High-frequency transcranial alternating current stimulation matching individual frequency of somatosensory evoked high-frequency oscillations can modulate the somatosensory system through thalamocortical pathway.

tACS (transcranial alternating current stimulation) is a technique for modulating brain activity through electrical current. Its effects depend on cortical entrainment, which is most effective when transcranial alternating current stimulation matches the brain's natural rhythm. High-frequency oscillations produced by external stimuli are useful for studying the somatosensory pathway. Our study aims to explore transcranial alternating current stimulation's impact on the somatosensory system when synchronized with individual high-frequency oscillation frequencies. We conducted a randomized, sham-controlled study with 14 healthy participants. The study had three phases: Individualized transcranial alternating current stimulation (matching the individual's high-frequency oscillation rhythm), Standard transcranial alternating current stimulation (600 Hz), and sham stimulation. We measured early and late HFO components after median nerve electrical stimulation at three time points: before (T0), immediately after (T1), and 10 min after transcranial alternating current stimulation (T2). Compared to Sham and Standard stimulation Individualized transcranial alternating current stimulation significantly enhanced high-frequency oscillations, especially the early component, immediately after stimulation and for at least 15 min. No other effects were observed for other high-frequency oscillation measures. In summary, our study provides initial evidence that transcranial alternating current stimulation synchronized with an individual's high-frequency oscillation frequency can precisely and time-specifically modulate thalamocortical activity. These insights may pave the way for innovative, personalized neuromodulation methods for the somatosensory system.

Advances in Cell-Conductive Polymer Biointerfaces and Role of the Plasma Membrane.

The plasma membrane (PM) is often described as a wall, a physical barrier separating the cell cytoplasm from the extracellular matrix (ECM). Yet, this wall is a highly dynamic structure that can stretch, bend, and bud, allowing cells to respond and adapt to their surrounding environment. Inspired by shapes and geometries found in the biological world and exploiting the intrinsic properties of conductive polymers (CPs), several biomimetic strategies based on substrate dimensionality have been tailored in order to optimize the cell-chip coupling. Furthermore, device biofunctionalization through the use of ECM proteins or lipid bilayers have proven successful approaches to further maximize interfacial interactions. As the bio-electronic field aims at narrowing the gap between the electronic and the biological world, the possibility of effectively disguising conductive materials to "trick" cells to recognize artificial devices as part of their biological environment is a promising approach on the road to the seamless platform integration with cells.

Unusual CLIPPERS presentation with a predominant spinal cord involvement: case report and review of the literature.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a discrete nosological entity characterized by punctate and curvilinear gadolinium enhancement "peppering" the pons and a strong response to steroids. MRI images typically show pontine and cerebellar punctate-enhancing lesions, which occasionally spread up to the juxtacortical areas and down to the spinal cord. Interestingly, the more distant the lesion is from the pons, the less intense they become. Herein, we describe an extremely rare case of CLIPPERS presenting with predominant spinal cord involvement; then, we searched in the literature the available cases with a similar presentation. Our case focuses attention on a rare MRI CLIPPERS presentation. Since CLIPPERS has a dramatic response to corticosteroid treatment, it is fundamental to promptly recognize its MRI pattern to start treatment as soon as possible.

Modulation of Early Stage Neuronal Outgrowth through Out-of-Plane Graphene.

The correct wiring of a neural network requires neuron to integrate an incredible repertoire of cues found in their extracellular environment. The astonishing efficiency of this process plays a pivotal role in the correct wiring of the brain during development and axon regeneration. Biologically inspired micro- and nanostructured substrates have been shown to regulate axonal outgrowth. In parallel, several studies investigated graphene's potential as a conductive neural interface, able to enhance cell adhesion, neurite sprouting and outgrowth. Here, we engineered a 3D single- to few-layer fuzzy graphene morphology (3DFG), 3DFG on a collapsed Si nanowire (SiNW) mesh template (NT-3DFGc), and 3DFG on a noncollapsed SiNW mesh template (NT-3DFGnc) as neural-instructive materials. The micrometric protruding features of the NWs templates dictated neuronal growth cone establishment, as well as influencing axon elongation and branching. Furthermore, neurons-to-graphene coupling was investigated with comprehensive view of integrin-mediated contact adhesion points and plasma membrane curvature processes.

