Single-trial detection of auditory cues from the rat brain using memristors.

Implantable devices hold the potential to address conditions currently lacking effective treatments, such as drug-resistant neural impairments and prosthetic control. Medical devices need to be biologically compatible while providing enhanced performance metrics of low-power consumption, high accuracy, small size, and minimal latency to enable ongoing intervention in brain function. Here, we demonstrate a memristor-based processing system for single-trial detection of behaviorally meaningful brain signals within a timeframe that supports real-time closed-loop intervention.

A live mammalian cells electroporation array for on-chip immunofluorescence.

The detection of intracellular proteins in vitro is commonly realized with immunofluorescence techniques, through which antibodies or markers are delivered into fixed cells and recognize specific proteins. Many innovative techniques, however, avoid cells fixation by chemical compounds and, among the others, electroporation is widely used. Here we demonstrate that in situ electroporation on thin film SiO capacitive microelectrodes can be realized with high efficiency to deliver fluorescent markers and antibodies into mammalian cell lines and primary neuronal cells to detect intracellular proteins, like actin.

Early Detection of Alzheimer's Disease From Cortical and Hippocampal Local Field Potentials Using an Ensembled Machine Learning Model.

Early diagnosis of Alzheimer's disease (AD) is a very challenging problem and has been attempted through data-driven methods in recent years. However, considering the inherent complexity in decoding higher cognitive functions from spontaneous neuronal signals, these data-driven methods benefit from the incorporation of multimodal data. This work proposes an ensembled machine learning model with explainability (EXML) to detect subtle patterns in cortical and hippocampal local field potential signals (LFPs) that can be considered as a potential marker for AD in the early stage of the disease.

Interfacing Biology and Electronics with Memristive Materials.

Memristive technologies promise to have a large impact on modern electronics, particularly in the areas of reconfigurable computing and artificial intelligence (AI) hardware. Meanwhile, the evolution of memristive materials alongside the technological progress is opening application perspectives also in the biomedical field, particularly for implantable and lab-on-a-chip devices where advanced sensing technologies generate a large amount of data. Memristive devices are emerging as bioelectronic links merging biosensing with computation, acting as physical processors of analog signals or in the framework of advanced digital computing architectures.

Disentangling the critical signatures of neural activity.

The critical brain hypothesis has emerged as an attractive framework to understand neuronal activity, but it is still widely debated. In this work, we analyze data from a multi-electrodes array in the rat's cortex and we find that power-law neuronal avalanches satisfying the crackling-noise relation coexist with spatial correlations that display typical features of critical systems. In order to shed a light on the underlying mechanisms at the origin of these signatures of criticality, we introduce a paradigmatic framework with a common stochastic modulation and pairwise linear interactions inferred from our data.

Classification of Whisker Deflections From Evoked Responses in the Somatosensory Barrel Cortex With Spiking Neural Networks.

Spike-based neuromorphic hardware has great potential for low-energy brain-machine interfaces, leading to a novel paradigm for neuroprosthetics where spiking neurons in silicon read out and control activity of brain circuits. Neuromorphic processors can receive rich information about brain activity from both spikes and local field potentials (LFPs) recorded by implanted neural probes. However, it was unclear whether spiking neural networks (SNNs) implemented on such devices can effectively process that information.

Increased fMRI connectivity upon chemogenetic inhibition of the mouse prefrontal cortex.

While shaped and constrained by axonal connections, fMRI-based functional connectivity reorganizes in response to varying interareal input or pathological perturbations. However, the causal contribution of regional brain activity to whole-brain fMRI network organization remains unclear. Here we combine neural manipulations, resting-state fMRI and in vivo electrophysiology to probe how inactivation of a cortical node causally affects brain-wide fMRI coupling in the mouse.

Accelerated Aging Characterizes the Early Stage of Alzheimer's Disease.

For Alzheimer's disease (AD), aging is the main risk factor, but whether cognitive impairments due to aging resemble early AD deficits is not yet defined. When working with mouse models of AD, the situation is just as complicated, because only a few studies track the progression of the disease at different ages, and most ignore how the aging process affects control mice. In this work, we addressed this problem by comparing the aging process of PS2APP (AD) and wild-type (WT) mice at the level of spontaneous brain electrical activity under anesthesia.

