Maternal psychological distress associates with alterations in resting-state low-frequency fluctuations and distal functional connectivity of the neonate medial prefrontal cortex.

Prenatal stress exposure (PSE) has been observed to exert a programming effect on the developing infant brain, possibly with long-lasting consequences on temperament, cognitive functions and the risk for developing psychiatric disorders. Several prior studies have revealed that PSE associates with alterations in neonate functional connectivity in the prefrontal regions and amygdala. In this study, we explored whether maternal psychological symptoms measured during the 24th gestational week had associations with neonate resting-state network metrics. Twenty-one neonates (nine female) underwent resting-state fMRI scanning (mean gestation-corrected age at scan 26.95 days) to assess fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). The ReHo/fALFF maps were used in multiple regression analysis to investigate whether maternal self-reported anxiety and/or depressive symptoms associate with neonate functional brain features. Maternal psychological distress (composite score of depressive and anxiety symptoms) was positively associated with fALFF in the neonate medial prefrontal cortex (mPFC). Anxiety and depressive symptoms, assessed separately, exhibited similar but weaker associations. Post hoc seed-based connectivity analyses further showed that distal connectivity of mPFC covaried with PSE. No associations were found between neonate ReHo and PSE. These results offer preliminary evidence that PSE may affect functional features of the developing brain during gestation.

Prenatal maternal depressive symptoms are associated with neonatal left amygdala microstructure in a sex-dependent way.

Exposures to prenatal maternal depressive symptoms (PMDS) may lead to neurodevelopmental changes in the offspring in a sex-dependent way. Although a connection between PMDS and infant brain development has been established by earlier studies, the relationship between PMDS exposures measured at various prenatal stages and microstructural alterations in fundamental subcortical structures such as the amygdala remains unknown. In this study, we investigated the associations between PMDS measured during gestational weeks 14, 24 and 34 and infant amygdala microstructural properties using diffusion tensor imaging. We explored amygdala mean diffusivity (MD) alterations in response to PMDS in infants aged 11 to 54 days from birth. PMDS had no significant main effect on the amygdala MD metrics. However, there was a significant interaction effect for PMDS and infant sex in the left amygdala MD. Compared with girls, boys exposed to greater PMDS during gestational week 14 showed significantly higher left amygdala MD. These results indicate that PMDS are linked to infants' amygdala microstructure in boys. These associations may be relevant to later neuropsychiatric outcomes in the offspring. Further research is required to better understand the mechanisms underlying these associations and to develop effective interventions to counteract any potential adverse consequences.

Sex differences, asymmetry, and age-related white matter development in infants and 5-year-olds as assessed with tract-based spatial statistics.

The rapid white matter (WM) maturation of first years of life is followed by slower yet long-lasting development, accompanied by learning of more elaborate skills. By the age of 5 years, behavioural and cognitive differences between females and males, and functions associated with brain lateralization such as language skills are appearing. Diffusion tensor imaging (DTI) can be used to quantify fractional anisotropy (FA) within the WM and increasing values correspond to advancing brain development. To investigate the normal features of WM development during early childhood, we gathered a DTI data set of 166 healthy infants (mean 3.8 wk, range 2-5 wk; 89 males; born on gestational week 36 or later) and 144 healthy children (mean 5.4 years, range 5.1-5.8 years; 76 males). The sex differences, lateralization patterns and age-dependent changes were examined using tract-based spatial statistics (TBSS). In 5-year-olds, females showed higher FA in wide-spread regions in the posterior and the temporal WM and more so in the right hemisphere, while sex differences were not detected in infants. Gestational age showed stronger association with FA values compared to age after birth in infants. Additionally, child age at scan associated positively with FA around the age of 5 years in the body of corpus callosum, the connections of which are important especially for sensory and motor functions. Lastly, asymmetry of WM microstructure was detected already in infants, yet significant changes in lateralization pattern seem to occur during early childhood, and in 5-year-olds the pattern already resembles adult-like WM asymmetry.