Amyloid-Beta Co-Pathology Is a Major Determinant of the Elevated Plasma GFAP Values in Amyotrophic Lateral Sclerosis.

Recent studies reported increased plasma glial acidic fibrillary protein (GFAP) levels in amyotrophic lateral sclerosis (ALS) patients compared to controls. We expanded these findings in a larger cohort, including 156 ALS patients and 48 controls, and investigated the associations of plasma GFAP with clinical variables and other biofluid biomarkers. Plasma GFAP and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers were assessed by the single molecule array and the Lumipulse platforms, respectively. In ALS patients, plasma GFAP was higher than in controls (p < 0.001) and associated with measures of cognitive decline. Twenty ALS patients (12.8%) showed a positive amyloid status (A+), of which nine also exhibited tau pathology (A+T+, namely ALS-AD). ALS-AD patients showed higher plasma GFAP than A- ALS participants (p < 0.001) and controls (p < 0.001), whereas the comparison between A- ALS and controls missed statistical significance (p = 0.07). Plasma GFAP distinguished ALS-AD subjects more accurately (area under the curve (AUC) 0.932 ± 0.027) than plasma p-tau181 (AUC 0.692 ± 0.058, p < 0.0001) and plasma neurofilament light chain protein (AUC, 0.548 ± 0.088, p < 0.0001). Cognitive measures differed between ALS-AD and other ALS patients. AD co-pathology deeply affects plasma GFAP values in ALS patients. Plasma GFAP is an accurate biomarker for identifying AD co-pathology in ALS, which can influence the cognitive phenotype.

Bioinspired micro- and nano-structured neural interfaces.

The development of a functional nervous system requires neurons to interact with and promptly respond to a wealth of biochemical, mechanical and topographical cues found in the neural extracellular matrix (ECM). Among these, ECM topographical cues have been found to strongly influence neuronal function and behavior. Here, we discuss how the blueprint of the architectural organization of the brain ECM has been tremendously useful as a source of inspiration to design biomimetic substrates to enhance neural interfaces and dictate neuronal behavior at the cell-material interface. In particular, we focus on different strategies to recapitulate cell-ECM and cell-cell interactions. In order to mimic cell-ECM interactions, we introduce roughness as a first approach to provide informative topographical biomimetic cues to neurons. We then examine 3D scaffolds and hydrogels, as softer 3D platforms for neural interfaces. Moreover, we will discuss how anisotropic features such as grooves and fibers, recapitulating both ECM fibrils and axonal tracts, may provide recognizable paths and tracks that neuron can follow as they develop and establish functional connections. Finally, we show how isotropic topographical cues, recapitulating shapes, and geometries of filopodia- and mushroom-like dendritic spines, have been instrumental to better reproduce neuron-neuron interactions for applications in bioelectronics and neural repair strategies. The high complexity of the brain architecture makes the quest for the fabrication of create more biologically relevant biomimetic architectures in continuous and fast development. Here, we discuss how recent advancements in two-photon polymerization and remotely reconfigurable dynamic interfaces are paving the way towards to a new class of smart biointerfaces forin vitroapplications spanning from neural tissue engineering as well as neural repair strategies.

Living myofibroblast-silicon composites for probing electrical coupling in cardiac systems.

Traditional bioelectronics, primarily comprised of nonliving synthetic materials, lack cellular behaviors such as adaptability and motility. This shortcoming results in mechanically invasive devices and nonnatural signal transduction across cells and tissues. Moreover, resolving heterocellular electrical communication in vivo is extremely limited due to the invasiveness of traditional interconnected electrical probes. In this paper, we present a cell-silicon hybrid that integrates native cellular behavior (e.g., gap junction formation and biosignal processing) with nongenetically enabled photosensitivity. This hybrid configuration allows interconnect-free cellular modulation with subcellular spatial resolution for bioelectric studies. Specifically, we hybridize cardiac myofibroblasts with silicon nanowires and use these engineered hybrids to synchronize the electrical activity of cardiomyocytes, studying heterocellular bioelectric coupling in vitro. Thereafter, we inject the engineered myofibroblasts into heart tissues and show their ability to seamlessly integrate into contractile tissues in vivo. Finally, we apply local photostimulation with high cell specificity to tackle a long-standing debate regarding the existence of myofibroblast-cardiomyocyte electrical coupling in vivo.

