Regional homogeneity as a marker of sensory cortex dysmaturity in preterm infants.

Atypical perinatal sensory experience in preterm infants is thought to increase their risk of neurodevelopmental disabilities by altering the development of the sensory cortices. Here, we used resting-state fMRI data from preterm and term-born infants scanned between 32 and 48 weeks post-menstrual age to assess the effect of early ex-utero exposure on sensory cortex development. Specifically, we utilized a measure of local correlated-ness called regional homogeneity (ReHo). First, we demonstrated that the brain-wide distribution of ReHo mirrors the known gradient of cortical maturation. Next, we showed that preterm birth differentially reduces ReHo across the primary sensory cortices. Finally, exploratory analyses showed that the reduction of ReHo in the primary auditory cortex of preterm infants is related to increased risk of autism at 18 months. In sum, we show that local connectivity within sensory cortices has different developmental trajectories, is differentially affected by preterm birth, and may be associated with later neurodevelopment.

Experience of early-life pain in premature infants is associated with atypical cerebellar development and later neurodevelopmental deficits.

BACKGROUND: Infants born very and extremely premature (V/EPT) are at a significantly elevated risk for neurodevelopmental disorders and delays even in the absence of structural brain injuries. These risks may be due to earlier-than-typical exposure to the extrauterine environment, and its bright lights, loud noises, and exposures to painful procedures. Given the relative underdeveloped pain modulatory responses in these infants, frequent pain exposures may confer risk for later deficits. METHODS: Resting-state fMRI scans were collected at term equivalent age from 148 (45% male) infants born V/EPT and 99 infants (56% male) born at term age. Functional connectivity analyses were performed between functional regions correlating connectivity to the number of painful skin break procedures in the NICU, including heel lances, venipunctures, and IV placements. Subsequently, preterm infants returned at 18 months, for neurodevelopmental follow-up and completed assessments for autism risk and general neurodevelopment. RESULTS: We observed that V/EPT infants exhibit pronounced hyperconnectivity within the cerebellum and between the cerebellum and both limbic and paralimbic regions correlating with the number of skin break procedures. Moreover, skin breaks were strongly associated with autism risk, motor, and language scores at 18 months. Subsample analyses revealed that the same cerebellar connections strongly correlating with breaks at term age were associated with language dysfunction at 18 months. CONCLUSIONS: These results have significant implications for the clinical care of preterm infants undergoing painful exposures during routine NICU care, which typically occurs without anesthesia. Repeated pain exposures appear to have an increasingly detrimental effect on brain development during a critical period, and effects continue to be seen even 18 months later.

Ex-utero third trimester developmental changes in functional brain network organization in infants born very and extremely preterm.

Introduction: The latter half of gestation is a period of rapid brain development, including the formation of fundamental functional brain network architecture. Unlike in-utero fetuses, infants born very and extremely preterm undergo these critical maturational changes in the extrauterine environment, with growing evidence suggesting this may result in altered brain networks. To date, however, the development of functional brain architecture has been unexplored. Methods: From a prospective cohort of preterm infants, graph parameters were calculated for fMRI scans acquired prior to reaching term equivalent age. Eight graph properties were calculated, Clustering Coefficient (C), Characteristic Path Length (L), Modularity (Q), Local Efficiency (LE), Global Efficiency (GE), Normalized Clustering (λ), Normalized Path Length (γ), and Small-Worldness (σ). Properties were first compared to values generated from random and lattice networks and cost efficiency was evaluated. Subsequently, linear mixed effect models were used to assess relationship with postmenstrual age and infant sex. Results: A total of 111 fMRI scans were acquired from 85 preterm infants born at a mean GA 28.93 ± 2.8. Infants displayed robust small world properties as well as both locally and globally efficient networks. Regression models found that GE increased while L, Q, λ, γ, and σ decreased with increasing postmenstrual age following multiple comparison correction (r2Adj range 0.143-0.401, p < 0048), with C and LE exhibited trending increases with age. Discussion: This is the first direct investigation on the extra-uterine formation of functional brain architecture in preterm infants. Importantly, our results suggest that changes in functional architecture with increasing age exhibit a different trajectory relative to in utero fetus. Instead, they exhibit developmental changes more similar to the early postnatal period in term born infants.

