Rupa Radhakrishnan

Introduction: Prenatal substance exposure is an increasing problem that has been linked to multiple neurodevelopmental impairments and alterations to brain functional connectivity. Methods: Behavioral scores and functional network correlation data were obtained from the Adolescent Brain Cognitive Development ^SM (ABCD) Study. First, behavioral scores based on the child behavioral checklist were tested for associations with prenatal exposure to several substances along with demographic data. Then differences in resting‐state functional networks were assessed based on prenatal substance exposure. Third, we assessed the impact of resting‐state functional networks on behavioral scores. A linear regression was used for all these analyses, and a false discovery rate < 0.05 was considered significant. Results: Based on the selection criteria, 6674 subjects were included in the analysis. Prenatal tobacco exposure (PTE), prenatal marijuana exposure, household income, and food insecurity were associated with worse behavioral scores. Additionally, PTE was significantly associated with increased connectivity between the default mode network (DMN) and dorsal attention network (DAN) and decreased intra‐network connectivity within the DAN. Finally, there were five CBCL scales that were associated with differences in network connectivity. Conclusion: Taken together, these results suggest PTE to be associated with multiple functional networks, including those associated with several CBCL scales.

Opioid use disorder during pregnancy significantly increases the likelihood of adverse developmental outcomes in the offspring. Texture analysis serves as a quantitative technique that could be vital in identifying microstructural variations in placentas that have been exposed to opioids and other substances. This is a prospective, multisite cross-sectional study that recruited pregnant women that were greater than 16 weeks of gestation. We manually segmented placenta tissue from half-Fourier single-shot turbo spin-echo (HASTE) sequence MR images. We then assessed placental surface area and texture features using a radiomics pipeline. Using linear models, we assessed the association of substance use on placental surface area and texture features, accounting for demographic characteristics. There were 33 pregnant women with opioid use and 29 controls. Based on regression analysis, opioid exposure was associated with alterations in two texture features while tobacco exposure was associated with alterations in five texture features prior to multiple comparison correction. These were no longer significant after correcting for multiple comparisons. Additionally, tobacco exposure was significantly associated with greater placenta surface area.

There is growing interest in understanding the effects of opioid use on the brain, yet the effects of opioid use on the pregnant maternal brain are still relatively unknown. Pregnant women with opioid exposure during pregnancy are at high risk for adverse neurological and neuropsychiatric outcomes. Much of what is currently known about the impact of opioids on the maternal brain is mainly derived from studies in animal models; however, species-specific opioid pathways and other socio-environmental factors complicate the interpretation of results. A few studies in non-pregnant adults have shown the utility of magnetic resonance spectroscopy (MRS) in risk prediction in substance exposure. We know that pregnancy alters the pharmacodynamics and pharmacokinetics of opioid metabolism, and the impact of opioids on synapses may differ during pregnancy compared to the non-pregnant state. We, therefore, aimed to understand the neurometabolic alterations in pregnant women on medications for opioid use disorder (MOUD). In our multicenter study, we utilized 1H MRS to analyze metabolic alterations in the dorsal anterior cingulate cortex (dACC) in pregnant women on MOUD (12 subjects) vs. pregnant control women (21 subjects) without substance exposure. Using multivariable linear regression, we identified a positive association between opioid exposure and choline-to-creatine (Cho/Cr) ratios after correcting for gestational age and scanner site. We also identified a significant elevation in the Cho/Cr ratio in pregnant women on MOUD and concomitant polysubstance exposure when compared to pregnant women on MOUD without exposure to other substances and control pregnant women. These altered metabolite concentrations that we identified in the dACC may provide a mechanistic understanding of the neurobiology of MOUD and insights for better management and outcomes.

Background and Purpose: Morning glory disc anomaly (MGDA) is a rare congenital abnormality of the posterior globe with characteristic excavation of the optic disc. Associated abnormalities of the head and neck have been reported in individuals with MGDA as single or small series case reports. The goal of this retrospective study was to identify the prevalence of extraocular abnormalities in a single institution cohort of individuals with MGDA. Methods: This was an IRB‐approved retrospective case series including eighteen patients with fundoscopically confirmed MGDA by an ophthalmologist and a brain MRI available for review. Brain MRIs reviewed were acquired between 2007 and 2024. Imaging was reviewed by fellowship‐trained pediatric neuroradiologists for a descriptive analysis of associated abnormalities. Results: We identified associated abnormalities in 12 of the 18 patients with MGDA. The most common abnormalities were optic pathway anomalies, midline CNS and skull base anomalies, and intracranial vascular anomalies. Optic pathway enlargement was observed in seven patients (39%), and intracranial vascular anomalies were seen in four patients (22%). None of the individuals with MGDA and internal carotid artery stenosis exhibited lenticulostriate hypertrophy, typically seen with moyamoya vasculopathy. Conclusions: Based on our cohort and previous literature, optic pathway enlargement and vascular anomalies are common radiologic findings in MGDA. The results of this study strengthen the need for screening individuals with MGDA for further intracranial and vascular anomalies.

