Building spike representation in tetrodes

This paper presents a new technique for analyzing the recorded information from tetrodes in freely behaving rats, based on independent component analysis (ICA). The ion-specific pumps and channels allow fast transfer of charges such as Na+, K+, Cl- and eventually Ca2+ during each action potential (AP). These groups of charges under an electrical field have distinct spatial trajectories. Therefore, the generated signals within a tetrode are considered to be composed mainly by statistically independent signal sources that can be obtained by performing ICA. In order to compute the position of independent sources during AP generation, the triangulation method uses an iterative Newton-Raphson algorithm. The representation of the independent signal sources in three-dimensional tetrode space is then obtained. Since the charge movements are extensively spread on the neuron's surface, the representation in tetrode space reveals electrical spatial patterns of activation during each AP. The analysis of several spikes coming from the same neuron reveals small changes from spike to spike in the 3D shape. Since information within spikes is highly transferred by ionic fluxes these electrical patterns of activation reflect neuronal computation occurring during each AP.     

Spike source localization with tetrodes

The paper presents in detail a method for approximating the spatial position of neural spike activity from tetrode recordings. The method uses a nonlinear mapping of a set of tetrode tip amplitudes into three-dimensional (3D) space, followed by a self-organizing map clustering technique. Viewed as a spike sorting method, it performs better than tetrode peak amplitudes and it is roughly equivalent with amplitude ratios. The technique's appeal to physical location may be of advantage in many investigations.     

Tracking neurons recorded from tetrodes across time

Tetrodes allow isolation of multiple neurons at a single recording site by clustering spikes. Due to electrode drift and perhaps due to time-varying neuronal properties, positions and shapes of clusters change in time. As data is typically collected in sequential files, to track neurons across files one has to decide which clusters from different files belong to the same neuron. We report on a semi-automated neuron tracking procedure that uses computed similarities between the mean spike waveforms of the clusters. The clusters with the most similar waveforms are assigned to the same neuron, provided their similarity exceeds a threshold. To set this threshold, we calculate two distributions: of within-file similarities, and of best matches in the across adjacent file similarities. The threshold is set to the value that optimally separates the two distributions. We compare different measures of similarity (metrics) by their ability to separate these distributions. We find that these metrics do not differ drastically in their performance, but that taking into account the cross-channel noise correlation significantly improves performance of all metrics. We also demonstrate the method on an independent dataset and show that neurons, as assigned by the procedure, have consistent physiological properties across files.     

Neuronal spike trains with exponential decay

Stochastic models for the spike discharge activity of neurons are analyzed. Model I treats only excitatory impulses occurring as Poisson events with exponential density of the jump magnitude, and, in the absence of these events, the subthreshold potential decays exponentially. A closed solution for the Laplace transform of the renewal density of the discharge is obtained by the imbedding method. Model III takes care of both excitatory and inhibitory impulses with exponential decay of the subthreshold potential between the jumps. Analytical closed solutions for the first passage problem are obtained in this care also. The mean interval time between the spikes and the stationary density of firing are obtained.     

Natural movies evoke spike trains with low spike time variability in cat primary visual cortex

Neuronal responses in primary visual cortex have been found to be highly variable. This has led to the widespread notion that neuronal responses have to be averaged over large numbers of neurons to obtain suitably invariant responses that can be used to reliably encode or represent external stimuli. However, it is possible that the high variability of neuronal responses may result from the use of simple, artificial stimuli and that the visual cortex may respond differently to dynamic, naturalistic images. To investigate this question, we recorded the responses of primary visual cortical neurons in the anesthetized cat under stimulation with time-varying natural movies. We found that cortical neurons on the whole exhibited a high degree of spike count variability, but a surprisingly low degree of spike time variability. The spike count variability was further reduced when all but the first spike in a burst were removed. We also found that responses exhibiting low spike time variability exhibited low spike count variability, suggesting that rate coding and temporal coding might be more compatible than previously thought. In addition, we found the spike time variability to be significantly lower when stimulated by natural movies as compared with stimulation using drifting gratings. Our results indicate that response variability in primary visual cortex is stimulus dependent and significantly lower than previous measurements have indicated.     

