Electrical Recordings Research Articles

Multifunctional Neural Probes Enable Bidirectional Electrical, Optical, and Chemical Recording and Stimulation In Vivo.

Recording and modulation of neuronal activity enables the study of brain function in health and disease. While translational neuroscience relies on electrical recording and modulation techniques, mechanistic studies in rodent models leverage genetic precision of optical methods, such as optogenetics and fluorescent indicator imaging. In addition to electrical signal transduction, neurons produce and receive diverse chemical signals which motivate tools to probe and modulate neurochemistry. Although the past decade has delivered a wealth of technologies for electrophysiology, optogenetics, chemical sensing, and optical recording, combining these modalities within a single platform remains challenging. This work leverages materials selection and convergence fiber drawing to permit neural recording, electrical stimulation, optogenetics, fiber photometry, drug and gene delivery, and voltammetric recording of neurotransmitters within individual fibers. Composed of polymers and non-magnetic carbon-based conductors, these fibers are compatible with magnetic resonance imaging, enabling concurrent stimulation and whole-brain monitoring. Their utility is demonstrated in studies of the mesolimbic reward pathway by interfacing with the ventral tegmental area and nucleus accumbens in mice and characterizing the neurophysiological effects of a stimulant drug. This study highlights the potential of these fibers to probe electrical, optical, and chemical signaling across multiple brain regions in both mechanistic and translational studies.

Activation of hypoactive parvalbumin-positive fast-spiking interneurons restores dentate inhibition to reduce electrographic seizures in the mouse intrahippocampal kainate model of temporal lobe epilepsy

Parvalbumin-positive (PV+) GABAergic interneurons in the dentate gyrus provide powerful perisomatic inhibition of dentate granule cells (DGCs) to prevent overexcitation and maintain the stability of dentate gyrus circuits. Most dentate PV+ interneurons survive status epilepticus, but surviving PV+ interneuron mediated inhibition is compromised in the dentate gyrus shortly after status epilepticus, contributing to epileptogenesis in temporal lobe epilepsy. It is uncertain whether the impaired activity of dentate PV+ interneurons recovers at later times or if it continues for months following status epilepticus. The development of compensatory modifications related to PV+ interneuron circuits in the months following status epilepticus is unknown, although reduced dentate GABAergic inhibition persists long after status epilepticus. We employed whole-cell patch-clamp recordings from dentate PV+ interneurons and DGCs in slices from male and female sham controls and intrahippocampal kainate (IHK) treated mice that developed spontaneous seizures months after status epilepticus to study epilepsy-associated changes in dentate PV+ interneuron circuits. Electrical recordings showed that: 1) Action potential firing rates of dentate PV+ interneurons were reduced in IHK treated mice up to four months after status epilepticus; 2) spontaneous inhibitory postsynaptic currents (sIPSCs) in DGCs exhibited reduced frequency but increased amplitude in IHK treated mice; and 3) the amplitude of IPSCs in DGCs evoked by optogenetic activation of dentate PV+ cells was upregulated without changes in short-term plasticity. Video-EEG recordings revealed that IHK treated mice showed spontaneous electrographic seizures in the dentate gyrus and that chemogenetic activation of PV+ interneurons abolished electrographic seizures. Our results suggest not only that the compensatory changes in PV+ interneuron circuits develop after IHK treatment, but also that increased PV+ interneuron mediated inhibition in the dentate gyrus may compensate for cell loss and reduced intrinsic excitability of dentate PV+ interneurons to stop seizures in temporal lobe epilepsy.

First-in-human microelectrode recordings from the vagus nerve during clinical vagus nerve stimulation.