BACKGROUND AND PURPOSE: Sotos syndrome is a rare autosomal dominant condition caused by pathogenic mutations in the NSD1 gene that presents with craniofacial dysmorphism, overgrowth, seizures, and neurodevelopmental delay. Macrocephaly, ventriculomegaly, and corpus callosal dysmorphism are typical neuroimaging features that have been described in the medical literature. The purpose of this study was to expand on the neuroimaging phenotype by detailed analysis of a large cohort of patients with genetically proved Sotos syndrome. MATERIALS AND METHODS: This multicenter, multinational, retrospective observational cohort study systematically analyzed the clinical characteristics and neuroimaging features of 77 individuals with genetically diagnosed Sotos syndrome, via central consensus review with 3 pediatric neuroradiologists. RESULTS: In addition to previously described features, malformations of cortical development were identified in most patients (95.0%), typically dysgyria (92.2%) and polymicrogyria (22.1%), varying in location and distribution. Incomplete rotation of the hippocampus was observed in 50.6% of patients and was associated with other imaging findings, in particular with dysgyria (100% versus 84.2%, P = .012). CONCLUSIONS: Our findings show a link between the genetic-biochemical basis and the neuroimaging features and aid in better understanding the underlying clinical manifestations and possible treatment options. These findings have yet to be described to this extent and correspond with recent studies that show that NSD1 participates in brain development and has interactions with other known relevant genetic pathways.

New onset refractory status epilepticus (NORSE) is an etiologically heterogeneous condition that is associated with high morbidity and mortality. NORSE is often refractory to medical management prom

There has been an increase in the number of women using marijuana whilst pregnant. Previous studies have shown that children with prenatal marijuana exposure have developmental deficits in memory and decreased attentiveness. In this study, we assess whether prenatal marijuana exposure is associated with alterations in brain regional morphometry and functional and structural connectivity in adolescents. We downloaded behavioural scores and subject image files from the Adolescent Brain Cognitive Development^SM Study. A total of 178 anatomical and diffusion magnetic resonance imaging files (88 prenatal marijuana exposure and 90 age- and gender-matched controls) and 152 resting-state functional magnetic resonance imaging files (76 prenatal marijuana exposure and 76 controls) were obtained. Behavioural metrics based on the parent-reported child behavioural checklist were also obtained for each subject. The associations of prenatal marijuana exposure with 17 subscales of the child behavioural checklist were calculated. We assessed differences in brain morphometry based on voxel-based and surface-based morphometry in adolescents with prenatal marijuana exposure versus controls. We also evaluated group differences in structural and functional connectivity in adolescents for region-to-region connectivity and graph theoretical metrics. Interactions of prenatal marijuana exposure and graph networks were assessed for impact on behavioural scores. Multiple comparison correction was performed as appropriate. Adolescents with prenatal marijuana exposure had greater abnormal or borderline child behavioural checklist scores in 9 out of 17 subscales. There were no significant differences in voxel- or surface-based morphometry, structural connectivity or functional connectivity between prenatal marijuana exposure and controls. However, there were significant differences in prenatal marijuana exposure–graph network interactions with respect to behavioural scores. There were three structural prenatal marijuana exposure–graph network interactions and seven functional prenatal marijuana exposure–graph network interactions that were significantly associated with behavioural scores. Whilst this study was not able to confirm anatomical or functional differences between prenatal marijuana exposure and unexposed pre-adolescent children, there were prenatal marijuana exposure–brain structural and functional graph network interactions that were significantly associated with behavioural scores. This suggests that altered brain networks may underlie behavioural outcomes in adolescents with prenatal marijuana exposure. More work needs to be conducted to better understand the prognostic value of brain structural and functional network measures in prenatal marijuana exposure.

Dramatic advances in the management of congenital heart disease (CHD) have improved survival to adulthood from less than 10% in the 1960s to over 90% in the current era, such that adult CHD (ACHD) patients now outnumber their pediatric counterparts. ACHD patients demonstrate domain-specific neurocognitive deficits associated with reduced quality of life that include deficits in educational attainment and social interaction. Our hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits modified by behavioral and environmental enrichment proxies of cognitive reserve (e.g., level of education and lifestyle/social habits). This technical note describes an ancillary study to the National Heart, Lung, and Blood Institute (NHLBI)-funded Pediatric Heart Network (PHN) “Multi-Institutional Neurocognitive Discovery Study (MINDS) in Adult Congenital Heart Disease (ACHD)”. Leveraging clinical, neuropsychological, and biospecimen data from the parent study, our study will provide structural–physiological correlates of neurocognitive outcomes, representing the first multi-center neuroimaging initiative to be performed in ACHD patients. Limitations of the study include recruitment challenges inherent to an ancillary study, implantable cardiac devices, and harmonization of neuroimaging biomarkers. Results from this research will help shape the care of ACHD patients and further our understanding of the interplay between brain injury and cognitive reserve.