Measuring spike pattern reliability with the Lempel-Ziv-distance

Spike train distance measures serve two purposes: to measure neuronal firing reliability, and to provide a metric with which spike trains can be classified. We introduce a novel spike train distance based on the Lempel-Ziv complexity that does not require the choice of arbitrary analysis parameters, is easy to implement, and computationally cheap. We determine firing reliability in vivo by calculating the deviation of the mean distance of spike trains obtained from multiple presentations of an identical stimulus from a Poisson reference. Using both the Lempel-Ziv-distance (LZ-distance) and a distance focussing on coincident firing, the pattern and timing reliability of neuronal firing is determined for spike data obtained along the visual information processing pathway of macaque monkey (LGN, simple and complex cells of V1, and area MT). In combination with the sequential superparamagnetic clustering algorithm, we show that the LZ-distance groups together spike trains with similar but not necessarily synchronized firing patterns. For both applications, we show how the LZ-distance gives additional insights, as it adds a new perspective on the problem of firing reliability determination and allows neuron classifications in cases, where other distance measures fail.     

Presaccadic spike potentials with large horizontal eye movements

Presaccadic spike potentials were recorded from electrodes at the inner canthus and below the eye in 10 normal subjects for a range of horizontal saccades (5 degrees, 10 degrees, 20 degrees and 40 degrees). An eye movement trace was recorded for 20 abducting and 20 adducting saccades to determine the beginning of the saccade, and the spike potential back-averaged from this point. The latencies of the spike potential onset and peak were found with respect to the start of the eye movement and the amplitude from the onset to the peak was measured for each saccade size. The latency values remained constant throughout the range of eye movement sizes, although adducting saccades showed an earlier onset and peak latency than abducting saccades. The amplitude data, however, showed a definite relationship between saccade size and spike potential amplitude, with a significant increase in the amplitude for saccades between 10 degrees and 40 degrees (inner electrode abduction, lower electrode abduction and adduction P less than 0.01; inner electrode adduction P less than 0.05). A possible explanation of this increase in amplitude is hypothesised from a computer model of the action potential activity that may occur in the extraocular muscles before an eye movement.     

Severe epilepsy with multiple independent spike foci.

SUMMARY: Severe epilepsy with multiple independent spike foci is an electroclinical entity with the following characteristics: (1) EEG showing multiple independent spike foci (three or more foci in both hemisphere, i.e., at least one in each hemisphere) and diffuse slowing of the background activity, (2) very frequent multiple types of seizures but mainly generalized minor seizures, (3) frequent association with mental retardation and neurologic abnormalities, (4) underlying causes of various nonspecific prenatal, perinatal, and postnatal cerebral conditions, and (5) poor prognoses for seizures and psychomotor development. It represents a diffuse encephalopathy with mutual transition between other age-dependent epileptic encephalopathies. This electroclinical condition may be appropriately named Markand-Blume-Ohtahara syndrome, after Markand and Blume, who initially described in detail the EEG pattern of multifocal spike discharges with its major clinical correlates, and Ohtahara, who extensively studied the group of patients with both clinical and EEG characteristics and proposed the concept of severe epilepsy with multiple independent spike foci, classifying it as one type of generalized epilepsy.     

Changes in the presaccadic spike potential with age

Presaccadic spike potentials were recorded from an electrode below the eye to 20 degrees horizontal saccades in 2 groups of 10 subjects; a young group with a mean age of 26 years and an old group with a mean age of 77 years. The onset and peak latencies, relative to the beginning of the eye movement, and the onset-peak amplitudes were measured for abduction and adduction movements separately. There was no significant difference in the onset or peak latencies of the 2 groups with either abduction or adduction. The amplitude, however, was significantly greater in the young group with both abduction (P less than 0.01) and adduction (P less than 0.025). Possible explanations of these results are given and the implications of the findings on the investigation of presaccadic spike potentials in both normal and pathological subject groups are discussed.     