Vagus nerve stimulation (VNS) is an effective treatment for people with drug-resistant epilepsy. However, its mechanisms of action are poorly understood, including which nerve fibers are activated in humans during VNS in typical clinical settings and which are required for clinical efficacy. In particular, there have been no intraneural recordings of vagus nerve fiber activation in awake humans undergoing chronic VNS. In this study, for the first time, we report recordings from the vagus nerve in this setting. The recordings were performed using a sterile tungsten microelectrode inserted percutaneously into the cervical vagus nerve under ultrasound guidance. The clinical VNS systems were used to deliver stimulation while activity in the vagus nerve was recorded. In addition to activating myelinated axons at low currents, we provide evidence that VNS can also activate unmyelinated C fibers in the vagus nerve at currents <1 mA. These results add to our understanding of how VNS exerts its beneficial effects in drug-resistant epilepsy. Here we describe for the first time, electrical recordings from the vagus nerve in awake drug-resistant epilepsy patients with an implanted vagus nerve stimulation (VNS) device. We found that the VNS device was able to activate both myelinated and unmyelinated fibers within the vagus nerve, whichcontributes to our understanding of how VNS works in the context of drug-resistant epilepsy.

Heterozygous KCNJ10 Variants Affecting Kir4.1 Channel Cause Paroxysmal Kinesigenic Dyskinesia.

More than 60% of paroxysmal kinesigenic dyskinesia (PKD) cases are of uncertain variants. The aim was to elucidate novel genetic contribution to PKD. A total of 476 probands with uncertain genetic causes were enrolled for whole-exome sequencing. A method of case-control analysis was applied to identify the candidate genes. Whole-cell patch-clamp recording was applied to verify the electrophysiological impact of the identified variants. A mouse model with cerebellar heterozygous knockout of the candidate gene was developed via adeno-associated virus injection, and dystonia-like phenotype inducement and rotarod tests were performed. In vivo multiunit electrical recording was applied to investigate the change in neural excitability in knockout mice. Heterozygous variants of potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) clustered in PKD patients were compared with those in the control groups. Fifteen variants were detected in 16 of 522 probands (frequency = 3.07%). Patients with KCNJ10 variants tended to have a milder manifestation compared to those with PRRT2 (proline-rich transmembrane protein 2) variants. KCNJ10 variants partially altered the transmembrane location of inwardly rectifying potassium channel 4.1 (Kir4.1). The Kcnj10 expression is consistent with the natural course of PKD. Variants resulted in different degrees of reduction in cell Kir4.1 currents, and mice with heterozygous conditional knockout of Kcnj10 in the cerebellum presented dystonic posture, together with poor motor coordination and motor learning ability in rotarod tests. The firing rate of deep cerebellar nuclei was significantly elevated in Kcnj10-cKO mice. We identified heterozygous variants of KCNJ10 in PKD. Impaired function of Kir4.1 might lead to abnormal neuronal excitability, which attributed to PKD. © 2024 International Parkinson and Movement Disorder Society.

Flexible electronic-photonic 3D integration from ultrathin polymer chiplets

Integrating flexible electronics and photonics can create revolutionary technologies, but combining these components on a single polymer device has been difficult, particularly for high-volume manufacturing. Here, we present a robust chiplet-level heterogeneous integration of polymer-based circuits (CHIP), where ultrathin polymer electronic and optoelectronic chiplets are vertically bonded at room temperature and shaped into application-specific forms with monolithic Input/Output (I/O). This process was used to develop a flexible 3D integrated optrode with high-density microelectrodes for electrical recording, micro light-emitting diodes (μLEDs) for optogenetic stimulation, temperature sensors for bio-safe operations, and shielding designs to prevent optoelectronic artifacts. CHIP enables simple, high-yield, and scalable 3D integration, double-sided area utilization, and miniaturization of connection I/O. Systematic characterization demonstrated the scheme’s success and also identified frequency-dependent origins of optoelectronic artifacts. We envision CHIP being applied to numerous polymer-based devices for a wide range of applications.

A 1024-Channel Simultaneous Electrophysiological and Electrochemical Neural Recording System with In-Pixel Digitization and Crosstalk Compensation.

