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The Analyst Feb 2020Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes (CFMEs) is a versatile electrochemical technique to probe neurochemical dynamics in vivo. Progress in... (Review)
Review
Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes (CFMEs) is a versatile electrochemical technique to probe neurochemical dynamics in vivo. Progress in FSCV methodology continues to address analytical challenges arising from biological needs to measure low concentrations of neurotransmitters at specific sites. This review summarizes recent advances in FSCV method development in three areas: (1) waveform optimization, (2) electrode development, and (3) data analysis. First, FSCV waveform parameters such as holding potential, switching potential, and scan rate have been optimized to monitor new neurochemicals. The new waveform shapes introduce better selectivity toward specific molecules such as serotonin, histamine, hydrogen peroxide, octopamine, adenosine, guanosine, and neuropeptides. Second, CFMEs have been modified with nanomaterials such as carbon nanotubes or replaced with conducting polymers to enhance sensitivity, selectivity, and antifouling properties. Different geometries can be obtained by 3D-printing, manufacturing arrays, or fabricating carbon nanopipettes. Third, data analysis is important to sort through the thousands of CVs obtained. Recent developments in data analysis include preprocessing by digital filtering, principal components analysis for distinguishing analytes, and developing automated algorithms to detect peaks. Future challenges include multisite measurements, machine learning, and integration with other techniques. Advances in FSCV will accelerate research in neurochemistry to answer new biological questions about dynamics of signaling in the brain.
Topics: Data Analysis; Electrochemistry; Microelectrodes; Time Factors
PubMed: 31922162
DOI: 10.1039/c9an01925a -
The Journal of Neuroscience : the... Feb 2022Omnipause neurons (OPNs) in the nucleus raphe interpositus have tonic activity while the eyes are stationary ("fixation") but stop firing immediately before and during...
Omnipause neurons (OPNs) in the nucleus raphe interpositus have tonic activity while the eyes are stationary ("fixation") but stop firing immediately before and during saccades. To locate the source of suppression, we analyzed synaptic inputs from the rostral and caudal superior colliculi (SCs) to OPNs by using intracellular recording and staining, and investigated pathways transmitting the inputs in anesthetized cats of both sexes. Electrophysiologically or morphologically identified OPNs received monosynaptic excitation from the rostral SCs with contralateral dominance, and received disynaptic inhibition from the caudal SCs with ipsilateral dominance. Cutting the tectoreticular tract transversely between the contralateral OPN and inhibitory burst neuron (IBN) regions eliminated inhibition from the caudal SCs, but not excitation from the rostral SCs in OPNs. In contrast, a midline section between IBN regions eliminated disynaptic inhibition in OPNs from the caudal SCs but did not affect the monosynaptic excitation from the rostral SCs. Stimulation of the contralateral IBN region evoked monosynaptic inhibition in OPNs, which was facilitated by preconditioning SC stimulation. Three-dimensional reconstruction of HRP-stained cells revealed that individual OPNs have axons that terminate in the opposite IBN area, while individual IBNs have axon collaterals to the opposite OPN area. These results show that there are differences in the neural circuit from the rostral and caudal SCs to the brainstem premotor circuitry and that IBNs suppress OPNs immediately before and during saccades. Thus, the IBNs, which are activated by caudal SC saccade neurons, shut down OPN firing and help to trigger saccades and suppress ("latch") OPN activity during saccades. Saccades are the fastest eye movements to redirect gaze to an object of interest and bring its image on the fovea for fixation. Burst neurons (BNs) and omnipause neurons (OPNs) which behave reciprocally in the brainstem, are important for saccade generation and fixation. This study investigated unsolved important questions about where these neurons receive command signals and how they interact for initiating saccades from visual fixation. The results show that the rostral superior colliculi (SCs) excite OPNs monosynaptically for fixation, whereas the caudal SCs monosynaptically excite inhibitory BNs, which then directly inhibit OPNs for the initiation of saccades. This inhibition from the caudal SCs may account for the omnipause behavior of OPNs for initiation and maintenance of saccades in all directions.