Presaccadic spike potential with congenital lateral rectus palsy

Presaccadic spike potentials were recorded with 20 degrees horizontal eye movements in a subject with a congenital left lateral rectus palsy. Electrodes at the inner and outer canthi recorded the eye movements and an electrode below the eye recorded the presaccadic spikes. The responses to 20 abducting and 20 adducting saccades were back-averaged from the onset of the eye movement with the wave forms for abduction and adduction averaged separately. Recordings were made from each eye under 2 conditions: firstly with the eye from which the spikes were being recorded fixating and secondly with the eye from which the spikes were not being recorded fixating. In each case the non-fixating eye was occluded throughout. Recordings were made with eye position monitored initially in the eye from which the spikes were recorded and repeated with eye position monitored in the other eye. Results show that spikes could be recorded during abduction and adduction movements of both eyes but only if eye position was monitored in the right eye. Using the left eye as position monitor gave very broad low amplitude spikes. When eye position was monitored in the right eye the spikes recorded during abduction of the left eye had a low amplitude compared to those recorded during right eye abduction; right eye adduction spikes were also of low amplitude. A possible explanation for these findings and their implications on future recordings in pathological cases are discussed.     

A device for spike train sampling with built-in memory

The described interface to a digital computer measures interspike interval durations with a resolution of 10 microseconds. A built-in first-in first-out (FIFO) memory relieves the host computer from frequent I/O intensive tasks. The internal FIFO buffer can store up to 512 data words (wordlength is 16 bit) and works on the dual-port principle. This way the acquisition of a neuronal spike train is completely independent of the computer's simultaneously ongoing data access. A simple handshake protocol between the interface and the computer prevents any overhead communication. The buffer architecture of the instrument releases the host computer from high speed I/O handling schemes like real-time, clock-controlled, polling or interrupt procedures, that would request assembly language support. The body of two software, driver routines in the BASIC and the PASCAL language is presented. A complete and detailed schematic diagram of the circuitry is included.     

A tool for synthesizing spike trains with realistic interference

Spike detection and spike sorting techniques are often difficult to assess because of the lack of ground truth data (i.e., spike timings for each neuron). This is particularly important for in vitro recordings where the signal to noise ratio is poor (as is the case for multi-electrode arrays at the bottom of a cell culture dish). We present an analysis of the transmission of intracellular signals from neurons to an extracellular electrode, and a set of MATLAB functions based on this analysis. These produce realistic signals from neighboring neurons as well as interference from more distant neurons, and Gaussian noise. They thus generate realistic but controllable synthetic signals (for which the ground truth is known) for assessing spike detection and spike sorting techniques. They can also be used to generate realistic (non-Gaussian) background noise. We use signals generated in this way to compare two automated spike-sorting techniques. The software is available freely on the web.     

To spike or not to spike: A probabilistic spiking neuron model

Spiking neural networks (SNN) are promising artificial neural network (ANN) models as they utilise information representation as trains of spikes, that adds new dimensions of time, frequency and phase to the structure and the functionality of ANN. The current SNN models though are deterministic, that restricts their applications for large scale engineering and cognitive modelling of stochastic processes. This paper proposes a novel probabilistic spiking neuron model (pSNM) and suggests ways of building pSNN for a wide range of applications including classification, string pattern recognition and associative memory. It also extends previously published computational neurogenetic models.     

Measuring spike train synchrony

Estimating the degree of synchrony or reliability between two or more spike trains is a frequent task in both experimental and computational neuroscience. In recent years, many different methods have been proposed that typically compare the timing of spikes on a certain time scale to be optimized by the analyst. Here, we propose the ISI-distance, a simple complementary approach that extracts information from the interspike intervals by evaluating the ratio of the instantaneous firing rates. The method is parameter free, time scale independent and easy to visualize as illustrated by an application to real neuronal spike trains obtained in vitro from rat slices. In a comparison with existing approaches on spike trains extracted from a simulated Hindemarsh-Rose network, the ISI-distance performs as well as the best time-scale-optimized measure based on spike timing.     