Simultaneous electrophysiological and chemical recording allows for multi-modal neural instrumentation and provides insights into chemical synapses and ion channels across the cell membrane. However, intermodal interference can hinder highly synchronized recording in large-scale systems with high temporal and spatial resolution. In this work, we propose a 1024-channel lab-on-CMOS system for dual-modal neural recording with in-pixel digitization and interference suppression. A foreground calibration scheme with tunable capacitance is implemented in-pixel to compensate for the crosstalk between electrical and chemical recording. Active pixels for both electrical and chemical modalities are designed based on a pulse width modulation (PWM) analog-to-digital conversion scheme. CMOS-compatible post-processing is implemented to realize in-pixel electrodes and chemical sensing membranes. The prototype, implemented in a 180nm CMOS technology, occupies a total area of 33mm2 with 1024 pixels, and each unit pixel includes one electrical recording site and two chemical recording sites, with dimensions of 150μm×130 μm. The total system power consumption is 19.68mW at a frame rate of 9k and 3k for electrical and chemical imaging respectively. The in-vitro experiment demonstrated the concurrent high density electrophysilogical and electrochemical recording with sub millisecond temporal resolution.

An Opto-electrophysiology Neural Probe with Photoelectric Artifact-Free for Advanced Single-Neuron Analysis.

Opto-electrophysiology neural probes targeting single-cell levels offer an important avenue for elucidating the intrinsic mechanisms of the nervous system using different physical quantities, representing a significant future direction for brain-computer interface (BCI) devices. However, the highly integrated structure poses significant challenges to fabrication processes and the presence of photoelectric artifacts complicates the extraction and analysis of target signals. Here, we propose a highly miniaturized and integrated opto-electrophysiology neural probe for electrical recording and optical stimulation at the single-cell/subcellular level. The design of a total internal reflection layer addresses the photoelectric artifacts that are more pronounced in single-cell devices compared to conventional implantable BCI devices. Finite element simulations and electrical signal tests demonstrate that the opto-electrophysiology neural probe eliminates the photoelectric artifacts in the time domain, which represents a significant breakthrough for optoelectrical integrated BCI devices. Our proposed opto-electrophysiology neural probe holds substantial potential for promoting the development of in vivo BCI devices and developing advanced therapeutic strategies for neurological disorders.

Gut epithelial electrical cues drive differential localization of enterobacteria.

Salmonella translocate to the gut epithelium via microfold cells lining the follicle-associated epithelium (FAE). How Salmonella localize to the FAE is not well characterized. Here we use live imaging and competitive assays between wild-type and chemotaxis-deficient mutants to show that Salmonella enterica serotype Typhimurium (S. Typhimurium) localize to the FAE independently of chemotaxis in an ex vivo mouse caecum infection model. Electrical recordings revealed polarized FAE with sustained outward current and small transepithelial potential, while the surrounding villus is depolarized with inward current and large transepithelial potential. The distinct electrical potentials attracted S. Typhimurium to the FAE while Escherichia coli (E. coli) localized to the villi, through a process called galvanotaxis. Chloride flux involving the cystic fibrosis transmembrane conductance regulator (CFTR) generated the ionic currents around the FAE. Pharmacological inhibition of CFTR decreased S. Typhimurium FAE localization but increased E. coli recruitment. Altogether, our findings demonstrate that bioelectric cues contribute to S. Typhimurium targeting of specific gut epithelial locations, with potential implications for other enteric bacterial infections.

Magnetically coupled percutaneous connector for chronic electrical peripheral nerve stimulation and recording in awake rats.

Here we aimed to develop and validate a chronic magnetic percutaneous connector designed for placement on the dorsal-lumbar aspect of the spine of awake, freely moving rats. A pedestal and external connector was developed, bench tested to assess for continuity, durability and disconnection forces, and validated in awake rats chronically implanted with an abdominal vagus nerve electrode array. The implanted pedestal and external connector were designed with custom PCBs, spring-loaded pins, magnets and biocompatible 3D printed housing. The magnetic coupling mechanism allowed disconnection with minimal force, was highly reliable in maintaining electrical connection in awake rats and allowed recording of electrically evoked compound action potentials after chronic implantation. In conclusion, this percutaneous connector is a useful research tool for peripheral nerve stimulation studies. The connector described will allow investigation into the safety and efficacy of emerging neuromodulation therapies for the treatment of disease.

