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Automatic analysis and visualization of microelectrode recording trajectories to the subthalamic nucleus: preliminary results.

Although microelectrode recordings (MER) are commonly used to confirm stereotactic targets during surgery for movement disorders, there is no consensus on whether the additional risks and cost of MER are worth the benefits. This may be due, in part, to the inconsistency and inefficiency of subjective interpretation of MER data that is currently used in practice. We describe several fully automatic visualization methods for MER that efficiently and clearly indicate segments of the microelectrode trajectories with homogeneous neural activity that correspond to expected deep brain nuclei. Specifically we demonstrate that these visualization methods can help identify the subthalamic nucleus in Parkinson's disease patients. These methods have the potential to significantly improve patient outcome by helping neurosurgeons objectively identify target structures more quickly and accurately.

Aged↗

Neurotransplantation in Parkinson's disease: from open microsurgery to bilateral stereotactic approach: first clinical trial using microelectrode recording technique.

This paper summarizes the results of three controlled clinical trials related to the transplantation of embryonic ventral mesencephalic tissue into the striatum of 46 idiopathic parkinsonian patients exhibiting motor complications on standard levodopa therapy. From January 1988 to April 1990, 30 subjects with fluctuating Parkinson's disease received fetal dopaminergic tissue implants by the open microsurgical technique. In March 1992 the stereotactic approach was adopted for successive fetal mesencephalic cell suspension transplants (7 unilateral and 9 bilateral) into the caudate and putamen of parkinsonian patients with levodopa-induced complex fluctuations and dyskinesias. The neurological assessment performed 12 months before and 3-18 months after transplantation demonstrated a reduction of both the daily time spent in the 'off' condition and the number of daily 'off' periods, and a significant improvement of the motor scale. The stereotactic selective thalamotomy with microelectrode recording was introduced in January 1993, in order to provide a further potential treatment strategy; i.e., the combination of the two surgical trends in Parkinson's disease, the restorative neurotransplantation technique, and the selective lesional approach. In addition to that, microelectrode recording is also used for implantation site selection and functional characterization.

Adrenal Medulla↗

Microelectrode mapping of modality-specific somatic sensory cerebral neocortex in slow loris.

Microelectrode mapping methods and strategies were developed to map fine details of the somatotopic organization of somatic sensory cortex (SI) in slow loris. In-depth, multiple-unit recording, and threshold natural stimulation of skin and hari revealed three modality-specific cortical areas. The centrally located one was activated by extremely light touch and the somatopic organization of peripheral projections to it was mapped in detail. As many as 25 punctures/mm2 were made in delineating these details. The microelectrode mapping method used revealed smaller receptive fields, lesser degrees of overlap, a more differentiated pattern of peripheral projections, and a more precise correlation of electrophysiological results with underlying cytoarchitectonic details than did the usual macroelectrode surface recording method. These results and the correlations found between different physiologically defined areas and cortical sulci are discussed as they pertain to methodological advances in studies of cerebral localization of function.

Animals↗

Experience with microelectrode guided subthalamic nucleus deep brain stimulation.

OBJECTIVE: Subthalamic deep brain stimulation (DBS) has rapidly become the standard surgical therapy for medically refractory Parkinson disease. However, in spite of its wide acceptance, there is considerable variability in the technical approach. This study details our technique and experience in performing microelectrode recording (MER) guided subthalamic nucleus (STN) DBS in the treatment of Parkinson disease. METHODS: Forty patients underwent surgery for the implantation of 70 STN DBS electrodes. Stereotactic localization was performed using a combination of magnetic resonance and computed tomographic imaging. We used an array of three microelectrodes, separated by 2 mm, for physiological localization of the STN. The final location was selected based on MER and macrostimulation through the DBS electrode. RESULTS: The trajectory selected for the DBS electrode had an average pass through the STN of 5.6 +/- 0.4 mm on the left and 5.7 +/- 0.4 mm on the right. The predicted location was used in 42% of the cases but was modified by MER in the remaining 58%. Patients were typically discharged on the second postoperative day. Eighty-five percent of patients were sent home, 13% required short-term rehabilitation, and one patient required long-term nursing services. Seven complications occurred over 4 years. Four patients suffered small hemorrhages, one patient experienced a lead migration, one developed an infection of the pulse generator, and one patient suffered from a superficial cranial infection. CONCLUSION: Simultaneous bilateral MER-guided subthalamic DBS is a relatively safe and well-tolerated procedure. MER plays an important role in optimal localization of the DBS electrodes.

