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Microsystems & Nanoengineering 2024Targeted delivery of neurochemicals and biomolecules for neuromodulation of brain activity is a powerful technique that, in addition to electrical recording and...
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.
PubMed: 38947533
DOI: 10.1038/s41378-024-00685-6 -
International Journal of Cardiology.... Aug 2024It is currently unknown whether 3D-mapping and micro-electrodes add meaningful benefits in catheter ablation of Wolff-Parkinson-White (WPW) syndrome and challenging,...
BACKGROUND
It is currently unknown whether 3D-mapping and micro-electrodes add meaningful benefits in catheter ablation of Wolff-Parkinson-White (WPW) syndrome and challenging, e.g. -Hisian accessory pathways (APs).
OBJECTIVES
To compare the mapping resolution, acute success and complication rates in patients with WPW syndrome undergoing a first-time catheter ablation using only a contact force-sensing ablation catheter for mapping or a multi-electrode high-resolution mapping catheter.
METHODS
Fifty consecutive 3D-mapping procedures for WPW syndrome using a 3.5-mm ablation catheter (n = 27) or a multi-electrode high-resolution catheter (n = 23) were retrospectively analyzed regarding mapping resolution defined as first 5/10 msec isochronal activation area, number of RF applications to achieve AP block, occurence of AP automaticity during RF delivery, and acute success and complication rates.
RESULTS
Catheter ablation was successful in 48/50 patients with a median of 1 (IQR 1-2) RF applications. Compared to ablation catheter mapping, high-resolution mapping showed a significantly smaller isochronal activation area in the first 5/10 msec (1.25 ± 0.29 vs 0.15 ± 0.03 cm; < 0.001 and 3.41 ± 0.58 vs 0.55 ± 0.12 cm; < 0.0001) and significantly higher incidence of AP automaticity during RF delivery (0 vs 22 %; < 0.05). In -Hisian APs, micro-electrodes recorded distinct His electrograms and AP potentials without fusion and without AP bumping permitting safe and effective -Hisian AP ablation.
CONCLUSIONS
High-resolution mapping increases the mapping accuracy of the AP and its insertion site leading to a significantly higher incidence of AP automaticity during RF delivery. Micro-electrodes provide clinically relevant advantages in -hisian AP mapping improving efficacy and safety of -Hisian AP ablation.
PubMed: 38946712
DOI: 10.1016/j.ijcha.2024.101435 -
Clinical Neurophysiology : Official... Jun 2024We aimed to establish specific biomarkers of Parkinson's disease (PD) by comparing activity of more affected (MA) and less affected (LA) subthalamic nucleus (STN) of...
OBJECTIVE
We aimed to establish specific biomarkers of Parkinson's disease (PD) by comparing activity of more affected (MA) and less affected (LA) subthalamic nucleus (STN) of patients with prominent clinical asymmetry.
METHODS
We recorded single unit activity and local field potentials (LFP) of the STN during deep brain stimulation surgeries. Neuronal firing patterns and discharge rate, as well as oscillatory features of both single cells and LFP, were analyzed.
RESULTS
We observed notable differences in proportions of irregular-burst and pause-burst, but not tonic neurons, between the hemispheres. Oscillations of pause-burst neurons correlated significantly with the bradykinesia and rigidity scores of the corresponding hemibody. LFP derived from MA STN featured greater power in 12-15 Hz.
CONCLUSIONS
Our results provide evidence that the increased proportion of units with prolonged pauses may be associated with PD. We also speculate that some of them may gain rhythmicity in the alpha-beta range in relation to hypokinetic symptoms, long-term disease, or both.
SIGNIFICANCE
Our findings highlight the relation between specific oscillatory features of the STN, predominance of subthalamic pause-burst units and PD pathophysiology.
PubMed: 38943791
DOI: 10.1016/j.clinph.2024.06.003 -
BioImpacts : BI 2024A new analytical method based on the coupling of microextraction and microfluidics was developed and investigated for the pre-concentration, separation, and...
INTRODUCTION
A new analytical method based on the coupling of microextraction and microfluidics was developed and investigated for the pre-concentration, separation, and electrochemical detection of fenitrothion (FT) and parathion (PA) at the sub-ppm concentrations.
METHODS
In the first step, the microchip capillary electrophoresis technique was used to serve as a separation and detection system. Analytes were injected in the 40 mm long microchannel with 10 mm sidearms. Then, they were separated by applying a direct electrical field (+1800 V) between the buffer and detection reservoirs. 2-(n-morpholino)ethanesulfonic acid (MES) buffer (20 mM, pH 5) was used as a running buffer. The electrochemical detection was performed using three Pt microelectrodes with the width of working, counter, and reference electrodes (50, 250, and 250 µm, respectively) in the out-channel approach.
