Slow rhythmic activity of caudate neurons in the cat: Statistical analysis of caudate neuronal spike trains

Spike trains of caudate neurons initially having mean interspike intervals of less than 4 ms were analyzed with progressive administration of pentobarbital (5 to 20 mg/kg). Among the neurons investigated, 77% (N = 79) showed evidence of a rhythmic basis of their activity in first-order interspike interval histograms and/or autocorrelation histograms in the course of becoming silent due to progressive administration of pentobarbital. Although the rhythmicies of given units varied depending on the level of anesthesia the most prominent cycle was almost always within the range of 200 to 320 ms; the majority were not discernable on visual inspection of the spike trains. Cortical stimuli reset the cycle. Cross-correlation histograms constructed from pairs of caudate neurons provided some evidence that their spontaneous firing was mutually inhibited. The possibility that the rhythmicities might arise from such mutual inhibition of spontaneously firing caudate neurons is discussed.     

An improved method for the estimation of firing rate dynamics using an optimal digital filter

In most neural systems, neurons communicate by means of sequences of action potentials or 'spikes'. Information encoded by spike trains is often quantified in terms of the firing rate which emphasizes the frequency of occurrence of action potentials rather than their exact timing. Common methods for estimating firing rates include the rate histogram, the reciprocal interspike interval, and the spike density function. In this study, we demonstrate the limitations of these aforementioned techniques and propose a simple yet more robust alternative. By convolving the spike train with an optimally designed Kaiser window, we show that more robust estimates of firing rate are obtained for both low and high-frequency inputs. We illustrate our approach by considering spike trains generated by simulated as well as experimental data obtained from single-unit recordings of first-order sensory neurons in the vestibular system. Improvements were seen in the prevention of aliasing, phase and amplitude distortion, as well as in the noise reduction for sinusoidal and more complex input profiles. We review the generality of the approach, and show that it can be adapted to describe neurons with sensory or motor responses that are characterized by marked nonlinearities. We conclude that our method permits more robust estimates of neural dynamics than conventional techniques across all stimulus conditions.     

A nonparametric approach for detection of bursts in spike trains

In spike-train data, bursts are considered as a unit of neural information and are of potential interest in studies of responses to any sensory stimulus. Consequently, burst detection appears to be a critical problem for which the Poisson-surprise (PS) method has been widely used for 20 years. However, this method has faced some recurrent criticism about the underlying assumptions regarding the interspike interval (ISI) distributions. In this paper, we avoid such assumptions by using a nonparametric approach for burst detection based on the ranks of ISI in the entire spike train. Similar to the PS statistic, a “Rank surprise” (RS) statistic is extracted. A new algorithm performing an exhaustive search of bursts in the spike trains is also presented. Compared to the performances of the PS method on realizations of gamma renewal processes and spike trains recorded in cat auditory cortex, we show that the RS method is very robust for any type of ISI distribution and is based on an elementary formalization of the definition of a burst. It presents an alternative to the PS method for non-Poisson spike trains and is simple to implement.     

Paragigantocellularis stimulation induces beta-adrenergic hippocampal potentiation.

The nucleus paragigantocellularis (PGi) is the major excitatory glutamatergic input to the locus coeruleus (LC). Glutamate activation of the LC has previously been shown to produce beta-adrenergic-dependent potentiation of the perforant path- (PP) evoked population spike in the dentate gyrus (DG). The present study asks if electrical stimulation of the PGi, by activating the LC endogenously, can produce a parallel beta-receptor-dependent potentiation of the PP-evoked population spike. An optimal interstimulus interval (ISI) was determined for PGi-PP stimulation in urethane-anesthetized rats and propranolol was used to assess the role of noradrenergic beta-receptors. PGi stimulation potentiated the PP-evoked population spike at an optimal ISI of 30 ms. The population synaptic response slope and spike latency were not affected. Propranolol blocked the PGi-induced potentiation, as would be expected for beta-receptor-dependent modulation. The parallels between PGi- and LC-induced effects on the PP-evoked population spike suggest PGi stimulation offers an alternate method of LC activation for studies of LC's role in behavior.     

