Stretch-Induced Injury Affects Cortical Neuronal Networks in a Time- and Severity-Dependent Manner.

Traumatic brain injury (TBI) is the leading cause of accident-related death and disability in the world and can lead to long-term neuropsychiatric symptoms, such as a decline in cognitive function and neurodegeneration. TBI includes primary and secondary injury, with head trauma and deformation of the brain caused by the physical force of the impact as primary injury, and cellular and molecular cascades that lead to cell death as secondary injury. Currently, there is no treatment for TBI-induced cell damage and neural circuit dysfunction in the brain, and thus, it is important to understand the underlying cellular mechanisms that lead to cell damage. In the current study, we use stretchable microelectrode arrays (sMEAs) to model the primary injury of TBI to study the electrophysiological effects of physically injuring cortical cells. We recorded electrophysiological activity before injury and then stretched the flexible membrane of the sMEAs to injure the cells to varying degrees. At 1, 24, and 72 h post-stretch, we recorded activity to analyze differences in spike rate, Fano factor, burstlet rate, burstlet width, synchrony of firing, local network efficiency, and Q statistic. Our results demonstrate that mechanical injury changes the firing properties of cortical neuron networks in culture in a time- and severity-dependent manner. Our results suggest that changes to electrophysiological properties after stretch are dependent on the strength of synchronization between neurons prior to injury.

Development and Characterization of Isogenic Cardiac Organoids from Human-Induced Pluripotent Stem Cells Under Supplement Starvation Regimen.

The prevalence of cardiovascular risk factors is expected to increase the occurrence of cardiovascular diseases (CVDs) worldwide. Cardiac organoids are promising candidates for bridging the gap between in vitro experimentation and translational applications in drug development and cardiac repair due to their attractive features. Here we present the fabrication and characterization of isogenic scaffold-free cardiac organoids derived from human induced pluripotent stem cells (hiPSCs) formed under a supplement-deprivation regimen that allows for metabolic synchronization and maturation of hiPSC-derived cardiac cells. We propose the formation of coculture cardiac organoids that include hiPSC-derived cardiomyocytes and hiPSC-derived cardiac fibroblasts (hiPSC-CMs and hiPSC-CFs, respectively). The cardiac organoids were characterized through extensive morphological assessment, evaluation of cellular ultrastructures, and analysis of transcriptomic and electrophysiological profiles. The morphology and transcriptomic profile of the organoids were improved by coculture of hiPSC-CMs with hiPSC-CFs. Specifically, upregulation of Ca2+ handling-related genes, such as RYR2 and SERCA, and structure-related genes, such as TNNT2 and MYH6, was observed. Additionally, the electrophysiological characterization of the organoids under supplement deprivation shows a trend for reduced conduction velocity for coculture organoids. These studies help us gain a better understanding of the role of other isogenic cells such as hiPSC-CFs in the formation of mature cardiac organoids, along with the introduction of exogenous chemical cues, such as supplement starvation.

Is Seeing Believing? A Longitudinal Study of Vividness of the Future and Its Effects on Academic Self-Efficacy and Success in College.

This research followed students over their first 2 years of college. During this time, many students lose sight of their goals, leading to poor academic performance and leaving STEM and business majors. This research was the first to examine longitudinal changes in future vividness, how those changes impact academic success, and identify sex differences in those relationships. Students who started college with clear pictures of graduation and life after graduation, and those who gained clarity, were more likely to believe in their academic abilities, and, in turn, earn a higher cumulative GPA, and persist in STEM and business. Compared to men, women reported greater initial vividness in both domains. In vividness of graduation, women maintained their advantage with no sex differences in how vividness changed. However, men grew in vividness of life after graduation while women remained stagnant. These findings have implications for interventions to increase academic performance and persistence.

A Microclip Peripheral Nerve Interface (µcPNI) for Bioelectronic Interfacing with Small Nerves.

Peripheral nerves carry sensory (afferent) and motor (efferent) signals between the central nervous system and other parts of the body. The peripheral nervous system (PNS) is therefore rich in targets for therapeutic neuromodulation, bioelectronic medicine, and neuroprosthetics. Peripheral nerve interfaces (PNIs) generally suffer from a tradeoff between selectivity and invasiveness. This work describes the fabrication, evaluation, and chronic implantation in zebra finches of a novel PNI that breaks this tradeoff by interfacing with small nerves. This PNI integrates a soft, stretchable microelectrode array with a 2-photon 3D printed microclip (µcPNI). The advantages of this µcPNI compared to other designs are: a) increased spatial resolution due to bi-layer wiring of the electrode leads, b) reduced mismatch in biomechanical properties with the nerve, c) reduced disturbance to the host tissue due to the small size, d) elimination of sutures or adhesives, e) high circumferential contact with small nerves, f) functionality under considerable strain, and g) graded neuromodulation in a low-threshold stimulation regime. Results demonstrate that the µcPNIs are electromechanically robust, and are capable of reliably recording and stimulating neural activity in vivo in small nerves. The µcPNI may also inform the development of new optical, thermal, ultrasonic, or chemical PNIs as well.