Physical Vapor Deposition of Indium-Doped GeTe: Analyzing the Evaporation Process and Kinetics

Chalcogenide glasses have broad applications in the mid-infrared optoelectronics field and as phase-change materials (PCMs) due to their unique properties. Chalcogenide glasses can have crystalline and amorphous phases, making them suitable as PCMs for reversible optical or electrical recording. This study provides an in-depth analysis of the evaporation kinetics of indium-doped chalcogenides, GeTe4 and GeTe5, using the physical vapor deposition technique on glass substrates. Our approach involved a detailed examination of the evaporation process under controlled temperature conditions, allowing precise measurement of rate changes and energy dynamics. This study revealed a significant and exponential increase in the evaporation rate of GeTe4 and GeTe5 with the introduction of indium, which was particularly noticeable at higher temperatures. This increase in evaporation rate with indium doping suggests a more complex interplay of materials at the molecular level than previously understood. Furthermore, our findings indicate that the addition of indium affects the evaporation rate and elevates the energy requirements for the evaporation process, providing new insights into the thermal dynamics of these materials. This study’s outcomes contribute significantly to understanding deposition processes, paving the way for optimized manufacturing techniques that could lead to more efficient and higher-performing optoelectronic devices and memory storage solutions.

A widespread electrical brain network encodes anxiety in health and depressive states.

In rodents, anxiety is charactered by heightened vigilance during low-threat and uncertain situations. Though activity in the frontal cortex and limbic system are fundamental to supporting this internal state, the underlying network architecture that integrates activity across brain regions to encode anxiety across animals and paradigms remains unclear. Here, we utilize parallel electrical recordings in freely behaving mice, translational paradigms known to induce anxiety, and machine learning to discover a multi-region network that encodes the anxious brain-state. The network is composed of circuits widely implicated in anxiety behavior, it generalizes across many behavioral contexts that induce anxiety, and it fails to encode multiple behavioral contexts that do not. Strikingly, the activity of this network is also principally altered in two mouse models of depression. Thus, we establish a network-level process whereby the brain encodes anxiety in health and disease.

Fully flexible implantable neural probes for electrophysiology recording and controlled neurochemical modulation

Targeted delivery of neurochemicals and biomolecules for neuromodulation of brain activity is a powerful technique that, in addition to electrical recording and stimulation, enables a more thorough investigation of neural circuit dynamics. We have designed a novel, flexible, implantable neural probe capable of controlled, localized chemical stimulation and electrophysiology recording. The neural probe was implemented using planar micromachining processes on Parylene C, a mechanically flexible, biocompatible substrate. The probe shank features two large microelectrodes (chemical sites) for drug loading and sixteen small microelectrodes for electrophysiology recording to monitor neuronal response to drug release. To reduce the impedance while keeping the size of the microelectrodes small, poly(3,4-ethylenedioxythiophene) (PEDOT) was electrochemically coated on recording microelectrodes. In addition, PEDOT doped with mesoporous sulfonated silica nanoparticles (SNPs) was used on chemical sites to achieve controlled, electrically-actuated drug loading and releasing. Different neurotransmitters, including glutamate (Glu) and gamma-aminobutyric acid (GABA), were incorporated into the SNPs and electrically triggered to release repeatedly. An in vitro experiment was conducted to quantify the stimulated release profile by applying a sinusoidal voltage (0.5 V, 2 Hz). The flexible neural probe was implanted in the barrel cortex of the wild-type Sprague Dawley rats. As expected, due to their excitatory and inhibitory effects, Glu and GABA release caused a significant increase and decrease in neural activity, respectively, which was recorded by the recording microelectrodes. This novel flexible neural probe technology, combining on-demand chemical release and high-resolution electrophysiology recording, is an important addition to the neuroscience toolset used to dissect neural circuitry and investigate neural network connectivity.

