Simultaneous Neural Recording Research Articles

Social bonding in groups of humans selectively increases inter-status information exchange and prefrontal neural synchronization.

Social groups in various social species are organized with hierarchical structures that shape group dynamics and the nature of within-group interactions. In-group social bonding, exemplified by grooming behaviors among animals and collective rituals and team-building activities in human societies, is recognized as a practical adaptive strategy to foster group harmony and stabilize hierarchical structures in both human and nonhuman animal groups. However, the neurocognitive mechanisms underlying the effects of social bonding on hierarchical groups remain largely unexplored. Here, we conducted simultaneous neural recordings on human participants engaged in-group communications within small hierarchical groups (n = 528, organized into 176 three-person groups) to investigate how social bonding influenced hierarchical interactions and neural synchronizations. We differentiated interpersonal interactions between individuals of different (inter-status) or same (intra-status) social status and observed distinct effects of social bonding on inter-status and intra-status interactions. Specifically, social bonding selectively increased frequent and rapid information exchange and prefrontal neural synchronization for inter-status dyads but not intra-status dyads. Furthermore, social bonding facilitated unidirectional neural alignment from group leader to followers, enabling group leaders to predictively align their prefrontal activity with that of followers. These findings provide insights into how social bonding influences hierarchical dynamics and neural synchronization while highlighting the role of social status in shaping the strength and nature of social bonding experiences in human groups.

A multi-method approach to addressing the toddler data desert in attention research

Visual attention skills undergo robust development change during infancy and continue to co-develop with other cognitive processes in early childhood. Despite this, this is a general disconnect between measures of the earliest foundations of attention during infancy and later development of attention in relation to executive functioning during the toddler years. To examine associations between these different measures of attention, the current study administered an oculomotor task (infant orienting with attention, IOWA) and a manual response (Flanker) task with a group of toddlers. We collected simultaneous neural recordings (using functional near-infrared spectroscopy), eye-tracking, and behavioral responses in 2.5- and 3.5-year-olds to examine the neural and behavioral associations between these skills. Results revealed that oculomotor facilitation in the IOWA task was negatively associated with accuracy on neutral trials in the Flanker task. Second, conflict scores between the two tasks were positively associated. At the neural level, however, the tasks showed distinct patterns of activation. Left frontal cortex was engaged during the Flanker task whereas right frontal and parietal cortex was engaged during the IOWA task. Activation during the IOWA task differed based on how well children could control oculomotor behavior during the task. Children with high levels of stimulus reactivity activated parietal cortex more strongly, but children with more controlled oculomotor behavior activated frontal cortex more strongly.

General-Purpose Ultrasound Neuromodulation System for Chronic, Closed-Loop Preclinical Studies in Freely Behaving Rodents.

Transcranial focused ultrasound stimulation (tFUS) is an effective noninvasive treatment modality for brain disorders with high clinical potential. However, the therapeutic effects of ultrasound neuromodulation are not widely explored due to limitations in preclinical systems. The current preclinical studies are head-fixed, anesthesia-dependent, and acute, limiting clinical translatability. Here, this work reports a general-purpose ultrasound neuromodulation system for chronic, closed-loop preclinical studies in freely behaving rodents. This work uses microelectromechanical systems (MEMS) technology to design and fabricate a small and lightweight transducer capable of artifact-free stimulation and simultaneous neural recording. Using the general-purpose system, it can be observed that state-dependent ultrasound neuromodulation of the prefrontal cortex increases rapid eye movement (REM) sleep and protects spatial working memory to REMsleep deprivation. The system will allow explorative studies in brain disease therapeutics and neuromodulation using ultrasound stimulation for widespread clinical adoption.

Multisite Simultaneous Neural Recording of Motor Pathway in Free-Moving Rats.