Vestibular influence on tongue activity

The vestibular system was electrically stimulated in cats anesthetized with ketamine. Peripheral stimulation by an electrode positioned in the vestibule evoked torsional contralateral eye deviations and an electromyogram (EMG) response in a contralateral dorsal neck extensor. Consistently associated with this well documented vestibular pattern was an EMG response in tongue protrusive muscles, at a latency of 13 +/- 5 (means +/- SD) ms. Stimulation in a specific part of the rostroventral lateral vestibular nucleus elicited the same combination of responses: torsional contralateral eye deviations, dorsal neck EMG, and tongue EMG at a latency of 14 +/- 3 ms. Possible tongue activation by current spread to peripheral and central neural structures was examined in detail. Cerebellar, V, VII, cochlear, IX, X, and XII nerve influences were considered. On the basis of combined evidence, it was concluded that the vestibular system does influence tongue activity.     

The individual replicability of mismatch negativity at short and long inter-stimulus intervals.

OBJECTIVES: The individual replicability of the mismatch negativity (MMN) event-related brain potential (ERP) was studied at two different inter-stimulus intervals (ISIs), to establish its potential value for routine clinical evaluation of sound discrimination and auditory sensory memory. METHODS: Ten healthy young subjects were presented sequences of 3 stimulus trains, in two recording sessions approximately 1 month apart. The stimuli in the trains were delivered at an ISI of 300 ms, whereas the inter-train intervals (ITIs) were 0.4 s and 4.0 s in different blocks. ERPs were averaged to standard (75 ms) and deviant (25 ms) tones started equiprobably the stimulus trains. RESULTS: Significant Pearson product-moment correlations coefficients were found between sessions at all scalp locations for the short ITI, when the MMN was quantified as the mean amplitude in the 100-200 ms latency window around its peak. However, none of the correlations reached significance for the longer ITI. CONCLUSIONS: MMN appears to be a reliable measure for single-case assessment and follow-ups when obtained at short ISIs and quantified as an integrated window of neuroelectric activation over a temporal span.     

Habituation of the auditory evoked potential in a short interstimulus interval paradigm

The present experiment was carried out to investigate elicitation and habituation of the auditory event related potentials with stimulus trains utilizing a short interstimulus intervals (ISI) of 1500 ms. Scalp event related potentials elicited by auditory stimuli were recorded in 10 male subjects. Thirty auditory stimuli were presented binaurally over headphones to every subject with a duration of 1000 ms, each with a constant ISI of 1500 ms. No task relevance was given to the stimuli. Wave-forms were collected using a Pentium 100 computer. All analyses were carried out over the 30 trials. In each single trial event related potentials, latencies and amplitudes of N1-P2 components were analyzed separately for four frequency bands (0.3-70, 0.3-4, 4-7, 7-13 Hz). Trend effects were tested with linear-regression analyses (N1-P2 amplitude x stimuli number). We found that the amplitude from the first stimulus decreased reliably across trial blocks of the N1-P2 components and that it was directly affected by ISI. The relevance of these results for the habituation is discussed.     

Multiple spike-train analysis using mutual interval matrix

The principal-component approach is applied to the analysis of sequences of neuronal action potentials (spike trains). Multiple spike trains are represented as a sequence of vectors of mutual interspike intervals and are considered to be part of the trajectory of a dynamic system. The trajectory matrix is decomposed into a number of ‘basic spike patterns’ and their relative magnitudes by singular-value decomposition. The representation provides a convenient framework for analysis of dynamic relations and cooperation between neurons in an observed network. Examples of applications to simulated and cerebellar data are presented.     