Simultaneous Two-Photon Voltage or Calcium Imaging and Multi-Channel Local Field Potential Recordings in Barrel Cortex of Awake and Anesthetized Mice.

Neuronal population activity, both spontaneous and sensory-evoked, generates propagating waves in cortex. However, high spatiotemporal-resolution mapping of these waves is difficult as calcium imaging, the work horse of current imaging, does not reveal subthreshold activity. Here, we present a platform combining voltage or calcium two-photon imaging with multi-channel local field potential (LFP) recordings in different layers of the barrel cortex from anesthetized and awake head-restrained mice.

Neuronal Avalanches Across the Rat Somatosensory Barrel Cortex and the Effect of Single Whisker Stimulation.

Since its first experimental signatures, the so called "critical brain hypothesis" has been extensively studied. Yet, its actual foundations remain elusive. According to a widely accepted teleological reasoning, the brain would be poised to a critical state to optimize the mapping of the noisy and ever changing real-world inputs, thus suggesting that primary sensory cortical areas should be critical.

Understanding the Effects of Anesthesia on Cortical Electrophysiological Recordings: A Scoping Review.

General anesthesia in animal experiments is an ethical must and is required for all the procedures that are likely to cause more than slight or momentary pain. As anesthetics are known to deeply affect experimental findings, including electrophysiological recordings of brain activity, understanding their mechanism of action is of paramount importance. It is widely recognized that the depth and type of anesthesia introduce significant bias in electrophysiological measurements by affecting the shape of both spontaneous and evoked signals, e.

Plasticity and Adaptation in Neuromorphic Biohybrid Systems.

Neuromorphic systems take inspiration from the principles of biological information processing to form hardware platforms that enable the large-scale implementation of neural networks. The recent years have seen both advances in the theoretical aspects of spiking neural networks for their use in classification and control tasks and a progress in electrophysiological methods that is pushing the frontiers of intelligent neural interfacing and signal processing technologies. At the forefront of these new technologies, artificial and biological neural networks are tightly coupled, offering a novel "biohybrid" experimental framework for engineers and neurophysiologists.

Author Correction: Memristive synapses connect brain and silicon spiking neurons.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Memristive synapses connect brain and silicon spiking neurons.

Brain function relies on circuits of spiking neurons with synapses playing the key role of merging transmission with memory storage and processing. Electronics has made important advances to emulate neurons and synapses and brain-computer interfacing concepts that interlink brain and brain-inspired devices are beginning to materialise. We report on memristive links between brain and silicon spiking neurons that emulate transmission and plasticity properties of real synapses.

Dampened Slow Oscillation Connectivity Anticipates Amyloid Deposition in the PS2APP Mouse Model of Alzheimer's Disease.

To fight Alzheimer's disease (AD), we should know when, where, and how brain network dysfunctions initiate. In AD mouse models, relevant information can be derived from brain electrical activity. With a multi-site linear probe, we recorded local field potentials simultaneously at the posterior-parietal cortex and hippocampus of wild-type and double transgenic AD mice, under anesthesia.

Open-Source Tools for Processing and Analysis of In Vitro Extracellular Neuronal Signals.

The recent years have seen unprecedented growth in the manufacturing of neurotechnological tools. The latest technological advancements presented the neuroscientific community with neuronal probes containing thousands of recording sites. These next-generation probes are capable of simultaneously recording neuronal signals from a large number of channels.

Applications of Deep Learning and Reinforcement Learning to Biological Data.

Rapid advances in hardware-based technologies during the past decades have opened up new possibilities for life scientists to gather multimodal data in various application domains, such as omics, bioimaging, medical imaging, and (brain/body)-machine interfaces. These have generated novel opportunities for development of dedicated data-intensive machine learning techniques. In particular, recent research in deep learning (DL), reinforcement learning (RL), and their combination (deep RL) promise to revolutionize the future of artificial intelligence.

