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Expert-like performance of an autonomous spike tracking algorithm in isolating and maintaining single units in the macaque cortex.

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... But stereotrode or tetrode signals need to be combined with 3D spike recognition software tools (e.g., Spike2 from CED, Neuralynx, AutoClass or OpenElectrophy) to reduce the error level from 0–30 % with manual spike sorting to 0–8 % using a semiautomatic spike sorting program [24]. Improper spike sorting may be due to problems identifying single neurons in close proximity to each other when these fire both complex and single spikes (e.g., pyramidal neurons in hippocampus [24] and Purkinje cells in cerebellum [23]), or when spike amplitude varies over time resulting in cluster drift242526. Identification of the type of active neurons is not always done and multiunit activity (MUA) is reported instead. ...
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In order to assess perfusion and metabolic responses in relation to neural function, the cellular signaling network, including the types of neurons and astrocytes involved, and the timing of their activation need to be known/specified. Here, we present the basis for measuring brain activity and metabolism in rats and mice, which covers basic electrophysiological indicators of neuronal function, a short description of the methods commonly used for recording electrophysiological signals, examples of data analysis and (a brief look at the limitations of the methods. This chapter describes animal preparation, the origin of extracellularly recorded electrical signals, with special regard to the EEG, local field potentials, and spikes (action potentials?) in rodent preparations. We also describe methods for recording cerebral blood flow (CBF), tissue partial pressure of oxygen (tpO2), and cytosolic calcium transients. Lastly, we give examples of protocols in which electrophysiology, blood flow, cerebral rate of oxygen metabolism (CMRO2), and calcium transients have been studied together.
... One source of non-stationarity is the slight drift in the position of the recording electrode relative to the cell body over time which causes gradual changes in the waveform shapes of the recorded spikes ( Lewicki, 1998;Snider and Bonds, 1998). Heartbeat, respiration or mechanical perturbations by movements of the animal in awake preparations, can also cause non-stationarities ( Snider and Bonds, 1998;Chakrabarti et al., 2012). Non-stationary may be caused by a process of electrode encapsulation by fibrous tissue and cell death in the vicinity of the electrode ( Polikov et al., 2005). ...
Article
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The spiking activity of cortical neurons is correlated. For instance, trial-to-trial fluctuations in response strength are shared between neurons, and spikes often occur synchronously. Understanding the properties and mechanisms that generate these forms of correlation is critical for determining their role in cortical processing. We therefore investigated the spatial extent and functional specificity of correlated spontaneous and evoked activity. Because feedforward, recurrent, and feedback pathways have distinct extents and specificity, we reasoned that these measurements could elucidate the contribution of each type of input. We recorded single unit activity with microelectrode arrays which allowed us to measure correlation in many hundreds of pairings, across a large range of spatial scales. Our data show that correlated evoked activity is generated by two mechanisms that link neurons with similar orientation preferences on different spatial scales: one with high temporal precision and a limited spatial extent (approximately 3 mm), and a second that gives rise to correlation on a slow time scale and extends as far as we were able to measure (10 mm). The former is consistent with common input provided by horizontal connections; the latter likely involves feedback from extrastriate cortex. Spontaneous activity was correlated over a similar spatial extent, but approximately twice as strongly as evoked activity. Visual stimuli thus caused a substantial decrease in correlation, particularly at response onset. These properties and the circuit mechanism they imply provide new constraints on the functional role that correlation may play in visual processing.
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1. A particular firing pattern among simultaneously observed neurons represents a particular sequence of activity. If any multineuron pattern repeats significantly more than expected by chance, we may be observing a repeated state of a neural assembly as it processes similar units of information. 2. We present here an algorithm that rapidly finds all single or multineuron patterns that repeat two or more times within a block of data, as well as equations for calculating the number of patterns of given length and repetition that would be expected. The complexity of patterns for which it is practical to compute expected numbers is three to six spikes (inclusive). 3. Confidence limits are based on these expected numbers of patterns, so that is possible to identify groups of patterns that are worthy of further analysis. 4. These methods are tested against simulated multineuron data that has various types of known nonstationarities, with good agreement between observed and expected values. 5. Application to real spike trains shows a large excess of observed repeating patterns, of which some, but not all, are shown to be due to bursts of high frequency firing. 6. It should be possible to apply the new method as a filter in real time in order to search for an association between repeated pattern events and externally observable events (stimulus, behavior, etc.). Any repeated pattern events which cannot be so associated may represent a new indicator of internal events in the nervous system.
Article
We developed a new method for the insertion of thin-shaft probes into neural and muscular tissue. Axial forces for driving the probes into tissue and radial forces against buckling are both provided by a stretched elastic rubber tube in which the probe is guided outside the tissue. Various geometric arrangements of arrays with independently advanceable probes are possible. Prototypes with 7 linearly aligned fiber electrodes and computer-controlled positioning motors were successfully used in single- and multiple-unit recordings from the visual system of awake monkeys (Eckhorn et al., 1993). The method is suitable in a wide range of applications, including insertion of fine microprobe fibers and wire electrodes into brain and muscle through the skin or dura, provided that the tips of the probes are sharp and hard enough.
