Despite being roused a similar number of times, dream frequency was reduced in the patients compared to control participants, and the few dreams they reported were less episodic-like in nature and lacked content. These results suggest that hippocampal integrity may be necessary for typical dreaming to occur, and aligns dreaming with other hippocampal-dependent processes such as episodic memory that are central to supporting our mental life.

Dreaming has intrigued humans for thousands of years, but why we dream still remains somewhat of a mystery. Although dreams are not a precise replay of our memories, one idea is that dreaming helps people process past experiences as they sleep. If this is true, then part of the brain called the hippocampus that is important for memory should also be necessary for dreaming. Damage to the hippocampus can cause a condition called amnesia that prevents people from forming new memories and remembering past experiences. However, studies examining dreaming in people with amnesia have produced mixed results: some found that damage to the hippocampus had no effect on dreams, while others found it caused people to have repetitive dreams that lacked detail. One reason for these inconsistencies is that some studies asked participants about their dreams the next morning by which time most people, particularly those with amnesia, have forgotten if they dreamed. To overcome this limitation, Spanò et al. asked participants about their dreams immediately after being woken up at various points during the night. The experiment was carried out with four people who had damage to both the left and right hippocampus and ten healthy volunteers. Spanò et al. found that the people with hippocampal damage reported fewer dreams and the dreams they had were much less detailed. These findings suggest that a healthy hippocampus is necessary for both memory and dreaming, reinforcing the link between the two. Hippocampal damage is associated with a number of diseases, including dementia. If these diseases cause patients to dream less, this may worsen the memory difficulties associated with these conditions.

Correction to: Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity.

In the original publication of this article [1], the author name Leonard Abbeduto was misspelled as Leonardkk Abbeduto. The original article has been corrected.

Expressive language sampling as a source of outcome measures for treatment studies in fragile X syndrome: feasibility, practice effects, test-retest reliability, and construct validity.

BACKGROUND: The evaluation of treatment efficacy for individuals with fragile X syndrome (FXS) or intellectual disability (ID) more generally has been hampered by the lack of adequate outcome measures. We evaluated expressive language sampling (ELS) as a procedure for generating outcome measures for treatment research in FXS. We addressed: (a) feasibility, (b) practice effects over two administrations, (c) test-retest reliability over the repeated administrations, and (d) construct validity. We addressed these issues for the full sample as well as for subgroups defined by age, IQ, and ASD status. METHODS: Participants were 106 individuals with FXS between ages 6 and 23 years who had IQs within the range of intellectual disability (IQ < 70). ELS procedures for collecting samples in conversation and narration were followed and analyzed separately. Five measures were derived from transcripts segmented into C-units (i.e., an independent clause and its modifiers): number of C-units per minute (talkativeness), number of different word roots (vocabulary), C-unit length in morphemes (syntax), percentage of C-units containing dysfluency (utterance planning), and percentage of C-units that were fully or partly unintelligible (articulatory quality). ELS procedures were administered twice at 4-week intervals for each participant. Standardized tests and informant reports were administered and provided measures for evaluating construct validity of ELS measures. RESULTS: We found low rates of noncompliance, suggesting the task can be completed meaningfully by most individuals with FXS, although noncompliance was higher for younger, lower IQ, and more autistic participants. Minimal practice effects and strong test-retest reliability over the 4-week interval were observed for the full sample and across the range of ages, IQs, and autism symptom severity. Evidence of convergent construct validity was observed for the measures of vocabulary, syntax, and unintelligibility for the full sample and across the range of IQ and autism symptom severity, but not for participants under age 12. Conversation and narration yielded largely similar results in all analyses. CONCLUSIONS: The findings suggest that the ELS procedures are feasible and yield measures with adequate psychometric properties for a majority of 6 to 23 years with FXS who have ID. The procedures work equally well regardless of level of ID or degree of ASD severity. The procedures, however, are more challenging and have somewhat less adequate psychometric properties for individuals with FXS under age 12.

OSA and Neurocognitive Impairment in Children With Congenital Heart Disease.

