The COVID-19 pandemic significantly disrupted schools and learning formats. Children with epilepsy are at-risk for generalized academic difficulties. We investigated the potential impact of COVID-19 on learning in those with epilepsy by comparing achievement on well-established academic measures among school-age children with epilepsy referred prior to the COVID-19 pandemic and those referred during the COVID-19 pandemic.

This study included 466 children [52% male, predominately White (76%), MAge=10.75 years] enrolled in the Pediatric Epilepsy Research Consortium Epilepsy (PERC) Surgery database project who were referred for surgery and seen for neuropsychological testing. Patients were divided into two groups based on a proxy measure of pandemic timing completed by PERC research staff at each site (i.e., “were there any changes to typical in-person administration [of the evaluation] due to COVID?”). 31% of the sample (N = 144) were identified as having testing during the pandemic (i.e., “yes” response), while 69% were identified as having testing done pre-pandemic (i.e., “no” response). Of the 31% who answered yes, 99% of administration changes pertained to in-person testing or other changes, with 1% indicating remote testing. Academic achievement was assessed by performance measures (i.e., word reading, reading comprehension, spelling, math calculations, and math word problems) across several different tests. T-tests compared the two groups on each academic domain. Subsequent analyses examined potential differences in academic achievement among age cohorts that approximately matched grade level [i.e., grade school (ages 5-10), middle school (ages 11-14), and high school (ages 15-18)].

No significant differences were found between children who underwent an evaluation before the pandemic compared to those assessed during the pandemic based on age norms across academic achievement subtests (all p’s > .34). Similarly, there were no significant differences among age cohorts. The average performance for each age cohort generally fell in the low average range across academic skills. Performance inconsistently varied between age cohorts. The youngest cohort (ages 5-10) scored lower than the other cohorts for sight-word reading, whereas this cohort scored higher than the middle cohort (ages 11-14) for math word problems and reading comprehension. There were no significant differences between the two pandemic groups on demographic variables, intellectual functioning, or epilepsy variables (i.e., age of onset, number of seizure medications, seizure frequency).

Academic functioning was generally equivalent between children with epilepsy who underwent academic testing as part of a pre-surgical evaluation prior to the pandemic compared to those who received testing during the pandemic. Additionally, academic functioning did not significantly differ between age cohorts. Children with epilepsy may have entered the pandemic with effective academic supports and/or were accustomed to school disruptions given their seizure history. Replication is needed as findings are based on a proxy measure of pandemic timing and the extent to which children experienced in-person, remote, and hybrid learning is unknown. Children tested a year into the pandemic, after receiving instruction through varying educational methods, may score differently than those tested earlier. Future research can address these gaps. Although it is encouraging that academic functioning was not disproportionately impacted during the pandemic in this sample, children with epilepsy are at-risk for generalized academic difficulties and continued monitoring of academic functioning is necessary.

Pediatric cancer and cancer-related treatments may disrupt brain development and place survivors at risk for long term problems with cognitive functions. Processing efficiency has been operationalized as a nuanced cognitive skill that reflects both processing speed (PS) and working memory (WM) abilities and is sensitive to neurobiological disruption. Pediatric cancer survivors are at risk for processing efficiency deficits; however, a thorough characterization of processing efficiency skills across pediatric primary central nervous system (CNS) tumor and non-CNS cancer survivors has not yet been reported.

Participants were selected from a mixed retrospective clinical database of pediatric cancer survivors (Total n=160; primary CNS tumor n=33; Non-CNS n=127). Univariate analyses were conducted to examine differences in processing efficiency mean scores (t-tests) and percent impairment (scores >1 SD below mean; chi-squared tests) between the total sample and normative sample, and across groups (CNS vs. Non-CNS). Multiple linear regressions were utilized to evaluate the relationships between additional risk factors, including biological sex, age at diagnosis, time since treatment, and socioeconomic status, and processing efficiency outcomes.

The total sample obtained lower scores on WM (M=90.83, SD=13.35) and PS (M=88.86, SD=14.38) measures than normative samples (M=100, SD=15), p < 0.001. Greater percentage of pediatric cancer survivors demonstrated impairment across all processing efficiency measures (24.8-38.1%) than normative samples (15.9%), p < 0.001. Regarding group differences, the CNS group obtained lower mean WM (M=84.85, SD =11.77) and PS (M=80, SD=14.18) scores than the Non-CNS group (WM M=92.39, SD=13.32; PS M=91.16, SD=13.56), p < 0.001. Rates of impairment between groups only differed for PS scores, with 63.6% of the CNS group and 31.5% of the non-CNS group demonstrating impairment, p < 0.001. Primary CNS tumor cancer type and male biological sex emerged as the only significant risk factors that predicted processing efficiency skills, with male sex predicting lower scores on PS (ß=8.91 p<.001) and semantic fluency (ß=7.59, p=.007).

These findings indicate that both pediatric primary CNS tumor and non-CNS cancer survivors exhibit substantial weaknesses in processing efficiency skills after treatment. While both groups demonstrated deficits compared to normative samples, the CNS group was more susceptible to PS impairments than non-CNS group. A basic initial study of the relationships between risk factors and processing efficiency skills revealed that primary CNS cancer was a predictor of lower performance on working memory and processing speed measures, while male biological sex was a significant risk factor for worse performance on processing speed and semantic fluency measures. Continued focus on the construct of processing efficiency in pediatric cancer survivors is warranted. Applying a standardized approach to assessing and communicating this nuanced cognitive skill could contribute to advancing both clinical practice and outcomes research of pediatric cancer survivors.

Psychosocial factors show a significant relationship between child behavior problems, family functioning, and cognitive performance in children with Sickle Cell Disease, marking those as important targets for intervention among this population. The purpose of this research is to address the effects of psychosocial factors impact on specific cognitive domains.

Archival data from the National Institutes of Health’s Cooperative Study of Sickle Cell Disease was used. Data was restricted to individuals aged 14 or younger (N= 2,408), with 47.8% (n = 1,152) identified as female and 52.2% (n = 1,256) as male. Black or African American (96.9%, n = 2,334) children made up the majority of the sample, with the remainder coded as “other” (2.8%, n = 68). The measures utilized included the Wechsler Intelligence Scale for Children-Revised (WISC-R), Wechsler Intelligence Scale for Children-Third Edition (WISC-III), Peabody Picture Vocabulary Test (PPVT), Achenbach Child Behavior Checklist, and Family Environment Scale (FES).