Neural interfaces typically focus on one or two sites in the motoneuron system simultaneously due to the limitation of the recording technique, which restricts the scope of observation and discovery of this system. Herein, we built a system with various electrodes capable of recording a large spectrum of electrophysiological signals from the cortex, spinal cord, peripheral nerves, and muscles of freely moving animals. The system integrates adjustable microarrays, floating microarrays, and microwires to a commercial connector and cuff electrode on a wireless transmitter. To illustrate the versatility of the system, we investigated its performance for the behavior of rodents during tethered treadmill walking, untethered wheel running, and open field exploration. The results indicate that the system is stable and applicable for multiple behavior conditions and can provide data to support previously inaccessible research of neural injury, rehabilitation, brain-inspired computing, and fundamental neuroscience.

A Neural Recording and Stimulation Chip with Artifact Suppression for Biomedical Devices.

This paper presents chip implementation of the integrated neural recording and stimulation system with stimulation-induced artifact suppression. The implemented chip consists of low-power neural recording circuits, stimulation circuits, and action potential detection circuits. These circuits constitute a closed-loop simultaneous neural recording and stimulation system for biomedical devices, and a proposed artifact suppression technique is used in the system. Moreover, this paper also presents the measurement and experiment results of the implemented 4-to-4 channel neural recording and stimulation chip with 0.18 µm CMOS technology. The function and efficacy of simultaneous neural recording and stimulation is validated in both in vivo and animal experiments.

A Single-Chip Bidirectional Neural Interface With High-Voltage Stimulation and Adaptive Artifact Cancellation in Standard CMOS

A single-chip, bidirectional brain–computer interface (BBCI) enables neuromodulation through simultaneous neural recording and stimulation. This article presents a prototype BBCI application-specified integrated circuit (ASIC) consisting of a 64-channel time-multiplexed recording front-end, an area-optimized four-channel high-voltage compliant stimulator, and electronics to support the concurrent multi-channel stimulus artifact cancellation. Stimulator power generation is integrated on a chip, providing ±11-V compliance from low-voltage supplies with a resonant charge pump. High-frequency (~3 GHz) self-resonant clocking is used to reduce the pumping capacitor area while suppressing the associated switching losses. A 32-tap least mean square (LMS)-based digital adaptive filter achieves 60-dB artifact suppression, enabling simultaneous neural stimulation and recording. The entire chip occupies 4 mm2 in a 65-nm low power (LP) process and is powered by 2.5-/1.2-V supplies, dissipating $205~\mu \text{W}$ in recording and $142~\mu \text{W}$ in the stimulation and cancellation back-ends. The stimulation output drivers achieve 31% dc–dc efficiency at a maximum output power of 24 mW.

Hemispherical Microelectrode Array for Ex Vivo Retinal Neural Recording.

To investigate the neuronal visual encoding process in the retina, researchers have performed in vitro and ex vivo electrophysiological experiments using animal retinal tissues. The microelectrode array (MEA) has become a key component in retinal experiments because it enables simultaneous neural recording from a population of retinal neurons. However, in most retinal experiments, it is inevitable that the retinal tissue is flattened on the planar MEA, becoming deformed from the original hemispherical shape. During the tissue deforming process, the retina is subjected to mechanical stress, which can induce abnormal physiological conditions. To overcome this problem, in this study, we propose a hemispherical MEA with a curvature that allows retinal tissues to adhere closely to electrodes without tissue deformation. The electrode array is fabricated by stretching a thin, flexible polydimethylsiloxane (PDMS) electrode layer onto a hemispherical substrate. To form micro patterns of electrodes, laser processing is employed instead of conventional thin-film microfabrication processes. The feasibility for neural recording from retinal tissues using this array is shown by conducting ex vivo retinal experiments. We anticipate that the proposed techniques for hemispherical MEAs can be utilized not only for ex vivo retinal studies but also for various flexible electronics.

Differential Roles of Mediodorsal Nucleus of the Thalamus and Prefrontal Cortex in Decision-Making and State Representation in a Cognitive Control Task Measuring Deficits in Schizophrenia.