Myo-optogenetics: optogenetic stimulation and electrical recording in skeletal muscles.

Complex movements involve highly coordinated control of local muscle elements. Highly controlled perturbations of motor outputs can reveal insights into the neural control of movements. Here we introduce an optogenetic method, compatible with electromyography (EMG) recordings, to perturb muscles in transgenic mice. By expressing channelrhodopsin in muscle fibers, we achieved noninvasive, focal activation of orofacial muscles, enabling detailed examination of the mechanical properties of optogenetically evoked jaw muscle contractions. We demonstrated simultaneous EMG recording and optical stimulation, revealing the electrophysiological characteristics of optogenetically triggered muscle activity. Additionally, we applied optogenetic activation of muscles in physiologically and behaviorally relevant settings, mapping precise muscle actions and perturbing active behaviors. Our findings highlight the potential of muscle optogenetics to precisely manipulate muscle activity, offering a powerful tool for probing neuromuscular control systems and advancing our understanding of motor control.

The P2X7 Hypothesis of Central Post-Stroke Pain.

The present study examined how P2X7 receptor knockout (KO) modulates central post-stroke pain (CPSP) induced by lesions of the ventrobasal complex (VBC) of the thalamus in behaviors, molecular levels, and electrical recording tests. Following the experimental procedure, the wild-type and P2X7 receptor KO mice were injected with 10 mU/0.2 μL type IV collagenase in the VBC of the thalamus to induce an animal model of stroke-like thalamic hemorrhage. Behavioral data showed that the CPSP group induced thermal and mechanical pain. The P2X7 receptor KO group showed reduced thermal and mechanical pain responses compared to the CPSP group. Molecular assessments revealed that the CPSP group had lower expression of NeuN and KCC2 and higher expression of GFAP, IBA1, and BDNF. The P2X7 KO group showed lower expression of GFAP, IBA1, and BDNF but nonsignificant differences in KCC2 expression than the CPSP group. The expression of NKCC1, GABAa receptor, and TrkB did not differ significantly between the control, CPSP, and P2X7 receptor KO groups. Muscimol, a GABAa agonist, application increased multiunit numbers for monitoring many neurons and [Cl-] outflux in the cytosol in the CPSP group, while P2X7 receptor KO reduced multiunit activity and increased [Cl-] influx compared to the CPSP group. P2X4 receptor expression was significantly decreased in the 100 kDa but not the 50 kDa site in the P2X7 receptor KO group. Altogether, the P2X7 hypothesis of CPSP was proposed, wherein P2X7 receptor KO altered the CPSP pain responses, numbers of astrocytes and microglia, CSD amplitude of the anterior cingulate cortex and the medial dorsal thalamus, BDNF expression, [Cl-] influx, and P2X4 expression in 100 kDa with P2X7 receptors. The present findings have implications for the clinical treatment of CPSP symptoms.

Fiber-based Probes for Electrophysiology, Photometry, Optical and Electrical Stimulation, Drug Delivery, and Fast-Scan Cyclic Voltammetry In Vivo.