Bivariate correlations were completed with significant correlations found between FES and performance on the WISC-R/III and PPVT. Supportiveness subscale on the FES demonstrated several statistically significant correlations with WAIS FSIQ (r = .21, p = .000) as well as the Information (r = .22, p = .000), Similarities (r = .17, p = .001), Arithmetic (r = .13, p = .021), Block Design (r = .11, p = .036), Vocabulary (r = .22, p = .000), Object Assembly (r = .12, p = .033), Comprehension (r = .19, p = .000), and Digit Span (r = .13, p = .014) subscales. A statistically significant correlation was observed between the PPVT and the Supportiveness subscale (r = .34, p = .000).

Various areas of cognitive functioning are affected by family dynamics. Improvement in family functioning would benefit the cognitive functioning of children with SCD. To increase aspects of family functioning including supportiveness, early identification of children with SCD, targeted interventions, and family and/or individual therapy for caregivers are suggested.

Survivors of childhood ALL treated with CNS-directed chemotherapy are at risk for neurocognitive deficits that emerge during treatment and impact functional and quality of life outcomes throughout survivorship. Neurocognitive monitoring is the recommended standard of care for this population; however, information on assessment timing and recommendations for assessment measures are limited. We examined the role of serial neurocognitive monitoring completed during protocol-directed therapy in predicting parent-reported neurocognitive late effects during survivorship.

Parents of 61 survivors of childhood ALL completed a semi-structured survey focused on parent perspective of neurocognitive late effects as part of a quality improvement project. Survivors completed protocol-directed treatment for newly diagnosed ALL on two consecutive clinical trials (St. Jude Total Therapy Study 15, 47.5%; Total Therapy 16, 52.5%). The majority of survivors were White (86.9%), 52.5% were male, and 49% were treated for low risk disease. Mean age at diagnosis was 7.77 years (standard deviation [SD] = 5.31). Mean age at survey completion was 15.25 years (SD = 6.29). Survivors completed neurocognitive monitoring at two prospectively determined time points during and at the end of protocol-directed therapy for childhood ALL.

During survivorship, parents reported that 73.8% of survivors experienced neurocognitive late effects, with no difference in frequency of endorsement by protocol (p = .349), age at diagnosis (p = .939), patient sex (p = .417), or treatment risk arm (p = .095). In survivors with late effects, 44.3% sought intervention in the form of educational programming (i.e., 504 or Individualized Education Program). Among the group with late effects, compared to those without educational programming, those with educational programming had worse verbal learning (CVLT Trials 1-5 Total, Mean[SD]; T = 56.36 [11.19], 47.00 [10.12], p = .047) and verbal memory (CVLT Short Delay Free Recall, Z = 0.86 [0.67], -0.21 [1.01], p = .007); Long Delay Free Recall, Z = 0.91 [0.92], -0.25 [1.25], p = .020) during therapy. Compared to those without educational programming, survivors with educational programming had lower estimated IQ (SS = 109.25 [13.48], 98.07 [15.74], p = .045) and greater inattention [CPT Beta T = 56.80 [13.95], 75.70 [22.93], p = .017) at the end of therapy.

Parents report that nearly three quarters of children treated for ALL with chemotherapy only experience neurocognitive late effects during early survivorship, with no difference in frequency by established risk factors. Of those with late effects, nearly half required educational programming implemented after diagnosis, suggesting a significant impact on school performance. Results from neurocognitive monitoring beginning during therapy has utility for predicting educational need in survivors experiencing late effects. Our findings provide direction on the timing and content of neurocognitive monitoring, which is the recommended standard of care for childhood cancer patients treated with CNS-directed therapy.

Accumulating evidence suggests that corpus callosum development is critically involved in the emergence of behavioral and cognitive skills during the first two years of life and that structural abnormalities of the corpus callosum are associated with a variety of neurodevelopmental disorders. Indeed by adulthood ∼30% of individuals with agenesis of the corpus callosum (ACC), a congenital condition resulting in a partial or fully absent corpus callosum, exhibit phenotypic features consistent with autism spectrum disorder (ASD). However, very little is known about developmental similarities and/or differences among infants with ACC and infants who develop ASD. This study describes temperament in infants with ACC during the first year of life in comparison with a neurotypical control group. Additionally, it examines the potential contribution of disrupted callosal connectivity to early expression of temperament in ASD through comparison to children with high familial likelihood of ASD.

Longitudinal ratings of positive and negative emotionality were acquired at 6 and 12 months on the Infant Behavior Questionnaire-Revised across four groups of infants: isolated complete and partial ACC (n=104), high familial likelihood of ASD who do and do not have a confirmed ASD diagnosis (HL+ n=81, HL- n=282), and low-likelihood controls (LL- n=152).

Overall, the ACC group demonstrated blunted affect, with significantly lower positive and negative emotionality than LL controls at both timepoints. Specifically, the ACC group exhibited lower activity and approach dimensions of positive emotionality at both timepoints, with lower high-intensity pleasure at 6 months and lower vocal reactivity at 12 months. On negative emotionality subscales, the ACC group exhibited lower distress to limitations and sadness at both timepoints, as well as lower falling reactivity at 6 months. The ACC and HL groups did not differ significantly on positive emotionality at either timepoint. However, negative emotionality was lower in the ACC group than the HL- group at both timepoints and lower than the HL+ group at 12 months, with lower distress to limitations and sadness ratings than both HL groups at both timepoints.

These findings highlight the importance of interhemispheric connections in facilitating active engagement and pursuit of pleasurable activities during the first year of life, as well as expression of sadness and distress to limitations. Notably, similarities between infants with ACC and infants at elevated familial risk of ASD suggest that disrupted callosal connectivity may specifically contribute to reductions in positive emotionality.