Robust sex differences in functional brain connectivity are present in utero.

Sex-based differences in brain structure and function are observable throughout development and are thought to contribute to differences in behavior, cognition, and the presentation of neurodevelopmental disorders. Using multiple support vector machine (SVM) models as a data-driven approach to assess sex differences, we sought to identify regions exhibiting sex-dependent differences in functional connectivity and determine whether they were robust and sufficiently reliable to classify sex even prior to birth. To accomplish this, we used a sample of 110 human fetal resting state fMRI scans from 95 fetuses, performed between 19 and 40 gestational weeks. Functional brain connectivity patterns classified fetal sex with 73% accuracy. Across SVM models, we identified features (functional connections) that reliably differentiated fetal sex. Highly consistent predictors included connections in the somatomotor and frontal areas alongside the hippocampus, cerebellum, and basal ganglia. Moreover, high consistency features also implicated a greater magnitude of cross-region connections in females, while male weighted features were predominately within anatomically bounded regions. Our findings indicate that these differences, which have been observed later in childhood, are present and reliably detectable even before birth. These results show that sex differences arise before birth in a manner that is consistent and reliable enough to be highly identifiable.

Gestational age-related changes in the fetal functional connectome: in utero evidence for the global signal.

The human brain begins to develop in the third gestational week and rapidly grows and matures over the course of pregnancy. Compared to fetal structural neurodevelopment, less is known about emerging functional connectivity in utero. Here, we investigated gestational age (GA)-associated in vivo changes in functional brain connectivity during the second and third trimesters in a large dataset of 110 resting-state functional magnetic resonance imaging scans from a cohort of 95 healthy fetuses. Using representational similarity analysis, a multivariate analytical technique that reveals pair-wise similarity in high-order space, we showed that intersubject similarity of fetal functional connectome patterns was strongly related to between-subject GA differences (r = 0.28, P < 0.01) and that GA sensitivity of functional connectome was lateralized, especially at the frontal area. Our analysis also revealed a subnetwork of connections that were critical for predicting age (mean absolute error = 2.72 weeks); functional connectome patterns of individual fetuses reliably predicted their GA (r = 0.51, P < 0.001). Lastly, we identified the primary principal brain network that tracked fetal brain maturity. The main network showed a global synchronization pattern resembling global signal in the adult brain.

FetalGAN: Automated Segmentation of Fetal Functional Brain MRI Using Deep Generative Adversarial Learning and Multi-Scale 3D U-Net.

An important step in the preprocessing of resting state functional magnetic resonance images (rs-fMRI) is the separation of brain from non-brain voxels. Widely used imaging tools such as FSL's BET2 and AFNI's 3dSkullStrip accomplish this task effectively in children and adults. In fetal functional brain imaging, however, the presence of maternal tissue around the brain coupled with the non-standard position of the fetal head limit the usefulness of these tools. Accurate brain masks are thus generated manually, a time-consuming and tedious process that slows down preprocessing of fetal rs-fMRI. Recently, deep learning-based segmentation models such as convolutional neural networks (CNNs) have been increasingly used for automated segmentation of medical images, including the fetal brain. Here, we propose a computationally efficient end-to-end generative adversarial neural network (GAN) for segmenting the fetal brain. This method, which we call FetalGAN, yielded whole brain masks that closely approximated the manually labeled ground truth. FetalGAN performed better than 3D U-Net model and BET2: FetalGAN, Dice score = 0.973 ± 0.013, precision = 0.977 ± 0.015; 3D U-Net, Dice score = 0.954 ± 0.054, precision = 0.967 ± 0.037; BET2, Dice score = 0.856 ± 0.084, precision = 0.758 ± 0.113. FetalGAN was also faster than 3D U-Net and the manual method (7.35 s vs. 10.25 s vs. ∼5 min/volume). To the best of our knowledge, this is the first successful implementation of 3D CNN with GAN on fetal fMRI brain images and represents a significant advance in fully automating processing of rs-MRI images.

Neural correlates of schema-dependent episodic memory and association with behavioral flexibility in autism spectrum disorders and typical development.