The mediodorsal nucleus of the thalamus (MD) is reciprocally connected with the prefrontal cortex (PFC), and although the MD has been implicated in a range of PFC-dependent cognitive functions (Watanabe and Funahashi, 2012; Mitchell and Chakraborty, 2013; Parnaudeau et al., 2018), little is known about how MD neurons in the primate participate specifically in cognitive control, a capability that reflects the ability to use contextual information (such as a rule) to modify responses to environmental stimuli. To learn how the MD-PFC thalamocortical network is engaged to mediate forms of cognitive control that are selectively disrupted in schizophrenia, we trained male monkeys to perform a variant of the AX continuous performance task, which reliably measures cognitive control deficits in patients (Henderson et al., 2012) and used linear multielectrode arrays to record neural activity in the MD and PFC simultaneously. We found that the two structures made clearly different contributions to distributed processing for cognitive control: MD neurons were specialized for decision-making and response selection, whereas prefrontal neurons were specialized to preferentially encode the environmental state on which the decision was based. In addition, we observed that functional coupling between MD and PFC was strongest when the decision as to which of the two responses in the task to execute was being made. These findings delineate unique contributions of MD and PFC to distributed processing for cognitive control and characterized neural dynamics in this network associated with normative cognitive control performance.SIGNIFICANCE STATEMENT Cognitive control is fundamental to healthy human executive functioning (Miller and Cohen, 2001) and deficits in patients with schizophrenia relate to decreased functional activation of the MD thalamus and the prefrontal cortex (Minzenberg et al., 2009), which are reciprocally linked (Goldman-Rakic and Porrino, 1985; Xiao et al., 2009). We carry out simultaneous neural recordings in the MD and PFC while monkeys perform a cognitive control task translated from patients with schizophrenia to relate thalamocortical dynamics to cognitive control performance. Our data suggest that state representation and decision-making computations for cognitive control are preferentially performed by PFC and MD, respectively. This suggests experiments to parse decision-making and state representation deficits in patients while providing novel computational targets for future therapies.

Implementing EEG hyperscanning setups

Hyperscanning refers to obtaining simultaneous neural recordings from more than one person (Montage et al., 2002 [1]), that can be used to study interactive situations. In particular, hyperscanning with Electroencephalography (EEG) is becoming increasingly popular since it allows researchers to explore the interactive brain with a high temporal resolution. Notably, there is a 40-year gap between the first instance that simultaneous measurement of EEG activity was mentioned in the literature (Duane and Behrendt, 1965 [2]), and the first actual description of an EEG hyperscanning setup being implemented (Babiloni et al., 2006 [3]). To date, specific EEG hyperscanning devices have not yet been developed and EEG hyperscanning setups are not usually described with sufficient detail to be easily reproduced. Here, we offer a step-by-step description of solutions to many of these technological challenges. Specifically, we describe and provide customized implementations of EEG hyperscanning setups using hardware and software from different companies: Brain Products, ANT, EGI, and BioSemi.•Necessary details to set up a functioning EEG hyperscanning protocol are provided.•The setups allow independent measures and measures of synchronization between the signals of two different brains.•Individual electrical Ground and Reference is obtained in all discussed systems.

An Electrocorticography Device with an Integrated Microfluidic Ion Pump for Simultaneous Neural Recording and Electrophoretic Drug Delivery In Vivo.

The challenge of treating neurological disorders has motivated the development of implantable devices that can deliver treatment when and where it is needed. This study presents a novel brain implant capable of electrophoretically delivering drugs and recording local neural activity on the surface of the brain. The drug delivery is made possible by the integration of a microfluidic ion pump (µFIP) into a conformable electrocorticography (ECoG) device with recording cites embedded next to the drug delivery outlets. The µFIP ECoG device can deliver a high capacity of several biologically important cationic species on demand. The therapeutic potential of the device is demonstrated by using it to deliver neurotransmitters in a rodent model while simultaneously recording local neural activity. These developments represent a significant step forward for cortical drug-delivery systems.