BACKGROUND: Children with congenital heart disease (CHD) have an increased risk of neurocognitive impairment. No prior studies have evaluated the role of OSA, which is associated with neurocognitive impairment in children without CHD. RESEARCH QUESTION: Is OSA is associated with neurocognitive impairment in children with CHD? STUDY DESIGN AND METHODS: Children aged 6 to 17 years with corrected moderate to complex CHD without syndromes that may affect neurocognition were recruited from the pediatric cardiology clinic. Participants underwent home sleep testing and neurocognitive testing, including a validated Intellectual Quotient (IQ) test as well as validated tests of memory (Paired Associates Learning test), executive function (Intra-Extra Dimensional set shift test), and attention (Simple Reaction Test) from the CANTAB neurocognitive testing battery. RESULTS: Complete results were available for 30 children. Seventeen children (57%) were found to have OSA. Total IQ was markedly lower in children with CHD and comorbid OSA compared with children with CHD without comorbid OSA (mean, 86 ± 12 vs 98 ± 11; P = .01). Children with CHD and OSA did significantly worse on the Paired Associates Learning test, with a median of eight total errors (interquartile range [IQR], 2.25-15) compared with children with CHD without OSA (median total errors, 2, IQR, 1-8; P = .02). INTERPRETATION: Children with CHD and comorbid OSA have impaired neurocognition compared with children with CHD without comorbid OSA. OSA may be a reversible cause of neurocognitive impairment in children with CHD. Further research is needed to evaluate the effects of OSA treatment on neurocognitive impairment in children with CHD.

Sleeping with Hippocampal Damage.

The hippocampus plays a critical role in sleep-related memory processes [1-3], but it is unclear which specific sleep features are dependent upon this brain structure. The examination of sleep physiology in patients with focal bilateral hippocampal damage and amnesia could supply important evidence regarding these links. However, there is a dearth of such studies, despite these patients providing compelling insights into awake cognition [4, 5]. Here, we sought to identify the contribution of the hippocampus to the sleep phenotype by characterizing sleep via comprehensive qualitative and quantitative analyses in memory-impaired patients with selective bilateral hippocampal damage and matched control participants using in-home polysomnography on 4 nights. We found that, compared to control participants, patients had significantly reduced slow-wave sleep-likely due to decreased density of slow waves-as well as slow-wave activity. In contrast, slow and fast spindles were indistinguishable from those of control participants. Moreover, patients expressed slow oscillations (SOs), and SO-fast spindle coupling was observed. However, on closer scrutiny, we noted that the timing of spindles within the SO cycle was delayed in the patients. The shift of patients' spindles into the later phase of the up-state within the SO cycle may indicate a mismatch in timing across the SO-spindle-ripple events that are associated with memory consolidation [6, 7]. The substantial effect of selective bilateral hippocampal damage on large-scale oscillatory activity in the cortex suggests that, as with awake cognition, the hippocampus plays a significant role in sleep physiology, which may, in turn, be necessary for efficacious episodic memory.

The "eyes have it," but when in development?: The importance of a developmental perspective in our understanding of behavioral memory formation and the hippocampus.

Lynn Nadel has been a trailblazer in memory research for decades. In just one example, Nadel and Zola-Morgan [Infantile amnesia, In Infant memory, Springer, Boston, MA, 1984, pp. 145-172] were the first to present the provocative notion that the extended development of the hippocampus may underlie the period of infantile amnesia. In this special issue of Hippocampus to honor Lynn Nadel, we review some of his major contributions to the field of memory development, with an emphasis on his observations that behavioral memory assessments follow an uneven, yet protracted developmental course. We present data emphasizing this point from memory-related eye movements [Hannula & Ranganath, Neuron, 2009, 63(5), 592-599]. Eye tracking is a sensitive behavioral measure, allowing for an indication of memory function even without overt responses, which is seemingly ideal for the investigation of memory in early childhood or in other nonverbal populations. However, the behavioral manifestation of these eye movements follows a U-shaped trajectory-and one that must be understood before these indictors could be broadly used as a marker of memory. We examine the change in preferential looking time to target stimuli in school-aged children and adults, and compare these eye movement responses to explicit recall measures. Our findings indicate change in the nature and timing of these eye movements in older children, causing us to question how 6-month-old infants may produce eye movements that initially appear to have the same properties as those measured in adulthood. We discuss these findings in the context of our current understanding of memory development, particularly the period of infantile amnesia.