Topics: Animals; Brain Stem; Cats; Female; Fixation, Ocular; Inhibitory Postsynaptic Potentials; Male; Microelectrodes; Nerve Net; Saccades; Superior Colliculi; Synaptic Potentials
PubMed: 34880121
DOI: 10.1523/JNEUROSCI.1731-21.2021 -
Neurobiology of Disease Aug 2022Deep brain stimulation (DBS) is commonly and safely performed for selective Parkinson's disease patients. Many centers perform DBS lead positioning exclusively under...
BACKGROUND
Deep brain stimulation (DBS) is commonly and safely performed for selective Parkinson's disease patients. Many centers perform DBS lead positioning exclusively under local anesthesia, to optimize brain microelectrode recordings (MER) and testing of stimulation-related therapeutic and side effects. These measures enable physiological identification of the DBS borders and subdomains based on electrophysiological properties like firing rates and patterns, intra-operative evaluation of therapeutic window, and improvement of lead placement accuracy. Nevertheless, due to the challenges of awake surgery, some centers use sedation or general anesthesia, despite the distortion of discharge properties and interference with clinical testing, resulting in potential impact on surgical outcomes. Thus, there is a need for a novel anesthesia regimen that enables sedation without compromising intra-operative monitoring.
OBJECTIVE
This open-label study investigates the use of low-dose ketamine for conscious sedation during microelectrode recordings and lead positioning in subthalamic nucleus (STN) DBS for Parkinson's disease patients.
METHODS
Three anesthetic regimens were retrospectively compared in 38 surgeries (74 MER trajectories, 5962 recording sites) across three DBS centers: 1) Interleaved propofol-ketamine (PK), 2) Interleaved propofol-awake (PA), and 3) Fully awake (AA).
RESULTS
All anesthesia regimens achieved satisfactory MER. Detection of STN borders and subdomains by expert electrophysiologist was similar between the groups. Electrophysiological signature of the STN under ketamine was not inferior to either control group. All patients completed stimulation testing.
CONCLUSIONS
This study supports a low-dose ketamine anesthesia regimen for DBS which allows microelectrode recordings and stimulation testing that are not inferior to those conducted under awake and propofol-awake regimens and may optimize patient experience. A prospective double-blind study that would also compare patients' satisfaction level and clinical outcome should be performed to confirm these findings.
Topics: Anesthesia, General; Brain Neoplasms; Deep Brain Stimulation; Humans; Ketamine; Microelectrodes; Parkinson Disease; Propofol; Prospective Studies; Retrospective Studies; Wakefulness
PubMed: 35550159
DOI: 10.1016/j.nbd.2022.105747 -
Brain Communications 2020With their 'all-or-none' action potential responses, single neurons (or units) are accepted as the basic computational unit of the brain. There is extensive animal... (Review)
Review
With their 'all-or-none' action potential responses, single neurons (or units) are accepted as the basic computational unit of the brain. There is extensive animal literature to support the mechanistic importance of studying neuronal firing as a way to understand neuronal microcircuits and brain function. Although most studies have emphasized physiology, there is increasing recognition that studying single units provides novel insight into system-level mechanisms of disease. Microelectrode recordings are becoming more common in humans, paralleling the increasing use of intracranial electroencephalography recordings in the context of presurgical evaluation in focal epilepsy. In addition to single-unit data, microelectrode recordings also record local field potentials and high-frequency oscillations, some of which may be different to that recorded by clinical macroelectrodes. However, microelectrodes are being used almost exclusively in research contexts and there are currently no indications for incorporating microelectrode recordings into routine clinical care. In this review, we summarize the lessons learnt from 65 years of microelectrode recordings in human epilepsy patients. We cover the electrode constructs that can be utilized, principles of how to record and process microelectrode data and insights into ictal dynamics, interictal dynamics and cognition. We end with a critique on the possibilities of incorporating single-unit recordings into clinical care, with a focus on potential clinical indications, each with their specific evidence base and challenges.
PubMed: 32954332
DOI: 10.1093/braincomms/fcaa082 -
Toxicological Sciences : An Official... Jan 2021Seizure liability remains a significant cause of attrition in drug discovery and development, leading to loss of competitiveness, delays, and increased costs. Current...