RESULTS
The system was devised to have the optimum detection potential equal to -1.2 V vs. pseudo-reference electrode. The dimensions of the SU-8 channel have 20 µm depth and 50 µm width. In the second step, an air-assisted liquid-liquid microextraction technique was used to extract and preconcentration of analytes from human blood plasma. Then, 1, 2 di-bromoethan was used as extractant solvent, the analytes were preconcentrated, and the sedimented solvent (50 µL) was evaporated in a 60 ˚C water bath followed by substitution of running buffer containing 10% ethanol. The optimal extraction cycles were found to be 8 with adding 1% NaCl to the aqueous phase. Analyzing time of the mentioned analytes was less than 100s, the precision range was 3.3 - 8.2 with a linear range of 0.8-100 ppm and 1.2-100 ppm for FT and PA, respectively. The extraction recoveries were about 91% and 87% for FT and PA, respectively. The detection limits for FT and PA were 240 and 360 ppb, respectively. Finally, the reliability of the method was investigated by GC-FID.
CONCLUSION
The proposed method and device were validated and can be used as in situ and portable detection systems for detecting fenitrothion and parathion insecticides.
PubMed: 38938753
DOI: 10.34172/bi.2023.25288 -
Stereotactic and Functional Neurosurgery Jun 2024We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson's...
INTRODUCTION
We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson's disease (PD).
METHODS
We conducted a retrospective chart review of all PD patients that received STN DBS in our DBS center between 1998 and 2023. Outcomes were complications resulting in neurological deficit or additional surgery. Potential risk factors (number of microelectrode recording tracks, age, anesthesia method, hypertension, and sex) for symptomatic intracerebral hemorrhage (ICH) were analyzed. Furthermore, lead fixation techniques were compared.
RESULTS
Eight hundred PD patients (507 men, 293 women) received unilateral (n = 11) or bilateral (n = 789) implantation of STN electrodes. Neurological deficit due to ICH, edema, delirium, or infarction was seen in 8.4% of the patients (7.4% transient, 1.0% permanent). Twenty-two patients (2.8%) had a symptomatic ICH following STN DBS, for which we did not find any risk factors, and five had permanent sequelae due to ICH (0.6%). Of all patients, 18.4% required additional surgery; the proportion was reduced from 27% in the first 300 cases to 13% in the last 500 cases (p < 0.001). The infection rate was 3.5%, which decreased from 5.3% in the first 300 cases to 2.2% in the last 500 cases. The use of a lead anchoring device led to significantly less lead migrations than miniplate fixation.
CONCLUSION
STN DBS leads to permanent neurological deficit in a small number of patients (1.0%), but a substantial proportion needs some additional surgical procedure after the first DBS system implantation. The risk of revision surgery was reduced over time but remained significant. These findings need to be discussed with the patient in the preoperative informed consent process in addition to the expected health benefit.
PubMed: 38934196
DOI: 10.1159/000539483 -
Stereotactic and Functional Neurosurgery Jun 2024The aim of this study was to present a novel technique for subthalamic nucleus (STN) deep brain stimulation (DBS) implantation under general anesthesia by using...
Mapping of Capsular Side Effects by using Intraoperative Motor-Evoked Potentials during Asleep Deep Brain Stimulation Surgery of the Subthalamic Nucleus for Parkinson's Disease.
INTRODUCTION
The aim of this study was to present a novel technique for subthalamic nucleus (STN) deep brain stimulation (DBS) implantation under general anesthesia by using intraoperative motor-evoked potentials (MEPs) through direct lead stimulation and determining their correlation to the thresholds of postoperative stimulation-induced side effects.
METHODS
This study included 22 consecutive patients with advanced Parkinson's disease who underwent surgery in our institution between January 2021 and September 2023. All patients underwent bilateral implantation in the STN (44 leads) under general anesthesia without microelectrode recordings (MERs) by using MEPs with electrostimulation directly through the DBS lead. No cortical stimulation was performed during this process. Intraoperative fluoroscopic guidance and immediate postoperative computed tomography were used to verify the electrode's position. The lowest MEP thresholds were recorded and were correlated to the postoperative stimulation-induced side-effect threshold. The predictive values of the MEPs were analyzed. Five DBS leads were repositioned intraoperatively due to the MEP results.
RESULTS
A moderately strong positive correlation was found between the MEP threshold and the capsular side-effect threshold (RS = 0.425, 95% CI, 0.17-0.67, p = 0.004). The highest sensitivity and specificity for predicting a side-effect threshold of 5 mA were found to be at 2.4 mA MEP threshold (sensitivity 97%, specificity 87.5%, positive predictive value 97%, and negative predictive value 87.5%). We also found high sensitivity and specificity (100%) at 1.15 mA MEP threshold and 3 mA side-effect threshold. Out of the total 44 leads, 5 (11.3%) leads were repositioned intraoperatively due to MEP thresholds lower than 1 mA (4 leads) or higher than 5 mA (1 lead). The mean accuracy on postoperative CT was 1.05 mm, and there were no postoperative side-effects under 2.8 mA.
CONCLUSION
Intraoperative MEPs with electrostimulation directly through the contacts of the DBS lead correlate with the stimulation-induced capsular side effects. The lead reposition based on intraoperative MEP may enlarge the therapeutic window of DBS stimulation.
PubMed: 38934180
DOI: 10.1159/000539433 -
Micromachines Jun 2024This paper demonstrates the potential of anisotropic 3D printing for alignable carbon nanomaterials. The ferrite-decorated nanocarbon material was synthesized via a...