A test of a triadic conceptualization of future self-identification.

People encounter intertemporal decisions every day and often engage in behaviors that are not good for their future. One factor that may explain these decisions is the perception of their distal future self. An emerging body of research suggests that individuals vary in how they perceive their future self and many perceive their future self as a different person. The present research aimed to (1) build on and extend Hershfield's et al. (2011) review of the existing literature and advance the conceptualization of the relationship between the current and future self, (2) extend and develop measures of this relationship, and (3) examine whether and how this relationship predicts intrapsychic and achievement outcomes. The results of the literature review suggested that prior research mostly focused on one or two of the following components: (a) perceived relatedness between the current and future self in terms of similarity and connectedness, (b) vividness in imagining the future self, and (c) degree of positivity felt toward the future self. Additionally, differences in how researchers have labeled the overall construct lead us to propose future self-identification as a new label for the three-component construct. Our research built on existing measures to test the validity of a three-component model of future self-identification. Across three samples of first-year undergraduates, this research established the psychometric properties of the measure, and then examined the relationships between the components and four outcome domains of interest: (1) psychological well-being (self-esteem, hope), (2) imagination of the future (visual imagery of future events, perceived temporal distance), (3) self-control, and (4) academic performance. We demonstrated that the three components of future self-identification were correlated but independent factors. Additionally, the three components differed in their unique relationships with the outcome domains, demonstrating the utility of measuring all three components of future self-identification when seeking to predict important psychological and behavioral outcomes.

A soft and stretchable bilayer electrode array with independent functional layers for the next generation of brain machine interfaces.

OBJECTIVE: Brain-Machine Interfaces (BMIs) hold great promises for advancing neuroprosthetics, robotics, and for providing treatment options for severe neurological diseases. The objective of this work is the development and in vivo evaluation of electrodes for BMIs that meet the needs to record brain activity at sub-millimeter resolution over a large area of the cortex while being soft and electromechanically robust (i.e. stretchable). APPROACH: Current electrodes require a trade-off between high spatiotemporal resolution and cortical coverage area. To address the needs for simultaneous high resolution and large cortical coverage, the prototype electrode array developed in this study employs a novel bilayer routing of soft and stretchable lead wires from the recording sites on the surface of the brain (electrocorticography, ECoG) to the data acquisition system. MAIN RESULTS: To validate the recording characteristics, the array was implanted in healthy felines for up to 5 months. Neural signals recorded from both layers of the device showed elevated mid-frequency structures typical of local field potential (LFP) signals that were stable in amplitude over implant duration, and also exhibited consistent frequency-dependent modulation after anesthesia induction by Telazol. SIGNIFICANCE: The successful development of a soft and stretchable large-area, high resolution micro ECoG electrode array (lahrµECoG) is an important step to meet the neurotechnological needs of advanced BMI applications.

Feeling Closer to the Future Self and Doing Better: Temporal Psychological Mechanisms Underlying Academic Performance.

This research examined the function of future self-continuity and its potential downstream consequences for academic performance through relations with other temporal psychological factors and self-control. We also addressed the influence of cultural factors by testing whether these relations differed by college generation status. Undergraduate students enrolled at a large public university participated in two studies (Study 1: N = 119, Mage = 20.55, 56.4% women; Study 2: N = 403, Mage = 19.83, 58.3% women) in which they completed measures of temporal psychological factors and psychological resources. In Study 2, we also obtained academic records to link responses to academic performance. Future self-continuity predicted subsequent academic performance and was related positively to future focus, negatively to present focus, and positively to self-control. Additionally, the relation between future focus and self-control was stronger for continuing-generation college students than first-generation college students. Future self-continuity plays a pivotal role in academic contexts. Findings suggest that it may have positive downstream consequences on academic achievement by directing attention away from the present and toward the future, which promotes self-control. Further, the strategy of focusing on the future may be effective in promoting self-control only for certain cultural groups.

Alterations in Hippocampal Network Activity after In Vitro Traumatic Brain Injury.