Membrane curvature underlies actin reorganization in response to nanoscale surface topography.

Surface topography profoundly influences cell adhesion, differentiation, and stem cell fate control. Numerous studies using a variety of materials demonstrate that nanoscale topographies change the intracellular organization of actin cytoskeleton and therefore a broad range of cellular dynamics in live cells. However, the underlying molecular mechanism is not well understood, leaving why actin cytoskeleton responds to topographical features unexplained and therefore preventing researchers from predicting optimal topographic features for desired cell behavior. Here we demonstrate that topography-induced membrane curvature plays a crucial role in modulating intracellular actin organization. By inducing precisely controlled membrane curvatures using engineered vertical nanostructures as topographies, we find that actin fibers form at the sites of nanostructures in a curvature-dependent manner with an upper limit for the diameter of curvature at ∼400 nm. Nanotopography-induced actin fibers are branched actin nucleated by the Arp2/3 complex and are mediated by a curvature-sensing protein FBP17. Our study reveals that the formation of nanotopography-induced actin fibers drastically reduces the amount of stress fibers and mature focal adhesions to result in the reorganization of actin cytoskeleton in the entire cell. These findings establish the membrane curvature as a key linkage between surface topography and topography-induced cell signaling and behavior.

A biohybrid synapse with neurotransmitter-mediated plasticity.

Brain-inspired computing paradigms have led to substantial advances in the automation of visual and linguistic tasks by emulating the distributed information processing of biological systems1. The similarity between artificial neural networks (ANNs) and biological systems has inspired ANN implementation in biomedical interfaces including prosthetics2 and brain-machine interfaces3. While promising, these implementations rely on software to run ANN algorithms. Ultimately, it is desirable to build hardware ANNs4,5 that can both directly interface with living tissue and adapt based on biofeedback6,7. The first essential step towards biologically integrated neuromorphic systems is to achieve synaptic conditioning based on biochemical signalling activity. Here, we directly couple an organic neuromorphic device with dopaminergic cells to constitute a biohybrid synapse with neurotransmitter-mediated synaptic plasticity. By mimicking the dopamine recycling machinery of the synaptic cleft, we demonstrate both long-term conditioning and recovery of the synaptic weight, paving the way towards combining artificial neuromorphic systems with biological neural networks.

Silicon Nanowires for Intracellular Optical Interrogation with Subcellular Resolution.

Current techniques for intracellular electrical interrogation are limited by substrate-bound devices, technically demanding methods, or insufficient spatial resolution. In this work, we use freestanding silicon nanowires to achieve photoelectric stimulation in myofibroblasts with subcellular resolution. We demonstrate that myofibroblasts spontaneously internalize silicon nanowires and subsequently remain viable and capable of mitosis. We then show that stimulation of silicon nanowires at separate intracellular locations results in local calcium fluxes in subcellular regions. Moreover, nanowire-myofibroblast hybrids electrically couple with cardiomyocytes in coculture, and photostimulation of the nanowires increases the spontaneous activation rate in coupled cardiomyocytes. Finally, we demonstrate that this methodology can be extended to the interrogation of signaling in neuron-glia interactions using nanowire-containing oligodendrocytes.

Dynamic Manipulation of Cell Membrane Curvature by Light-Driven Reshaping of Azopolymer.

