Emma G. Duerden

Characterized by depression, anxiety, irritability, and fatigue, maternal perinatal distress influences infants’ neurodevelopment through biological and environmental pathways. The cerebellum is particularly vulnerable due to rapid growth and myelination after birth. While atypical cerebellar myelination is related to developmental impairments in children, its association with maternal distress remains unclear. This study examined associations between postnatal anxiety and depression, neonatal cerebellar myelination, and neurodevelopmental outcomes at 18 months. Participants were recruited from St. Thomas’ Hospital in London, UK, and a sample of 291 mother-child dyads participated. Maternal distress was assessed using the Edinburgh Prenatal/Postnatal Depression Scale (EPDS). Neonates underwent MRI between 0–5 weeks after birth, and T1- and T2-weighted images were acquired. T1w/T2w ratio was used to create a proxy of cerebellar myelination maps. Neurodevelopmental outcomes were assessed with the Cognitive-, Language-, and Motor- scales of the Bayley Scales of Infant and Toddler Development, Third Edition. Anxiety symptoms were associated with increased Average T1w/T2w Ratio (proxy for myelination) (B = 0.009, 95% CI = 0.001 – 0.017, p = 0.024). In turn, average T1w/T2w Ratio was associated with lower receptive communication scores at 18 months (B = −5.02, 95% CI = −8.38 – −1.66, p =0.003). Mediation analysis revealed a significant direct effect of anxiety symptoms on receptive communication (B = –0.19, SE = 0.096, p = 0.046) and a significant indirect effect through average T1w/T2w ratio (B = –0.032, 95% CI [–0.070, –0.0003]), indicating that average T1w/T2w ratio partially mediated the association between maternal perinatal/postnatal anxiety and receptive communication. These findings suggest that neonatal myelination may partially mediate the influence of maternal distress on infant outcomes, suggesting that maternal distress may, in part, shape the trajectory of cerebellar maturation and early neurodevelopment.

The hippocampus is essential for learning and memory and undergoes prolonged development throughout childhood and adolescence. Evidence concerning hippocampal maturation is based primarily on volumetric measures. However, macrostructural growth and myelination processes may represent distinct biological processes. Using Hippunfold, we quantified hippocampal subfield volumes and myelin-sensitive tissue concentrations as proxies for tissue maturation using T1w/T2w ratios in 175 community-recruited participants aged 9 months to 21 years. Hippocampal subfield volumes were best described by quadratic developmental trajectories, whereas T1w/T2w ratios increased linearly with age across all subfields. Males exhibited larger hippocampal volumes, and females demonstrated higher and steeper age-related increases in T1w/T2w ratios. Sex-related hippocampal subfield differences were observed despite largely comparable cognitive and behavioural profiles. Hippocampal subfield volumes and myelin follow distinct developmental pathways, revealing sex-specific patterns of development that are not fully captured by morphology alone.

Autism is diagnosed more frequently in males than females, although evidence suggests that autistic females may present with a behavioral phenotype and are often under-recognized. Social attention (SA) behaviors, including attention to stimuli and engagement in social interactions, are considered a core feature of autism. However, SA behaviors may differ between autistic females and males, potentially limiting the sensitivity of approaches identifying autistic girls. We examined sex differences in SA behaviors at 2 years of age in children with an increased familial likelihood of autism. Behavioral data from the Vineland Adaptive Behavior Scales-II (VABS-II) were obtained from 415 children enrolled in the Infant Brain Imaging Study (IBIS) Network who did and did not later receive an autism classification. Nineteen VABS-II items related to SA were identified through a keyword-based selection process and examined using binomial logistic regression analyses. Six SA-related items significantly differentiated biological sex within the autistic group only. Autistic girls were more likely to demonstrate behaviors related to social engagement and interaction, whereas autistic boys showed greater scores on behaviors related to attention to commands and non-specific bids for attention. These findings suggest that sex differences in SA behaviors emerge as early as the second year of life.

