Stimulation Of Neural Activity Research Articles

High-density transparent graphene arrays for predicting cellular calcium activity at depth from surface potential recordings.

Optically transparent neural microelectrodes have facilitated simultaneous electrophysiological recordings from the brain surface with the optical imaging and stimulation of neural activity. A remaining challenge is to scale down the electrode dimensions to the single-cell size and increase the density to record neural activity with high spatial resolution across large areas to capture nonlinear neural dynamics. Here we developed transparent graphene microelectrodes with ultrasmall openings and a large, transparent recording area without any gold extensions in the field of view with high-density microelectrode arrays up to 256 channels. We used platinum nanoparticles to overcome the quantum capacitance limit of graphene and to scale down the microelectrode diameter to 20 µm. An interlayer-doped double-layer graphene was introduced to prevent open-circuit failures. We conducted multimodal experiments, combining the recordings of cortical potentials of microelectrode arrays with two-photon calcium imaging of the mouse visual cortex. Our results revealed that visually evoked responses are spatially localized for high-frequency bands, particularly for the multiunit activity band. The multiunit activity power was found to be correlated with cellular calcium activity. Leveraging this, we employed dimensionality reduction techniques and neural networks to demonstrate that single-cell and average calcium activities can be decoded from surface potentials recorded by high-density transparent graphene arrays.

Learning to control the brain through adaptive closed-loop patterned stimulation

Objective. Stimulation of neural activity is an important scientific and clinical tool, causally testing hypotheses and treating neurodegenerative and neuropsychiatric diseases. However, current stimulation approaches cannot flexibly control the pattern of activity in populations of neurons. To address this, we developed a model-free, adaptive, closed-loop stimulation (ACLS) system that learns to use multi-site electrical stimulation to control the pattern of activity of a population of neurons. Approach. The ACLS system combined multi-electrode electrophysiological recordings with multi-site electrical stimulation to simultaneously record the activity of a population of 5–15 multiunit neurons and deliver spatially-patterned electrical stimulation across 4–16 sites. Using a closed-loop learning system, ACLS iteratively updated the pattern of stimulation to reduce the difference between the observed neural response and a specific target pattern of firing rates in the recorded multiunits. Main results. In silico and in vivo experiments showed ACLS learns to produce specific patterns of neural activity (in ∼15 min) and was robust to noise and drift in neural responses. In visual cortex of awake mice, ACLS learned electrical stimulation patterns that produced responses similar to the natural response evoked by visual stimuli. Similar to how repetition of a visual stimulus causes an adaptation in the neural response, the response to electrical stimulation was adapted when it was preceded by the associated visual stimulus. Significance. Our results show an ACLS system that can learn, in real-time, to generate specific patterns of neural activity. This work provides a framework for using model-free closed-loop learning to control neural activity.

Integration of Micro-Patterned Carbon Fiber Mats into Polyimide for the Development of Flexible Implantable Neural Devices.

Polymer-derived carbon as neural electrode material has recently been subject of interest due to its ability to act as a multimodal platform for simultaneous recording and stimulation of neural activity and neurotransmitter detection. Its mechanical properties and the inverse fabrication protocol commonly used for the manufacturing of pyrolyzed carbon thin-film devices, however, only allow for its use as the electrode material and not as material for interconnects and other conductive components. In this study -for the first time-a process to fabricate flexible neural devices entirely made of carbon fibers (CFs) and polyimide (PI) was developed. The devices consist of carbonized polyacrylonitrile (PAN) fiber mats embedded in polyimide, which were patterned into the desired shapes using reactive ion etching (RIE). This method allowed for the fabrication of miniaturized, flexible and conductive carbon components with critical dimensions of 12.5 μm. Tensile tests were performed to evaluate the mechanical stability of the CF/PI composite, to detect potential electrical resistance changes due to bending and to study the adhesion of different PI layers onto each other. A strong mechanical interlock between CFs and PI was demonstrated and no significant change in the resistance of the CFs was detected after 100k cycles of tensile bending (r = 3 mm). The fabrication approach proposed here successfully yielded entirely metal-free and entirely flexible electrodes. It opens the door to further studies with the guarantee of highly stable electrodes, both mechanically and electrically.

Recent Progress on Non-Conventional Microfabricated Probes for the Chronic Recording of Cortical Neural Activity.