Traumatic brain injury (TBI) alters function and behavior, which can be characterized by changes in electrophysiological function in vitro. A common cognitive deficit after mild-to-moderate TBI is disruption of persistent working memory, of which the in vitro correlate is long-lasting, neuronal network synchronization that can be induced pharmacologically by the gamma-aminobutyric acid A antagonist, bicuculline. We utilized a novel in vitro platform for TBI research, the stretchable microelectrode array (SMEA), to investigate the effects of TBI on bicuculline-induced, long-lasting network synchronization in the hippocampus. Mechanical stimulation significantly disrupted bicuculline-induced, long-lasting network synchronization 24 h after injury, despite the continued ability of the injured neurons to fire, as revealed by a significant increase in the normalized spontaneous event rate in the dentate gyrus (DG) and CA1. A second challenge with bicuculline 24 h after the first challenge significantly decreased the normalized spontaneous event rate in the DG. In addition, we illustrate the utility of the SMEA for TBI research by combining multiple experimental paradigms in one platform, which has the potential to enable novel investigations into the mechanisms responsible for functional consequences of TBI and speed the rate of drug discovery.

Encapsulating Elastically Stretchable Neural Interfaces: Yield, Resolution, and Recording/Stimulation of Neural Activity.

A high resolution elastically stretchable microelectrode array (SMEA) to interface with neural tissue is described. The SMEA consists of an elastomeric substrate, such as poly(dimethylsiloxane) (PDMS), elastically stretchable gold conductors, and an electrically insulating encapsulating layer in which contact holes are opened. We demonstrate the feasibility of producing contact holes with 40 µm × 40 µm openings, show why the adhesion of the encapsulation layer to the underlying silicone substrate is weakened during contact hole fabrication, and provide remedies. These improvements result in greatly increased fabrication yield and reproducibility. An SMEA with 28 microelectrodes was fabricated. The contact holes (100 µm × 100 µm) in the encapsulation layer are only ~10% the size of the previous generation, allowing a larger number of microelectrodes per unit area, thus affording the capability to interface with a smaller neural population per electrode. This new SMEA is used to record spontaneous and evoked activity in organotypic hippocampal tissue slices at 0% strain before stretching, at 5 % and 10 % equibiaxial strain, and again at 0% strain after relaxation. The noise of the recordings increases with increasing strain. The frequency of spontaneous neural activity also increases when the SMEA is stretched. Upon relaxation, the noise returns to pre-stretch levels, while the frequency of neural activity remains elevated. Stimulus-response curves at each strain level are measured. The SMEA shows excellent biocompatibility for at least two weeks.

Controlling the morphology of gold films on poly(dimethylsiloxane).

Gold films on poly(dimethylsiloxane) (PDMS) have applications in stretchable electronics, tunable diffraction gratings, soft lithography and as neural interfaces. The electrical and optical properties of these films depend critically on the morphology of the gold. Therefore, we examine qualitatively and quantitatively the factors that affect the morphology of the gold film. Three morphologies can be produced controllably: microcracked, buckled, and smooth. Which morphology a gold film will adopt depends on the film stress and the growth mode of the film. The factors that affect the film stress and growth mode, and thus the morphology, are as follows: deposition temperature, film thickness, elastic modulus, adhesion layer thickness, surface properties of the PDMS, and mechanical prestrain applied during deposition. We discuss how the different components of the film stress and growth mode of the film affect the morphology.

Flexible and stretchable micro-electrodes for in vitro and in vivo neural interfaces.

Microelectrode arrays (MEAs) are designed to monitor and/or stimulate extracellularly neuronal activity. However, the biomechanical and structural mismatch between current MEAs and neural tissues remains a challenge for neural interfaces. This article describes a material strategy to prepare neural electrodes with improved mechanical compliance that relies on thin metal film electrodes embedded in polymeric substrates. The electrode impedance of micro-electrodes on polymer is comparable to that of MEA on glass substrates. Furthermore, MEAs on plastic can be flexed and rolled offering improved structural interface with brain and nerves in vivo. MEAs on elastomer can be stretched reversibly and provide in vitro unique platforms to simultaneously investigate the electrophysiological of neural cells and tissues to mechanical stimulation. Adding mechanical compliance to MEAs is a promising vehicle for robust and reliable neural interfaces.

Neural sensing of electrical activity with stretchable microelectrode arrays.