Traumatic brain injury (TBI) is a prevalent cause of long-term morbidity in children and adolescents and can lead to persistent difficulties with social and behavioral function. TBI may impact brain structures that support social cognition, social perception, and day-to-day social interactions—termed the social brain network (SBN). We examined differences in links among the SBN and regions of interest from other neural networks thought to support social outcomes, i.e., the default mode network (DMN) and salience network (SN). Furthermore, we examined how differences in co-activation among the SBN and these other key networks were associated with ratings of social and day-to-day adaptive outcomes.

Participants included children and adolescents with moderate to severe TBI (msTBI; n=11, Mage=11.78, 6 male), complicated-mild TBI (cmTBI; n=12, Mage=12.59, 9 male), and orthopedic injury (OI; n=22, Mage=11.69, 15 male). Participants underwent resting-state functional MRI on a 3Tesla Siemens Prisma scanner. Parents rated their child’s social and adaptive function on the Child Behavior Checklist (CBCL) and Adaptive Behavior Assessment System-Third Edition (ABAS-3). Resting-state connectivity was assessed using the CONN Toolbox, including preprocessing, denoising, and alignment to the participants’ processed T1 MPRAGE sequence followed by seed-to-voxel analysis using a SBN mask and targeted regions of interest within the DMN and SN. Individual-level r-to-z correlations were extracted from resulting clusters of co-activation with the SBN mask and exported into SPSSv28.0 for integration with behavioral data.

One-way ANOVAs used to examine group differences in social and adaptive outcome revealed significant group differences in CBCL Social Competence (F=4.49, p=.019) and all composite scores on the ABAS-3 (Fs=3.78 to 5.17, ps=.031 to .010). In each domain, children with msTBI were rated as having elevated difficulties relative to cmTBI or OI, whereas cmTBI and OI groups did not differ. Connectivity also differed significantly between groups, with children with OI demonstrating greater connectivity between the SBN and the anterior cingulate cortex of the SN (t=5.19, p(FDR)<.0001) and posterior cingulate cortex of the DMN (f=4.30, p(FDR)<.001) than children with msTBI. Children with cmTBI also showed greater connectivity between the SBN and left temporal pole of the DMN (t=7.45, p(FDR)<.000001) than children with msTBI. Degree of connectivity between the SBN and posterior cingulate was significantly positively correlated across all domains of adaptive function (rs=.451 to .504, ps=.010 to .003), whereas degree of connectivity between the SBN and left temporal pole was strongly positively related to Social Competence (a=.633, p=.006) and conceptual adaptive skills on the ABAS (A=.437, p=.037).

Our findings provide insights into the neural substrates of social and adaptive morbidity after pediatric TBI, particularly msTBI, by linking alterations in connectivity among the SBN, DMN, and SN with measures of social and adaptive outcome. While the posterior cingulate was broadly associated with adaptive outcome, the temporal pole was particularly strongly associated with social competence. This may reflect the diverse functions and high degree of interconnectivity of the posterior cingulate, which contributes to various cognitive and attentional processes, relative to the strong amygdala/limbic connections of the temporal pole.

Inflicted traumatic brain injury (TBI) is one of the leading causes of childhood injury and death. Studies have consistently demonstrated worse outcomes for children with inflicted TBIs compared to accidental TBIs. Out of home placement, a known developmental risk factor, is a frequent occurrence in inflicted TBI, which may also contribute to worse outcomes for children. Little is known about what injury, child, and family factors predict out-of-home versus in-home placements. We hypothesize that injury severity, child, and family risk factors will be predictive of out-of-home placement after hospital discharge from an inflicted TBI.

Participants included 175 children with inflicted head injuries ages who received care at a large children’s hospital from 2012 to 2021. 88% of children were alive at discharge and were included in the study. The total sample included 154 children. Ages ranged from 0.2 to 76 months (M = 11.81, SD = 14.50) and 64.9 % were male. Race/Ethnicity distribution was as follows: 66.9% White, 29.9% Latinx or Hispanic, 4.6% Black, 3.3% American Indian or Alaskan, and 22.5% identified another race or ethnicity or identified as multiracial. Measures included injury severity (e.g., days spent in the PICU, post-resuscitation GCS), child (e.g., race/ethnicity, gender), and family factors (e.g., prior history of domestic violence, type of insurance). Individual logistic regressions were run to assess the effect of each injury severity, child, and family factor on placement after hospital discharge.

Results indicated that having a caregiver with a history of mental health difficulties and/or a history of substance abuse increased the likelihood of an out-of-home placement for the child after an inflicted TBI. Results also demonstrated that the more caregiver psychosocial concerns reported, the higher the risk of an out-of-home placement for the child after discharge from the hospital. Finally, results indicated that having public insurance significantly increased the risk of an out-of-home placement for the child after discharge from the hospital. Post-hoc analyses were conducted to assess the effect of insurance type on out-of-home placement, while controlling for psychosocial concerns. Results indicated that, even when taking total psychosocial concerns into account, having public insurance significantly increased the risk of an out-of-home placement. Logistic regressions were carried out to assess the effect of injury severity, child, and every other family factor (e.g., prior criminal history) on placement after hospital discharge and the overall models were not significant.

One explanation for these findings is that families with public insurance have less of a social safety net and, thus, are unable to meet the needs of a child with an inflicted TBI. However, we cannot rule out the effect of bias in child welfare practices. Similarly, caregivers with histories of mental health difficulties and substance abuse are likely to have a harder time meeting their child’s needs and providing a stable household, increasing the likelihood of an out-of-home placement. Despite expectations, child and injury severity factors did not play a role in placement decisions after an inflicted TBI, indicating that placement decisions rely more heavily on caregivers’ abilities to meet the child’s needs rather than the child’s medical complexity or the severity of the inflicted TBI.

Social determinants of health (SDOH) are social conditions (e.g., employment, access to healthcare, quality schools) which are shown by a growing body of literature to impact many health outcomes, including cognition. The development of community-level measures including the Child Opportunity Index (COI) have allowed for increased understanding of the resources and conditions in neighborhoods and their impact on children’s health. Given the limited existing research on how neighborhood factors impact cognitive development, this study aimed to examine associations between neighborhood context (COI) and cognitive outcomes in children and adolescents who presented for neuropsychological evaluations.