Mother Knows Best? Comparing Child Report and Parent Report of Sleep Parameters With Polysomnography.

STUDY OBJECTIVES: Parent report or child report is commonly used to obtain information on sleep in children. Data are lacking comparing the validity of parent-reported versus child-reported sleep parameters. METHODS: A total of 285 children (age 9 to 17 years) from the Tucson Children's Assessment of Sleep Apnea community cohort study were assessed. Parent report and child report of total sleep time (TST), sleep latency (SL), and sleep efficiency (SE) for a single night were compared to polysomnography (PSG). Intraclass correlations (ICCs) were used to evaluate agreement between child report, parent report, and PSG findings. RESULTS: When compared to PSG, children overestimated TST by a median of 32 minutes (interquartile range [IQR] 6 to 68), whereas parents overestimated TST by 36 minutes (IQR 13-70) (P = .006). Children overestimated SL by 4 minutes (IQR -8 to 20), whereas parents overestimated SL by 2 minutes (IQR -10 to 13) (P = .001). Children overestimated SE by 5% (IQR 0% to 11%), whereas parents overestimated SE by 6% (IQR 2% to 11%, P = .04). Both child-reported TST (ICC 0.722, P < .001) and parent-reported TST (ICC 0.776, P < .001) agreed substantially with PSG. Child-reported SL (ICC 0.467, P < .001) and parent-reported SL (r = .419, P < .001) moderately agreed with PSG. Least agreement with PSG was seen between child-reported SE (ICC 0.404, P < .001) and parent-reported SE (ICC 0.473, P < .001), but significant agreement was still present. CONCLUSIONS: When compared to PSG, children overestimate TST to a smaller degree than their parents and overestimate SL to a larger degree than their parents, but these differences appear small. Child and parent reports appear to be equally valid for TST, SL, and SE.

Associations Between Medical History, Cognition, and Behavior in Youth With Down Syndrome: A Report From the Down Syndrome Cognition Project.

The cause of the high degree of variability in cognition and behavior among individuals with Down syndrome (DS) is unknown. We hypothesized that birth defects requiring surgery in the first years of life (congenital heart defects and gastrointestinal defects) might affect an individual's level of function. We used data from the first 234 individuals, age 6-25 years, enrolled in the Down Syndrome Cognition Project (DSCP) to test this hypothesis. Data were drawn from medical records, parent interviews, and a cognitive and behavior assessment battery. Results did not support our hypothesis. That is, we found no evidence that either birth defect was associated with poorer outcomes, adjusting for gender, race/ethnicity, and socioeconomic status. Implications for study design and measurement are discussed.

REM sleep in naps differentially relates to memory consolidation in typical preschoolers and children with Down syndrome.

Sleep is recognized as a physiological state associated with learning, with studies showing that knowledge acquisition improves with naps. Little work has examined sleep-dependent learning in people with developmental disorders, for whom sleep quality is often impaired. We examined the effect of natural, in-home naps on word learning in typical young children and children with Down syndrome (DS). Despite similar immediate memory retention, naps benefitted memory performance in typical children but hindered performance in children with DS, who retained less when tested after a nap, but were more accurate after a wake interval. These effects of napping persisted 24 h later in both groups, even after an intervening overnight period of sleep. During naps in typical children, memory retention for object-label associations correlated positively with percent of time in rapid eye movement (REM) sleep. However, in children with DS, a population with reduced REM, learning was impaired, but only after the nap. This finding shows that a nap can increase memory loss in a subpopulation, highlighting that naps are not universally beneficial. Further, in healthy preschooler's naps, processes in REM sleep may benefit learning.

Functional neural bases of numerosity judgments in healthy adults born preterm.

High rates of mathematics learning disabilities among individuals born preterm (<37weeksGA) have spurred calls for a greater understanding of the nature of these weaknesses and their neural underpinnings. Groups of healthy, high functioning young adults born preterm and full term (n=20) completed a symbolic and non-symbolic magnitude comparison task while undergoing functional MRI scanning. Collectively, participants showed activation in superior and inferior frontal and parietal regions previously linked to numeric processing when comparing non-symbolic magnitude arrays separated by small numeric distances. Simultaneous deactivation of the default mode network also was evident during these trials. Individuals born preterm showed increased signal change relative to their full term peers in right inferior frontal and parietal regions when comparing the non-symbolic magnitude arrays. Elevated signal change during non-symbolic task blocks was associated with poorer performance on a calculation task administered outside of the scanner. These findings indicate that healthy, high-functioning adults born preterm may recruit fronto-parietal networks more extensively when processing non-symbolic magnitudes, suggesting that approximate number system training may be an inroad for early intervention to prevent mathematics difficulties in this population.