Structural brain correlates of non-verbal cognitive ability in 5-year-old children: Findings from the FinnBrain birth cohort study.

Non-verbal cognitive ability predicts multiple important life outcomes, for example, school and job performance. It has been associated with parieto-frontal cortical anatomy in prior studies in adult and adolescent populations, while young children have received relatively little attention. We explored the associations between cortical anatomy and non-verbal cognitive ability in 165 5-year-old participants (mean scan age 5.40 years, SD 0.13; 90 males) from the FinnBrain Birth Cohort study. T1-weighted brain magnetic resonance images were processed using FreeSurfer. Non-verbal cognitive ability was measured using the Performance Intelligence Quotient (PIQ) estimated from the Block Design and Matrix Reasoning subtests from the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). In vertex-wise general linear models, PIQ scores associated positively with volumes in the left caudal middle frontal and right pericalcarine regions, as well as surface area in left the caudal middle frontal, left inferior temporal, and right lingual regions. There were no associations between PIQ and cortical thickness. To the best of our knowledge, this is the first study to examine structural correlates of non-verbal cognitive ability in a large sample of typically developing 5-year-olds. The findings are generally in line with prior findings from older age groups, with the important addition of the positive association between volume / surface area in the right medial occipital region and non-verbal cognitive ability. This finding adds to the literature by discovering a new brain region that should be considered in future studies exploring the role of cortical structure for cognitive development in young children.

Association of cumulative prenatal adversity with infant subcortical structure volumes and child problem behavior and its moderation by a coexpression polygenic risk score of the serotonin system.

Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother-infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years (N = 1568, 45.3% female), (b) infant amygdalar and hippocampal volumes (subsample N = 122), and (c) its moderation by a hippocampal-specific coexpression polygenic risk score based on the serotonin transporter (SLC6A4) gene. We found that higher PRE-AS was linked to greater child emotional and behavioral problems at both time points, with partly stronger associations in boys than in girls. Higher PRE-AS was associated with larger bilateral infant amygdalar volumes in girls compared to boys, while no associations were found for hippocampal volumes. Further, hyperactivity/inattention in 4-year-old girls was related to both genotype and PRE-AS, the latter partially mediated by right amygdalar volumes as preliminary evidence suggests. Our study is the first to demonstrate a dose-dependent sexually dimorphic relationship between cumulative prenatal adversity and infant amygdalar volumes.

Cognitive functions and symptoms predicting later use of psychiatric services following mild traumatic brain injury in school-age.

OBJECTIVE: To investigate whether neuropsychological test performance or presence of some specific injury symptoms at 1-3 months following pediatric mild traumatic brain injury (mTBI) can help to identify the children at risk for developing post-traumatic psychiatric symptoms. METHODS: Data from 120 children and adolescents aged 7-15 years, treated at Turku University Hospital between 2010 and 2016 due to mTBI, and who had undergone neuropsychological evaluation at 1-3 months following injury, were enrolled from the hospital records. Neuropsychological test performancesand injury symptom reports were retrospectively retrieved from the patient files. RESULTS: Slow information processing speed (p = 0.044), emotion regulation deficit (p = 0.014), impulsivity (p = 0.013), verbal processing difficulties (p = 0.042) and headache (p = 0.026) were independent predictors for having later contact in psychiatric care. CONCLUSIONS: Neuropsychological examination containing measure of information processing speed, injury symptom interview, and parental questionnaires on behavioural issues of the child at 1-3 months following mTBI seems to be useful in detecting children with risk for post traumatic psychiatric symptoms. Targeted support and guidance for this group of children and adolescents and their families are recommended to prevent the development of an unfavorable psychosocial outcome.

Subcortical and hippocampal brain segmentation in 5-year-old children: Validation of FSL-FIRST and FreeSurfer against manual segmentation.