Participants included 4,633 youth (ages 2-22; M = 10.8 years; SD = 4.1 years; 63% Male; 33% with a medical condition involving the central nervous system [CNS]) living in the DC-VA-MD-WV Metro Area who presented to an outpatient clinic for evaluation and completed an intellectual functioning (IQ) measure (88% Weschler, 11% DAS, <1% Leiter, <1% RIAS). COI values were extracted from electronic medical records based on home address. COI values include an overall index and three domain scores in educational (educational access, quality, and outcomes), health/environment (access to healthy food, healthcare, and greenspace) and social/economic (income, employment, poverty); higher scores indicate higher opportunity. Using metro-based norms, children from all opportunity levels were represented (14% Very Low, 13% Low, 18% Moderate, 21% High, 34% Very High). Multiple regression analyses were conducted to examine main effect associations between COI and Full-Scale IQ (FSIQ), Verbal IQ (VIQ), and Non-Verbal IQ (NVIQ) and explore moderation of age, gender, and medical condition on these associations. Additional regression analyses examined these relationships for the three COI domains.

Controlling for age, gender, and medical condition, neighborhood opportunity was positively associated with cognitive function (FSIQ: ß=0.198; VIQ: ß=0.202; NVIQ: ß=0.148, p’s <0.01). Models accounted for approximately 10-14% percent of the variance in cognitive outcomes (FSIQ: F[6,4476]=180.331), Adj.R2=0.138; VIQ: F[6,4556]=161.931), Adj.R2=0.124; NVIQ: F[6,4548]=123.893), Adj.R2=0.098). Age moderated the association between overall COI and cognitive outcomes (FSIQ: ß=0.005, p=0.018; VIQ: ß=0.005, p=0.043; NVIQ: ß=0.005, p<0.01) such that the association between neighborhood opportunity and cognitive outcomes was stronger at older ages, though this was a small effect. When examining subdomains of COI, cognitive outcomes were associated with educational (FSIQ: ß=0.094; VIQ: ß=0.099; NVIQ: ß=0.078, p’s <0.01) and social/economic opportunity (FSIQ: ß=0.115; VIQ: B=0.121; NVIQ: ß=0.084, p’s <0.01) but not health/environmental opportunity (FSIQ: ß=-0.001, p=0.991; VIQ: ß=-0.008, p=0.581; NVIQ: ß=-0.008, p=0.553). Medical diagnosis moderated the association between social/economic opportunity and FSIQ; there was a stronger association between IQ and COI in youth with a medical diagnosis (ß=-0.071, p<0.05).

These findings demonstrate the importance of neighborhood factors, especially education and social/economic opportunities, on cognitive development. Children living in higher opportunity neighborhoods showed higher cognitive functioning. Older age and CNS-involved medical conditions were associated with higher risk in the context of reduced neighborhood opportunities. These findings emphasize the need for advocacy and other efforts to improve community resources (e.g., access to early childhood education) to address inequities in cognitive development.

Children who suffer from brain insults (i.e., traumatic brain injury (TBI), chemotherapy and radiation treatment for brain tumors) are susceptible to late-emerging cognitive sequelae. Even with similar neurological risk variables, variability in long-term cognitive outcomes remains an area of investigation for researchers of acquired brain injury. Given the potential for genetic factors to influence response to chemoradiation, researchers have examined associations between germline, inherited, single nucleotide polymorphisms (SNPs), and neurocognitive outcomes for cancer survivors. Children who sustain an uncomplicated mild TBI generally recover without long-term neuropsychological consequences. However, TBI survivors have overlapping mechanism categories with cancer survivors through secondary injury variables that can be influenced by genomic variation (e.g., oxidative stress and neuroinflammation). Furthermore, the study of genomic vulnerability is limited in heterogenous groups of pediatric TBI survivors. This study aims to identify associations between genotype and long-term neurocognitive outcomes for acquired brain injury survivors by utilizing machine learning to uncover pathophysiological similarities and differences between groups.

Fourteen brain tumor survivors, 139 traumatic brain injury survivors, and 63 healthy, age-matched controls completed the Letter N-back task to obtain performances on core neurocognitive skills (attention, working memory, and processing speed). Ten targeted genotypes were examined across five pathophysiological pathways (neurotransmission, oxidative stress, neuroinflammation, plasticity, growth and repair, and folate metabolism). Data were trained and tested utilizing three regression machine learning models. Mean estimated error and R2 were generated for each neurocognitive outcome. A feature importance score for models with positive variance was generated to determine how predictive a given SNP is for neurocognitive outcomes.

Genotype only accounted for a small amount of variance in cognitive outcomes when all clinical groups were combined. The mean absolute error for the best-fitting models from analyses where all groups were combined decreased when groups were examined separately; however, the differences in model R2 values were not significant. The relationship between brain tumor survivors and processing speed performance depended on genotype. Two SNPs had positive feature importance at the interaction level (rs58225473 and rs1801394). These SNPs are located on the CACNB2 and MTR genes and have functional consequences for neurotransmission and folate metabolism. Models of traumatic brain injury survivors did not explain positive variance and could not be examined for feature importance. Additionally, even when removing the only mechanism of action that should not be relevant for TBI survivors (folate metabolism polymorphisms), the TBI models still did not explain positive variance.

Findings of the importance of two key SNPs on MTR and CACNB2 genes align with recent systematic reviews, which found associations between these polymorphisms and neuropsychological outcomes in more than one group or cohort of pediatric cancer survivors. Models for TBI survivors were limited by the heterogeneity of the group and ceiling effects on performance. An understanding of genetic vulnerabilities influenced by treatment and injury-related factors in acquired brain injury will inform our understanding of the developing and recovering childhood brain. The current study is an initial contribution to this goal and highlights the utility of machine learning methodology for future studies that examine the influence of genetic heterogeneity in pediatric acquired brain injury.