Aged↗

Quantitative analysis of resting membrane electrogenesis in insect (diptera) skeletal muscle. I. Intracellular K+, Na+ and Cl- activities, measured using liquid ion-exchanger and neutral ion-carrier microelectrodes.

Electrophysiological properties of skeletal body-wall muscles of prepupal Calliphora erythrocephala were investigated using double-barrelled intracellular ion-sensitive microelectrodes. The most realistic estimate of the intracellular K+ activity, obtained using K+-sensitive microelectrodes based on a neutral carrier, was 115 mmoll-1. The K+ equilibrium potential was consistently more negative than the prevailing resting potential, the average difference being -15 mV. The intracellular Na+ activity and the Na+ equilibrium potential were 7 mmoll-1 and +46 mV on average, respectively. The mean value of the intracellular Cl- activity was 40 mmoll-1, and this was apparently higher than that required for passive distribution of Cl-. However, when reversibly exposed to a Ringer containing no Cl-, cells could rapidly exchange most of their intracellular Cl-, although the resting membrane potentials were only transiently affected. It is concluded that an anionic interferent exists inside muscles, that this artefactually elevates the measured intracellular Cl- activities, and that Cl- makes no contribution to resting membrane electrogenesis.

Animals↗

Investigating neuronal activity with planar microelectrode arrays: achievements and new perspectives.

Neuronal networks underlie memory storage and information processing in the human brain, and ultimately participate in what Eccles referred to as "the creation of consciousness". Moreover, as physiological dysfunctions of neurons almost always translate into serious health issues, the study of the dynamics of neuronal networks has become a major avenue of research, as well as their response to pharmacological tampering. Planar microelectrode arrays represent a unique tool to investigate such dynamics and interferences, as they allow one to observe the activity of neuronal networks spread in both space and time. We will here review the major results obtained with microelectrode arrays and give an overview of the latest technological developments in the field, including our own efforts to develop the potential of this already powerful technology.

Microelectrodes↗

New double-barreled, ion-sensitive microelectrodes for measuring intracellular Cl- activities in rabbit renal collecting ducts.

The use of the conventional ion-sensitive double-barreled microelectrodes has been unsuccessful for studying small epithelial cells such as those of the collecting duct because of the difficulty in obtaining the ideal electrodes for impaling cells. We developed a new type of ion-sensitive, double-barreled microelectrode of a size and tip configuration ideal for use in impaling small cells such as the principal cells (PCs) of the cortical collecting ducts, and remaining therein, for more than 30 min. The electrodes were pulled in two steps. The first includes the reciprocal twisting of two parallel glass capillaries, without pulling, to form a round, nontortuous fused glass capillary in the puller. In the second step, the round, fused straight capillaries are pulled so as to form the tip. This resulting procedure enabled us to impale the PCs without altering their cell membrane potentials. The basolateral membrane voltage (Vb) in PCs of the cortical collecting ducts was -69.1 +/- 1.6 mV (n = 8) and intracellular Cl- activity ([Cl]i) in PCs of the cortical collecting duct was 11.8 +/- 0.9 mmol/liter (n = 5). Changing the concentration of Cl- in the ambient solution showed that the basolateral cell membrane of the PCs was highly permeable to Cl-. This new electrode will help to obtain new information on intracellular ion handling, with the electrodes applied to the collecting duct cells.

Animals↗

Real-time measurement of PMA-induced cellular alterations by microelectrode array-based impedance spectroscopy.