Developing accurate subcortical volumetric quantification tools is crucial for neurodevelopmental studies, as they could reduce the need for challenging and time-consuming manual segmentation. In this study, the accuracy of two automated segmentation tools, FSL-FIRST (with three different boundary correction settings) and FreeSurfer, were compared against manual segmentation of the hippocampus and subcortical nuclei, including the amygdala, thalamus, putamen, globus pallidus, caudate and nucleus accumbens, using volumetric and correlation analyses in 80 5-year-olds. Both FSL-FIRST and FreeSurfer overestimated the volume on all structures except the caudate, and the accuracy varied depending on the structure. Small structures such as the amygdala and nucleus accumbens, which are visually difficult to distinguish, produced significant overestimations and weaker correlations with all automated methods. Larger and more readily distinguishable structures such as the caudate and putamen produced notably lower overestimations and stronger correlations. Overall, the segmentations performed by FSL-FIRST's default pipeline were the most accurate, whereas FreeSurfer's results were weaker across the structures. In line with prior studies, the accuracy of automated segmentation tools was imperfect with respect to manually defined structures. However, apart from amygdala and nucleus accumbens, FSL-FIRST's agreement could be considered satisfactory (Pearson correlation > 0.74, intraclass correlation coefficient (ICC) > 0.68 and Dice score coefficient (DSC) > 0.87) with highest values for the striatal structures (putamen, globus pallidus, caudate) (Pearson correlation > 0.77, ICC > 0.87 and DSC > 0.88, respectively). Overall, automated segmentation tools do not always provide satisfactory results, and careful visual inspection of the automated segmentations is strongly advised.

Allometry in the corpus callosum in neonates: Sexual dimorphism.

The corpus callosum (CC) is the largest fiber tract in the human brain, allowing interhemispheric communication by connecting homologous areas of the two cerebral hemispheres. In adults, CC size shows a robust allometric relationship with brain size, with larger brains having larger callosa, but smaller brains having larger callosa relative to brain size. Such an allometric relationship has been shown in both males and females, with no significant difference between the sexes. But there is some evidence that there are alterations in these allometric relationships during development. However, it is currently not known whether there is sexual dimorphism in these allometric relationships from birth, or if it only develops later. We study this in neonate data. Our results indicate that there are already sex differences in these allometric relationships in neonates: male neonates show the adult-like allometric relationship between CC size and brain size; however female neonates show a significantly more positive allometry between CC size and brain size than either male neonates or female adults. The underlying cause of this sexual dimorphism is unclear; but the existence of this sexual dimorphism in neonates suggests that sex-differences in lateralization have prenatal origins.

Sex-specific associations between maternal pregnancy-specific anxiety and newborn amygdalar volumes - preliminary findings from the FinnBrain Birth Cohort Study.

Previous literature links maternal pregnancy-specific anxiety (PSA) with later difficulties in child emotional and social cognition as well as memory, functions closely related to the amygdala and the hippocampus. Some evidence also suggests that PSA affects child amygdalar volumes in a sex-dependent way. However, no studies investigating the associations between PSA and newborn amygdalar and hippocampal volumes have been reported. We investigated the associations between PSA and newborn amygdalar and hippocampal volumes and whether associations are sex-specific in 122 healthy newborns (68 males/54 females) scanned at 2-5 weeks postpartum. PSA was measured at gestational week 24 with the Pregnancy-Related Anxiety Questionnaire Revised 2 (PRAQ-R2). The associations were analyzed with linear regression controlling for confounding variables. PSA was associated positively with left amygdalar volume in girls, but no significant main effect was found in the whole group or in boys. No significant main or sex-specific effect was found for hippocampal volumes. Although this was an exploratory study, the findings suggest a sexually dimorphic association of mid-pregnancy PSA with newborn amygdalar volumes.

Neuroimaging and neurological outcome of children with acute encephalitis.