Local curvatures on the cell membrane serve as signaling hubs that promote curvature-dependent protein interactions and modulate a variety of cellular processes including endocytosis, exocytosis, and the actin cytoskeleton. However, precisely controlling the location and the degree of membrane curvature in live cells has not been possible until recently, where studies show that nanofabricated vertical structures on a substrate can imprint their shapes on the cell membrane to induce well-defined curvatures in adherent cells. Nevertheless, the intrinsic static nature of these engineered nanostructures prevents dynamic modulation of membrane curvatures. In this work, we engineer light-responsive polymer structures whose shape can be dynamically modulated by light and thus change the induced-membrane curvatures on-demand. Specifically, we fabricate three-dimensional azobenzene-based polymer structures that change from a vertical pillar to an elongated vertical bar shape upon green light illumination. We observe that U2OS cells cultured on azopolymer nanostructures rapidly respond to the topographical change of the substrate underneath. The dynamically induced high membrane curvatures at bar ends promote local accumulation of actin fibers and actin nucleator Arp2/3 complex. The ability to dynamically manipulate the membrane curvature and analyze protein response in real-time provides a new way to study curvature-dependent processes in live cells.

Three-dimensionally Patterned Scaffolds Modulate the Biointerface at the Nanoscale.

The main aim of cell instructive materials is to guide in a controlled way cellular behavior by fine-tuning cell-material crosstalk. In the last decades, several efforts have been spent in elucidating the relations between material cues and cellular fate at the nanoscale and in the development of novel strategies for gaining a superior control over cellular function modulation. In this context, a particular attention has been recently paid to the role played by cellular membrane rearrangement in triggering specific molecular pathways linked to the regulation of different cellular functions. Here, we characterize the effect of linear microtopographies upon cellular behavior in three-dimensional (3D) environments, with particular focus on the relations linking cytoskeleton structuration to membrane rearrangement and internalization tuning. The performed analysis shown that, by altering the cellular adhesion processes at the micro- and nanoscale, it is possible to alter the membrane physical state and cellular internalization capability. More specifically, our findings pointed out that an increased cytoskeletal structuration influences the formation of nanoinvagination membrane process at the cell-material interface and the expression of clathrin and caveolin, two of the main proteins involved in the endocytosis regulation. Moreover, we proved that such topographies enhance the engulfment of inert polystyrene nanoparticles attached on 3D patterned surfaces. Our results could give new guidelines for the design of innovative and more efficient 3D cell culture systems usable for diagnostic, therapeutic, and tissue engineering purposes.

Cells Adhering to 3D Vertical Nanostructures: Cell Membrane Reshaping without Stable Internalization.

The dynamic interface between the cellular membrane and 3D nanostructures determines biological processes and guides the design of novel biomedical devices. Despite the fact that recent advancements in the fabrication of artificial biointerfaces have yielded an enhanced understanding of this interface, there remain open questions on how the cellular membrane reacts and behaves in the presence of sharp objects on the nanoscale. Here we provide a multifaceted characterization of the cellular membrane's mechanical stability when closely interacting with high-aspect-ratio 3D vertical nanostructures, providing strong evidence that vertical nanostructures spontaneously penetrate the cellular membrane to form a steady intracellular coupling only in rare cases and under specific conditions. The cell membrane is able to conform tightly over the majority of structures with various shapes while maintaining its integrity.

Geosystemics View of Earthquakes.

Earthquakes are the most energetic phenomena in the lithosphere: their study and comprehension are greatly worth doing because of the obvious importance for society. Geosystemics intends to study the Earth system as a whole, looking at the possible couplings among the different geo-layers, i.e., from the earth's interior to the above atmosphere. It uses specific universal tools to integrate different methods that can be applied to multi-parameter data, often taken on different platforms (e.g., ground, marine or satellite observations). Its main objective is to understand the particular phenomenon of interest from a holistic point of view. Central is the use of entropy, together with other physical quantities that will be introduced case by case. In this paper, we will deal with earthquakes, as final part of a long-term chain of processes involving, not only the interaction between different components of the Earth's interior but also the coupling of the solid earth with the above neutral or ionized atmosphere, and finally culminating with the main rupture along the fault of concern. Particular emphasis will be given to some Italian seismic sequences.

Defined patterns of neuronal networks on 3D thiol-functionalized microstructures.

It is very challenging to study the behavior of neuronal cells in a network due to the multiple connections between the cells. Our idea is then to simplify such a network with a configuration where cells can have just a fixed number of connections in order to create a well-defined and ordered network. Here, we report about guiding primary cortical neurons with three-dimensional gold microspines selectively functionalized with an amino-terminated molecule.

