This letter discusses the recent study by Izzo et al., which explored intraoperative microelectrode recording (MER) during asleep deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson\'s disease. The study\'s integration of a systematic review positions its findings within the broader context of neurosurgical advances. Highlighting the practicality and patient comfort of the frameless technique under general anesthesia, it emphasizes the significance of MER in optimizing electrode placement, thereby potentially enhancing patient outcomes. The letter suggests future research directions, including randomized clinical trials, to assess the clinical benefits of this methodology further.

The use of microelectrode recording (MER) during deep brain stimulation (DBS) for Parkinson Disease is controversial. Furthermore, in asleep DBS anesthesia can impair the ability to record single-cell electric activity.The purpose of this study was to describe our surgical and anesthesiologic protocol for MER assessment during asleep subthalamic nucleus (STN) DBS and to put our findings in the context of a systematic review of the literature. Sixty-three STN electrodes were implanted in 32 patients under general anesthesia. A frameless technique using O-Arm scanning was adopted in all cases. Total intravenous anesthesia, monitored with bispectral index, was administered using a target controlled infusion of both propofol and remifentanil. A systematic review of the literature with metanalysis on MER in asleep vs awake STN DBS for Parkinson Disease was performed. In our series, MER could be reliably recorded in all cases, impacting profoundly on electrode positioning: the final position was located within 2 mm from the planned target only in 42.9% cases. Depth modification > 2 mm was necessary in 21 cases (33.3%), while in 15 cases (23.8%) a different track was used. At 1-year follow-up we observed a significant reduction in LEDD, UPDRS Part III score off-medications, and UPDRS Part III score on medications, as compared to baseline. The systematic review of the literature yielded 23 papers; adding the cases here reported, overall 1258 asleep DBS cases using MER are described. This technique was safe and effective: metanalysis showed similar, if not better, outcome of asleep vs awake patients operated using MER. MER are a useful and reliable tool during asleep STN DBS, leading to a fine tuning of electrode position in the majority of cases. Collaboration between neurosurgeon, neurophysiologist and neuroanesthesiologist is crucial, since slight modifications of sedation level can impact profoundly on MER reliability.

METHODS: Systematic review of the literature.
OBJECTIVE: In recent years, brain-computer interface (BCI) has emerged as a potential treatment for patients with spinal cord injury (SCI). This is the first systematic review of the literature on invasive closed-loop BCI technologies for the treatment of SCI in humans.
METHODS: A comprehensive search of PubMed MEDLINE, Web of Science, and Ovid EMBASE was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS: Of 8316 articles collected, 19 studies met all the inclusion criteria. Data from 21 patients were extracted from these studies. All patients sustained a cervical SCI and were treated using either a BCI with intracortical microelectrode arrays (n = 18, 85.7%) or electrocorticography (n = 3, 14.3%). To decode these neural signals, machine learning and statistical models were used: support vector machine in eight patients (38.1%), linear estimator in seven patients (33.3%), Hidden Markov Model in three patients (14.3%), and other in three patients (14.3%). As the outputs, ten patients (47.6%) underwent noninvasive functional electrical stimulation (FES) with a cuff; one (4.8%) had an invasive FES with percutaneous stimulation, and ten (47.6%) used an external device (neuroprosthesis or virtual avatar). Motor function was restored in all patients for each assigned task. Clinical outcome measures were heterogeneous across all studies.
CONCLUSIONS: Invasive techniques of BCI show promise for the treatment of SCI, but there is currently no technology that can restore complete functional autonomy in patients with SCI. The current techniques and outcomes of BCI vary greatly. Because invasive BCIs are still in the early stages of development, further clinical studies should be conducted to optimize the prognosis for patients with SCI.

