Abnormal neural sensitivity to rewards as a candidate process of high depression risk in the FMR1 premutation: A pilot study.

The etiological heterogeneity of depression poses a challenge for prevention and intervention efforts. One solution is to map unique etiological pathways for subgroups defined by a singular risk factor. A relevant population for this approach is women who carry the premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene, who are at high risk for adult-onset depression. This study explores a candidate neurophysiological marker of depression risk: reduced reward sensitivity, indexed by the reward positivity (RewP). The RewP has been linked to depression risk in the general population, but is unexplored within FMR1 premutation carriers. 16 women with the FMR1 premutation and a matched control group completed a simple guessing task while the electroencephalogram was recorded. Among premutation carriers, RewP difference score (win versus loss) was reduced. These preliminary finding suggest that the FMR1 premutation may confer increased risk for depression in part through abnormal neural sensitivity to rewards.

Resting-state EEG power differences in autism spectrum disorder: a systematic review and meta-analysis.

Narrative reviews have described various resting-state EEG power differences in autism across all five canonical frequency bands, with increased power for low and high frequencies and reduced power for middle frequencies. However, these differences have yet to be quantified using effect sizes and probed robustly for consistency, which are critical next steps for clinical translation. Following PRISMA guidelines, we conducted a systematic review of published and gray literature on resting-state EEG power in autism. We performed 10 meta-analyses to synthesize and quantify differences in absolute and relative resting-state delta, theta, alpha, beta, and gamma EEG power in autism. We also conducted moderator analyses to determine whether demographic characteristics, methodological details, and risk-of-bias indicators might account for heterogeneous study effect sizes. Our literature search and study selection processes yielded 41 studies involving 1,246 autistic and 1,455 neurotypical individuals. Meta-analytic models of 135 effect sizes demonstrated that autistic individuals exhibited reduced relative alpha (g = -0.35) and increased gamma (absolute: g = 0.37, relative: g = 1.06) power, but similar delta (absolute: g = 0.06, relative: g = 0.10), theta (absolute: g = -0.03, relative: g = -0.15), absolute alpha (g = -0.17), and beta (absolute: g = 0.01, relative: g = 0.08) power. Substantial heterogeneity in effect sizes was observed across all absolute (I2: 36.1-81.9%) and relative (I2: 64.6-84.4%) frequency bands. Moderator analyses revealed that age, biological sex, IQ, referencing scheme, epoch duration, and use of gold-standard autism diagnostic instruments did not moderate study effect sizes. In contrast, resting-state paradigm type (eyes-closed versus eyes-open) moderated absolute beta, relative delta, and relative alpha power effect sizes, and resting-state recording duration moderated relative alpha power effect sizes. These findings support further investigation of resting-state alpha and gamma power as potential biomarkers for autism.

Mother-infant convergence of event-related potentials elicited by face and object processing.

Prior work has provided conceptual support for developmental changes in face and object processing, such that: face processing, as captured by the N290 event-related potential (ERP) component in infancy, may develop into the N170 in adulthood; and motivated attention, as captured by the negative central (Nc) in infancy, may develop into the late positive potential (LPP). The present study examined these neural correlates in 12-month-old infants and their mothers (N = 33 dyads). Dyads completed a viewing task consisting of familiar and novel face and toy stimuli while electroencephalography was recorded. Results suggest that for mothers, the N170 was larger for faces than toys, regardless of familiarity, and the LPP was largest for familiar faces. In infants, the N290 was somewhat larger for faces than toys (p < .10); the Nc did not vary by condition. Adult ERPs demonstrated fair to good reliability; reliability of infant ERPs was lower and was influenced by looking behaviors. Intergenerational associations were strongest between the LPP and Nc, particularly when electrode and time window were taken into account. Refinement of data handling and ERP scoring procedures for infant ERPs are crucial next steps for estimation of intergenerational associations and further examination of developmental changes in face and object processing.

Did you say my name? Congruency of 12-month-old infants' behavioral and cardiac responses to name.

Reduced orienting to name is an early behavioral risk marker for neurodevelopmental disorders. However, individual instances of infants' behavioral responses to name are limited in both reliability and predictive validity. Physiological responses such as heart rate (HR) deceleration may serve as more sensitive metrics than behavioral methods. As a first step toward validating HR deceleration as a candidate psychophysiological measure of name processing, we examined the congruency of behavioral and cardiac responses to name in 12-month-old typically developing infants. Infants exhibited greater median HR deceleration and spent a larger proportion of time in HR deceleration when they behaviorally oriented to their names than when they failed to do so; however, maximum HR deceleration was not related to behavioral responses. These findings provide preliminary evidence that specific HR deceleration metrics may be useful indices of infants' responses to name and may inform psychophysiological mechanisms underlying behavioral responses.

Structural validity of the Child Behavior Checklist (CBCL) for preschoolers with neurogenetic syndromes.