AIM: To investigate the severity of acute phase magnetic resonance imaging (MRI) findings and severity of acute illness as risk factors for disability after recovery from encephalitis. METHOD: Children with encephalitis (n = 98; median age 6 years 10 months, interquartile range 3 years-11 years 6 months; 59 males, 39 females) treated in Turku University Hospital during the years 1995 to 2016 were identified in this retrospective cohort study. The acute phase (<2 months of symptom onset) brain MRIs were re-evaluated and classified based on the severity of neuroimaging finding by a neuroradiologist. Neurological outcome at discharge, at short-term (<3 months from discharge) follow-up, and at long-term (>1 year from discharge) follow-up was assessed from medical records using the Glasgow Outcome Scale. RESULTS: Long-term recovery was poor in 24 of 82 (29%) children with follow-up data. Two children died, eight had severe disability, and 14 had moderate disability. Acute phase MRI was available for re-evaluation from 74 of 82 patients with follow-up data. The increasing severity of MRI findings was associated with need for ventilator therapy and with poor recovery. INTERPRETATION: The risk for poor recovery in paediatric encephalitis is high, and it is associated with the severity of MRI findings. WHAT THIS PAPER ADDS: Poor long-term recovery was found in 29% of children with encephalitis. Severe disability measured by Glasgow Outcome Scale was found in 8%. The most severe neuroimaging findings were a risk factor for severe acute illness and poor long-term recovery.

Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder.

Polygenic risk scores for major depressive disorder (PRS-MDD) have been identified in large genome-wide association studies, and recent findings suggest that PRS-MDD might interact with environmental risk factors to shape human limbic brain development as early as in the prenatal period. Striatal structures are crucially involved in depression; however, the association of PRS-MDD with infant striatal volumes is yet unknown. In this study, 105 Finnish mother-infant dyads (44 female, 11-54 days old) were investigated to reveal how infant PRS-MDD is associated with infant dorsal striatal volumes (caudate, putamen) and whether PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant striatal volumes. A robust sex-specific main effect of PRS-MDD on bilateral infant caudate volumes was observed. PRS-MDD were more positively associated with caudate volumes in boys compared to girls. No significant interaction effects of genotype PRS-MDD with the environmental risk factor "prenatal maternal depressive symptoms" (genotype-by-environment interaction) nor significant interaction effects of genotype with prenatal maternal depressive symptoms and sex (genotype-by-environment-by-sex interaction) were found for infant dorsal striatal volumes. Our study showed that a higher PRS-MDD irrespective of prenatal exposure to maternal depressive symptoms is associated with smaller bilateral caudate volumes, an indicator of greater susceptibility to major depressive disorder, in female compared to male infants. This sex-specific polygenic effect might lay the ground for the higher prevalence of depression in women compared to men.

Test-retest reliability of Diffusion Tensor Imaging metrics in neonates.

Diffusion tensor imaging (DTI) has been widely used in children and adults to study the microstructural features of the brain. Its use in neonate brains has been limited. Neonate brains are almost completely unmyelinated, and this together with the tendency for babies to move during a scanning session may affect the reliability of the measurements. Here we divided a 96 direction acquisition into three segments, and analysed the intra scan test-retest reliability for pairs of segments. Each segment was subjected to a rigorous quality control, and from the surviving data we chose 25 diffusion encoding directions from each segment, and assessed the pairwise reliability of the most common DTI metrics. This pairwise reliability was assessed for data from 86 infants. We used tract-based spatial statistics (TBSS), voxelwise and ROI analysis schemes, to see potential differential effects of analysis strategy and post processing on the obtained DTI metrics. We found that intra class correlation coefficient (ICC) values were generally high (ICC > 0.80). Residual motion in the data, after quality control, was not found to associate with the diffusion metrics. The results indicate that DTI metrics from neonate data can be reliable, even at relatively low angular resolution that are common for neonate scans. The results lend confidence to the use of neonate DTI data in cross sectional and longitudinal analyses in brain white matter skeleton. Future studies should assess the reliability of fiber tracking techniques in neonate data.