In situ physiological signals of in vitro neural disease models are essential for studying pathogenesis and drug screening. Currently, an increasing number of in vitro neural disease models are established using human-induced pluripotent stem cell (hiPSC) derived neurons (hiPSC-DNs) to overcome interspecific gene expression differences. Microelectrode arrays (MEAs) can be readily interfaced with two-dimensional (2D), and more recently, three-dimensional (3D) neural stem cell-derived in vitro models of the human brain to monitor their physiological activity in real time. Therefore, MEAs are emerging and useful tools to model neurological disorders and disease in vitro using human iPSCs. This is enabling a real-time window into neuronal signaling at the network scale from patient derived. This paper provides a comprehensive review of MEA\'s role in analyzing neural disease models established by hiPSC-DNs. It covers the significance of MEA fabrication, surface structure and modification schemes for hiPSC-DNs culturing and signal detection. Additionally, this review discusses advances in the development and use of MEA technology to study in vitro neural disease models, including epilepsy, autism spectrum developmental disorder (ASD), and others established using hiPSC-DNs. The paper also highlights the application of MEAs combined with hiPSC-DNs in detecting in vitro neurotoxic substances. Finally, the future development and outlook of multifunctional and integrated devices for in vitro medical diagnostics and treatment are discussed.

Our brain is an intricate neuromodulatory network, and various neurochemicals, including neurotransmitters, neuromodulators, gases, ions, and energy metabolites, play important roles in regulating normal brain function. Abnormal release or imbalance of these substances will lead to various diseases such as Parkinson\'s and Alzheimer\'s diseases, therefore, in situ and real-time analysis of neurochemical interactions in pathophysiological conditions is beneficial to facilitate our understanding of brain function. Implantable electrochemical biosensors are capable of monitoring neurochemical signals in real time in extracellular fluid of specific brain regions because they can provide excellent temporal and spatial resolution. However, in vivo electrochemical biosensing analysis mainly faces the following challenges: First, foreign body reactions induced by microelectrode implantation, non-specific adsorption of proteins and redox products, and aggregation of glial cells, which will cause irreversible degradation of performance such as stability and sensitivity of the microsensor and eventually lead to signal loss; Second, various neurochemicals coexist in the complex brain environment, and electroactive substances with similar formal potentials interfere with each other. Therefore, it is a great challenge to design recognition molecules and tailor functional surfaces to develop in vivo electrochemical biosensors with high selectivity. Here, we take the above challenges as a starting point and detail the basic design principles for improving in vivo stability, selectivity and sensitivity of microsensors through some specific functionalized surface strategies as case studies. At the same time, we summarize surface modification strategies for in vivo electrochemical biosensing analysis of some important neurochemicals for researchers\' reference. In addition, we also focus on the electrochemical detection of low basal concentrations of neurochemicals in vivo via amperometric waveform techniques, as well as the stability and biocompatibility of reference electrodes during long-term sensing, and provide an outlook on the future direction of in vivo electrochemical neurosensing.

Rapid, high-sensitivity, and real-time characterization of microorganisms plays a significant role in several areas, including clinical diagnosis, human healthcare, early detection of outbreaks, and the protection of living beings. Integrating microbiology and electrical engineering promises the development of low-cost, miniaturized, autonomous, and high-sensitivity sensors to quantify and characterize bacterial strains at various concentrations. Electrochemical-based biosensors are receiving particular attention in microbiological applications among the different biosensing devices. Several approaches have been adopted to design and fabricate cutting-edge, miniaturized, and portable electrochemical biosensors to track and monitor bacterial cultures in real time. These techniques differ in their sensing interface circuits and microelectrode fabrication. The goals of this review are (1) to summarize the current state of CMOS sensing circuit designs in label-free electrochemical biosensors for bacteria monitoring and (2) to discuss the material and size of the electrodes used in electrochemical biosensors in microbiological applications. In this paper, we reviewed the latest and most advanced CMOS integrated interface circuits that have recently been used in electrochemical biosensors to identify and characterize bacteria species, such as impedance spectroscopy, capacitive, amperometry, and voltammetry, etc. In addition to the interface circuit design, other crucial factors, such as the material and scale of the electrodes, must be considered to increase the sensitivity of electrochemical biosensors. Surveying the literature in this field improves our knowledge about the impact of electrode designs and materials on sensing precision and will help future designers adapt, design, and fabricate appropriate electrode configurations based on their application. Thus, we summarized the conventional microelectrode designs and materials mainly employed in microbial sensors, including interdigitated electrodes (IDEs), microelectrode arrays (MEAs), paper, and carbon-based electrodes, etc.