For a feasible and cost-effective impedance measurement of cellular alterations in real-time, we combined commercially available microelectrode arrays (MEAs), consisting of 60 microelectrodes, with a conventional impedance analyzer. For proof of principle, a breast carcinoma cell line (MCF-7) was cultured on MEAs, and cellular alterations were measured by impedance spectroscopy at a frequency ranging from 10 Hz to 1 MHz. Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) at different concentrations to activate protein kinase C (PKC)-mediated extra- and intracellular changes. By addition of 0.03 microM PMA, an increase of the relative impedance (Z(rel)) was observed after 10 min with a maximum at 1 kHz. Moreover a gradual elevation of the impedance was measured 60 min after stimulation with PMA. If 0.3 microM PMA was applied, the maximal amplitude of the relative impedance after 60 min shifted from 1 kHz (0.03 microM PMA) to 150 Hz. Subsequently, the impedance was further increased up to 90 min after PMA application, after which the impedance reduced after 240 min. Since we could use MEAs for at least 10 times without affecting the sensitivity, our study revealed that commercially available MEAs comprising nanocolumnar titanium nitrite electrodes are suitable microstructures for a highly reproducible and cost-effective multisite measurement of intracellular processes by impedance spectroscopy.

Alloys↗

Stratification and oxidation-reduction potential change in an aerobic and sulfate-reducing biofilm studied using microelectrodes.

Recent studies in aerobic-nitrifying biofilms demonstrated the heterogeneity of biofilms used in wastewater treatment and led to modifications of the homogeneous assumptions in the conventional biofilm kinetic models. However, the stratification in aerobic-anaerobic biofilms has not been well investigated because of a lack of effective experimental tools. In this study a suite of microelectrodes, recently developed in the authors' laboratory, was used to examine the stratification of microbial processes and the change of oxidation-reduction potential (ORP) within an aerobic, sulfate-reducing biofilm. The microelectrodes have tip diameters of 3 to 20 microm and a high spatial resolution. They were used to measure the profiles of oxygen, total dissolved sulfide, ORP, and pH as a function of depth in the biofilm. The biofilm reactor was used to treat an azo-dye-containing wastewater with a chemical oxygen demand of 160 mg/L. The reactor bulk-phase dissolved oxygen concentration of the biofilm was 1.7 mg/L. The experimental results demonstrated that the microbial processes in the biofilm were stratified. In this biofilm, aerobic oxidation took place only in a shallow layer of 0.55 mm near the surface and sulfate reduction occurred in the deeper anoxic zone. The ORP changed with the shift of primary microbial process. The ORP was +362 mV at the biofilm surface and -166 mV near the substratum. Near the interface between the aerobic zone and the sulfate reduction zone, a surprisingly sharp decrease of ORP from a positive potential of +194 mV to a negative potential of -77 mV was observed. This occurred within a narrow band of 50 microm in depth. These new experimental findings support the concept of stratification of microbial processes and the associated ORP change in biofilms.

Azo Compounds↗

A method for marking the position of nichrome microelectrode tips in nervous tissue.

A method for revealing nickel deposits from nichrome microelectrodes in the mammalian central nervous system is described. These deposits are stained red by dimethylglyoxime and can be observed directly or in Nissl stained sections. This method allows one to identify the exact position of a nichrome electrode in a microelectrode bundle chronically implanted in the brain.

Animals↗

A technique for minimally altering anatomically based subthalamic electrode targeting by microelectrode recording.