Sub 100 nW Volatile Nano-Metal-Oxide Memristor as Synaptic-Like Encoder of Neuronal Spikes.

Advanced neural interfaces mediate a bioelectronic link between the nervous system and microelectronic devices, bearing great potential as innovative therapy for various diseases. Spikes from a large number of neurons are recorded leading to creation of big data that require online processing under most stringent conditions, such as minimal power dissipation and on-chip space occupancy. Here, we present a new concept where the inherent volatile properties of a nano-scale memristive device are used to detect and compress information on neural spikes as recorded by a multielectrode array.

Algorithm and software to automatically identify latency and amplitude features of local field potentials recorded in electrophysiological investigation.

Background: Local field potentials (LFPs) evoked by sensory stimulation are particularly useful in electrophysiological research. For instance, spike timing and current transmembrane current flow estimated from LFPs recorded in the barrel cortex in rats and mice are exploited to investigate how the brain represents sensory stimuli. Recent improvements in microelectrodes technology enable neuroscientists to acquire a great amount of LFPs during the same experimental session, calling for algorithms for their quantitative automatic analysis.

Intranasal Oxytocin and Vasopressin Modulate Divergent Brainwide Functional Substrates.

The neuropeptides oxytocin (OXT) and vasopressin (AVP) have been identified as modulators of emotional social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction. Experimental and therapeutic use of OXT and AVP via the intranasal route is the subject of extensive clinical research. However, the large-scale functional substrates directly engaged by these peptides and their functional dynamics remain elusive.

Early hippocampal hyperexcitability in PS2APP mice: role of mutant PS2 and APP.

Alterations of brain network activity are observable in Alzheimer's disease (AD) together with the occurrence of mild cognitive impairment, before overt pathology. However, in humans as well in AD mouse models, identification of early biomarkers of network dysfunction is still at its beginning. We performed in vivo recordings of local field potential activity in the dentate gyrus of PS2APP mice expressing the human amyloid precursor protein (APP) Swedish mutation and the presenilin-2 (PS2) N141I.

Trends and Challenges in Neuroengineering: Toward "Intelligent" Neuroprostheses through Brain-"Brain Inspired Systems" Communication.

Future technologies aiming at restoring and enhancing organs function will intimately rely on near-physiological and energy-efficient communication between living and artificial biomimetic systems. Interfacing brain-inspired devices with the real brain is at the forefront of such emerging field, with the term "neurobiohybrids" indicating all those systems where such interaction is established. We argue that achieving a "high-level" communication and functional synergy between natural and artificial neuronal networks , will allow the development of a heterogeneous world of neurobiohybrids, which will include "living robots" but will also embrace "intelligent" neuroprostheses for augmentation of brain function.

A tunable local field potentials computer simulator to assess minimal requirements for phase-amplitude cross-frequency-coupling estimation.

The quantitative study of cross-frequency coupling (CFC) is a relevant issue in neuroscience. In local field potentials (LFPs), measured either in the cortex or in the hippocampus, how γ-oscillation amplitude is modulated by changes in θ-rhythms-phase is thought to be important in memory formation. Several methods were proposed to quantify CFC, but reported evidence suggests that experimental parameters affect the results.

Real-time encoding and compression of neuronal spikes by metal-oxide memristors.

Advanced brain-chip interfaces with numerous recording sites bear great potential for investigation of neuroprosthetic applications. The bottleneck towards achieving an efficient bio-electronic link is the real-time processing of neuronal signals, which imposes excessive requirements on bandwidth, energy and computation capacity. Here we present a unique concept where the intrinsic properties of memristive devices are exploited to compress information on neural spikes in real-time.

Processing and Analysis of Multichannel Extracellular Neuronal Signals: State-of-the-Art and Challenges.

In recent years multichannel neuronal signal acquisition systems have allowed scientists to focus on research questions which were otherwise impossible. They act as a powerful means to study brain (dys)functions in in-vivo and in in-vitro animal models. Typically, each session of electrophysiological experiments with multichannel data acquisition systems generate large amount of raw data.