Article
Although a number of methods have been proposed for classification of individual action potentials embedded in multi-unit activity, they have been challenged by non-stationarity. The waveform shapes of action potentials can change rapidly over time as a result of shifts in membrane conductances during extended burst firing sequences and more slowly over time due to electrode drift. These changes are typically non-Gaussian. We present an algorithm for waveform identification that makes no assumptions on the distribution of these shapes other than the change in waveform shape for a particular neuron should not be discontinuous. We apply this algorithm to the resolution of multi-unit neural signals recorded in the cat visual cortex and we compare this approach to a spike sorting method that is based on the Bayesian likelihood of a spike fitting a particular model (Lewicki, M. Bayesian modeling and classification of neural signals. Neural Comput 1994;6(5):1005-1030.
Article
Ensemble recording in cerebellar cortex of awake rats presents unique methodological challenges not encountered when recording from the cerebral cortex or from deep brain structures with more homogeneous cell populations. Compared to the cerebral cortex, removal of dura over the cerebellum evokes pronounced swelling, and insertion of multiple closely spaced electrodes in the cerebellar cortex causes considerable dimpling (Welsh JP, Schwartz C. Multielectrode recording from the cerebellum. In: Nicolelis MAL, editor. Methods for Neural Ensemble Recordings, CRC Methods in Neuroscience Series. Boca Raton, FL: CRC Press LLC, 1999, pp. 79-100). Also, a repetitious and well-defined neural circuit characterizes the cerebellar cortex across its entire surface. With conventional multi-electrode methods, such as chronically implanted bundles or arrays of microwires, the risk of disrupting the cerebellar cytoarchitecture is high. In most conventional multi-electrode systems, electrodes have rather low impedance and cannot be moved independently after implantation. These limitations make proper unit isolation, necessary to identify each of the recorded cerebellar units, very difficult. We designed a lightweight (14 g), miniature (base plate: 19 x 23 mm; total height: 16 mm) multi-electrode system to allow for the chronic implantation of six independently moveable sharp electrodes with high impedance, in the cerebellar cortex. The six electrodes are arranged in a 2 x 3 matrix (inter-electrode distance: 0.6 mm). At any time after the implantation the vertical position of each individual electrode can be adjusted by screwing spring-loaded electrode heads up or down. The system preserves the integrity of the cerebellar cytoarchitecture, and enables easy isolation and identification of individual cerebellar units in awake, freely moving rats.
Article
Simultaneous recording from multiple single neurones presents many technical difficulties. However, obtaining such data has many advantages, which make it highly worthwhile to overcome the technical problems. This report describes methods which we have developed to permit recordings in awake behaving monkeys using the 'Eckhorn' 16 electrode microdrive. Structural magnetic resonance images are collected to guide electrode placement. Head fixation is achieved using a specially designed headpiece, modified for the multiple electrode approach, and access to the cortex is provided via a novel recording chamber. Growth of scar tissue over the exposed dura mater is reduced using an anti-mitotic compound. Control of the microdrive is achieved by a computerised system which permits several experimenters to move different electrodes simultaneously, considerably reducing the load on an individual operator. Neurones are identified as pyramidal tract neurones by antidromic stimulation through chronically implanted electrodes; stimulus control is integrated into the computerised system. Finally, analysis of multiple single unit recordings requires accurate methods to correct for non-stationarity in unit firing. A novel technique for such correction is discussed.
Article
Real-time direct interfaces between the brain and electronic and mechanical devices could one day be used to restore sensory and motor functions lost through injury or disease. Hybrid brain-machine interfaces also have the potential to enhance our perceptual, motor and cognitive capabilities by revolutionizing the way we use computers and interact with remote environments.
Article
As long as 150 years ago, when Fritz and Hitzig demonstrated the electrical excitability of the motor cortex, scientists and fiction writers were considering the possibility of interfacing a machine with the human brain. Modern attempts have been driven by concrete technological and clinical goals. The most advanced of these has brought the perception of sound to thousands of deaf individuals by means of electrodes implanted in the cochlea. Similar attempts are underway to provide images to the visual cortex and to allow the brains of paralyzed patients to re-establish control of the external environment via recording electrodes. This review focuses on two challenges: (1) establishing a 'closed loop' between sensory input and motor output and (2) controlling neural plasticity to achieve the desired behavior of the brain-machine system. Meeting these challenges is the key to extending the impact of the brain-machine interface.