Prenatal exposures and infant brain: Review of magnetic resonance imaging studies and a population description analysis.

Brain development is most rapid during the fetal period and the first years of life. This process can be affected by many in utero factors, such as chemical exposures and maternal health characteristics. The goal of this review is twofold: to review the most recent findings on the effects of these prenatal factors on the developing brain and to qualitatively assess how those factors were generally reported in studies on infants up to 2 years of age. To capture the latest findings in the field, we searched articles from PubMed 2012 onward with search terms referring to magnetic resonance imaging (MRI), brain development, and infancy. We identified 19 MRI studies focusing on the effects of prenatal environment and summarized them to highlight the recent advances in the field. We assessed population descriptions in a representative sample of 67 studies and conclude that prenatal factors that have been shown to affect brain metrics are not generally reported comprehensively. Based on our findings, we propose some improvements for population descriptions to account for plausible confounders and in time enable reliable meta-analyses to be performed. This could help the pediatric neuroimaging field move toward more reliable identification of biomarkers for developmental outcomes and to better decipher the nuances of normal and abnormal brain development.

Dental staining after doxycycline use in children.

Background: The use of doxycycline has been avoided before 8 years of age due to known dental staining caused by tetracyclines, although doxycycline differs from classical tetracyclines in many ways. Doxycycline is still an important antimicrobial agent, but its dental safety is not well studied. Objectives: To examine the state of permanent teeth after doxycycline exposure in children <8 years of age. Methods: Details of doxycycline treatment were collected from medical records. After the eruption of permanent teeth the dental status was examined by an experienced paediatric dentist for detection of dental staining and enamel hypoplasia. The resulting dental photographs were evaluated by a second independent experienced paediatric dentist. Results: The mean age of 38 study subjects at the time of doxycycline treatment was 4.7 years (range 0.6-7.9 years, SD 2.3). The doxycycline dose was 10 mg/kg/day (varying from 8 to 10 mg/kg/day) for the first 2-3 days and 5 mg/kg/day (varying from 2.5 to 10 mg/kg/day) thereafter. The mean length of the treatment was 12.5 days (SD 6.0) and ranged from 2 to 28 days. Tetracycline-like staining or enamel hypoplasia of developing teeth was detected in none of the subjects. Conclusions: Doxycycline treatment of small children does not seem to induce permanent tooth staining.

Use of endocrinological and neurological medication among 5-year survivors of young onset brain tumors.

The burden of late-effects for young onset brain tumor (BT) survivors needs more careful evaluation. Our aim was to assess the need for endocrinological and neurological medication among this specific group. We identified 5-year survivors diagnosed at the age of 0-24 years between 1988 and 2004 from the Finnish Cancer Registry (N = 602). Data on endocrinological and neurological drug purchases were collected from the Social Insurance Institution of Finland. Five years after diagnosis the most commonly purchased drugs had been: antiepileptics (44.8 %), systemic hydrocortisone (18.3 %), female sex hormones (17.6 %), thyroid hormones (11.2 %), and growth hormone (10.0 %). The survivors showed an increased hazard ratio (HR) for a need for new types of drugs still 5 years after diagnosis. Thyroid hormones (HR 10.6, 95 % CI 5.1-21.4), estrogens (HR 8.0, 95 % CI 2.1-25.7), and antiepileptics (HR 6.3, 95 % CI 3.4-11.2) were bought with high frequencies. Irradiation increased the hazard for drug-purchases other than antiepileptics. Cumulative incidence of purchases of estrogens or androgens increased still 15 years after diagnosis. The cumulative incidence of purchasing thyroid hormones and antiepileptics showed continuous increase for the youngest group, whereas survivors diagnosed at 15-24 years of age reached stable level before 15 years from diagnosis. The need for new medication continued more than a decade after BT diagnosis. Especially the need for new thyroid or sex hormone medication among childhood BT survivors may emerge long after diagnosis.