Comparing neuronal spike trains with inhomogeneous Poisson distribution: evaluation procedure and experimental application in cases of cyclic activity

A procedure is proposed to compare single-unit spiking activity elicited in repetitive cycles with an inhomogeneous Poisson process (IPP). Each spike sequence in a cycle is discretized and represented as a point process on a circle. The interspike interval probability density predicted for an IPP is computed on the basis of the experimental firing probability density; differences from the experimental interval distribution are assessed. This procedure was applied to spike trains which were repetitively induced by opening-closing movements of the distal article of a lobster leg. As expected, the density of short interspike intervals, less than 20-40 ms in length, was found to lie greatly below the level predicted for an IPP, reflecting the occurrence of the refractory period. Conversely, longer intervals, ranging from 20-40 to 100-120 ms, were markedly more abundant than expected; this provided evidence for a time window of increased tendency to fire again after a spike. Less consistently, a weak depression of spike generation was observed for longer intervals. A Monte Carlo procedure, implemented for comparison, produced quite similar results, but was slightly less precise and more demanding as concerns computation time.     

New concept for the recovery function of short-latency somatosensory evoked cortical potentials following median nerve stimulation.

OBJECTIVES: We investigated the recovery function of the cortical components of somatosensory evoked potentials (SEP) at a very short interstimulus interval (ISI, less than 10 ms) using an integrative computer system in 10 healthy subjects (age, 27-38 years). METHODS: The SEP and nerve action potentials were recorded at P3 with a reference of Fz in the International 10-20 System and the ipsilateral Erb's point, respectively. Double stimulation of the right median nerve with an ISI from 0.5 to 100 ms was performed to analyze the N20 and P30 components at less than 10 ms. RESULTS: The P30 component was recognized following the second stimulation at an ISI of over 1 ms, while N20 was not identified at an ISI of less than 9 ms. There appeared a sub-component of SEP at 1-12 ms ISI, which was not identified following a single stimulation under control conditions. CONCLUSIONS: The results indicated that the recovery function of given SEP components was not simply determined by the number of synapses interposed between the stimulus site and the generator source of the response in the central nervous system, but there might be a structural or functional process of low-cut filtering in the primary sensory cortex. We also considered that the final SEP waveform determined by the excitatory and inhibitory balance of the components, which could be changed with ISI, and that the existence of the sub-component might cause the complexity of the recovery curve and large inter-individual difference of the waveform.     

Effects of superimposed electrical stimulation on perceived discomfort and torque increment size and variability

Superimposed electrical stimulation techniques can be used to detect central activation failure (CAF), that is, incomplete central nervous system recruitment or suboptimal activation of motor units. The purpose of this study was to evaluate the effects of two stimulation parameters on perceived discomfort and torque increment size and variability. Discomfort was evaluated using a visual analog scale (0-100 mm) for pain. The rectus femoris muscle of the dominant leg of 24 young healthy men was stimulated during submaximal (80% maximal) voluntary contractions. The size and variability of torque increments and perceived discomfort were assessed following stimulation with: (1) pulse trains (100 HZ, 150 V, 0.2-ms pulse duration) of different lengths (50 ms and 100 ms); and (2) pulse trains (100 HZ, 100 ms, 150 V) with different pulse durations (0.2 ms and 0.1 ms). Pulse trains of 100 ms generated larger torque increments and produced less variability, but caused more discomfort than pulse trains of 50 ms. Average discomfort ratings for pulse trains of 100 ms were 43.1 mm, and of 50 ms were 53.2 mm. There was no difference in torque increment size or in variability between pulse trains with pulse durations of 0.1 ms and 0.2 ms, whereas discomfort was less for the shorter pulse durations; average discomfort ratings were 53.1 mm and 58.1 mm for pulse durations of 0.1 ms and 0.2 ms, respectively. Thus, the appropriate selection of stimulation parameters can reduce discomfort but maintain the ability to detect CAF.     

The refractory period of fast conducting corticospinal tract axons in man and its implications for intraoperative monitoring of motor evoked potentials.