Seizure liability remains a significant cause of attrition in drug discovery and development, leading to loss of competitiveness, delays, and increased costs. Current detection methods rely on observations made in in vivo studies intended to support clinical trials, such as tremors or other abnormal movements. These signs could be missed or misinterpreted; thus, definitive confirmation of drug-induced seizure requires a follow-up electroencephalogram study. There has been progress in in vivo detection of seizure using automated video systems that record and analyze animal movements. Nonetheless, it would be preferable to have earlier prediction of seizurogenic risk that could be used to eliminate liabilities early in discovery while there are options for medicinal chemists making potential new drugs. Attrition due to cardiac adverse events has benefited from routine early screening; could we reduce attrition due to seizure using a similar approach? Specifically, microelectrode arrays could be used to detect potential seizurogenic signals in stem-cell-derived neurons. In addition, there is clear evidence implicating neuronal voltage-gated and ligand-gated ion channels, GPCRs and transporters in seizure. Interactions with surrounding glial cells during states of stress or inflammation can also modulate ion channel function in neurons, adding to the challenge of seizure prediction. It is timely to evaluate the opportunity to develop an in vitro assessment of seizure linked to a panel of ion channel assays that predict seizure, with the aim of influencing structure-activity relationship at the design stage and eliminating compounds predicted to be associated with pro-seizurogenic state.
Topics: Animals; Cells, Cultured; Electroencephalography; Humans; Microelectrodes; Neurons; Seizures
PubMed: 33165543
DOI: 10.1093/toxsci/kfaa167 -
Clinical Neurophysiology : Official... Dec 2023To assess transcranial sonography (TCS) as stand-alone tool and in combination with microelectrode recordings (MER) as a method for the postoperative localization of...
OBJECTIVE
To assess transcranial sonography (TCS) as stand-alone tool and in combination with microelectrode recordings (MER) as a method for the postoperative localization of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN).
METHODS
Individual dorsal and ventral boundaries of STN (n = 12) were determined on intraoperative MER. Postoperatively, a standardized TCS protocol was applied to measure medio-lateral, anterior-posterior and rostro-caudal electrode position using visualized reference structures (midline, substantia nigra). TCS and combined TCS-MER data were validated using fusion-imaging and clinical outcome data.
RESULTS
Test-retest reliability of standard TCS measures of electrode position was excellent. Computed tomography and TCS measures of distance between distal electrode contact and midline agreed well (Pearson correlation; r = 0.86; p < 0.001). Comparing our "gold standard" of rostro-caudal electrode localization relative to STN boundaries, i.e. combining MRI-based stereotaxy and MER data, with the combination of TCS and MER data, the measures differed by 0.32 ± 0.87 (range, -1.35 to 1.25) mm. Combined TCS-MER data identified the clinically preferred electrode contacts for STN-DBS with high accuracy (Coheńs kappa, 0.86).
CONCLUSIONS
Combined TCS-MER data allow for exact localization of STN-DBS electrodes.
SIGNIFICANCE
Our method provides a new option for monitoring of STN-DBS electrode location and guidance of DBS programming in Parkinson's disease.
Topics: Humans; Parkinson Disease; Microelectrodes; Reproducibility of Results; Deep Brain Stimulation; Subthalamic Nucleus; Magnetic Resonance Imaging; Electrodes, Implanted
PubMed: 37972531
DOI: 10.1016/j.clinph.2023.11.001 -
Advanced Healthcare Materials Oct 2019Though neural interface systems (NISs) can provide a potential solution for mitigating the effects of limb loss and central nervous system damage, the microelectrode... (Review)
Review
Though neural interface systems (NISs) can provide a potential solution for mitigating the effects of limb loss and central nervous system damage, the microelectrode array (MEA) component of NISs remains a significant limiting factor to their widespread clinical applications. Several strategies can be applied to MEA designs to increase their biocompatibility. Herein, an overview of NISs and their applications is provided, along with a detailed discussion of strategies for alleviating the foreign body response (FBR) and abnormalities seen at the interface of MEAs and the brain tissue following MEA implantation. Various surface modifications, including natural/synthetic surface coatings, hydrogels, and topography alterations, have shown to be highly successful in improving neural cell adhesion, reducing gliosis, and increasing MEA longevity. Different MEA surface geometries, such as those seen in the Utah and Michigan arrays, can help alleviate the resultant FBR by reducing insertion damage, while providing new avenues for improving MEA recording performance and resolution. Increasing overall flexibility of MEAs as well as reducing their stiffness is also shown to reduce MEA induced micromotion along with FBR severity. By combining multiple different properties into a single MEA, the severity and duration of an FBR postimplantation can be reduced substantially.