Recording and modulation of neuronal activity enables the study of brain function in health and disease. While translational neuroscience relies on electrical recording and modulation techniques, mechanistic studies in rodent models leverage genetic precision of optical methods, such as optogenetics and imaging of fluorescent indicators. In addition to electrical signal transduction, neurons produce and receive diverse chemical signals which motivate tools to probe and modulate neurochemistry. Although the past decade has delivered a wealth of technologies for electrophysiology, optogenetics, chemical sensing, and optical recording, combining these modalities within a single platform remains challenging. This work leverages materials selection and convergence fiber drawing to permit neural recording, electrical stimulation, optogenetics, fiber photometry, drug and gene delivery, and voltammetric recording of neurotransmitters within individual fibers. Composed of polymers and non-magnetic carbon-based conductors, these fibers are compatible with magnetic resonance imaging, enabling concurrent stimulation and whole-brain monitoring. Their utility is demonstrated in studies of the mesolimbic reward pathway by simultaneously interfacing with the ventral tegmental area and nucleus accumbens in mice and characterizing the neurophysiological effects of a stimulant drug. This study highlights the potential of these fibers to probe electrical, optical, and chemical signaling across multiple brain regions in both mechanistic and translational studies.

Ethanol Solvation of Polymer Residues in Graphene Solution-Gated Field Effect Transistors.

The persistence of photoresist residues from microfabrication procedures causes significant obstacles in the technological advancement of graphene-based electronic devices. These residues induce undesired chemical doping effects, diminish carrier mobility, and deteriorate the signal-to-noise ratio, making them critical in certain contexts, including sensing and electrical recording applications. In graphene solution-gated field-effect transistors (gSGFETs), the presence of polymer contaminants makes it difficult to perform precise electrical measurements, introducing response variability and calibration challenges. Given the absence of viable short to midterm alternatives to polymer-intensive microfabrication techniques, a postpatterning treatment involving THF and ethanol solvents was evaluated, with ethanol being the most effective, environmentally sustainable, and safe method for residue removal. Employing a comprehensive analysis with XPS, AFM, and Raman spectroscopy, together with electrical characterization, we investigated the influence of residual polymers on graphene surface properties and transistor functionality. Ethanol treatment exhibited a pronounced enhancement in gSGFET performance, as evidenced by a shift in the charge neutrality point and reduced dispersion. This systematic cleaning methodology holds the potential to improve the reproducibility and precision in the manufacturing of graphene devices. Particularly, by using ethanol for residue removal, we align our methodology with the principles of green chemistry, minimizing environmental impact while advancing diverse graphene technology applications.

In vivo magnetic recording of single-neuron action potentials Abbreviated title: In vivo magnetic single-neuron action potentials.

Measuring fast neuronal signals is the domain of electrophysiology and magnetophysiology. While electrophysiology is easier to perform, magnetophysiology avoids tissue-based distortions and measures a signal with directional information. At the macroscale, magnetoencephalography (MEG) is established, and at the mesoscale, visually evoked magnetic fields have been reported. At the microscale however, while benefits of recording magnetic counterparts of electric spikes would be numerous, they are also highly challenging in vivo. Here, we combine magnetic and electric recordings of neuronal action potentials in anesthetized rats using miniaturized giant magneto-resistance (GMR) sensors. We reveal the magnetic signature of action potentials of well-isolated single units. The recorded magnetic signals showed a distinct waveform and considerable signal strength. This demonstration of in vivo magnetic action potentials opens a wide field of possibilities to profit from the combined power of magnetic and electric recordings and thus to significantly advance the understanding of neuronal circuits.

Improved filtering methods to suppress cardiovascular contamination in electrical impedance tomography recordings

Objective. Electrical impedance tomography (EIT) produces clinical useful visualization of the distribution of ventilation inside the lungs. The accuracy of EIT-derived parameters can be compromised by the cardiovascular signal. Removal of these artefacts is challenging due to spectral overlapping of the ventilatory and cardiovascular signal components and their time-varying frequencies. We designed and evaluated advanced filtering techniques and hypothesized that these would outperform traditional low-pass filters. Approach. Three filter techniques were developed and compared against traditional low-pass filtering: multiple digital notch filtering (MDN), empirical mode decomposition (EMD) and the maximal overlap discrete wavelet transform (MODWT). The performance of the filtering techniques was evaluated (1) in the time domain (2) in the frequency domain (3) by visual inspection. We evaluated the performance using simulated contaminated EIT data and data from 15 adult and neonatal intensive care unit patients. Main result. Each filter technique exhibited varying degrees of effectiveness and limitations. Quality measures in the time domain showed the best performance for MDN filtering. The signal to noise ratio was best for DLP, but at the cost of a high relative and removal error. MDN outbalanced the performance resulting in a good SNR with a low relative and removal error. MDN, EMD and MODWT performed similar in the frequency domain and were successful in removing the high frequency components of the data. Significance. Advanced filtering techniques have benefits compared to traditional filters but are not always better. MDN filtering outperformed EMD and MODWT regarding quality measures in the time domain. This study emphasizes the need for careful consideration when choosing a filtering approach, depending on the dataset and the clinical/research question.