OBJECTIVE: To determine the absolute and relative refractory period (RRP) of fast conducting axons of the corticospinal tract in response to paired high intensity (HI or supramaximal) and moderate intensity (MI or submaximal) electrical stimuli. The importance of the refractory period of fast conducting corticospinal tract axons has to be considered if repetitive transcranial electrical stimulation (TES) is to be effective for eliciting motor evoked potentials (MEPs) intraoperatively. METHODS: Direct (D) waves were recorded from the epidural space of the spinal cord in 14 patients, undergoing surgical correction of spinal deformities. To assess the absolute and RRPs of the corticospinal tract, paired transcranial electrical stimuli at interstimulus intervals (ISI) from 0.7 to 4.1 ms were applied. Recovery of conditioned D wave at short (2 ms) and long (4 ms) ISI was correlated with muscle MEP threshold. The refractory period for peripheral nerve was tested in comparison to that for the corticospinal tract. In four healthy subjects sensory nerve action potentials of the median nerve were studied after stimulation with paired stimuli. RESULTS: HI TES revealed a mean duration of 0.82 ms for the absolute refractory period of the corticospinal tract, while MI stimulation resulted in a mean refractory period duration of 1.47 ms. Stimuli of HI produced faster recovery of D wave amplitude during the RRP. Furthermore, short trains of transcranial electrical stimuli did not elicit MEPs when D wave showed incomplete recovery. A similar influence of stimulus intensity on recovery time was found for the refractory period of peripheral nerve. CONCLUSIONS: The recovery of D wave amplitude is dependent upon stimulus intensity. High intensity produces fast recovery. This is an important factor for the generation of MEPs. When HI TES is used to elicit MEPs, short and long ISIs are equally effective. When MI TES is used to elicit MEPs, only a long ISI of 4 ms is effective.     

Analog calculation of cumulative sums from peri-stimulus time histograms and application of the technique to the analysis of rhythmic discharge of lung afferents

This paper describes an analog circuit for calculating cumulative sums which makes the use of a programmable computer unnecessary. The circuit is simple, inexpensive and reliable. We found the cumulative sum analysis significantly improved our ability to detect quickly small trends in PSTHs constructed from the spike trains of lung stretch afferents.     

CENTRAL EFFECT OF BOTULINUM TOXIN TYPE A IN HUMANS

This study investigated the changes in the cortical excitability with a paired-pulse transcranial magnetic stimulation (TMS) model after a botulinum toxin type A (BTA) injection in normal humans. Ten healthy subjects were enrolled in the study, which involved applying paired TMS to the motor cortex and recording the motor evoked potentials (MEP) before and after the BTA injection. BTA (2.5 mouse units) was injected into the right extensor digitorium brevis muscle. The amplitudes of MEP during rest and the cortical silent period (CSP) for the period of the tonic muscle contraction were measured at an interstimulus interval (ISI) of 3 ms and 20 ms. One month and three months after BTA injection, the level of intracortical inhibition increased significantly at an ISI of 3 ms and the intracortical facilitation decreased at an ISI of 20 ms. The duration of CSP shortened significantly at an ISI of 3 ms 1 month after BTA injection, which was also shortened significantly at an ISI of 20 ms. These findings were maintained until 3 months after the injection. It was concluded that cortical excitability could be modified by BTA injection in normal humans.     

The mismatch negativity as an index of temporal processing in audition

Objectives: The relation of the mismatch negativity (MMN) elicitation with behavioral stimulus discrimination as well as the replicability of the MMN was evaluated for intervals between paired tones.Methods: The MMN, obtained in a passive oddball paradigm in two sessions separated by 4–21 days and behavioral responses (button presses to target stimuli) in a separate session were recorded from 10 adult healthy subjects. The standard stimulus (P=0.79) was a tone pair separated by a 120 ms silent inter-stimulus interval (ISI) and the deviant stimuli were tone pairs with an ISI of 100, 60, and 20 ms (P=0.07 for each).Results: The 20 and 60 ms ISI deviant tone pairs elicited a significant MMN during both recording sessions and they were also behaviorally discriminated, whereas neither did the 100 ms ISI deviant pair elicit significant MMN nor was it behaviorally discriminated. Furthermore, there was a significant correlation between the MMN and reaction times to the 20 and 60 ms ISI deviant pairs. The 20 ms ISI deviant stimulus elicited highly replicable MMNs (r=0.75), whereas the less well discriminated 60 ms ISI deviant pair did not (r=0.60).Conclusions: The MMN reflects discrimination accuracy of temporal sound intervals. Furthermore, when the physical difference between the standard and deviant tone pair in the temporal domain is large, it is elicited with high reliability.     