OBJECT: Implantation of a subthalamic nucleus (STN) deep brain stimulation (DBS) electrode is increasingly recognized as an effective treatment for advanced Parkinson disease (PD). Despite widespread use of microelectrode recording (MER) to delineate the boundaries of the STN prior to stimulator implantation, it remains unclear to what extent MER improves the clinical efficacy of this procedure. In this report, the authors analyze a series of patients who were treated at one surgical center to determine to what degree final electrode placement was altered, based on readings obtained with MER, from the calculated anatomical target. METHODS: Subthalamic DBS devices were placed bilaterally in nine patients with advanced PD. Frame-based volumetric magnetic resonance images were acquired and then transferred to a stereotactic workstation to determine the anterior and posterior commissure coordinates and plane. The initial anatomical target was 4 mm anterior, 4 mm deep, and 12 mm lateral to the midcommissural point. The MERs defined the STN boundaries along one or more parallel tracks, refining the final electrode placement by comparison of results with illustrations in a stereotactic atlas. In eight of 18 electrodes, the MER results did not prompt an alteration in the anatomically derived target. In another eight placements, MER altered the target by less than 1 mm and two of 18 electrode positions differed by less than 2 mm. The anterior-posterior difference was 0.53 +/- 0.65 mm, whereas the medial-lateral direction differed by 0.25 +/- 0.43 mm. The ventral boundary of the STN defined by MER was 2 +/- 0.72 mm below the calculated target (all values are the means +/- standard deviation). All patients attained clinical improvement, similar to previous reports. CONCLUSIONS: In this series of patients, microelectrode mapping of the STN altered the anatomically based target only slightly. Because it is not clear whether such minor adjustments improve clinical efficacy, a prospective clinical comparison of MER-refined and anatomical targeting may be warranted.

Brain Mapping↗

A hybrid clinical-research depth electrode for acute and chronic in vivo microelectrode recording of human brain neurons. Technical note.

For several decades, important scientific information has been gained from in vivo microelectrode recordings of individual human cerebral cortical neurons in patients with epilepsy. The experimental methods used, however, are technically complex and require a highly skilled intraoperative team. There are also significant experimental time limitations, as well as constraints on the type of behavioral tests conducted, and the brain regions that may be safely studied. In this report, a new method is described for obtaining in vivo microelectrode recordings using a hybrid depth electrode (HDE). High-impedance research recording contacts are interspersed between low-impedance clinical electroencephalographic (EEG) contacts along the HDE shaft. The HDE has the same external physical properties as a standard clinical depth electrode (DE). Following preclinical laboratory testing, 15 HDEs were used in the evaluation of six patients with medically refractory epilepsy. High-quality EEG recordings were obtained in all cases (two acute intraoperative, four from the chronic epilepsy monitoring unit). Action potentials from individual neurons were successfully recorded during all experimental sessions; however, the chronic preparations were clearly superior. Chronic HDEs are placed using a standard stereotactic system, and the locations of recording contacts are documented on a postimplantation imaging study. The quality of the chronic research recordings was excellent over study periods ranging from 5 to 14 days. The patients rested comfortably on the ward and were able to cooperate with complex experimental instructions. Basic neuroscientists participated fully in all aspects of the chronic investigations. The use of an HDE in place of a standard clinical DE may now allow detailed physiological investigations of any brain region targeted for clinical DE implantation.

Brain↗

Microelectrode-guided posteroventral pallidotomy for treatment of Parkinson's disease: postoperative magnetic resonance imaging analysis.

The authors report the postoperative magnetic resonance (MR) imaging findings in 36 patients with advanced Parkinson's disease who underwent unilateral microelectrode-guided posteroventral pallidotomy. The lesions were placed within 1 mm of the ventral border of the globus pallidus internus (GPi) to include pallidothalamic outflow pathways. Sequential MR studies were obtained within 1 to 3 days postoperatively and at 6-month follow-up examination. Thirty-four (94%) of the 36 patients enjoyed sustained moderate or marked improvement of their parkinsonian symptoms 6 months postoperatively. Transient side effects occurred in five patients (14%), but there were no persistent complications. The pallidal radiofrequency lesions were prolate spheroid shaped and were composed of three concentric zones in the early postoperative studies. The mean volume of the middle zone, corresponding to the area of hemorrhagic coagulation necrosis, was 44.4 +/- 17.6 mm3; the mean lesion volume as defined by the outer zone, corresponding to perilesional edema, was 262.2 +/- 111.6 mm3. Additional edema spreading to the internal capsule was noted in 32 of 34 cases and to the optic tract in 11 of 34 cases. In two patients small ischemic infarctions involving the corona radiata were found, and in one a venous infarction was detected. Ischemic infarction resulted in mild transient Broca's aphasia in one patient, but there was no detectable neurological deficit in the other two. The mean volume of late-phase (6 months) lesions was 22 +/- 28.8 mm3. In three patients no lesion was identified despite sustained clinical improvement. The lesion was located in the posteroventral GPi in all cases except in one patient in whom it was confined to the GP externus (GPe). This 49-year-old woman did not experience sustained benefit. The authors found no consistent correlations between lesion size and location and clinical outcome as measured by a global outcome score, the Unified Parkinson's Disease Rating Scale motor, activities of daily living, and bradykinesia "off" scores or rating of dyskinesias. Lesioning of pallidal and subpallidal pathways may contribute to the sustained clinical benefit in this series. Magnetic resonance imaging analysis showed that intraoperative microelectrode recording facilitated accurate placement of the lesion in this critical area.