Whole-Brain Calcium Imaging during Physiological Vestibular Stimulation in Larval Zebrafish

SummaryThe vestibular apparatus provides animals with postural and movement-related information that is essential to adequately execute numerous sensorimotor tasks. In order to activate this sensory system in a physiological manner, one needs to macroscopically rotate or translate the animal’s head, which in turn renders simultaneous neural recordings highly challenging. Here we report on a novel miniaturized, light-sheet microscope that can be dynamically co-rotated with a head-restrained zebrafish larva, enabling controlled vestibular stimulation. The mechanical rigidity of the microscope allows one to perform whole-brain functional imaging with state-of-the-art resolution and signal-to-noise ratio while imposing up to 25° in angular position and 6,000°/s2 in rotational acceleration. We illustrate the potential of this novel setup by producing the first whole-brain response maps to sinusoidal and stepwise vestibular stimulation. The responsive population spans multiple brain areas and displays bilateral symmetry, and its organization is highly stereotypic across individuals. Using Fourier and regression analysis, we identified three major functional clusters that exhibit well-defined phasic and tonic response patterns to vestibular stimulation. Our rotatable light-sheet microscope provides a unique tool for systematically studying vestibular processing in the vertebrate brain and extends the potential of virtual-reality systems to explore complex multisensory and motor integration during simulated 3D navigation.

SiNAPS: An implantable active pixel sensor CMOS-probe for simultaneous large-scale neural recordings

Large-scale neural recordings with high spatial and temporal accuracy are instrumental to understand how the brain works. To this end, it is of key importance to develop probes that can be conveniently scaled up to a high number of recording channels. Despite recent achievements in complementary metal-oxide semiconductor (CMOS) multi-electrode arrays probes, in current circuit architectures an increase in the number of simultaneously recording channels would significantly increase the total chip area. A promising approach for overcoming this scaling issue consists in the use of the modular Active Pixel Sensor (APS) concept, in which a small front-end circuit is located beneath each electrode. However, this approach imposes challenging constraints on the area of the in-pixel circuit, power consumption and noise. Here, we present an APS CMOS-probe technology for Simultaneous Neural recording that successfully addresses all these issues for whole-array read-outs at 25 kHz/channel from up to 1024 electrode-pixels. To assess the circuit performances, we realized in a 0.18 μm CMOS technology an implantable single-shaft probe with a regular array of 512 electrode-pixels with a pitch of 28 μm. Extensive bench tests showed an in-pixel gain of 45.4 ± 0.4 dB (low pass, F-3 dB = 4 kHz), an input referred noise of 7.5 ± 0.67 μVRMS (300 Hz to 7.5 kHz) and a power consumption <6 μW/pixel. In vivo acute recordings demonstrate that our SiNAPS CMOS-probe can sample full-band bioelectrical signals from each electrode, with the ability to resolve and discriminate activity from several packed neurons both at the spatial and temporal scale. These results pave the way to new generations of compact and scalable active single/multi-shaft brain recording systems.

A novel device for real-time measurement and manipulation of licking behavior in head-fixed mice.

The mouse has become an influential model system for investigating the mammalian nervous system. Technologies in mice enable recording and manipulation of neural circuits during tasks where they respond to sensory stimuli by licking for liquid rewards. Precise monitoring of licking during these tasks provides an accessible metric of sensory-motor processing, particularly when combined with simultaneous neural recordings. There are several challenges in designing and implementing lick detectors during head-fixed neurophysiological experiments in mice. First, mice are small, and licking behaviors are easily perturbed or biased by large sensors. Second, neural recordings during licking are highly sensitive to electrical contact artifacts. Third, submillisecond lick detection latencies are required to generate control signals that manipulate neural activity at appropriate time scales. Here we designed, characterized, and implemented a contactless dual-port device that precisely measures directional licking in head-fixed mice performing visual behavior. We first determined the optimal characteristics of our detector through design iteration and then quantified device performance under ideal conditions. We then tested performance during head-fixed mouse behavior with simultaneous neural recordings in vivo. We finally demonstrate our device's ability to detect directional licks and generate appropriate control signals in real time to rapidly suppress licking behavior via closed-loop inhibition of neural activity. Our dual-port detector is cost effective and easily replicable, and it should enable a wide variety of applications probing the neural circuit basis of sensory perception, motor action, and learning in normal and transgenic mouse models. NEW & NOTEWORTHY Mice readily learn tasks in which they respond to sensory cues by licking for liquid rewards; tasks that involve multiple licking responses allow study of neural circuits underlying decision making and sensory-motor integration. Here we design, characterize, and implement a novel dual-port lick detector that precisely measures directional licking in head-fixed mice performing visual behavior, enabling simultaneous neural recording and closed-loop manipulation of licking.