Children born preterm are at increased risk of deviation from the typical developmental trajectory. The probability of adverse developmental sequelae is increased in those with history of major perinatal complications. Retinopathy of prematurity (ROP) is a pathological disordered growth of retinal blood vessels occurring in very preterm neonates who require supplemental oxygen. ROP has been linked to intermittent hypoxemic events and blood gas derangements occurring in the Neonatal Intensive Care Unit (NICU), particularly in ventilated infants. Though presence and severity of ROP have been linked to neurodevelopmental impairment, little is known about the relationship between ROP severity and motor development in the preschool age. Because the same hypoxemic events and blood gas changes that lead to severe ROP may also lead to greater developmental deficits in motor control, we hypothesized that ROP severity will be inversely linked to the quality of motor functioning even in NICU graduates without neurological impairments.

We included 95 preterm (23.6 - 33.6 weeks gestation) preschoolers (49 females, 44 members of twin pairs or triplets). The participants' age ranged from 3.3 - 4.1 years (adjusted for prematurity). ROP screening was conducted during NICU stay and rated from immature retina (0) to grade 4. Motor abilities were assessed with the Peabody Developmental Motor Scales (PDMS-2). Cases with diagnosed perinatal brain pathology (moderate to severe) or cerebral palsy were excluded from analyses.

We used linear mixed regression analyses with multiple gestation as a random factor. Severity of ROP was our predictor of interest, whereas socioeconomic status, sex, gestational age, and birth-weight SD served as covariates. Separate analyses were conducted using the PDMS-2 Total Motor, Fine Motor, and Gross Motor Quotients as dependent variables. ROP severity explained a unique portion of the variance in the Total Motor Quotient (F[1, 89] = 5.59, p = .02). Examination of the relationship between ROP severity and motor skill domains yielded a significant association for the Fine Motor Quotient (F[1, 89] = 6.19, p = .015) and a trend for the Gross Motor Quotient (F[1, 89] = 3.64, p = .06).

The results of this study reveal that increase in ROP severity is linked to poorer motor skills in preterm-born preschoolers without major disabilities or perinatal diagnosis of moderate to severe brain pathology. This association was evident for both fine and gross motor skills, though only the relationship between ROP severity and the former motor index reached conventional statistical significance. Importantly, ROP severity accounted for a unique portion of the variance in motor performance, over and above the variance explained by other perinatal risk factors. This result is consistent with previous research findings indicating that ROP is linked to the occurrence of multiple, subtle hypoxemic events and 'exposure' to blood gas derangements during NICU stay in very preterm neonates who require respiratory support.

Various forms of social media have been investigated as platforms for science and health communication, with a recent growing interest in TikTok. TikTok has more than one billion active users. Sixty-two percent of TikTok users are under the age of 29, making it a platform of particular interest when considering the impact of social media content dissemination in pediatric neuropsychology. Personal communication suggests that children, adolescents, and young adults internationally reference specific information from TikToks about attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), tic disorder, and specific learning disorders in the context of clinical neuropsychological assessment. Despite the emerging prevalence of TikTok observed clinically and discussed informally among clinicians, there has yet to be a synthesis of available empirical information of TikTok as a health communication platform for discussing neurodevelopmentally relevant conditions.

A systematic review of research regarding TikTok and neurodevelopmentally relevant conditions was conducted using PRISMA guidelines. The following databases were searched: Ovid MEDLINE (to 20 July 2022), PsycINFO (to 20 July 2022), and PubMed (to 20 July 2022) using search terms TikTok AND ADHD OR autism OR tic OR learning disorder. Searches using search terms TikTok AND learning disability OR dyslexia OR dysgraphia OR dyscalculia were also conducted but were excluded as they yielded no results. Articles were eligible for inclusion if they presented original data (e.g., case series, descriptive analyses, etc.) related to information about neurodevelopmentally relevant conditions on TikTok. A final sample of 5 original papers met criteria for inclusion.

The systematic review sample included a mixture of clinical case series and empirical analyses using primary data from TikTok. Across publications, there was an emphasis on the prevalence of misinformation about disorders on TikTok, the frequency of atypical presentations of neurodevelopmental disorders on TikTok, and the potential for an iatrogenic impact on children and adolescents who view TikTok videos.

Despite the increasing frequency with which patients access TikTok for health-related information, there is a relative dearth of published research on TikTok regarding neurodevelopmentally relevant conditions. This is in contrast to other health-related areas (e.g., there are a far greater number of published articles on TikTok and COVID-19 and dermatology compared to neuropsychological disorders). These findings suggest a missed opportunity for researchers and clinicians alike to engage with TikTok. Based on clinical experience and a review of the available literature, the following recommendations are provided and will be presented in-depth:

1. 1. Clinicians should gain familiarity with virally spread information via TikTok, particularly as it relates to symptoms and presentations of neuropsychological and neurodevelopmental conditions.

2. 2. Clinicians should explicitly assess for knowledge content and source regarding neuropsychological and neurodevelopmental conditions during intake and/or feedback in order to address misinformation and myths, validate lived experiences, and develop rapport with patients.

3. 3. Clinicians and researchers should consider a strengths-based approach to TikTok usage that highlights the value of sharing resources, building community, and decreasing stigma.

4. 4. Clinicians and researchers should be aware of information shared via TikTok as a potential concern for test security.

Word finding or “naming” difficulty is a symptom of multiple neurological disorders; therefore, naming assessment is an integral component of neuropsychological evaluation. Prior work has found weaker second-language naming in healthy proficient bilingual youth than monolingual youth, and similar findings have been shown in adults with epilepsy. Considering the potential influences of both early onset epilepsy and bilingualism on brain development, we compared naming in English second language (ESL) and monolingual youth with epilepsy. To assess the impact of bilingualism independent of the known effects of seizure laterality (i.e., poor naming in those with left, dominant-hemisphere seizures), we excluded patients with left language dominance and unilateral seizures. We hypothesized that like other groups, naming would be weaker in ESL than in monolingual youth with epilepsy.