Microfabrication technology for cortical interfaces has advanced rapidly over the past few decades for electrophysiological studies and neuroprosthetic devices offering the precise recording and stimulation of neural activity in the cortex. While various cortical microelectrode arrays have been extensively and successfully demonstrated in animal and clinical studies, there remains room for further improvement of the probe structure, materials, and fabrication technology, particularly for high-fidelity recording in chronic implantation. A variety of non-conventional probes featuring unique characteristics in their designs, materials and fabrication methods have been proposed to address the limitations of the conventional standard shank-type (“Utah-” or “Michigan-” type) devices. Such non-conventional probes include multi-sided arrays to avoid shielding and increase recording volumes, mesh- or thread-like arrays for minimized glial scarring and immune response, tube-type or cylindrical probes for three-dimensional (3D) recording and multi-modality, folded arrays for high conformability and 3D recording, self-softening or self-deployable probes for minimized tissue damage and extensions of the recording sites beyond gliosis, nanostructured probes to reduce the immune response, and cone-shaped electrodes for promoting tissue ingrowth and long-term recording stability. Herein, the recent progress with reference to the many different types of non-conventional arrays is reviewed while highlighting the challenges to be addressed and the microfabrication techniques necessary to implement such features.

A Wireless, Bidirectional Interface for <em>In Vivo</em> Recording and Stimulation of Neural Activity in Freely Behaving Rats

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described. The system operates through a single portable head stage that both transmits recorded activity and can be targeted in real-time for brain stimulation using a telemetry-based multichannel software. The head stage is equipped with a preamplifier and a rechargeable battery, allowing stable long-term recordings or stimulation for up to 1 h. Importantly, the head stage is compact, weighs 12 g (including battery) and thus has minimal impact on the animal´s behavioral repertoire, making the method applicable to a broad set of behavioral tasks. Moreover, the method has the major advantage that the effect of brain stimulation on neural activity and behavior can be measured simultaneously, providing a tool to assess the causal relationships between specific brain activation patterns and behavior. This feature makes the method particularly valuable for the field of deep brain stimulation, allowing precise assessment, monitoring, and adjustment of stimulation parameters during long-term behavioral experiments. The applicability of the system has been validated using the inferior colliculus as a model structure.

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats.

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described. The system operates through a single portable head stage that both transmits recorded activity and can be targeted in real-time for brain stimulation using a telemetry-based multichannel software. The head stage is equipped with a preamplifier and a rechargeable battery, allowing stable long-term recordings or stimulation for up to 1 h. Importantly, the head stage is compact, weighs 12 g (including battery) and thus has minimal impact on the animal´s behavioral repertoire, making the method applicable to a broad set of behavioral tasks. Moreover, the method has the major advantage that the effect of brain stimulation on neural activity and behavior can be measured simultaneously, providing a tool to assess the causal relationships between specific brain activation patterns and behavior. This feature makes the method particularly valuable for the field of deep brain stimulation, allowing precise assessment, monitoring, and adjustment of stimulation parameters during long-term behavioral experiments. The applicability of the system has been validated using the inferior colliculus as a model structure.

Flexible Neural Electrode Array Based-on Porous Graphene for Cortical Microstimulation and Sensing.

Neural sensing and stimulation have been the backbone of neuroscience research, brain-machine interfaces and clinical neuromodulation therapies for decades. To-date, most of the neural stimulation systems have relied on sharp metal microelectrodes with poor electrochemical properties that induce extensive damage to the tissue and significantly degrade the long-term stability of implantable systems. Here, we demonstrate a flexible cortical microelectrode array based on porous graphene, which is capable of efficient electrophysiological sensing and stimulation from the brain surface, without penetrating into the tissue. Porous graphene electrodes show superior impedance and charge injection characteristics making them ideal for high efficiency cortical sensing and stimulation. They exhibit no physical delamination or degradation even after 1 million biphasic stimulation cycles, confirming high endurance. In in vivo experiments with rodents, same array is used to sense brain activity patterns with high spatio-temporal resolution and to control leg muscles with high-precision electrical stimulation from the cortical surface. Flexible porous graphene array offers a minimally invasive but high efficiency neuromodulation scheme with potential applications in cortical mapping, brain-computer interfaces, treatment of neurological disorders, where high resolution and simultaneous recording and stimulation of neural activity are crucial.

Rhythmic sensory stimulation and Alzheimer’s disease

Background: Rhythmic Sensory Simulation (RSS) is stimulation of neural activity with sound applied rhythmically to the body or auditory system. The RSS and Alzheimer’s (AD) study sought to assess the behavioural effect of stimulating AD patients with sound-activated vibro-tactile stimulation of the somatosensory system at a rate of 40 HZ.Objective: To present an overview of the study with a look to the literature on sound stimulation with persons having AD.Methods: In this AB cross-over study design, 18 AD participants each received a total of 13 sessions. Treatment consisted of: 40 HZ stimulation and visual stimulation, each provided 6 times. Data sources included: the St. Louis University Mental Status Test, the Observed Emotion Rating Scale and behavioural observation by the researcher.Discussion: Quantitative and qualitative data analysis will be shared, alongside discussion on limitations and future research.Conclusions: With the incidence of AD and dementia expected to increase, further research and...