A pattern grouping algorithm for analysis of spatiotemporal patterns in neuronal spike trains. 1. Detection of repeated patterns

The existence of precise temporal relations in sequences of spike intervals, referred to as 'spatiotemporal patterns', is suggested by brain theories that emphasize the role of temporal coding. Specific analytical methods able to assess the significance of such patterned activity are extremely important to establish its function for information processing in the brain. This study proposes a new method called 'pattern grouping algorithm' (PGA), designed to identify and evaluate the statistical significance of patterns which differ from each other by a defined and small jitter in spike timing of the order of few ms. The algorithm performs a pre-selection of template patterns with a fast computational approach, optimizes the jitter for each spike in the template and evaluates the statistical significance of the pattern group using three complementary statistical approaches. Simulated data sets characterized by various types of known non stationarities are used for validation of PGA and for comparison of its performance to other methods. Applications of PGA to experimental data sets of simultaneously recorded spike trains are described in a companion paper (Tetko IV, Villa AEP. A pattern grouping algorithm for analysis of spatiotemporal patterns in neuronal spike trains. 2. Application to simultaneous single unit recordings. J Neurosci Method 2000; accompanying article).     

Central effect of botulinum toxin type A in humans

This study investigated the changes in the cortical excitability with a paired-pulse transcranial magnetic stimulation (TMS) model after a botulinum toxin type A (BTA) injection in normal humans. Ten healthy subjects were enrolled in the study, which involved applying paired TMS to the motor cortex and recording the motor evoked potentials (MEP) before and after the BTA injection. BTA (2.5 mouse units) was injected into the right extensor digitorum brevis muscle. The amplitudes of MEP during rest and the cortical silent period (CSP) for the period of the tonic muscle contraction were measured at an interstimulus interval (ISI) of 3 ms and 20 ms. One month and three months after BTA injection, the level of intracortical inhibition increased significantly at an ISI of 3 ms and the intracortical facilitation decreased at an ISI of 20 ms. The duration of CSP shortened significantly at an ISI of 3 ms 1 month after BTA injection, which was also shortened significantly at an ISI of 20 ms. These findings were maintained until 3 months after the injection. It was concluded that cortical excitability could be modified by BTA injection in normal humans.     

Phase locking of neuronal responses to the vertical refresh of computer display monitors in cat lateral geniculate nucleus and striate cortex

The proliferation of low-cost microcomputer systems has led to the use of these systems as alternatives to expensive display devices for visual physiology and psychophysics experiments. The video displays of these systems often lack the flexibility of achieving wide linear luminance ranges and high vertical refresh rates — two parameters which may influence data acquisition. We have examined the responses of neurons and pairs of neurons in cat LGN and striate cortex to bar and sinusoidal grating stimuli generated by a conventional PC-based VGA graphics card and displayed on a NEC Multisync + color monitor with a 60 Hz vertical (display) refresh rate. Responses to these stimuli were autocorrelated and power spectral densities (PSD) were calculated, revealing that the majority of simple and complex cortical cells and nearly all LGN cells exhibited significant peaks in their autocorrelations at 16.7 ms and in the PSD at 60 Hz. Responses to identical stimuli generated with an optical bench using an incandescent light source contained no power at 60 Hz. Furthermore, cross-correlations between the spike trains of neuron-pairs were severely contaminated by peaks directly attributable to the entrainment of the two elements of the pair to the vertical refresh signal. Thus, we suggest that the use of conventional computer displays introduces a temporal artifact into neuronal spike trains in both single and multiple spike train analysis.