The Arizona Cognitive Test Battery for Down Syndrome: Test-Retest Reliability and Practice Effects.

A multisite study investigated the test-retest reliability and practice effects of a battery of assessments to measure neurocognitive function in individuals with Down syndrome (DS). The study aimed to establish the appropriateness of these measures as potential endpoints for clinical trials. Neurocognitive tasks and parent report measures comprising the Arizona Cognitive Test Battery (ACTB) were administered to 54 young participants with DS (7-20 years of age) with mild to moderate levels of intellectual disability in an initial baseline evaluation and a follow-up assessment 3 months later. Although revisions to ACTB measures are indicated, results demonstrate adequate levels of reliability and resistance to practice effects for some measures. The ACTB offers viable options for repeated testing of memory, motor planning, behavioral regulation, and attention. Alternative measures of executive functioning are required.

Young children with Down syndrome show normal development of circadian rhythms, but poor sleep efficiency: a cross-sectional study across the first 60 months of life.

OBJECTIVES: To evaluate sleep consolidation and circadian activity rhythms in infants and toddlers with Down syndrome (DS) under light and socially entrained conditions within a familiar setting. Given previous human and animal data suggesting intact circadian regulation of melatonin across the day and night, it was hypothesized that behavioral indices of circadian rhythmicity would likewise be intact in the sample with DS. METHODS: A cross-sectional study of 66 infants and young children with DS, aged 5-67 months, and 43 typically developing age-matched controls. Sleep and measures of circadian robustness or timing were quantified using continuous in-home actigraphy recordings performed over seven days. Circadian robustness was quantified via time series analysis of rest-activity patterns. Phase markers of circadian timing were calculated alongside these values. Sleep efficiency was also estimated based on the actigraphy recordings. RESULTS: This study provided further evidence that general sleep quality is poor in infants and toddlers with DS, a population that has sleep apnea prevalence as high as 50% during the preschool years. Despite poor sleep quality, circadian rhythm and phase were preserved in children with DS and displayed similar developmental trajectories in cross-sectional comparisons with a typically developing (TD) cohort. In line with past work, lower sleep efficiency scores were quantified in the group with DS relative to TD children. Infants born with DS exhibited the worst sleep fragmentation; however, in both groups, sleep efficiency and consolidation increased across age. Three circadian phase markers showed that 35% of the recruitment sample with DS was phase-advanced to an earlier morning schedule, suggesting significant within-group variability in the timing of their daily activity rhythms. CONCLUSIONS: Circadian rhythms of wake and sleep are robust in children born with DS. The present results suggest that sleep fragmentation and any resultant cognitive deficits are likely not confounded by corresponding deficits in circadian rhythms.

The medial temporal memory system in Down syndrome: Translating animal models of hippocampal compromise.

Recent studies have highlighted the dentate gyrus as a region of increased vulnerability in mouse models of Down syndrome (DS). It is unclear to what extent these findings are reflected in the memory profile of people with the condition. We developed a series of novel tasks to probe distinct medial temporal functions in children and young adults with DS, including object, spatial, and temporal order memory. Relative to mental age-matched controls (n = 45), individuals with DS (n = 28) were unimpaired on subtests involving short-term object or configural recall that was divorced from spatial or temporal contexts. By contrast, the DS group had difficulty recalling spatial locations when contextual information was salient and recalling the order in which objects were serially presented. Results are consistent with dysfunction of spatial and temporal contextual pattern separation abilities in individuals with DS, mediated by the hippocampus, including the dentate gyrus. Amidst increasing calls to bridge human and animal work, the memory profile demonstrated here in humans with DS is strikingly similar to that of the Ts65Dn mouse model of DS. The study highlights the trisynaptic circuit as a potentially fruitful intervention target to mitigate cognitive impairments associated with DS.