Feasibility of FreeSurfer Processing for T1-Weighted Brain Images of 5-Year-Olds: Semiautomated Protocol of FinnBrain Neuroimaging Lab.

Pediatric neuroimaging is a quickly developing field that still faces important methodological challenges. Pediatric images usually have more motion artifact than adult images. The artifact can cause visible errors in brain segmentation, and one way to address it is to manually edit the segmented images. Variability in editing and quality control protocols may complicate comparisons between studies. In this article, we describe in detail the semiautomated segmentation and quality control protocol of structural brain images that was used in FinnBrain Birth Cohort Study and relies on the well-established FreeSurfer v6.0 and ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium tools. The participants were typically developing 5-year-olds [n = 134, 5.34 (SD 0.06) years, 62 girls]. Following a dichotomous quality rating scale for inclusion and exclusion of images, we explored the quality on a region of interest level to exclude all regions with major segmentation errors. The effects of manual edits on cortical thickness values were relatively minor: less than 2% in all regions. Supplementary Material cover registration and additional edit options in FreeSurfer and comparison to the computational anatomy toolbox (CAT12). Overall, we conclude that despite minor imperfections FreeSurfer can be reliably used to segment cortical metrics from T1-weighted images of 5-year-old children with appropriate quality assessment in place. However, custom templates may be needed to optimize the results for the subcortical areas. Through visual assessment on a level of individual regions of interest, our semiautomated segmentation protocol is hopefully helpful for investigators working with similar data sets, and for ensuring high quality pediatric neuroimaging data.

Prenatal and early-life environmental factors, family demographics and cortical brain anatomy in 5-year-olds: an MRI study from FinnBrain Birth Cohort.

The human brain develops dynamically during early childhood, when the child is sensitive to both genetic programming and extrinsic exposures. Recent studies have found links between prenatal and early life environmental factors, family demographics and the cortical brain morphology in newborns measured by surface area, volume and thickness. Here in this magnetic resonance imaging study, we evaluated whether a similar set of variables associates with cortical surface area and volumes measured in a sample of 170 healthy 5-year-olds from the FinnBrain Birth Cohort Study. We found that child sex, maternal pre-pregnancy body mass index, 5 min Apgar score, neonatal intensive care unit admission and maternal smoking during pregnancy associated with surface areas. Furthermore, child sex, maternal age and maternal level of education associated with brain volumes. Expectedly, many variables deemed important for neonatal brain anatomy (such as birth weight and gestational age at birth) in earlier studies did not associate with brain metrics in our study group of 5-year-olds, which implies that their effects on brain anatomy are age-specific. Future research may benefit from including pre- and perinatal covariates in the analyses when such data are available. Finally, we provide evidence for right lateralization for surface area and volumes, except for the temporal lobes which were left lateralized. These subtle differences between hemispheres are variable across individuals and may be interesting brain metrics in future studies.

Maternal sensitivity at the age of 8 months associates with local connectivity of the medial prefrontal cortex in children at 5 years of age.

The quality of mother-child interaction, especially maternal sensitivity in caregiving behavior, plays an important role in a child's later socioemotional development. Numerous studies have indicated associations between poor mother-child interaction and offspring brain structure and function, but more knowledge on how variation in the characteristics of early caregiving is associated with children's brain structure and function is needed. We investigated whether maternal sensitivity at 8 or 30 months is associated with functional connectivity in a child's brain at 5 years of age based on the FinnBrain Birth Cohort Study (17 and 39 mother-child dyads at 8 and 30 months, respectively, with an overlap of 13 dyads). Maternal sensitivity was assessed during a free play interaction using the Emotional Availability Scales at 8 and 30 months of the children's age. Task-free functional magnetic resonance imaging (fMRI) was acquired at the age of 5 years in 7-min scans while watching the Inscapes movie. Regional homogeneity (ReHo) maps were created from the fMRI data, and multiple regression analysis was performed to assess the relation between maternal sensitivity and ReHo. Maternal sensitivity at the age of 8 months was positively associated with children's ReHo values within the medial prefrontal cortex. Distal connectivity of this region showed no significant association with maternal sensitivity in a seed-based connectivity analysis. No associations were found between maternal sensitivity during toddlerhood and brain functional connectivity. Together, these results suggest that maternal sensitivity, especially in infancy, may influence offspring brain functional connectivity. However, studies with larger sample sizes are warranted.