BACKGROUND: Psychologists routinely use the Child Behavior Checklist for Ages 1½-5 (CBCL) to assess challenging behaviors of preschoolers with developmental disabilities. However, the CBCL has not been thoroughly validated in neurogenetic syndromes (NGS). AIM: We investigated the structural validity of the CBCL in NGS. METHODS: Based on 152 preschoolers with Angelman, fragile X, Prader-Willi, and Williams syndromes, we employed confirmatory factor analysis (CFA) to evaluate the goodness-of-fit of CBCL narrowband, broadband, and DSM-oriented scales. RESULTS: CFA models largely supported the unidimensionality of most narrowband scales and the two-factor structure of internalizing and externalizing broadband scales. However, there was limited evidence for the unidimensionality of most DSM-oriented scales. CONCLUSIONS: Psychologists may consider using the CBCL as a psychometrically sound narrowband and broadband measure of challenging behaviors but should exercise caution when interpreting DSM-oriented scales for preschoolers with NGS. Our findings underscore a continued need to enhance assessment measures for identifying early precursors of child psychopathology in pediatric populations with atypical developmental trajectories.

Bringing the Laboratory Home: PANDABox Telehealth-Based Assessment of Neurodevelopmental Risk in Children.

BACKGROUND: Advances in clinical trials have revealed a pressing need for outcome measures appropriate for children with neurogenetic syndromes (NGS). However, the field lacks a standardized, flexible protocol for collecting laboratory-grade experimental data remotely. To address this challenge, we developed PANDABox (Parent-Administered Neurodevelopmental Assessment), a caregiver-facilitated, remotely administered assessment protocol for collecting integrated and high quality clinical, behavioral, and spectral data relevant to a wide array of research questions. Here, we describe PANDABox development and report preliminary data regarding: (1) logistics and cost, (2) caregiver fidelity and satisfaction, and (3) data quality. METHODS: We administered PANDABox to a cohort of 16 geographically diverse caregivers and their infants with Down syndrome. Tasks assessed attention, language, motor, and atypical behaviors. Behavioral and physiological data were synchronized and coded offline by trained research assistants. RESULTS: PANDABox required low resources to administer and was well received by families, with high caregiver fidelity (94%) and infant engagement (91%), as well as high caregiver-reported satisfaction (97% positive). Missing data rates were low for video frames (3%) and vocalization recordings (6%) but were higher for heart rate (25% fully missing and 13% partially missing) and discrete behavioral presses (8% technical issues and 19% not enough codable behavior), reflecting the increased technical demands for these activities. CONCLUSION: With further development, low-cost laboratory-grade research protocols may be remotely administered by caregivers in the family home, opening a new frontier for cost-efficient, scalable assessment studies for children with NGS other neurodevelopmental disorders.

Intergenerational Transmission of Frontal Alpha Asymmetry Among Mother-Infant Dyads.

BACKGROUND: Frontal alpha asymmetry (FAA) is a well-established neurobiological indicator of depression risk. Reduced FAA relates to current and remitted depression in adults and is seen in offspring of mothers with depression as young as 3 months of age, suggesting a potentially transmittable mechanism of depression risk. It is unclear, however, whether direct familial associations exist for FAA. To address this gap, we evaluated the intergenerational transmission of FAA in a nonclinical cohort of mother-infant dyads. METHODS: Mothers and their 12-month-old infants (n = 34 dyads) completed parallel resting-state tasks while electroencephalography was recorded. We measured FAA across a range of putative frequency bands and calculated its reliability in mothers and infants. Finally, we evaluated the heritability of FAA based on the parent-offspring correlation. RESULTS: Mother and infant FAA convergence was strongest in the high alpha range for mothers (11-13 Hz) and broad alpha range for infants (6-9 Hz). Mother high FAA exhibited excellent split-half reliability (rSB = .99) and internal consistency after 80 seconds (α = .90); infant FAA exhibited good split-half reliability (rSB = .81) and fair internal consistency after 70 seconds (α = .74). Mother-infant FAA were moderately correlated (r = .41), which indicates narrow-sense heritability of up to 82%. CONCLUSIONS: FAA can be assessed reliably and relatively quickly in both adults and infants. There is a robust association of FAA between mothers and their infants, supporting intergenerational transmission. This finding is consistent with the possibility that reduced FAA may directly confer depression risk at the individual-family level.

Brief Report: Challenging Behaviors in Toddlers and Preschoolers with Angelman, Prader-Willi, and Williams Syndromes.

Children with neurogenetic syndromes (NGS) experience comorbid challenging behaviors and psychopathology. We examined challenging behaviors in 86 toddlers and preschoolers across three NGS [Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Williams syndrome (WS)] and 43 low-risk controls (LRC), using the Child Behavior Checklist for Ages 1½-5. Challenging behavior profiles differed across NGS, with generally elevated behaviors in AS and WS, but not PWS, relative to LRC. Withdrawn and autism spectrum symptoms were particularly elevated in AS. Although several profiles were similar to those previously reported in older children and adults, we also observed inconsistencies that suggest non-linear developmental patterns of challenging behaviors. These findings underscore the importance of characterizing early challenging behaviors to inform atypical phenotypic development and targeted intervention.