BACKGROUND: Conceptual knowledge frameworks termed schemas facilitate memory formation and are posited to support flexible behavior. In adults, the medial temporal lobe (MTL) and medial prefrontal cortex (mPFC) trade-off in supporting schema-based memory formation, such that encoding of subsequently remembered schema-congruent information relies on mPFC, whereas schema-incongruent information relies on MTL. Whether this is true in the immature brain and relates to behavioral flexibility is unknown. In this preliminary investigation, we aimed to replicate the adult findings in typically developing (TD) children and to investigate the relevance to behavioral flexibility by examining a disorder with pathognomonic behavioral rigidity, autism spectrum disorder (ASD). METHODS: Children completed an associative subsequent memory paradigm, encoding object-scene pairs in an MRI scanner and subsequently completing a recognition test outside the scanner after a delay. Recognition performance was back sorted to construct remembered vs forgotten contrasts. One-way ANOVAS were conducted in MTL and mPFC masks for schema-congruency, followed by congruency by flexibility scores. Exploratory analyses were then conducted within the whole brain. RESULTS: As reported in adults, episodic memory was strongest for schema-congruent object-scene pairs, followed by intermediate pairs, and lowest for schema-incongruent pairs in both TD and ASD groups. However, the trade-off between mPFC and MTL in TD children differed from adult reports such that mPFC supported memory for intermediate schema-congruency and left anterior MTL supported memory for schema-congruent pairs. In ASD, mPFC engagement interacted with flexibility such that activation supporting memory for intermediate schema-congruency varied with parent-reported flexibility and was higher in those with more flexible behavior. A similar interaction was also observed in both the left dorsolateral and rostrolateral PFC in whole-brain analysis. CONCLUSION: Our findings provide the first preliminary evidence for the association of schema-based episodic memory formation and behavioral flexibility, an executive function impaired in multiple developmental disorders. Upon replication, this line of research holds promise for memory-based interventions addressing executive problems of behavioral rigidity.

Effect of oxidation of carbon material on suspension electrodes for flow electrode capacitive deionization.

Flow electrode deionization (FCDI) is an emerging area for continuous and scalable deionization, but the electrochemical and flow properties of the flow electrode need to be improved to minimize energy consumption. Chemical oxidation of granular activated carbon (AC) was examined here to study the role of surface heteroatoms on rheology and electrochemical performance of a flow electrode (carbon slurry) for deionization processes. Moreover, it was demonstrated that higher mass densities could be used without increasing energy for pumping when using oxidized active material. High mass-loaded flow electrodes (28% carbon content) based on oxidized AC displayed similar viscosities (∼21 Pa s) to lower mass-loaded flow electrodes (20% carbon content) based on nonoxidized AC. The 40% increased mass loading (from 20% to 28%) resulted in a 25% increase in flow electrode gravimetric capacitance (from 65 to 83 F g(-1)) without sacrificing flowability (viscosity). The electrical energy required to remove ∼18% of the ions (desalt) from of the feed solution was observed to be significantly dependent on the mass loading and decreased (∼60%) from 92 ± 7 to 28 ± 2.7 J with increased mass densities from 5 to 23 wt %. It is shown that the surface chemistry of the active material in a flow electrode effects the electrical and pumping energy requirements of a FCDI system.

Crystal structure of tetra-kis-(µ-N-phenyl-acetamidato)-κ(4) N:O;κ(4) O:N-bis-[(2-methyl-benzo-nitrile-κN)rhodium(II)](Rh-Rh).

The complex molecule of the title compound, [Rh2{N(C6H5)COCH3}4(C8H7N)2], exhibits inversion symmetry. The four acetamidate ligands bridging the dirhodium core are arranged in a 2,2-trans manner with two N atoms and two O atoms coordinating to each Rh(II) atom trans to one another. The Neq-Rh-Rh-Oeq torsion angles on the acetamidate bridge vary between -4.07 (5) and -6.78 (7)°. The axial nitrile ligands complete the distorted octa-hedral coordination sphere of each Rh(II) atom and show a nonlinear coordination with Rh-N-C bond angles of 151.6 (3) and 152.5 (3)°. The bond lengths of the two nitrile triple bonds are 1.133 (5) and 1.137 (5) Å.