Nowadays, micro-sized sensors have become a hot topic in electroanalysis. Because of their excellent analytical features, microelectrodes are well-accepted tools for clinical, pharmaceutical, food safety, and environmental applications. In this brief review, we highlight the state-of-art electrochemical non-enzymatic microsensors for quantitative detection of ascorbic acid (also known as vitamin C). Ascorbic acid is a naturally occurring water-soluble organic compound with antioxidant properties and its quantitative determination in biological fluids, foods, cosmetics, etc., using electrochemical microsensors is of wide interest. Various electrochemical techniques have been applied to detect ascorbic acid with extremely high sensitivity, selectivity, reproducibility, and reliability, and apply to in vivo measurements. This review paper aims to give readers a clear view of advances in areas of electrode modification, successful strategies for signal amplification, and miniaturization techniques used in the electroanalytical devices for ascorbic acid. In conclusion, current challenges related to the microelectrodes design, and future perspectives are outlined.

Neural probes, as an invasive physiological tool at the mesoscopic scale, can decipher the code of brain connections and communications from the cellular or even molecular level, and realize information fusion between the human body and external machines. In addition to traditional electrodes, two new types of neural probes have been developed in recent years: optoprobes based on optogenetics and magnetrodes that record neural magnetic signals. In this review, we give a comprehensive overview of these three kinds of neural probes. We firstly discuss the development of microelectrodes and strategies for their flexibility, which is mainly represented by the selection of flexible substrates and new electrode materials. Subsequently, the concept of optogenetics is introduced, followed by the review of several novel structures of optoprobes, which are divided into multifunctional optoprobes integrated with microfluidic channels, artifact-free optoprobes, three-dimensional drivable optoprobes, and flexible optoprobes. At last, we introduce the fundamental perspectives of magnetoresistive (MR) sensors and then review the research progress of magnetrodes based on it.

Deep brain stimulation is a common treatment for Parkinson\'s disease (PD). Despite strong efficacy in well-selected patients, complications can occur. Intraoperative micro-electrode recording (MER) can enhance efficacy by improving lead accuracy. However, there is controversy as to whether MER increases risk of hemorrhage.
To provide a comprehensive systematic review and meta-analysis reporting complication rates from deep brain stimulation in PD. We also interrogate the association between hemorrhage and MER.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were implemented while querying the Pubmed, Embase, and Cochrane databases. All included studies were randomized controlled trials and prospective case series with 5 or more patients. Primary outcomes included rates of overall revision, infection, lead malposition, surgical site and wound complications, hardware-related complications, and seizure. The secondary outcome was the relationship between number of MER tracks and hemorrhage rate.
262 articles with 21,261 patients were included in the analysis. Mean follow-up was 25.8 months (range 0-133). Complication rates were: revision 4.9%, infection 4.2%, lead malposition 3.3%, surgical site complications 2.8%, hemorrhage 2.4%, hardware-related complications 2.4%, and seizure 1.9%. While hemorrhage rate did not increase with single-track MER (odds ratio, 3.49; P = 0.29), there was a significant non-linear increase with each additional track.
Infection and lead malposition were the most common complications. Hemorrhage risk increases with more than one MER track. These results highlight the challenge of balancing surgical accuracy and perioperative risk.

Carbon is a popular electrode material for neurotransmitter detection due to its good electrochemical properties, high biocompatibility, and inert chemistry. Traditional carbon electrodes, such as carbon fibers, have smooth surfaces and fixed shapes. However, newer studies customize the shape and nanostructure the surface to enhance electrochemistry for different applications. In this review, we show how changing the structure of carbon electrodes with methods such as chemical vapor deposition (CVD), wet-etching, direct laser writing (DLW), and 3D printing leads to different electrochemical properties. The customized shapes include nanotips, complex 3D structures, porous structures, arrays, and flexible sensors with patterns. Nanostructuring enhances sensitivity and selectivity, depending on the carbon nanomaterial used. Carbon nanoparticle modifications enhance electron transfer kinetics and prevent fouling for neurochemicals that are easily polymerized. Porous electrodes trap analyte momentarily on the scale of an electrochemistry experiment, leading to thin layer electrochemical behavior that enhances secondary peaks from chemical reactions. Similar thin layer cell behavior is observed at cavity carbon nanopipette electrodes. Nanotip electrodes facilitate implantation closer to the synapse with reduced tissue damage. Carbon electrode arrays are used to measure from multiple neurotransmitter release sites simultaneously. Custom-shaped carbon electrodes are enabling new applications in neuroscience, such as distinguishing different catecholamines by secondary peaks, detection of vesicular release in single cells, and multi-region measurements in vivo.