Adult↗

Stereotactic pallidotomy performed without using microelectrode guidance in patients with Parkinson's disease: surgical technique and 2-year results.

OBJECT: Pallidotomy for the treatment of medically refractory Parkinson's disease (PD) has enjoyed renewed popularity. However, the optimal surgical technique, lesion location, and long-term effectiveness of pallidotomy remain subjects of debate. In this article the authors describe their surgical technique for performing pallidotomy without using microelectrode guidance, and the clinical and radiological results of this procedure. METHODS: Patients were evaluated preoperatively by using a battery of validated clinical rating scales and magnetic resonance (MR) imaging of the brain. Individuals with severe treatment-refractory idiopathic PD who were believed to be good candidates for surgery underwent computerized tomography scanning- and MR imaging-guided stereotactic pallidotomy. Intraoperative macrostimulation was used to optimize lesion placement and to avoid injury to nearby structures. Lesion location and size were calculated from MR imaging sequences of the brain obtained within the first 24 hours after surgery and again 3 months later. Clinical examinations were conducted at 1.5, 3, 6, 12, and 24 months after surgery. Seventy-five patients (mean age 61 years, range 38-79 years) underwent unilateral pallidotomy. Significant improvements were observed in the "off' period scores for the activities of daily living portion of the Unified Parkinson's Disease Rating Scale (UPDRS), the UPDRS motor scores, total "on" time, levodopa-induced dyskinesias, and contralateral tremor. These improvements were maintained 24 months postoperatively. The mean lesion volume measured on the immediate postoperative MR image was 73 +/- 5.4 mm3. Radiological analysis suggests that initial lesion volume does not predict outcome. The only permanent major complication was a single visual field defect. CONCLUSIONS: Pallidotomy performed without using microelectrode guidance is a safe and effective treatment for selected patients with medically refractory PD.

Adult↗

Microelectrode and impedance analysis of anion secretion in Calu-3 cells.

Calu-3 cells secrete HCO(3)(-) in response to cAMP agonists but can be stimulated to secrete Cl(-) with K(+) channel activating agonists. Microelectrode and impedance analysis experiments were performed to obtain a better understanding of the conductances and driving forces involved in these different modes of anion secretion in Calu-3 cells. Microelectrode studies revealed apical and basolateral membrane depolarizations upon the addition of forskolin (V(ap) -52 mV vs. -21 mV; V(bl) -60 mV vs. -44 mV) that paralleled the hyperpolarization of the mucosal negative transepithelial voltage (V(T) -8 mV vs. -23 mV). These changes were accompanied by a decrease in the apical membrane fractional resistance (F(Rap)) from approximately 0.50 to 0.08, consistent with the activation of an apical membrane conductance. The subsequent addition of 1-ethyl-2-benzimidazolinone (1-EBIO), a K(+) channel activator, hyperpolarized V(ap) to -27 mV, V(bl) to -60 mV and V(T) to -33 mV. Impedance analysis revealed the apical membrane resistance (R(ap)) of the forskolin-stimulated cells was less than 20 ohm cm(2), indeed in most monolayers R(ap) fell to less than 5 ohm cm(2). The impedance derived estimate of the basolateral membrane resistance (R(bl)) was approximately 170 ohm cm(2) in forskolin treated cells and fell to 50 ohm cm(2) with the addition of 1-EBIO. Using these values for the R(bl) and the F(Rap) value of 0.08 yields a R(ap) of approximately 14 ohm cm(2) in the presence of forskolin and 4 ohm cm(2) in the presence of forskolin plus 1-EBIO. Thus, by two independent methods, forskolin-stimulated Calu-3 cells are seen to have a very high apical membrane conductance of 50 to 200 mS/cm(2). Therefore, we would assert that even at one-tenth the anion selectivity for Cl(-), this high conductance could support the conductive exit of HCO(3)(-) across the apical membrane. We further propose that this high apical membrane conductance serves to clamp the apical membrane potential near the equilibrium potential for Cl(-) and thereby provides the driving force for HCO(3)(-) secretion in forskolin-stimulated Calu-3 cells. The hyperpolarization of V(ap) and V(bl) caused by 1-EBIO provides a driving force for Cl(-) exit across the apical membrane, inhibits the influx of HCO(3)(-) on the Na(+):HCO(3)(-) cotransporter across the basolateral membrane, activates the basolateral membrane Na(+):K:2Cl(-) cotransporter and thereby provides the switch from HCO(3)(-) secretion to Cl(-) secretion.