(3-Methyl-benzo-nitrile-1κN)-cis-tetra-kis(µ-N-phenyl-acetamidato)-1:2κ(4) N:O;1:2κ(4) O:N-dirhodium(II)(Rh-Rh).

The complex molecule of the title compound, [Rh2{N(C6H5)COCH3}4(NCC7H7)], has crystallographically-imposed mirror symmetry. The four acetamide ligands bridging the dirhodium core are arranged in a 2,2-cis manner with two N atoms and two O atoms coordinating to the unique Rh(II) atom cis to one another. The Neq-Rh-Rh-Oeq torsion angles on the acetamide bridge are 0.75 (7) and 1.99 (9)°. The axial nitrile ligand completes the distorted octa-hedral coordination sphere of one Rh(II) atom and shows a nonlinear coordination, with an Rh-N-C bond angle of 162.8 (5)°; the N-C bond length is 1.154 (7) Å.

Transparent Conductive Two-Dimensional Titanium Carbide Epitaxial Thin Films.

Since the discovery of graphene, the quest for two-dimensional (2D) materials has intensified greatly. Recently, a new family of 2D transition metal carbides and carbonitrides (MXenes) was discovered that is both conducting and hydrophilic, an uncommon combination. To date MXenes have been produced as powders, flakes, and colloidal solutions. Herein, we report on the fabrication of ∼1 × 1 cm2 Ti3C2 films by selective etching of Al, from sputter-deposited epitaxial Ti3AlC2 films, in aqueous HF or NH4HF2. Films that were about 19 nm thick, etched with NH4HF2, transmit ∼90% of the light in the visible-to-infrared range and exhibit metallic conductivity down to ∼100 K. Below 100 K, the films' resistivity increases with decreasing temperature and they exhibit negative magnetoresistance-both observations consistent with a weak localization phenomenon characteristic of many 2D defective solids. This advance opens the door for the use of MXenes in electronic, photonic, and sensing applications.

New two-dimensional niobium and vanadium carbides as promising materials for Li-ion batteries.

New two-dimensional niobium and vanadium carbides have been synthesized by selective etching, at room temperature, of Al from Nb2AlC and V2AlC, respectively. These new matrials are promising electrode materials for Li-ion batteries, demonstrating good capability to handle high charge-discharge rates. Reversible capacities of 170 and 260 mA·h·g(-1) at 1 C, and 110 and 125 mA·h·g(-1) at 10 C were obtained for Nb2C and V2C-based electrodes, respectively.

Spatially selective formation of hydrocarbon, fluorocarbon, and hydroxyl-terminated monolayers on a microelectrode array.

A protection-deprotection strategy, using gold oxide as a passivating layer, was used to direct the self-assembly of monolayers (SAMs) selectively at individual gold microelectrodes in an array. This approach allowed the formation of hydroxyl-terminated monolayers, without side reactions, in addition to hydrocarbon and fluorocarbon SAMs. Fluorescence microscopy was used to visualize selective dewetting of hydrophobic monolayers by an aqueous dye solution, and spatially resolved X-ray photoelectron spectroscopy was used to demonstrate a lack of cross-contamination on neighboring microelectrodes in the array.

Promoting and measuring family caregiver self-efficacy in caregiver-physician interactions.

This article describes the development of a 5-item scale that assesses family caregivers' self-efficacy in communicating with physicians about ill family members (Perceived Efficacy in Caregiver-Physician Interactions-PECPI) in the context of an evaluation study of an online training in health care communication skills for caregivers. A national sample of 197 self-identified family caregivers participated in an online webinar and completed a brief evaluation instrument before and immediately after the training. Results indicated that the webinar was effective in increasing perceived self-efficacy and self-reported knowledge about and level of preparation for medical visits. Principal component analysis indicates that the PECPI is unidimensional with a Cronbach's alpha of .91.

Gold oxide as a protecting group for regioselective surface chemistry.

Selective modification of electrode surfaces is a vital step in the development of many practical applications of self-assembled monolayers (SAMs). This paper describes a protection-deprotection strategy similar to that commonly utilized in organic synthesis, with gold oxide as a protecting layer, to direct self-assembly on one gold electrode in the presence of another.