Generalized convulsions with diffuse spike and wave bursts emerging with Graves' disease

Thyroid hormone lowers the seizure threshold. We present the case of a female patient who developed generalized convulsions emerging with Graves' disease, and clarified the clinico-electroencephalographic characteristics. Before treatment, electroencephalography (EEG) showed 2- to 2.5-Hz diffuse spike and wave (SW) bursts, apparent during and after hyperventilation without any distinct absence seizure. Thiamazole treatment without any anticonvulsant led to a euthyroid state, convulsions resolved and EEG abnormalities normalized promptly. Clinical seizures were generalized tonic-clonic convulsions during sleep, and EEG showed diffuse SW bursts induced by hyperventilation. These characteristics suggested that epilepsy might correspond to idiopathic generalized epilepsy (IGE). IGE might be susceptible to hyperthyroidism. Cases of IGE emerging with hyperthyroidism, even if EEG paroxysms are advanced, may be improved using antithyroid pharmacotherapy alone.     

Factors affecting interictal spike discharges in adults with epilepsy.

We investigated various factors affecting interictal spike discharges (ISDs) in standard interictal EEGs of 203 consecutive cases with seizure(s). 94 EEGs (46%) showed ISDs. Yield was maximum (68%) when recordings were done within 2 days of a seizure; beyond this period, incidence of ISD did not change with time from the last seizure. EEGs of patients having greater than 12 seizures/year were more likely to contain ISD (68%) than the records of cases with less than 12 attacks/year (37-41%; P less than 0.001). Age and neurological status at the time of EEG, etiology and anticonvulsants did not influence the frequency of ISD. Analysis of serial EEGs (n = 512) from the study group showed that if initial 3 EEGs lacked ISD, yield from further standard EEGs is small.     

SPECT and epilepsy with continuous spike waves during slow-wave sleep

Ten cases of epilepsy with continuous spike waves in slow-wave sleep (CSWS) were evaluated using single photon emission computed tomography (SPECT); in eight patients the EEG paroxysmal abnormalities showed a predominant localization. SPECT carried out using^99mTc-HMPAO allows study of cerebral blood flow (CBF); the examination was performed during phases of drowsiness and the results compared to the EEG data. In four cases SPECT revealed areas of low CBF in sites corresponding to those of the prevalent EEG discharges; in two cases the areas of hypoperfusion did not correspond to those indicated by the EEG; lastly, in four cases SPECT results were negative. The areas of hypoperfusion were predominantly located in the frontal, temporal, and parietal regions. Furthermore, the percentage of positive SPECT results was significantly higher (five cases out of six) in the group in which the CSWS phase was prolonged for at least 1 year, compared to the group in which this phase lasted less than 1 year. Thus, in this type of epilepsy, SPECT reveals focal cortical areas of decreased CBF which correlated generally to the predominant sites of EEG abnormalities. A longer duration of the CSWS phase seems to be associated with a more significant cortical disorder, documented by the presence of areas of hypoperfusion.     

Participation of low-threshold Ca2+ spike in the Purkinje cells complex spike

In Purkinje cells from cerebellar slice cultures, low-threshold Ca spike (LTS) gives rise to complex bursts in the soma that resemble the complex spike induced by climbing fibers stimulation. We show that LTS is reduced by T-type and R-type Ca channel blockers (SNX-482, nickel, or mibefradil). We propose that LTS is generated by openings of T-type Ca channels (alpha-1G and/or alpha-1I subunits) and R-type Ca channels (alpha-1E subunit isoforms with a weak sensitivity to SNX-482 and to nickel). Using mibefradil we show that climbing fiber stimulation activates LTS, which contributes to the shape of the response. This Ca entry may be involved in Ca-dependent synaptic plasticity of the parallel fiber input induced by climbing fiber activation.