This paper demonstrates the potential of anisotropic 3D printing for alignable carbon nanomaterials. The ferrite-decorated nanocarbon material was synthesized via a sodium solvation process using epichlorohydrin as the coupling agent. Employing a one-pot synthesis approach, the novel material was incorporated into a 3D photopolymer, manipulated, and printed using a low-cost microscale 3D printer, equipped with digital micromirror lithography, monitoring optics, and magnetic actuators. This technique highlights the ability to control the microstructure of 3D-printed objects with sub-micron precision for applications such as microelectrode sensors and microrobot fabrication.
PubMed: 38930733
DOI: 10.3390/mi15060763 -
Micromachines May 2024Arsenic contamination poses a significant public health risk worldwide, with chronic exposure leading to various health issues. Detecting and monitoring arsenic exposure...
Arsenic contamination poses a significant public health risk worldwide, with chronic exposure leading to various health issues. Detecting and monitoring arsenic exposure accurately remains challenging, necessitating the development of sensitive detection methods. In this study, we introduce a novel approach using fast-scan cyclic voltammetry (FSCV) coupled with carbon-fiber microelectrodes (CFMs) for the electrochemical detection of As. Through an in-depth pH study using tris buffer, we optimized the electrochemical parameters for both acidic and basic media. Our sensor demonstrated high selectivity, distinguishing the As signal from those of As and other potential interferents under ambient conditions. We achieved a limit of detection (LOD) of 0.5 μM (37.46 ppb) and a sensitivity of 2.292 nA/μM for bare CFMs. Microscopic data confirmed the sensor's stability at lower, physiologically relevant concentrations. Additionally, using our previously reported double-bore CFMs, we simultaneously detected As-Cu and As-Cd in tris buffer, enhancing the LOD of As to 0.2 μM (14.98 ppb). To our knowledge, this is the first study to use CFMs for the rapid and selective detection of As via FSCV. Our sensor's ability to distinguish As from As in a physiologically relevant pH environment showcases its potential for future in vivo studies.
PubMed: 38930703
DOI: 10.3390/mi15060733 -
Micromachines May 2024Modern microtechnology methods are widely used to create neural networks on a chip with a connection architecture demonstrating properties of modularity and hierarchy...
Modern microtechnology methods are widely used to create neural networks on a chip with a connection architecture demonstrating properties of modularity and hierarchy similar to brain networks. Such in vitro networks serve as a valuable model for studying the interplay of functional architecture within modules, their activity, and the effectiveness of inter-module interaction. In this study, we use a two-chamber microfluidic platform to investigate functional connectivity and global activity in hierarchically connected modular neural networks. We found that the strength of functional connections within the module and the profile of network spontaneous activity determine the effectiveness of inter-modular interaction and integration activity in the network. The direction of intermodular activity propagation configures the different densities of inhibitory synapses in the network. The developed microfluidic platform holds the potential to explore function-structure relationships and efficient information processing in two- or multilayer neural networks, in both healthy and pathological states.
PubMed: 38930702
DOI: 10.3390/mi15060732 -
Brain Sciences Jun 2024Cerebral intraparenchymal hemorrhage due to electrode implantation (CIPHEI) is a rare but serious complication of deep brain stimulation (DBS) surgery. This study...
Cerebral Intraparenchymal Hemorrhage due to Implantation of Electrodes for Deep Brain Stimulation: Insights from a Large Single-Center Retrospective Cross-Sectional Analysis.
Cerebral intraparenchymal hemorrhage due to electrode implantation (CIPHEI) is a rare but serious complication of deep brain stimulation (DBS) surgery. This study retrospectively investigated a large single-center cohort of DBS implantations to calculate the frequency of CIPHEI and identify patient- and procedure-related risk factors for CIPHEI and their potential interactions. We analyzed all DBS implantations between January 2013 and December 2021 in a generalized linear model for binomial responses using bias reduction to account for sparse sampling of CIPHEIs. As potential risk factors, we considered age, gender, history of arterial hypertension, level of invasivity, types of micro/macroelectrodes, and implanted DBS electrodes. If available, postoperative coagulation and platelet function were exploratorily assessed in CIPHEI patients. We identified 17 CIPHEI cases across 839 electrode implantations in 435 included procedures in 418 patients (3.9%). Exploration and cross-validation analyses revealed that the three-way interaction of older age (above 60 years), high invasivity (i.e., use of combined micro/macroelectrodes), and implantation of directional DBS electrodes accounted for 82.4% of the CIPHEI cases. Acquired platelet dysfunction was present only in one CIPHEI case. The findings at our center suggested implantation of directional DBS electrodes as a new potential risk factor, while known risks of older age and high invasivity were confirmed. However, CIPHEI risk is not driven by the three factors alone but by their combined presence. The contributions of the three factors to CIPHEI are hence not independent, suggesting that potentially modifiable procedural risks should be carefully evaluated when planning DBS surgery in patients at risk.
PubMed: 38928612
DOI: 10.3390/brainsci14060612