Participants included 84 children with seizures that could not be lateralized clinically (n=36), bilateral seizures (n=20), centrotemporal spikes (n=3), and those with unilateral seizures and atypical language dominance (n=25), ages 6-15 years old: 66 monolingual, English (mean age: 10.87 ± 2.70 years) and 18 ESL (mean age: 10.78 ± 2.88 years). Those with FSIQ < 70 and vocabulary SS < 6 were excluded to ensure English proficiency. Independent samples t-tests, multivariate ANOVA, and chi-square tests compared groups on demographic factors and test performance. All measures (FSIQ, WISC/WASI Vocabulary, letter and category fluency, Children’s Auditory (AN) and Visual Naming (VN) Tests) were administered in English.

Monolingual and ESL groups did not differ in: age, sex, SES, seizure type (i.e., non-lateralized, bilateral, centrotemporal spikes, or atypical language dominance), epilepsy onset age, or number of AEDs. Comparisons also showed no differences in FSIQ, vocabulary, letter fluency, or category fluency (all ps > 0.05). By contrast, auditory and visual naming performances were weaker among ESL patients than monolingual patients: AN accuracy, F(1,81) = 10.89, p = 0.001; AN tip-of-the-tongues (TOTs), F(1,81) = 6.35, p = 0.014; AN Summary Scores (SS), F(1,81) = 6.17, p = 0.015; VN accuracy, F(1,81) = 4.66, p = 0.034; VN SS, F(1,81) = 4.87, p = 0.030, with the exception of VN TOTs, which approached significance, F(1,81) = 3.55, p = 0.063.

Consistent with findings in bilingual healthy youth and ESL adults with epilepsy, naming in ESL youth with epilepsy was weaker than in monolingual children. The groups did not differ on other aspects of language. Thus, unlike other expressive verbal functions, naming is adversely affected in the second language of bilingual people with epilepsy across the age span. These results suggest that poor naming in ESL patients cannot be used to infer a naming deficit, and/or left (dominant) temporal lobe dysfunction.

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a complex, yet treatable autoimmune disorder characterized by a fairly abrupt onset of a constellation of symptoms attributable to diffuse brain dysfunction (Tarantino et al., 2021). Despite the potential for a severe disease course, most patients have a favorable outcome with substantial recovery (Dalmau et al., 2011; Titulaer et al., 2013). Nevertheless, there is limited literature discussing the long-term outcomes in patients with anti-NMDARE, particularly in pediatric patients. The primary objective of this study is to examine and describe behavioral, emotional, adaptive, and executive functioning outcomes in pediatric and young adult patients with this disease. This study also sought to provide information on the perceived health-related quality of life (HRQoL) of patients and their parents and investigate the impact of anti-NMDARE on parents and family functioning.

All individuals known to have been diagnosed and treated for anti-NMDARE at The Children’s Hospital of Philadelphia (CHOP) between January 1, 2005, and October 1, 2020, were contacted with both patients and their parents/guardians invited to participate. Eighteen pediatric patients between the ages of 6 and 26 and/or their parents/caregivers participated in the study. Of the 18 patients represented in the sample, 50% were white/Caucasian, and 67% were female. The mean duration of time since symptom onset was 7.1 years. Primary outcomes were measured through standardized questionnaires of emotional, behavioral, and adaptive functioning (BASC-3) and executive functioning (BRIEF2 or BRIEF-A). Secondary outcomes related to family functioning and HRQoL were measured through (PedsQL™ and PedsQL™ Family Impact Module.)

All aggregate T-scores for the BASC and BRIEF placed children with anti-NMDARE within an age-appropriate range regarding behavioral, emotional, adaptive, and executive functioning outcomes. Children with anti-NMDARE were not found to have lower HRQoL compared to their healthy same-age peers. Moreover, parents of children with anti-NMDARE did not endorse a prolonged impact of this illness on family functioning and adjustment.

This study aimed to better understand the neurobehavioral profile and the long-term outcomes of children diagnosed with anti-NMDARE, with the ultimate goal of advancing understanding of this encephalitis. Consistent with findings from several reviewed studies on long-term follow-up, the present study suggests that most children with a history of anti-NMDARE show good functional recovery over time. However, data on the neurobehavioral sequelae, quality of life, and adaptive behavior in patients diagnosed with anti-NMDARE are still sparse, especially at pediatric age. In order to understand and learn to manage the needs of patients with anti-NMDARE, particularly regarding the impact this disease can have on daily life and school performance, additional neuropsychological research involving larger samples, longitudinal studies, and increased methodological consistency is required.

Children who sustain a mild traumatic brain injury (mTBI) are at increased odds of additive injury and continue to show altered motor performance relative to never-injured peers after being medically cleared (MC) to return to normal activities. There is a critical need to determine when children can return to activities without risk of short and long-term adverse effects, with research showing high reinjury rates for 3-12 months after RTP. The Physical and Neurological Examination for Subtle Signs (PANESS) measures subtle signs of motor impairment during gait, balance, and timed motor functions. Recent literature has demonstrated that PANESS timed motor function can distinguish between children medically cleared post-mTBI compared to never-injured controls. The present study examined performance on timed motor tasks in youth medically cleared from mTBI following medical clearance and 3-months later, compared to never-injured peers.

25 children (Mage=14.16, SD=2.46; Male=68%) were enrolled within 6 weeks of medical clearance from mTBI (Mdays post MC=33, SD=13.4, Range=2-59) along with 66 typically developing, never-injured controls (Mage=13.9, SD=2.22; Male=50%). Group differences were evaluated for the Timed Motor section of the PANESS at enrollment and at a 3-month follow-up (Mdays from enrollment to follow-up=95.90, SD=12.69, Range=62-129). This 3-month follow-up occurred on average 4 months after medical clearance (Mdays from MC to follow-up=130.08, SD=17.58, Range=92 - 164). The Timed Motor section includes Repetitive (foot tapping, hand patting, and finger tapping) and Sequential (heel-toe rocking, hand pronate/supinate, finger sequencing) raw time scores, measured in seconds. The Total Timed Motor Speed score is the combination of Repetitive and Sequential Movement and the side-to-side tongue item.