Temporal lobe epilepsy and emotion recognition without amygdala: a case study of Urbach-Wiethe disease and review of the literature.

We describe the epilepsy features and emotion recognition abilities (recognition of basic facial emotions and recognition of emotional prosody) in a patient with Urbach-Wiethe disease with bilateral amygdala calcifications. Our data, supported by ictal video-EEG recording, indicated that our patient suffered from mesial temporal lobe epilepsy. Emotion recognition abilities were compared to those of healthy controls and those of patients with bilateral mesial temporal lobe epilepsy. Our patient showed a selective impairment of the recognition of facial expression of fear, whereas recognition of emotional prosody was preserved, in contrast to bilateral mesial temporal lobe epilepsy patients that presented with deficits in both domains. We also reviewed the literature on epilepsy in Urbach-Wiethe disease (41 patients). Our findings suggest that in Urbach-Wiethe disease, the circumscribed damage of both amygdalae results in a selective dysfunction of fearful face processing, in contrast to bilateral mesial temporal lobe epilepsy patients who present with a widespread and multimodal impairment in the judgement of emotional stimuli.

On chip guidance and recording of cardiomyocytes with 3D mushroom-shaped electrodes.

The quality of the recording and stimulation capabilities of multielectrode arrays (MEAs) substantially depends on the interface properties and the coupling of the cell with the underlying electrode area. The purpose of this work was the investigation of a three-dimensional nanointerface, enabling simultaneous guidance and recording of electrogenic cells (HL-1) by utilizing nanostructures with a mushroom shape on MEAs.

Introduction to memristors and neuromorphic systems.

Recent generative artificial intelligence (AI) has exerted a profound and far-reaching global impact across diverse fields and society. However, it comes at the cost of substantial energy and computational resource consumption. Neuromorphic computing endeavors to create highly efficient computing hardware that emulates biological neural networks and even mimics some human brain functions, and it is expected to play an essential role in the next-generation computing hardware. Memristors open up novel opportunities for neuromorphic computing due to their feasible ability to mimic neural functions. Innovation in memristors may lead to novel algorithms and contribute to conventionally challenging tasks like nondeterministic polynomial time (NP)-hard problem. To this end, we present a themed collection in Materials Horizons and Nanoscale Horizons, in which we publish the latest developments in memristive materials, device fabrication, characterization, and circuit design for neuromorphic systems.

An organic brain-inspired platform with neurotransmitter closed-loop control, actuation and reinforcement learning.

Organic neuromorphic platforms have recently received growing interest for the implementation and integration of artificial and hybrid neuronal networks. Here, achieving closed-loop and learning/training processes as in the human brain is still a major challenge especially exploiting time-dependent biosignalling such as neurotransmitter release. Here, we present an integrated organic platform capable of cooperating with standard silicon technologies, to achieve brain-inspired computing via adaptive synaptic potentiation and depression, in a closed-loop fashion. The microfabricated platform could be interfaced and control a robotic hand which ultimately was able to learn the grasping of differently sized objects, autonomously.

Concealing Organic Neuromorphic Devices with Neuronal-Inspired Supported Lipid Bilayers.

Neurohybrid systems have gained large attention for their potential as in vitro and in vivo platform to interrogate and modulate the activity of cells and tissue within nervous system. In this scenario organic neuromorphic devices have been engineered as bioelectronic platforms to resemble characteristic neuronal functions. However, aiming to a functional communication with neuronal cells, material synthesis, and surface engineering can yet be exploited for optimizing bio-recognition processes at the neuromorphic-neuronal hybrid interface. In this work, artificial neuronal-inspired lipid bilayers have been assembled on an electrochemical neuromorphic organic device (ENODe) to resemble post-synaptic structural and functional features of living synapses. Here, synaptic conditioning has been achieved by introducing two neurotransmitter-mediated biochemical signals, to induce an irreversible change in the device conductance thus achieving Pavlovian associative learning. This new class of in vitro devices can be further exploited for assembling hybrid neuronal networks and potentially for in vivo integration within living neuronal tissues.