Neurological and Cognitive Performance After Childhood Encephalitis.

Background: Children with encephalitis have increased risk for long-term neurological sequelae. We investigated minor neurological dysfunction (MND) and cognitive performance as a measurement for long-term outcome of encephalitis in childhood. Materials and Methods: Children with encephalitis (n = 98) treated in Turku University Hospital during the years 1995-2016 were retrospectively identified. We included the patients without severe developmental delay before the encephalitis and without recorded neurological disability caused by encephalitis. MND was assessed using the Touwen examination. Age-appropriate Wechsler Intelligence Scale was used to determine the full-scale intelligence quotient (IQ). Residual symptoms in everyday life were evaluated using a questionnaire. Results: Forty-two subjects participated in the study and returned the questionnaire regarding residual symptoms. The median age was 4.3 years at the time of encephalitis, and 11.3 years at the time of the Touwen examination (n = 41) and the cognitive assessment (n = 38). The Touwen examination indicated MND in 29 of 41 participants (71%; simple MND in 16 and complex MND in 13 patients). The median full-scale IQ was lower in participants with MND compared with participants without MND (98 vs. 110, p = 0.02). Participants with IQ < 85 (n = 5) had lower median age at acute encephalitis compared to participants with IQ ≥ 85 (n = 33) (1.8 vs. 5.3 years, p = 0.03). Problems in daily performance were reported in participant with MND (p = 0.2) and low full-scale IQ (p = 0.008). Conclusions: The prevalence of MND was high and it was related to lower cognitive performance after childhood encephalitis. Younger age at acute encephalitis was a risk factor for lower cognitive performance.

Maternal pre-pregnancy BMI associates with neonate local and distal functional connectivity of the left superior frontal gyrus.

Maternal obesity/overweight during pregnancy has reached epidemic proportions and has been linked with adverse outcomes for the offspring, including cognitive impairment and increased risk for neuropsychiatric disorders. Prior neuroimaging investigations have reported widespread aberrant functional connectivity and white matter tract abnormalities in neonates born to obese mothers. Here we explored whether maternal pre-pregnancy adiposity is associated with alterations in local neuronal synchrony and distal connectivity in the neonate brain. 21 healthy mother-neonate dyads from uncomplicated pregnancies were included in this study (age at scanning 26.14 ± 6.28 days, 12 male). The neonates were scanned with a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) during natural sleep. Regional homogeneity (ReHo) maps were computed from obtained rs-fMRI data. Multiple regression analysis was performed to assess the association of pre-pregnancy maternal body-mass-index (BMI) and ReHo. Seed-based connectivity analysis with multiple regression was subsequently performed with seed-ROI derived from ReHo analysis. Maternal adiposity measured by pre-pregnancy BMI was positively associated with neonate ReHo values within the left superior frontal gyrus (SFG) (FWE-corrected p < 0.005). Additionally, we found both positive and negative associations (p < 0.05, FWE-corrected) for maternal pre-pregnancy BMI and seed-based connectivity between left SFG and prefrontal, amygdalae, basal ganglia and insular regions. Our results imply that maternal pre-pregnancy BMI associates with local and distal functional connectivity within the neonate left superior frontal gyrus. These findings add to the evidence that increased maternal pre-pregnancy BMI has a programming influence on the developing neonate brain functional networks.