The human face is central to social interactions, supporting the ability to interpret others’ mental states using theory of mind (ToM). We examined whether functional near-infrared spectroscopy (fNIRS) would reveal brain-activation differences between live and pre-recorded social conversations in brain regions implicated in ToM. Furthermore, we examined whether activation depended on the visual realism of a social partner – viewed as a human or an animated avatar. By one view, social interactions may be dependent on how natural the social partner appears; by another view, social interactions may depend only upon the attribution of responses to a real human regardless of visual appearance. Neural activation for pre-recorded compared to live interactions was prolonged, consistent with extended cognitive effort. Activation patterns in the right temporoparietal junction differed between interacting with humans versus avatars, along with a stronger preference for looking at the eyes when interacting with a human (vs. avatar), underscoring the social relevance of real faces. Findings highlight the importance of both live interactions and facial realism in shaping social-cognitive processing, a finding with relevance for optimizing online social interactions.

Apathy is characterized by reduced motivation for goal-directed behaviour and may emerge following brain injury. Currently, little is known about apathy in children and adolescents with neurodevelopmental disorders (NDDs) exposed to repetitive head impacts. This exploratory study investigated associations between apathy, repetitive head-banging behaviour, and substantia nigra neuromelanin-sensitive MRI (NM-MRI) signal in youth with NDDs. Forty-seven participants (14 typically developing; 33 ADHD/ASD) completed Behaviour Assessment System for Children (BASC-3) measures, from which apathy-related items were harmonized across developmental forms and subjected to principal component analysis. A one-component solution explained 47.3% of variance and was used to derive apathy scores. Although head-banging severity and NM-MRI signal were not independently associated with apathy, a significant interaction emerged, whereby greater head-banging severity strengthened the relationship between apathy and substantia nigra NM-MRI signal. These preliminary findings suggest repetitive self-injurious head impacts may influence dopaminergic systems linked to motivational dysfunction in youth with NDDs.

Resting-state networks (RSNs), measured through functional connectivity (FC), emerge in utero and are detectable within hours of birth. Although neonatal growth metrics predict later neurodevelopmental outcomes and structural brain maturation, their relationship to early functional network organization remains poorly understood. We examined associations between anthropometric growth metrics and resting-state FC in a cohort of healthy near-term and term-born neonates using functional near-infrared spectroscopy (fNIRS) acquired during the first few days of life. Task-free fNIRS data were recorded in 121 neonates (67 males [55%]; mean postnatal age=25.6 hours; mean gestational age=38.63 weeks). Based on birthweight percentiles, 12 (9%) newborns were small for gestational age (SGA) and 13 (11%) were large for gestational age (LGA). Growth metrics included birth weight–for–gestational age z-score (BGZ), head circumference–for–gestational age z-score (HGZ), birth weight–for–length z-score (BLZ), and z-scored Ponderal Index (PI-z). Whole-brain FC was calculated as the mean Fisher-Z-transformed correlation across valid channel pairs. Channel-wise associations were examined using general linear and linear mixed-effects models controlling for gestational age, postnatal age and sex. Linear and quadratic terms were tested, and multiple comparisons were controlled using the false discovery rate. None of the anthropometric measures were associated with global FC; however, significant nonlinear (quadratic) relationships emerged at the channel-pair level. BGZ (β range= −0.102 to −0.074; FDR-corrected p<0.005) and PI-z (β range= −0.088 to −0.074; FDR-corrected p < 0.001) demonstrated negative quadratic associations with inter- and intrahemispheric connectivity, such that newborns with both lower (SGS) and higher (LGA) growth values showed reduced FC relative to those with average growth. In contrast, HGZ demonstrated positive quadratic associations (β range=0.051 to 0.074; FDR-corrected p<0.001), with infants at the lower and higher ends of the head-size distribution exhibiting increased FC relative to infants near the mean. BLZ showed no significant associations after correction. Results indicate that early somatic growth is reflected in the organization of neonatal functional brain networks and that deviations from average growth whether smaller or larger are associated with altered regional connectivity. Findings suggest that neonatal growth metrics may provide an accessible marker of early brain health, reflected in regionally specific functional connectivity patterns.