At 3-month follow-up, mTBI participants (M=67.55, SD=8.26, Range=53.66-83.88) performed worse than controls (M=63.09, SD=10.23, Range=39.86-100.51) on Total Timed Motor Speed, t(89)= 1.95, p<0.05), including when controlling for age and sex, F(1, 87)=4.67, p<0.05. At the same time point, mTBI participants (M=36.54, SD=5.47, Range=28.74-49.17) performed worse on Sequential Speed than controls (M=32.93, SD=6.1, Range=21.49-56.76), t(89)=2.59, p<0.01, including when controlling for age and sex, F(1, 87)=7.687, p<0.01). Although groups performed similarly on Sequential Speed at the initial time point, mTBI participants exhibited a trend of less improvement from initial to follow-up (MmTBI=-1.69, Mcontrol=-3.68, t(90)=1.445, p=0.076).

Although groups did not significantly differ on Timed Motor Speed items at the initial time point, the mTBI group showed consistently lower scores than controls at both time points and less improvement over time. Results indicate that Total Timed Motor Speed, specifically Sequential Speed, may be a sensitive marker of persisting differences in high-level motor and cognitive learning/control in children who have been medically cleared after mTBI. More data are needed to evaluate these findings over a longer time period, and future studies should examine behavioral markers concurrently with physiologic brain recovery over time.

Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers less radiation to healthy brain tissue. PRT has been associated with improved long term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory outcomes.

Survivors of pediatric brain tumor treated with either XRT (n = 29) or PRT (n = 51) completed neuropsychological testing > 1 year following radiotherapy. XRT and PRT groups were similar with respect to sex, handedness, race, age at diagnosis, age at evaluation, tumor characteristics, and treatment history (i.e., craniospinal irradiation, craniotomy, shunting, chemotherapy, radiation dose). Verbal learning and memory were assessed using the age-appropriate version of the California Verbal Learning Test (CVLT-II/CVLT-C). Measures of intellectual functioning, executive functioning, attention and adaptive behavior were also collected. Performance on neuropsychological measures was compared between treatment groups (XRT vs. PRT) using analysis of covariance (ANCOVA). On the CVLT, each participant was classified as having an encoding deficit profile (i.e., impaired learning, recall, and recognition), retrieval deficit profile (i.e., impaired recall but intact recognition), intact profile, or other profile. Chi-squared tests of independence were used to compare the probability of each memory profile between treatment groups. Pearson correlation was used to examine associations between memory performance and strategy use, intellectual functioning, adaptive behavior, attention, and executive functioning.

Overall, patients receiving PRT demonstrated superior verbal learning (CVLT Trials 1-5; t(76) = 2.61, p = .011), recall (CVLT Long Delay Free; t(76) = 3.57, p = .001) and strategy use (CVLT Semantic Clustering; t(76) = 2.29, p = .025) compared to those treated with XRT. Intact performance was more likely in the PRT group than the XRT group (71% PRT, 38% XRT; X2 = 8.14, p = .004). Encoding and retrieval deficits were both more common in the XRT group, with encoding problems being most prevalent (Encoding Deficits: 31% XRT, 12% PRT, X2 = 4.51, p = .034; Retrieval Deficits: 17% XRT, 4% PRT, X2 = 4.11, p = .043). Across all participants, semantic clustering predicted better encoding (r = .28, p = .011) and retrieval (r = .26, p = .022). Better encoding predicted higher intellectual (r = .56, p < .001) and adaptive functioning (r = .30, p = .011), and fewer parent-reported concerns about day-today attention (r = -.36, p = .002), and cognitive regulation (r = -.35, p = .002).

Results suggest that PRT is associated with superior verbal memory outcomes compared to XRT, which may be driven by encoding skills and use of learning strategies. Moreover, encoding ability predicted general intellectual ability and day-to-day functioning. Future work may help to clarify underlying neural mechanisms associated with verbal memory decline following radiotherapy, which will better inform treatment approaches for survivors of pediatric brain tumor.

Radiotherapy for pediatric brain tumor is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to conventional photon radiotherapy (XRT), presumably due to sparing of healthy brain tissue. This study examined long-term white matter change and neuropsychological performance in pediatric brain tumor survivors treated with XRT vs. PRT.

Pediatric brain tumor survivors treated with either XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging > 7 years following radiotherapy. A healthy control group (n = 23) was also recruited. Groups had similar demographic characteristics, except for handedness (p = .01), mean years of age at testing (XRT = 21.7, PRT = 16.9, Control = 15.5; p = .01), and mean years since radiation (XRT =14.7, PRT = 8.9, p < .001). Age and handedness were selected as covariates; analyses were not adjusted for time since radiation due to redundancy with treatment group (i.e., standard of care transitioned from XRT to PRT in 2007). Participants completed age-appropriate versions of the Weschler Intelligence Scales (WAISIV/WISC-IV/WISC-V) and the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI and Motor Coordination subtests). Tractography was conducted using automated fiber quantification (AFQ), and fractional anisotropy (FA) was extracted from 12 tracts of interest. Linear mixed models were used to summarize group differences in FA, with tracts nested within subjects. Neuropsychological performance and tract-level FA were compared between groups using analysis of covariance (ANCOVA). Pearson correlation was used to examine associations between cognitive functioning and tract-level FA.

Across all tracts, FA was significantly lower in the XRT group than the PRT group (t(514) = -2.58, p = .01), but did not differ between PRT and Control groups (t(514) = .65, p = .51). For individual tracts, FA differed significantly between treatment groups (XRT < PRT) in the left inferior fronto-occipital fasciculus (IFOF), right IFOF, left inferior longitudinal fasciculus (ILF) and right uncinate (all t < -2.05, all p < .05). No significant differences in FA were found between PRT and Control participants for any tract. All neuropsychological scores were significantly lower for XRT than PRT patients (all p < .03), while PRT and Control groups performed similarly on these measures (all p >.19). Cognitive functioning was most consistently associated with FA of the corpus callosum major forceps (4/7 domains; all r > .33, all p < .04) and the left ILF (4/7 domains; all r > .37, all p <.02).

Both white matter integrity and neuropsychological performance were generally reduced in patients with a history of XRT, but not in those who received PRT. The PRT group was similar to healthy control participants with respect to both FA and cognitive scores, suggesting improved long-term outcomes compared to patients receiving XRT. This exploratory study is the first to provide direct support for white matter integrity as a mechanism of cognitive sparing in PRT. Future work with larger samples is necessary to replicate these findings.

