Channel Microelectrode Arrays Research Articles

Spinal cord stimulation mitigates the myocardial ischemia induced sympathoexcitation by suppressing the spinal neural synchrony and intermediolateral nucleus hyperactivity

BackgroundMyocardial ischemia disrupts the cardiospinal neural network which leads to cardiac sudden death. Spinal cord stimulation (SCS) suppresses the sympathoexcitation caused by myocardial ischemia. However, how SCS modulates the spinal neural network is not known.HypothesisWe hypothesize that SCS decreases myocardial ischemia‐induced sympathoexcitation by suppressing the spinal neural synchrony and intermediolateral nucleus (IML) activity.Materials and MethodsEight Yorkshire pigs (50‐55 kg) with chronic left circumflex coronary artery myocardial infarction (MI) were anesthetized and underwent laminectomy and a sternotomy, 5 weeks post MI. Extracellular in‐vivo spinal neural recordings were done by using a 64 channel microelectrode array inserted at the T2 segment of the spinal cord. SCS was performed at 1 kHz, 0.03 ms, 90% motor threshold for 30 mins. Acute (3 min) left anterior descending coronary artery occlusion (LAD CAO) was performed pre‐ and 1 min post‐SCS to evaluate the impact of SCS on spinal neural network processing during myocardial ischemia. Dorsal horn (DH) and IML neural interactions, including normalized neuronal synchrony, activation recovery interval (ARI), and dispersion of repolarization (DOR) (markers of cardiac arrhythmogenesis) were evaluated during myocardial ischemia pre‐ vs. post‐ SCS.ResultsFiring rate of 1283 recorded spinal neurons increased during 3 mins LAD CAO and 1 min reperfusion pre‐SCS (baseline(BL): 0.516 ± 0.038 Hz; LAD CAO: 0.559 ± 0.038 Hz ,P<0.001 vs. BL; reperfusion: 0.524 ± 0.037 Hz ,P<0.001 vs. BL). SCS at 1kHz, mitigated the spinal neural network response to the LAD CAO (BL: 0.509 ± 0.039 Hz; LAD CAO: 0.486 ± 0.036 Hz; reperfusion: 0.489 ± 0.038 Hz, P<0.001 vs. BL). This suppression of neural firing by SCS was observed in both IML (pre‐SCS: BL: 0.208 ± 0.033 Hz; LAD CAO: 0.308 ± 0.042Hz ,P<0.001 vs. BL; reperfusion: 0.374 ± 0.048 Hz ,P<0.001 vs. BL; post‐SCS: BL: 0.069 ± 0.010 Hz; LAD CAO: 0.080 ± 0.011Hz; reperfusion: 0.109 ± 0.018 Hz) and DH neurons (pre‐SCS: BL: 0.033 ± 0.003 Hz; LAD CAO: 0.039 ± 0.003 Hz ,P<0.001 vs. BL; reperfusion: 0.041 ± 0.003 Hz ,P<0.001 vs. BL; post‐SCS: BL: 0.036 ± 0.003 Hz; LAD CAO: 0.035 ± 0.003 Hz; reperfusion: 0.029 ± 0.002 Hz, P<0.001 vs. BL). ARI shortening due to LAD CAO was mitigated by SCS (pre‐SCS: ‐43.200 ± 5.206 ms; post‐SCS: ‐29.810 ± 6.495 ms, P< 0.05 vs. pre‐SCS). SCS decreased the LAD CAO induced augmented DOR (pre‐SCS: 2461.00 ± 350.40 ms2; post‐SCS: 1996.00 ± 302.00 ms2, P<0.05 vs. pre‐SCS)ConclusionMyocardial ischemia induces sympathoexcitation by increasing the IML activity which is caused by activation of DH neurons and increased spinal neural synchrony. SCS mitigates the adverse effect of myocardial ischemia by suppressing the spinal neural synchrony and IML hyperactivity.

Fabrication and Characterization of 60 Channel Microelectrode Arrays for Recording and Stimulation from Cardiac Cells in Culture

Stimulation and recording of nerve cells is a procedure used for several applications, such as clinical therapies, study of basic neuroscience, and neural prostheses. Microtechnology and advances in material science have allowed to produce more sophisticated devices and with more functions. This paper focuses on the fabrication of planar 60 – channel Microelectrode Arrays (MEAs). The electrical characterization of the noise level from the TiN electrodes showed good sensitivity to noise, compatible with commercial systems. These electrodes received an artificial electrocardiogram signal (ECG) from a function generator and registered the same input signal but with lower amplitude. Finally, both cyclic voltammetry curves of the produced MEA and the commercial MEA exhibited similar shape, but the current density of the first one was significantly higher than in MCS – MEA, with an order difference of magnitude.

Injectable Flexible Subcutaneous Electrode Array Technology for Electrocardiogram Monitoring Device.

