Application of point-process system identification techniques to complex physiological systems

This thesis is concerned with the application of system identification techniques to the analysis of complex physiological systems. The techniques are applied to neuronal spike-train data obtained from elements of the neuromuscular system. A brief description of the neuromuscular system is given in chapter 1, along with a more detailed discussion of the muscle spindle, which is the component of the neuromuscular system which this study deals with. In addition, some possibilities for system identification studies of the muscle spindle are discussed. The identification procedure is based on statistical methods for the treatment of point-process data. The point-process representation of a spike-train is introduced in chapter 2 with definitions of time and frequency domain point-process parameters. Estimates for these parameters are given, along with expressions for their asymptotic distributions. The linear point-process system identification model is introduced and estimates are described for the model parameters in terms of the previously defined point-process parameters. These point-process and linear parameter estimates are applied to muscle spindle spike-train data. In the analysis of a single spike-train certain important features only show up in the frequency domain, and for input and output spike-trains a linear transfer function type description is constructed in the frequency domain. The mathematical model of this transfer function is used as the basis for an analogue computer simulation of a subsystem of the muscle spindle. This consists of a linear first order filter followed by an encoder which generates output spikes. Data logged from the simulation is processed in the same manner as experimental data, and the effect of varying the simulation parameters on the linear model estimates is looked at. It is shown that in general the linear model description reflects the properties of the linear filter in the simulation, and varying the simulation parameters can be used to accurately match results from simulated data with those obtained from real data. Chapter 3 compares the point-process approach with a more conventional filtering and sampled data approach to estimate power spectra. The filtering of spike-trains with broad band spectra is investigated, and this shows up a pitfall in the choice of filter cut-off frequency. It is concluded that the point-process approach is preferable due to shorter computational times, and the well documented statistical propeties of the point-process estimates. The application of the point-process techniques described in chapter 2 to the analysis of more general spike-train data is considered in chapter 4. Three techniques for measuring the degree of coupling between two spike-trains are compared, and the point-process frequency domain measure is found to be the most sensitive. This measure is also applied to a data set containing a strong single periodicity, and the ability to detect coupling at a single harmonic is demonstrated. The analysis of coupling between spike-trains in the frequency domain is extended to deal with multiple spike-trains, and the ability to distinguish genuine coupling from the effect of a common input is shown to be a powerful tool which can be used to investigate communications pathways in neural systems. Finally, one special feature of the muscle spindle response to a spike-train input is analysed using the simulation. It is demonstrated that the point-process approach can produce results about a particular phenomenon from a single experiment much more rapidly than using a repetitive trial and error approach. Chapter 5 considers the extension of the linear point-process identification model introduced in chapter 2. Higher order time and frequency domain point-process parameters are defined and estimates given. In the time domain, a new technique for rapidly generating higher order time domain parameters is developed. The quadratic point-process model is introduced and solutions for its parameters given. These estimates are applied to muscl

Neurons with stereotyped and rapid responses provide a reference frame for relative temporal coding in primate auditory cortex

The precise timing of spikes of cortical neurons relative to stimulus onset carries substantial sensory information. To access this information the sensory systems would need to maintain an internal temporal reference that reflects the precise stimulus timing. Whether and how sensory systems implement such reference frames to decode time-dependent responses, however, remains debated. Studying the encoding of naturalistic sounds in primate (Macaca mulatta) auditory cortex we here investigate potential intrinsic references for decoding temporally precise information. Within the population of recorded neurons, we found one subset responding with stereotyped fast latencies that varied little across trials or stimuli, while the remaining neurons had stimulus-modulated responses with longer and variable latencies. Computational analysis demonstrated that the neurons with stereotyped short latencies constitute an effective temporal reference for relative coding. Using the response onset of a simultaneously recorded stereotyped neuron allowed decoding most of the stimulus information carried by onset latencies and the full spike train of stimulus-modulated neurons. Computational modeling showed that few tens of such stereotyped reference neurons suffice to recover nearly all information that would be available when decoding the same responses relative to the actual stimulus onset. These findings reveal an explicit neural signature of an intrinsic reference for decoding temporal response patterns in the auditory cortex of alert animals. Furthermore, they highlight a role for apparently unselective neurons as an early saliency signal that provides a temporal reference for extracting stimulus information from other neurons

The Spatial Structure of Stimuli Shapes the Timescale of Correlations in Population Spiking Activity

Throughout the central nervous system, the timescale over which pairs of neural spike trains are correlated is shaped by stimulus structure and behavioral context. Such shaping is thought to underlie important changes in the neural code, but the neural circuitry responsible is largely unknown. In this study, we investigate a stimulus-induced shaping of pairwise spike train correlations in the electrosensory system of weakly electric fish. Simultaneous single unit recordings of principal electrosensory cells show that an increase in the spatial extent of stimuli increases correlations at short (~10 ms) timescales while simultaneously reducing correlations at long (~100 ms) timescales. A spiking network model of the first two stages of electrosensory processing replicates this correlation shaping, under the assumptions that spatially broad stimuli both saturate feedforward afferent input and recruit an open-loop inhibitory feedback pathway. Our model predictions are experimentally verified using both the natural heterogeneity of the electrosensory system and pharmacological blockade of descending feedback projections. For weak stimuli, linear response analysis of the spiking network shows that the reduction of long timescale correlation for spatially broad stimuli is similar to correlation cancellation mechanisms previously suggested to be operative in mammalian cortex. The mechanism for correlation shaping supports population-level filtering of irrelevant distractor stimuli, thereby enhancing the population response to relevant prey and conspecific communication inputs. © 2012 Litwin-Kumar et al

The information transmitted by spike patterns in single neurons

Spike patterns have been reported to encode sensory information in several brain areas. Here we assess the role of specific patterns in the neural code, by comparing the amount of information transmitted with different choices of the readout neural alphabet. This allows us to rank several alternative alphabets depending on the amount of information that can be extracted from them. One can thereby identify the specific patterns that constitute the most prominent ingredients of the code. We finally discuss the interplay of categorical and temporal information in the amount of synergy or redundancy in the neural code.Comment: To be published in Journal of Physiology Paris 200

Information transmission in oscillatory neural activity

Periodic neural activity not locked to the stimulus or to motor responses is usually ignored. Here, we present new tools for modeling and quantifying the information transmission based on periodic neural activity that occurs with quasi-random phase relative to the stimulus. We propose a model to reproduce characteristic features of oscillatory spike trains, such as histograms of inter-spike intervals and phase locking of spikes to an oscillatory influence. The proposed model is based on an inhomogeneous Gamma process governed by a density function that is a product of the usual stimulus-dependent rate and a quasi-periodic function. Further, we present an analysis method generalizing the direct method (Rieke et al, 1999; Brenner et al, 2000) to assess the information content in such data. We demonstrate these tools on recordings from relay cells in the lateral geniculate nucleus of the cat.Comment: 18 pages, 8 figures, to appear in Biological Cybernetic

Bootstrap testing for cross-correlation under low firing activity

A new cross-correlation synchrony index for neural activity is proposed. The index is based on the integration of the kernel estimation of the cross-correlation function. It is used to test for the dynamic synchronization levels of spontaneous neural activity under two induced brain states: sleep-like and awake-like. Two bootstrap resampling plans are proposed to approximate the distribution of the test statistics. The results of the first bootstrap method indicate that it is useful to discern significant differences in the synchronization dynamics of brain states characterized by a neural activity with low firing rate. The second bootstrap method is useful to unveil subtle differences in the synchronization levels of the awake-like state, depending on the activation pathway.Comment: 22 pages, 7 figure