Electrocardiographic approach strategies in patients with Parkinson disease treated with deep brain stimulation.

Deep brain stimulation (DBS) is an interdisciplinary and reversible therapy that uses high-frequency electrical stimulation to correct aberrant neural pathways in motor and cognitive neurological disorders. However, the high frequency of the waves used in DBS can interfere with electrical recording devices (e.g., electrocardiogram, electroencephalogram, cardiac monitor), creating artifacts that hinder their interpretation. The compatibility of DBS with these devices varies and depends on factors such as the underlying disease and the configuration of the neurostimulator. In emergencies where obtaining an electrocardiogram is crucial, the need for more consensus on reducing electrical artifacts in patients with DBS becomes a significant challenge. Various strategies have been proposed to attenuate the artifact generated by DBS, such as changing the DBS configuration from monopolar to bipolar, temporarily deactivating DBS during electrocardiographic recording, applying frequency filters both lower and higher than those used by DBS, and using non-standard leads. However, the inexperience of medical personnel, variability in DBS models, or the lack of a controller at the time of approach limit the application of these strategies. Current evidence on their reproducibility and efficacy is limited. Due to the growing elderly population and the rising utilization of DBS, it is imperative to create electrocardiographic methods that are easily accessible and reproducible for general physicians and emergency services.

Flexible and Stretchable Electrodes for In Vivo Electrophysiological and Electrochemical Monitoring†

Comprehensive SummaryIn vivo monitoring of bioelectrical and biochemical signals with implanted electrodes has received great interest over the past decades. However, this faces huge challenges because of the severe mechanical mismatch between conventional rigid electrodes and soft biological tissues. In recent years, the emergence of flexible and stretchable electrodes offers seamless and conformable biological‐electronic interfaces and has demonstrated significant advantages for in vivo electrochemical and electrophysiological monitoring. This review first summarizes the strategies for electrode fabrication from the point of substrate and conductive materials. Next, recent progress in electrode functionalization for improved performance is presented. Then, the advances of flexible and stretchable electrodes in exploring bioelectrical and biochemical signals are introduced. Finally, we present some challenges and perspectives ranging from electrode fabrication to application.Key ScientistsIn 2001, a seminal work by Kipke et al. first showed flexible polyimide‐based intracortical electrode arrays.[1] This electrode was further expanded to 252‐channel using microelectromechanical systems technology by Stieglitz et al. in 2009 and achieved large‐scale cortical recordings.[2] Later, Lieber et al. created mesh electronics that allow for seamless and minimally invasive three‐dimensional interpenetration with nerve tissues, opening up unique applications for flexible electronics.[3] Subsequently, Rogers et al. described bioresorbable electronics for transient electrical activity recordings in 2016.[4] And Frank et al. proposed polymer electrode arrays capable of resolving single neurons in 2019.[5] It wasn't until 2020 that a significant breakthrough in biochemical signals monitoring by Peng et al. demonstrated functionalized carbon nanotube fibre bundles for multiple disease biomarkers monitoring.[6] Later on, Mooney et al. established the first fully viscoelastic electrode arrays for neural recordings from the brain and heart in 2021.[7] Recently, Bao et al. presented tissue‐mimicking, stretchable neurotransmitter interfaces for monitoring the brain and gut.[8]