Implantable cardiac monitors have undergone considerable miniaturization. However, they continue to be associated with complications such as infection, bleeding/bruising, and device extrusion or migration. In this paper, we demonstrate the feasibility of using a small, flexible, injectable, subcutaneous microelectrode-based device to record electrocardiograms (ECGs). We describe the fabrication process and demonstrate the ease of insertion of the injectable ECG device in vivo swine model. We also demonstrate our device's high-density channel microelectrode array's ability to detect the P, R, and T waves. The amplitude of these waves showed excellent correlation with distance of the bipolar electrodes used to detect them. Given the success of our initial studies, this device has the potential to improve the safety profile of implantable cardiac monitors and simplify the implantation procedure to allow for placement in a primary care setting.

Spike Detection for Large Neural Populations Using High Density Multielectrode Arrays

An emerging generation of high-density microelectrode arrays (MEAs) is now capable of recording spiking activity simultaneously from thousands of neurons with closely spaced electrodes. Reliable spike detection and analysis in such recordings is challenging due to the large amount of raw data and the dense sampling of spikes with closely spaced electrodes. Here, we present a highly efficient, online capable spike detection algorithm, and an offline method with improved detection rates, which enables estimation of spatial event locations at a resolution higher than that provided by the array by combining information from multiple electrodes. Data acquired with a 4096 channel MEA from neuronal cultures and the neonatal retina, as well as synthetic data, was used to test and validate these methods. We demonstrate that these algorithms outperform conventional methods due to a better noise estimate and an improved signal-to-noise ratio (SNR) through combining information from multiple electrodes. Finally, we present a new approach for analyzing population activity based on the characterization of the spatio-temporal event profile, which does not require the isolation of single units. Overall, we show how the improved spatial resolution provided by high density, large scale MEAs can be reliably exploited to characterize activity from large neural populations and brain circuits.

Patterns of information flow in local cortical networks

Structural and functional connectivity of macroscopic brain regions has been very widely researched [1] in the last decade, however very little work has been done on the effective connectivity between individual neurons, largely because of limitations on the simultaneous measurement of large numbers of neurons at high spatiotemporal resolution. We recorded spontaneous single neuron activity from 15 organotypic cultures (prepared from the mouse cortex), with a 512 channel micro-electrode array at a temporal resolution of less than 1 ms and a spatial resolution of 60 μm. The average number of recorded neurons was 347 ± 119. Effective connectivity matrices, both binary and weighted, were constructed from the spike trains using transfer entropy (TE) analysis to estimate directed neuronal interactions [2]. The strength of information flow from neuron i to j was quantified in terms of the TE value calculated from neuron i to j. We observed that only 20% of the recorded neurons accounted for 80% of the total information flow in these networks (see Figure 1A) which we define as the network’s set of rich nodes. The rich nodes were characterized by a higher firing rate, and graph theoretic analysis revealed their participation in a number of highly non-random network features. The networks were highly clustered with small average path

A Micromachined SiO2/Silicon Probe for Neural SignalRecordings

The development of an implantable five channel microelectrode array ispresented for neural signal recordings. The detailed fabricationprocess is outlined with four masks used. The SEM images show that theprobe shank is 1.2 mm long, 100 μm wide and 30 μm thick withthe recording sites spaced 200 μm apart for good signal isolation.The plot of the single recording site impedance versus frequency isshown by test in vitro and the impedance declines with the increasingfrequency. Experiment in vivo using this probe is under way.

Azaspiracid-1 inhibits bioelectrical activity of spinal cord neuronal networks

Azaspiracid-1 (AZA-1) is a recently identified phycotoxin that accumulates in molluscs and can cause severe human intoxications. For this study, we utilized murine spinal cord and frontal cortex neuronal networks grown over 64 channel microelectrode arrays (MEAs) to gain insights into the mechanism of action of AZA-1 on neuronal cells. Extracellular recordings of spontaneous action potentials were performed by monitoring mean spike rate as an assay of the efficacy of AZA-1 to alter the bioelectrical activity of neurons in the networks. Via slow onset, AZA-1 decreased the mean spike rate of the spinal cord neurons with an IC 50 of ca. 2.1 nM, followed by partial recovery of original activity when toxin was removed. Pre-treatment with the GABA A receptor antagonist bicuculline led to an increased response of the neuronal networks to AZA-1 exposure and resulted in an irreversible inhibition of spike rate. AZA-1 did not cause any changes in frontal cortex networks upon drug exposure. In addition, whole-cell patch clamp recordings from spinal cord neurons showed that AZA-1 had no significant effect on the voltage-gated sodium (Na +) or calcium (Ca 2+) currents, suggesting that the toxin affected synaptic transmission in the neuronal networks through a mechanism independent of these voltage-gated channels.