Topics: Animals; Biocompatible Materials; Blood-Brain Barrier; Brain; Brain-Computer Interfaces; Drug Delivery Systems; Electrodes, Implanted; Extracellular Matrix; Foreign-Body Reaction; Humans; Microelectrodes; Motion; Neuroglia; Neurons; Polymers; Rats; Surface Properties
PubMed: 31464094
DOI: 10.1002/adhm.201900558 -
Advanced Science (Weinheim,... Nov 2023In situ physiological signals of in vitro neural disease models are essential for studying pathogenesis and drug screening. Currently, an increasing number of in vitro... (Review)
Review
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.
Topics: Humans; Induced Pluripotent Stem Cells; Microelectrodes; Neurons; Neural Stem Cells; Nervous System Diseases
PubMed: 37863819
DOI: 10.1002/advs.202301828 -
Scientific Reports Jul 2021We developed a method to non-invasively detect synaptic relationships among neurons from in vitro networks. Our method uses microelectrode arrays on which neurons are...
We developed a method to non-invasively detect synaptic relationships among neurons from in vitro networks. Our method uses microelectrode arrays on which neurons are cultured and from which propagation of extracellular action potentials (eAPs) in single axons are recorded at multiple electrodes. Detecting eAP propagation bypasses ambiguity introduced by spike sorting. Our methods identify short latency spiking relationships between neurons with properties expected of synaptically coupled neurons, namely they were recapitulated by direct stimulation and were sensitive to changing the number of active synaptic sites. Our methods enabled us to assemble a functional subset of neuronal connectivity in our cultures.
Topics: Action Potentials; Algorithms; Animals; Animals, Newborn; Cells, Cultured; Electrophysiology; Extracellular Space; Male; Mice; Mice, Inbred C57BL; Microelectrodes; Neurons; Synapses; Synaptic Potentials
PubMed: 34282275
DOI: 10.1038/s41598-021-94282-6 -
Cureus Aug 2022Parkinson's disease (PD) is a neurological disorder in which nigrostriatal pathways involving the basal ganglia experience a decrease in neural activity regarding... (Review)
Review
Parkinson's disease (PD) is a neurological disorder in which nigrostriatal pathways involving the basal ganglia experience a decrease in neural activity regarding dopaminergic neurons. PD symptoms, such as muscle stiffness and involuntary tremors, have an adverse impact on the daily lives of those affected. Current medical treatments seek to decrease the severity of these symptoms. Deep brain stimulation (DBS) has become the preferred safe, and reliable treatment approach. DBS involves implanting microelectrodes into subcortical areas that produce electrical impulses directly to high populations of dopaminergic neurons. The most common targets are the subthalamic nucleus (STN), and the basal ganglia's globus pallidus pars interna (GPi). Research studies suggest that DBS of the STN may cause a significant reduction in the daily dose of L-DOPA compared to DBS of the GPi. DBS of the STN has suggested that there may be sweet spots within the STN that provide hyper-direct cortical connectivity pathways to the primary motor cortex (M1), supplementary motor area (SMA), and prefrontal cortex (PFC). In addition, the pedunculopontine nucleus (PPN) may be a new target for DBS that helps treat locomotion problems associated with gait and posture. Both microelectrode recording (MER) and magnetic resonance imaging (MRI) are used to ensure electrode placement accuracy. Using MER, stimulation of the STN at high frequencies (140<) decreased oscillatory neuronal firing by 67%. This paper investigates methods of intraoperative neuromonitoring during DBS as a form of PD treatment.
PubMed: 36110462
DOI: 10.7759/cureus.27887