Anions↗

[Analysis of the isomers of dihydroxybenzenes by micellar electrokinetic capillary chromatography with on-column amperometric detection at carbon-fiber microelectrode].

The effects of the concentrations of beta-cyclodextrin(CD) in electrolyte on the cyclic voltammetric properties of o-, m-, p-dihydroxybenzenes at carbon-fiber microelectrode were studied. The inclusion between o-, m-, p-dihydroxybenzenes and beta-CD was investigated based on the molecular structures and experimental results. The study showed that the order of the inclusion interaction, from strong to weak, between dihydroxybenzenes and beta-CD, was m-, o- and p-dihydroxybenzenes. The effects of the concentrations of NH4Cl, SDS and beta-CD, and the pH values of the electrophoretic buffer on the migration time of o, m, p-dihydroxybenzenes were investigated. The assay of o, m, p-dihydroxybenzenes by micellar electrokinetic capillary chromatography with on-column amperometric detection at carbon-fiber microelectrode was developed. The recovery ranged from 98% to 103%.

Carbon↗

[Characteristics of dynamic membrane based on oxygen microelectrode].

Self-forming dynamic membrane coupled bioreactor is a technology using coarse pore-sized material modules to separate solid and liquid in the activated sludge. The cake layer formed on the coarse pore-sized material, i.e. dynamic membrane, can remove turbidity efficiently and some organic pollutants. Its biological activity can be studied by microelectrode. For measurement in-situ, a small bioreactor is designed to simulate the real filtration process. A microelectrode with micromanipulator is used to measure the dissolved oxygen profile in the dynamic membrane. The results indicate that bubble emerged in the dynamic membrane during operation of bioreactor. The dissolved oxygen concentration decreased with the increasing depth, and fell to 0 at 2.0 - 2.5mm depth. The specific oxygen uptake rates of the surface part of dynamic membrane were calculated to be 34.3, 10.6 and 12.4 mg/(g x h) respectively at the 1st, 5th and 8th day of the filtration.

Bioreactors↗

Dielectrophoresis of DNA: time- and frequency-dependent collections on microelectrodes.

This paper reports measurements that characterize the collection of DNA onto interdigitated microelectrodes by high-frequency dielectrophoresis. Measurements of time-dependent collection of 12 kilobase pair plasmid DNA onto microelectrodes by dielectrophoresis show significant reduction in the response as the frequency increases from 100 kHz to 20 MHz. Collection time profiles are quantitatively measured using fluorescence microscopy over the range 100 kHz to 5 MHz and are represented in terms of two parameters: the initial dielectrophoretic collection rate, and the initial to steady-state collection transition. Measured values for both parameters are consistent with trends in the frequency-dependent real part of the effective polarizability measured for the same plasmid DNA using dielectric spectroscopy. The experimentally measured parameters are qualitatively compared with trends predicted by theory that takes into account dielectrophoretic particle movement and diffusion. The differences between experiment and theory are discussed with suggested improvements to theoretical models, for example, including the effects of electrohydrodynamically driven fluid motion.

Computer Simulation↗