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes.

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.

Mechanisms of Augmentation in Proprioceptive Media Art

In this paper, I explore the phenomenon of augmentation by questioning its representational nature and analyzing aesthetic modes of our interrelationship with the environment. How can senses be augmented and how do they serve as mechanisms of enhancing the feeling of presence? Media art practices offer particularly valuable scenarios of activating such mechanisms, as the employment of digital technology allows them to operate on a more subtle level of perception. Given that these practices are continuously evolving, this analysis cannot claim to be a comprehensive one, but rather aims to introduce aspects of the specific relations between augmentation, sense of proprioception, technology, and art. Proprioception is one of the least detectable and track-able human senses because it involves our intuitive sense of positionality, which suggests a subtle equilibrium between a center (our individual bodies) and the periphery (our immediate environments). Yet, as any sense, proprioception implies a communicational chain, a network of signals traveling and exchanging information within the body-mind complex. The technological augmentation of this dynamic process produces an interference in our understanding of the structure and elements, the information sent/received. One way to understand the operations of the senses is to think about them as images that the mind creates for itself. Artistic intervention (usually) builds upon exactly this logic: representation of images generated in mind, supplementing or even supplanting the existing collection of inner images with new, created ones. Yet, in case of proprioception the only means to interfere with and augment these inner images is on bodily level. Hence, the question of communication through images (or representations) should be extended towards a more complex theory of embodied perception. Drawing on phenomenology, cognitive science, and techno-cultural studies, I focus on the potential of biofeedback technologies to challenge and transform our self-perception by conditioning new pathways of apprehension (sometimes by creating mechanisms of direct stimulation of neural activity). I am particularly interested in how the awareness of the self (grounded in the felt relationality of our body parts) is most significantly activated at the moments of disturbance of balance, in situations of perplexity and disorientation. Projects by Marco Donnarumma, Sean Montgomery, and other artists working with biofeedback aesthetically validate and instantiate current research about neuroplasticity, with technologically mediated sensory augmentation as one catalyst of this process.

Organic electronics for precise delivery of neurotransmitters to modulate mammalian sensory function

Significant advances have been made in the understanding of the pathophysiology, molecular targets and therapies for the treatment of a variety of nervous-system disorders. Particular therapies involve electrical sensing and stimulation of neural activity, and significant effort has therefore been devoted to the refinement of neural electrodes. However, direct electrical interfacing suffers from some inherent problems, such as the inability to discriminate amongst cell types. Thus, there is a need for novel devices to specifically interface nerve cells. Here, we demonstrate an organic electronic device capable of precisely delivering neurotransmitters in vitro and in vivo. In converting electronic addressing into delivery of neurotransmitters, the device mimics the nerve synapse. Using the peripheral auditory system, we show that out of a diverse population of cells, the device can selectively stimulate nerve cells responding to a specific neurotransmitter. This is achieved by precise electronic control of electrophoretic migration through a polymer film. This mechanism provides several sought-after features for regulation of cell signalling: exact dosage determination through electrochemical relationships, minimally disruptive delivery due to lack of fluid flow, and on-off switching. This technology has great potential as a therapeutic platform and could help accelerate the development of therapeutic strategies for nervous-system disorders.

Large-scale multielectrode recording and stimulation of neural activity

Large circuits of neurons are employed by the brain to encode and process information. How this encoding and processing is carried out is one of the central questions in neuroscience. Since individual neurons communicate with each other through electrical signals (action potentials), the recording of neural activity with arrays of extracellular electrodes is uniquely suited for the investigation of this question. Such recordings provide the combination of the best spatial (individual neurons) and temporal (individual action-potentials) resolutions compared to other large-scale imaging methods. Electrical stimulation of neural activity in turn has two very important applications: it enhances our understanding of neural circuits by allowing active interactions with them, and it is a basis for a large variety of neural prosthetic devices. Until recently, the state-of-the-art in neural activity recording systems consisted of several dozen electrodes with inter-electrode spacing ranging from tens to hundreds of microns. Using silicon microstrip detector expertise acquired in the field of high-energy physics, we created a unique neural activity readout and stimulation framework that consists of high-density electrode arrays, multi-channel custom-designed integrated circuits, a data acquisition system, and data-processing software. Using this framework we developed a number of neural readout and stimulation systems: (1) a 512-electrode system for recording the simultaneous activity of as many as hundreds of neurons, (2) a 61-electrode system for electrical stimulation and readout of neural activity in retinas and brain-tissue slices, and (3) a system with telemetry capabilities for recording neural activity in the intact brain of awake, naturally behaving animals. We will report on these systems, their various applications to the field of neurobiology, and novel scientific results obtained with some of them. We will also outline future directions.