Children with neurofibromatosis type 1 (NF1) commonly have academic problems. While the neuropsychological profile of children with NF1 is variable, NF1 results in difficulties in a variety of cognitive domains including intellectual functioning, attention, executive functioning. Previous studies have suggested that cognitive functioning may relate to academic functioning in children with NF1; however, the evidence is limited and warrants further examination. Thus, this study will investigate the contribution of several cognitive domains (intellectual functioning, attention, working memory) on academic performance for school age children with NF1.

The association between cognitive functioning and academic performance was examined for school age children with NF1 (n = 40; ages 9-13). Intellectual functioning was assessed using the Differential Abilities Scales, Second Edition School-Age Version (DAS-II) General Conceptual Ability (GCA) score. Attention was examined using the DAS-II Recall of Digits-Forward (DF) subtest and Flanker Inhibitory Control and Attention Test (Flanker). Working memory was assessed using the DAS-II Recall of Digits-Backward (DB) subtest. Academic performance was measured using the Wechsler Individual Achievement Test, Third Edition (WIAT-III) Word Reading (WR), Pseudoword Decoding (PD), Reading Comprehension (RC), Numerical Operations (NO), and Math Problem Solving (MPS) subtests.

WR was significantly associated with DAS-II GCA (rs(38) = .689, p < .001) and DF (rs(38) = .470, p = .002) in addition to Flanker (rs(34) = .364, p = .029), but not DAS-II DB (rs(38) = .292, p = .072). PD was significantly correlated with DAS-II GCA (rs(38) = .695, p < .001), DF (rs(38) = .394, p = .012), and DB (rs(38) = .474, p = .002), but not Flanker (rs(34) = .306, p = .070). RC was significantly associated with DAS-II GCA (rs(38) = .483, p = .002) and DF (rs(38) = .346, p = .029), but not DAS-II DB (rs(38) = .306, p = .055) and Flanker (rs(34) = .269, p = .112). NO was significantly correlated with DAS-II GCA fc(38) = .777, p < .001), DF (rs(38) = .555, p = < .001), and DB (rs(38) = .576, p < .001) as well as Flanker (rs(34) = .386, p = .020). MPS was significantly associated with DAS-II GCA (rs(38) = .685, p < .001), DF (rs(38) = .586, p < .001), and DB (rs(38) = .543, p < .001), in addition to Flanker (rs(34) = .420, p = .011). Significant associations had medium to large effect sizes, while non-significant correlations had small to medium effect sizes. Notably, most of the non-significant correlations had trend-level statistical significance.

Concurrent cognitive functioning (intellectual functioning, attention, working memory) was associated with reading-related and mathematics functioning in school age children with NF1. Notably, intellectual functioning had the strongest association with academic performance across all reading-related and mathematics tasks. Future studies should examine the association between academic performance and additional cognitive domains (e.g., language, visuospatial abilities) in children with NF1 across a wider age range to allow for examination of developmental patterns.

Construction of predictive algorithms of concussion symptom recovery at 4 and 12 weeks post-injury using an evidence-based assessment (EBA) model to guide clinical decision-making, extending the 2016 5P decision rule.

Children and adolescents, ages 8-18 (n=1,551; mean age=12.78; 62% male), followed over 12 weeks in the prospective multicenter cohort study (Predicting Persistent Post-Concussive Problems in Pediatrics, 5P; Zemek et al., 2016). The age-specific PostConcussion Symptom Inventory (PCSI) (8-12, 17 items; 1318 years, 20 items) was completed at six timepoints from the ED and at 1, 2, 4, 8, and 12-weeks post-injury. Logistic regression analysis was applied to the set of key variables including the PCSI Total Retrospective-Adjusted PostInjury Difference (RAPID) scores, patient demographics and pre-injury history, and injury characteristics to predict participant recovery status (Recovered, Not Recovered) at the 4- and 12-week endpoints. The resulting recovery-predictive equations identified the significant sets of variables with symptom scores at four successive post-injury timepoints (ED, 1, 2, 4 weeks). Logistic Regression Threshold values were established at the 90th CI against which individual patient data was applied to determine recovery status. Participants with sub-threshold sums were deemed recovered at the target endpoint (4- or 12-weeks post-injury).

A total of 19 predictive equations were generated for the two age groups across the recovery timeline. Four sets of equations were developed to predict symptom recovery status at 4-weeks post-injury for the two age groups (8-12 AUC=0.679-0.884; 13-18 AUC=0.752-0.909). Prediction of symptom recovery status at 12-weeks post-injury yielded six equations for the 8-12 age group (AUC=0.723-0.825), and five equations for the 13-18 age group (AUC=0.724-0.887). Total PCSI RAPID score was identified as a significant variable in each of these 19 equations. Participant sex was identified as significant in 18 of the 19 constructed equations. Other variables that were identified as significant at varying timepoints included age, pre-injury history of learning disability and migraines, and an early post-injury sign in the ED (answering questions more slowly than usual). Examples of the equations include: Week 1 predicting symptom recovery status at 4-weeks: 8-12 yr group-(Sex*.802)+(week 1 Total RAPID Score*.142)+(Age2* .053)+(-3.851) with AUC=0.808; 13-18 yr group-(Sex*.980)+(Week 1 Total RAPID Score*.071)+(-3.261) with AUC=0.861.

Clinicians’ management of the concussion recovery of children and adolescents can benefit from EBA guidance. The 5P dataset (Zemek et al., 2016) provides an important window into “typical” and “atypical” recovery trajectories, establishing an initial predictive decision rule for a 4-week recovery endpoint, at the ED timepoint only, reporting AUC=0.69. The current study extends the prediction modeling using successive post-injury timepoints reflecting a typical management timeline. Symptom reports from both 1- and 2-weeks post injury with patient demographics/ history predicted symptom recovery status at 4- and 12-weeks post-injury, significantly improve predictive accuracy over the ED timepoint alone. These predictive equations, when applied to the individual patient, can serve to assist the clinician’s understanding of the patients’ recovery trajectory, i.e., on track for a typical or atypical recovery, further informing the intervention strategy.