Online Artifact Cancelation in Same-Electrode Neural Stimulation and Recording Using a Combined Hardware and Software Architecture.

Advancing studies of neural network dynamics and developments of closed-loop neural interfaces requires the ability to simultaneously stimulate and record the neural cells. Recording adjacent to or at the stimulation site produces artifact signals that are orders of magnitude larger than the neural responses of interest. These signals often saturate the recording amplifier causing distortion or loss of short-latency evoked responses. This paper proposes a method to cancel the artifact in simultaneous neural recording and stimulation on the same electrode. By combining a novel hardware architecture with concurrent software processing, the design achieves neural signal recovery in a wide range of conditions. The proposed system uniquely demonstrates same-electrode stimulation and recording, with neural signal recovery in presence of stimulation artifact 100dB larger in magnitude than the underlying signals. The system is tested both in vitro and in vivo, during concurrent stimulation and recording on the same electrode. In vivo results in a rodent model are compared to recordings made by a commercial neural amplifier system connected in parallel.

An Implantable Wireless Neural Interface System for Simultaneous Recording and Stimulation of Peripheral Nerve with a Single Cuff Electrode.

Recently, implantable devices have become widely used in neural prostheses because they eliminate endemic drawbacks of conventional percutaneous neural interface systems. However, there are still several issues to be considered: low-efficiency wireless power transmission; wireless data communication over restricted operating distance with high power consumption; and limited functionality, working either as a neural signal recorder or as a stimulator. To overcome these issues, we suggest a novel implantable wireless neural interface system for simultaneous neural signal recording and stimulation using a single cuff electrode. By using widely available commercial off-the-shelf (COTS) components, an easily reconfigurable implantable wireless neural interface system was implemented into one compact module. The implantable device includes a wireless power consortium (WPC)-compliant power transmission circuit, a medical implant communication service (MICS)-band-based radio link and a cuff-electrode path controller for simultaneous neural signal recording and stimulation. During in vivo experiments with rabbit models, the implantable device successfully recorded and stimulated the tibial and peroneal nerves while communicating with the external device. The proposed system can be modified for various implantable medical devices, especially such as closed-loop control based implantable neural prostheses requiring neural signal recording and stimulation at the same time.

An artifact-suppressed stimulator for simultaneous neural recording and stimulation systems.

This paper proposes an artifact-suppressed stimulator with a referenced and tuned push-pull stimulation (RTPPS) scheme where a tri-polar electrode is employed. The stimulation pulses delivered to two working electrodes are complementary and thus one counteracts with the other to suppress the artifact at the recording site. The prototype stimulator chip is implemented in 0.18-μm CMOS process technology. In-vivo experiments are carried out with the chip to demonstrate the proposed artifact-suppression technique in a simultaneous neural recording and stimulation system. The results show that the stimulation artifact can be greatly reduced. The amplitude of the measured stimulation artifact is therefore constrained in a negligible level (10%-20%) compared to recorded neural spikes.

A Toolbox for Optophysiological Experiments in Freely Moving Rats.