The spatiotemporal organization of auditory, visual, and auditory-visual evoked potentials in rat cortex

Four placements of an 8×8 channel microelectrode array were used to map auditory, visual, and combined auditory-visual evoked potentials (AEP, VEP, AVEP) from a total of 256 electrode sites over a 7×7 mm 2 area including most of somatosensory, auditory, and visual cortex in the right hemisphere of the rat. The unimodal AEP and VEP consisted of an archetypal response sequence representing a systematic spatial and temporal activation of primary and secondary sensory cortex. Spatiotemporal analysis of these waveforms indicated that they could be decomposed into a small number of spatial and temporal components; components that are related to patterns of specific and non-specific thalamocortical projections connecting the auditory and visual nuclei of the thalamus with primary and secondary auditory and visual cortex. These data suggest that the AEP and VEP complex are the cortical reflection of asynchronous activation of parallel thalamocortical projection systems. The areal distribution of the AEP and VEP also overlapped, primarily in secondary auditory visual cortex, indicating that these regions contain populations of cells responding to either modality. Polymodal auditory-visual stimulation resulted in unique activation of two isolated populations of neurons positioned in secondary auditory and secondary visual cortex which were revealed by difference waveforms, computed by subtracting the sum of the AEP and VEP and the AVEP complex. Retrograde labeling of the polymodal zones indicated that they receive parallel thalamocortical projections primarily from non-specific auditory and visual thalamic nuclei including the medial and dorsal divisions of the medial geniculate nucleus (MGm and MGd), the suprageniculate nucleus (SGN), and the lateral posterior nucleus (LP). The polymodal zone in visual cortex also receives specific projections from the dorsal division of the lateral geniculate nucleus (LGd). These data conform to a general model of thalamocortical organization in which specific thalamic nuclei with a high degree of modality specificity make restricted projections to primary sensory cortex and parts of secondary sensory cortex, and association thalamic nuclei with a high degree of sensory convergence make more divergent cortical projections. Primary and secondary sensory cortex, as well as distinct zones of polysensory cortex appear to be activated in tandem via parallel thalamocortical projections. Thus, the cerebral cortex must have simultaneous access to both unimodal and polymodal sensory information.

The anatomic organization of evoked potentials in rat parietal cortex: electrically evoked commissural responses

1. Two 8 x 8 channel microelectrode arrays were positioned over 3.5 x 3.5 mm2 areas in homologous regions of right and left parietal cortex of four rats. Potentials were evoked by delivering epicortical electrical stimulation to each electrode on one hemisphere while mapping the commissural response from the contralateral array. Spatial distributions of the electrically evoked potential (EECP) complex were compared directly with cytochrome oxidase-stained sections of the recorded region. 2. Electrode sites most capable of eliciting a commissural EECP were arranged along a diagonal band extending medially from the rostral to caudal region of each electrode array, approximating the pattern of dysgranular cortex separating primary auditory (Te1) from primary somatosensory (Par1) cortex. Electrode sites in the rostromedial and caudolateral region were ineffectual in eliciting an EECP in either hemisphere. Stimulation sites within secondary visual cortex (Oc2L) also produced strong responses. Only weak responses were elicited from stimulation of Te1 and no EECP could be evoked when stimulating within Par1. 3. When an EECP in the maximally sensitive diagonal region was elicited, its spatial distribution was typically asymmetrical throughout the recording array; the response was largest along a diagonal region also extending medially from the rostral to caudal area of each electrode array. Thus the pattern of EECP in each hemisphere closely matched the pattern of electrically excitable regions in the contralateral hemisphere. 4. The EECP was usually heterogeneous. EECP distributions within the strongly responding diagonal area often formed two regions of maximum amplitude separated by a less active zone. Although responses in Te1 were significantly weaker than those in the adjacent dysgranular cortex, they also revealed a heterogeneous spatial distribution with multiple closely spaced maxima. Only responses in Oc2L appeared consistently homogeneous, with a single maximum representing the EECP. 5. These results provide functional evidence supporting a model of parietal cortex in which there are two basic types of recipient regions, densely granular regions, which are the termination sites of specific thalamocortical fibers, and dysgranular or agranular regions, which receive both ipsilateral and contralateral projections. The functional parceling of rodent parietal cortex on the basis of the spatial and temporal distribution of the epicortical evoked potential complex may be superimposed onto the anatomic parceling into granular and dysgranular zones. Implications for stages of sensory information processing are discussed.

Polysensory evoked potentials in rat parietotemporal cortex: combined auditory and somatosensory responses

A 64 channel microelectrode array was used to map auditory evoked potentials (AEP), somatosensory evoked potentials (SEP) as well as combined auditory and somatosensory evoked potentials (ASEP) from a 7 × mm 2 area in rat parietotemporal neocortex. Cytochrome oxidase (CO) stained sections of layer IV were obtained in the same animals to provide anatomical information underlying epicortical field potentials. Epicortical responses evoked by click or vibrissa stimuli replicated earlier findings from our laboratory, and appeared as a family of waveforms centered on primary auditory (AI) or somatosensory (SI) cortical areas as determined from CO histology. Selective microinjections of HRP to AI and SI further confirmed their specific sensory relay nuclei in the thalamus. A small polysensory area between AI and SI, responded uniquely with an enhanced negative sharp wave to combined auditory and somatosensory stimuli. HRP retrograde labeling revealed that the thalamocortical projections to this area were from the posterior nuclear group (Po) and medial division of the medial geniculate (MGm). These data establish close relationships between epicortical AEP, SEP, and especially ASEP and corresponding cortical structures and thalamocortical projections. The neurogenesis of unimodal and polysensory evoked potentials is discussed in terms of specific and non-specific systems.