Sensing neural activity within mechanically active tissues poses particular hurdles because most electrodes are much stiffer than biological tissues. As the tissue deforms, the rigid electrodes may damage the surrounding tissue. The problem is exacerbated when sensing neural activity in experimental models of traumatic brain injury (TBI) which is caused by the rapid and large deformation of brain tissue. We have developed a stretchable microelectrode array (SMEA) that can withstand large elastic deformations (>5% biaxial strain) while continuing to function. The SMEA were fabricated from thin metal conductors patterned on polydimethylsiloxane (PDMS) and encapsulated with a photo-patternable silicone. SMEA were used to record spontaneous activity from brain slice cultures, as well as evoked activity after stimulating through SMEA electrodes. Slices of brain tissue were grown on SMEA in long-term culture and then mechanically injured with our well-characterized in vitro injury model by stretching the SMEA and the adherent culture, which was confirmed by image analysis. Because brain tissue was grown on the substrate-integrated SMEA, post-injury changes in electrophysiological function were normalized to pre-injury function since the SMEA deformed with the tissue and remained in place during mechanical stimulation. The combination of our injury model and SMEA could help elucidate mechanisms responsible for post-traumatic neuronal dysfunction in the quest for TBI therapies. The SMEA may have additional sensing applications in other mechanically active tissues such as peripheral nerve and heart.

Monitoring hippocampus electrical activity in vitro on an elastically deformable microelectrode array.

Interfacing electronics and recording electrophysiological activity in mechanically active biological tissues is challenging. This challenge extends to recording neural function of brain tissue in the setting of traumatic brain injury (TBI), which is caused by rapid (within hundreds of milliseconds) and large (greater than 5% strain) brain deformation. Interfacing electrodes must be biocompatible on multiple levels and should deform with the tissue to prevent additional mechanical damage. We describe an elastically stretchable microelectrode array (SMEA) that is capable of undergoing large, biaxial, 2-D stretch while remaining functional. The new SMEA consists of elastically stretchable thin metal films on a silicone membrane. It can stimulate and detect electrical activity from cultured brain tissue (hippocampal slices), before, during, and after large biaxial deformation. We have incorporated the SMEA into a well-characterized in vitro TBI research platform, which reproduces the biomechanics of TBI by stretching the SMEA and the adherent brain slice culture. Mechanical injury parameters, such as strain and strain rate, can be precisely controlled to generate specific levels of damage. The SMEA allowed for quantification of neuronal function both before and after injury, without breaking culture sterility or repositioning the electrodes for the injury event, thus enabling serial and long-term measurements. We report tests of the SMEA and an initial application to study the effect of mechanical stimuli on neuron function, which could be employed as a high-content, drug-screening platform for TBI.

Disproportionation of Ag(II) to Ag(I) and Ag(III) in Fluoride Systems and Syntheses and Structures of (AgF(+))(2)AgF(4)(-)MF(6)(-) Salts (M = As, Sb, Pt, Au, Ru).

Interaction of Ag(+) salts in anhydrous liquid hydrogen fluoride, aHF, with AgF(4)(-) salts gives amorphous red-brown diamagnetic Ag(I)Ag(III)F(4), which transforms exothermally to brown, paramagnetic, microcrystalline Ag(II)F(2) below 0 degrees C. Ag(I)Au(III)F(4) prepared from Ag(+) and AuF(4)(-) in aHF has a tetragonal unit cell and a KBrF(4) type lattice, with a = 5.788(1) Å, c = 10.806(2) Å, and Z = 4. Blue-green Ag(II)FAsF(6) disproportionates in aHF (in the absence of F(-) acceptors) to colorless Ag(I)AsF(6) and a black pseudotrifluoride, (Ag(II)F(+))(2)Ag(III)F(4)(-)AsF(6)(-). The latter and other (AgF)(2)AgF(4)MF(6) salts are also generated by oxidation of AgF(2) or AgF(+) salts in aHF with F(2) or in solutions of O(2)(+)MF(6)(-) salts (M = As, Sb, Pt, Au, Ru). Single crystals of (AgF)(2)AgF(4)AsF(6) were grown from an AgFAsF(6)/AsF(5) solution in aHF standing over AgF(2) or AgFBF(4), with F(2) as the oxidant. They are monoclinic, P2/c, at 20 degrees C, with a = 5.6045(6) Å, b = 5.2567(6) Å, c = 7.8061(8) Å, beta = 96.594(9) degrees, and Z = 1. The structure consists of (AgF)(n)()(n)()(+) chains (F-Ag-F = 180 degrees, Ag-F-Ag = 153.9(11) degrees, Ag-F = 2.003(4) Å), parallel to c, that enclose stacks of alternating AgF(4)(-) and AsF(6)(-), each anion making bridging contact with four Ag(II) cations of the four surrounding chains "caging" them. There is no registry between the ordered array in one "cage" and that in any neighboring "cage". The F-ligand anion bridges between the anions and, with the Ag(II) of the chains, generates a trifluoride-like structure. (AgF)(2)AgF(4)AsF(6) [like other (AgF)(n)()(n)()(+) salts] is a temperature-independent paramagnet except for a Curie "tail" below 50 K.