Simultaneous recordings and manipulations of neural circuits that control the behavior of animals is one of the key techniques in modern neuroscience. Rapid advances in optogenetics have led to a variety of probes combining multichannel readout and optogenetic write in. Given the complexity of the brain, it comes as no surprise that the choice of the device is constrained by several factors such as the animal model, the structure and location of the brain area of interest, as well as the behavioral read out. Here we provide an overview of available devices for chronic simultaneous neural recordings and optogenetic manipulation in awake behaving rats. We focus on two fixed arrays and two moveable drives. For both options, we present data from one custom-made (in house) and one commercially available device. Here we provide evidence that simultaneous neural recordings and optogenetic manipulations are feasible with all four tested devices. Further we give detailed information about the recording quality, and also contrast the different features of the probes. As we provide detailed information about equipment and building procedures for combined chronic multichannel readout and optogenetic control with maximum performance at minimized costs, this overview might help especially researchers who want to enter the field of in vivo optophysiology.

Localization of Metal Electrodes in the Intact Rat Brain Using Registration of 3D Microcomputed Tomography Images to a Magnetic Resonance Histology Atlas.

Simultaneous neural recordings taken from multiple areas of the rodent brain are garnering growing interest because of the insight they can provide about spatially distributed neural circuitry. The promise of such recordings has inspired great progress in methods for surgically implanting large numbers of metal electrodes into intact rodent brains. However, methods for localizing the precise location of these electrodes have remained severely lacking. Traditional histological techniques that require slicing and staining of physical brain tissue are cumbersome and become increasingly impractical as the number of implanted electrodes increases. Here we solve these problems by describing a method that registers 3D computed tomography (CT) images of intact rat brains implanted with metal electrode bundles to a magnetic resonance imaging histology (MRH) atlas. Our method allows accurate visualization of each electrode bundle’s trajectory and location without removing the electrodes from the brain or surgically implanting external markers. In addition, unlike physical brain slices, once the 3D images of the electrode bundles and the MRH atlas are registered, it is possible to verify electrode placements from many angles by “reslicing” the images along different planes of view. Furthermore, our method can be fully automated and easily scaled to applications with large numbers of specimens. Our digital imaging approach to efficiently localizing metal electrodes offers a substantial addition to currently available methods, which, in turn, may help accelerate the rate at which insights are gleaned from rodent network neuroscience.

A wireless implantable switched-capacitor based optogenetic stimulating system.

This paper presents a power-efficient implantable optogenetic interface using a wireless switched-capacitor based stimulating (SCS) system. The SCS efficiently charges storage capacitors directly from an inductive link and periodically discharges them into an array of micro-LEDs, providing high instantaneous power without affecting wireless link and system supply voltage. A custom-designed computer interface in LabVIEW environment wirelessly controls stimulation parameters through the inductive link, and an optrode array enables simultaneous neural recording along with optical stimulation. The 4-channel SCS system prototype has been implemented in a 0.35-μm CMOS process and combined with the optrode array. In vivo experiments involving light-induced local field potentials verified the efficacy of the SCS system. An implantable version of the SCS system with flexible hermetic sealing is under development for chronic experiments.

Simultaneous Neural and Movement Recording in Large-Scale Immersive Virtual Environments

Virtual reality (VR) allows precise control and manipulation of rich, dynamic stimuli that, when coupled with on-line motion capture and neural monitoring, can provide a powerful means both of understanding brain behavioral relations in the high dimensional world and of assessing and treating a variety of neural disorders. Here we present a system that combines state-of-the-art, fully immersive, 3D, multi-modal VR with temporally aligned electroencephalographic (EEG) recordings. The VR system is dynamic and interactive across visual, auditory, and haptic interactions, providing sight, sound, touch, and force. Crucially, it does so with simultaneous EEG recordings while subjects actively move about a 20 × 20 ft² space. The overall end-to-end latency between real movement and its simulated movement in the VR is approximately 40 ms. Spatial precision of the various devices is on the order of millimeters. The temporal alignment with the neural recordings is accurate to within approximately 1 ms. This powerful combination of systems opens up a new window into brain-behavioral relations and a new means of assessment and rehabilitation of individuals with motor and other disorders.