Article
Micro-machined neural prosthetic devices can be designed and fabricated to permit recording and stimulation of specific sites in the nervous system. Unfortunately, the long-term use of these devices is compromised by cellular encapsulation. The goals of this study were to determine if device size, surface characteristics, or insertion method affected this response. Devices with two general designs were used. One group had chisel-shaped tips, sharp angular corners, and surface irregularities on the micrometer size scale. The second group had rounded corners, and smooth surfaces. Devices of the first group were inserted using a microprocessor-controlled inserter. Devices of the second group were inserted by hand. Comparisons were made of responses to the larger devices in the first group with devices from the second group. Responses were assessed 1 day and 1, 2, 4, 6, and 12 weeks after insertions. Tissues were immunochemically labeled for glial fibrillary acidic protein (GFAP) or vimentin to identify astrocytes, or for ED1 to identify microglia. For the second comparison devices from the first group with different cross-sectional areas were analyzed. Similar reactive responses were observed following insertion of all devices; however, the volume of tissue involved at early times, <1 week, was proportional to the cross-sectional area of the devices. Responses observed after 4 weeks were similar for all devices. Thus, the continued presence of devices promotes formation of a sheath composed partly of reactive astrocytes and microglia. Both GFAP-positive and -negative cells were adherent to all devices. These data indicate that device insertion promotes two responses-an early response that is proportional to device size and a sustained response that is independent of device size, geometry, and surface roughness. The early response may be associated with the amount of damage generated during insertion. The sustained response is more likely due to tissue-device interactions.
Article
METAL microelectrodes suitable for recording from single cells externally or after penetration have been described by various authors1-3. The procedures of Svaetichin2 and Grundfest1 call for special apparatus, and the method of Hubel3, employing tungsten, in our hands gives rather noisy electrodes which are difficult to straighten. Steel electrodes, which have the advantages of low noise, low electrode potential, ease of straightening and, in particular, offer the possibility of accurate localization of the recording site, may be made as follows.
Article
The implantation of chronic recording electrodes in the brain has been shown to be a valuable method for simultaneously recording from many neurons. However, precise placement of these electrodes, crucial for successful recording, is challenging if the target area is not on the brain surface. Here we present a stereotaxic implantation procedure to chronically implant bundles of recording electrodes into macaque cortical sulci, employing magnetic resonance (MR) imaging to determine stereotaxic coordinates of target location and sulcus orientation. Using this method in four animals, we recorded simultaneously the spiking activity and the local field potential from the parietal reach region (PRR), located in the medial bank of the intraparietal sulcus (IPS), while the animal performed a reach movement task. Fifty percent of all electrodes recorded spiking activity during the first 2 post-operative months, indicating their placement within cortical gray matter. Chronic neural activity was similar to standard single electrode recordings in PRR, as reported previously. These results indicate that this MR image-guided implantation technique can provide sufficient placement accuracy in cortical sulci and subcortical structures. Moreover, this technique may be useful for future cortical prosthesis applications in humans that require implants within sulci.
Article
Correlations among simultaneously recorded signals are mostly analyzed pairwise and include temporal averaging. However, pairwise methods are not suitable for characterizing relationships among multiple channels for signals which vary temporally in an unpredictable way. Here we develop a time-resolved spatio-temporal correlation (STC) measure among simultaneously recorded signals. We demonstrate the capabilities of the method with artificial data sets and with multiple-channel recordings from striate cortex of awake monkeys. We concentrate on correlations in the gamma-frequency range (gamma: 30-90 Hz) because they were prominent in the analyzed recordings and gained high interest in the recent years due to their assumed role in associative processing, including perceptual binding. Former analyses of gamma-activities in visual cortex, using pairwise correlation methods, mostly revealed zero-delay correlation, indicating synchrony. In cat and monkey visual cortex this gamma-synchrony is restricted to 1.5-3.0 mm (half-height decline). However, our spatio-temporal correlation (STC)-method demonstrates for striate cortex from awake monkeys that gamma-synchrony is a local phenomenon of more global traveling plane waves that appear stimulus-induced at randomly varying orientations. These gamma-waves are coupled over much larger cortical distances (approximately 7 mm half-height decline) than the gamma-synchrony ranges obtained by pairwise correlation analyses from the same data. Our STC-method therefore suggests that the previously reported results of short-range and zero-delay correlations were often due to temporal averaging of traveling gamma-waves.
Article
Implantable silicon microelectrode array technology is a useful technique for obtaining high-density, high-spatial resolution sampling of neuronal activity within the brain and holds promise for a wide range of neuroprosthetic applications. One of the limitations of the current technology is inconsistent performance in long-term applications. Although the brain tissue response is believed to be a major cause of performance degradation, the precise mechanisms that lead to failure of recordings are unknown. We observed persistent ED1 immunoreactivity around implanted silicon microelectrode arrays implanted in adult rat cortex that was accompanied by a significant reduction in nerve fiber density and nerve cell bodies in the tissue immediately surrounding the implanted silicon microelectrode arrays. Persistent ED1 up-regulation and neuronal loss was not observed in microelectrode stab controls indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response. In addition, we found that explanted electrodes were covered with ED1/MAC-1 immunoreactive cells and that the cells released MCP-1 and TNF-alpha under serum-free conditions in vitro. Our findings suggest a potential new mechanism for chronic recording failure that involves neuronal cell loss, which we speculate is caused by chronic inflammation at the microelectrode brain tissue interface.