Alexa Riehle

Measurement of variability dynamics in cortical spike trains

We propose a method for the time-resolved joint analysis of two related aspects of single neuron variability, the spiking irregularity measured by the squared coefficient of variation (CV(2)) of the ISIs and the trial-by-trial variability of the spike count measured by the Fano factor (FF). We provide a calibration of both estimators using the theory of renewal processes, and verify it for spike trains recorded in vitro. Both estimators exhibit a considerable bias for short observations that count less than about 5-10 spikes on average. The practical difficulty of measuring the CV(2) in rate modulated data can be overcome by a simple procedure of spike train demodulation which was tested in numerical simulations and in real spike trains. We propose to test neuronal spike trains for deviations from the null-hypothesis FF=CV(2). We show that cortical pyramidal neurons, recorded under controlled stationary input conditions in vitro, comply with this assumption. Performing a time-resolved joint analysis of CV(2) and FF of a single unit recording from the motor cortex of a behaving monkey we demonstrate how the dynamic change of their quantitative relation can be interpreted with respect to neuron intrinsic and extrinsic factors that influence cortical variability in vivo. Finally, we discuss the effect of several additional factors such as serial interval correlation and refractory period on the empiric relation of FF and CV(2).

Preshaping and continuous evolution of motor cortical representations during movement preparation

While a goal‐directed movement is prepared, motor cortical neurons selectively change their activity in relation to prior information about movement direction. Only little is known, however, about the neuronal representation of partial information about this parameter. We investigated this question by training monkeys in a multidirectional centre‐out pointing task. A preparatory signal provided prior information about one, two or three possible adjacent targets, thus manipulating the level of certainty about movement direction. After a 1‐s delay, the response signal specified one of the precued targets to indicate the actual movement to be performed. Based on the directional tuning curves of individual motor cortical neurons determined during the reaction time interval, we constructed distributions of the population activation (DPAs), which we were then able to estimate as well during the preparatory period. We found that these distributions were preshaped by prior information, with peaks of activation centred over the range of precued movement directions. These peaks sharpened as the response signal approached, and shifted to the specified movement direction subsequent to that signal. Wider ranges of precued movement directions were represented by broader DPAs. Trials in which monkeys produced short reaction times were characterized by narrower distributions than trials with long reaction times. Our study thus provides evidence for (i) a graded preshaping of the neuronal population representation of movement direction by partial information about this parameter, and (ii) the continuous evolution of the preshaped population representation during the preparatory period towards movement initiation.

The predictive value for performance speed of preparatory changes in neuronal activity of the monkey motor and premotor cortex

Three monkeys were trained in a precued reaction time (RT) paradigm. An initial preparatory signal (PS) provided complete, partial or no information about direction and extent of a wrist flexion/extension movement which was executed after the second, response signal (RS). A PS providing information about direction shortened the RT much more than a PS indicating movement extent. The activity of 464 task-related neurons was recorded in the primary motor (MI) and premotor (PM) cortex. Not only the timing and amplitude of mean activity changes were analyzed, but also trial-by-trial correlation analyses between RT and discharge frequency during the PS-RS interval were conducted. Correlations were stronger in the condition of information about direction than in conditions of information about extent or no information. Considering directionally selective neurons, correlations were stronger when the neurons preferred direction than the opposite direction was precued. Correlation distributions were similar for MI and PM. Correlations were negative when preparatory activity increased during the PS-RS interval, and positive when activity decreased. Correlation analyses between behavioral performance and neuronal activity can thus be considered as a powerful tool to obtain a deeper insight into the functional mechanism of motor preparation.

Prior information preshapes the population representation of movement direction in motor cortex.

SINGLE neuron activity was recorded in monkey motor cortex during the execution of pointing movements in six directions. The amount of prior information was manipulated by varying the range of precued directions. A distribution of neural population activation was constructed in the space of movement directions. This population representation of movement direction was preshaped by the precue. Peak location and width reflected the precued range of movement directions. From this preshaped form, the population representation evolved continuously in time and gradually in parameter space toward a more sharply peaked distribution centered on the parameter value specified by the response signal. A theoretical model of motor programming generated a similar temporal evolution of an activation field representing movement direction.

Visually induced signal-locked neuronal activity changes in precentral motor areas of the monkey: hierarchical progression of signal processing

In the precuing paradigm, two successive visual signals were presented to trained monkeys. The first one, the preparatory signal, provided complete, partial or no prior information about parameters, such as direction and extent of the forthcoming wrist movement. After a delay, the illumination of a second visual signal, the response signal, called for execution of the movement and indicated the target. Signal-locked neuronal activity changes, i.e. those which occurred time-locked to the signal onset, were recorded in the premotor cortex and the primary motor cortex of the monkey and classified as selective or non-selective. Selective neurons were defined as those responding to particular information, for instance information about movement direction, provided by the signal, while non-selective neurons responded to all signals irrespective of any contained information. Clear latency differences according to both the selectivity of the neuronal response and the area in which the neuron was recorded could be discerned. The mean latency of non-selective activity changes was significantly shorter than that of selective activity changes. Furthermore, the mean latency of premotor cortical responses was significantly shorter than that of primary motor cortical responses. The data indicate the existence of distinct levels of signal processing from the very general to the highly specific.

The Local Field Potential Reflects Surplus Spike Synchrony

While oscillations of the local field potential (LFP) are commonly attributed to the synchronization of neuronal firing rate on the same time scale, their relationship to coincident spiking in the millisecond range is unknown. Here, we present experimental evidence to reconcile the notions of synchrony at the level of spiking and at the mesoscopic scale. We demonstrate that only in time intervals of significant spike synchrony that cannot be explained on the basis of firing rates, coincident spikes are better phase locked to the LFP than predicted by the locking of the individual spikes. This effect is enhanced in periods of large LFP amplitudes. A quantitative model explains the LFP dynamics by the orchestrated spiking activity in neuronal groups that contribute the observed surplus synchrony. From the correlation analysis, we infer that neurons participate in different constellations but contribute only a fraction of their spikes to temporally precise spike configurations. This finding provides direct evidence for the hypothesized relation that precise spike synchrony constitutes a major temporally and spatially organized component of the LFP.

The distribution of neuronal population activation (DPA) as a tool to study interaction and integration in cortical representations

In many cortical areas, simple stimuli or task conditions activate large populations of neurons. We hypothesize that such populations support processes of interaction within parametric representations and integration of multiple sources of input and we propose to study these processes using distributions of population activation (DPAs) as a tool. Such distributions can be viewed as neuronal representations of continuous stimulus or task parameters. They are built from basis functions contributed by each neuron. These functions may be explicitly chosen based on tuning curves or receptive field profiles. Or they may be determined by minimizing the distance between chosen target distributions and the constructed DPAs. In both cases, construction of the DPA is based on a set of reference conditions in which the stimulus or task parameters are sampled experimentally. In a second step, basis functions are kept fixed, and the DPAs are used to explore time dependent processing, interaction and integration of information. For instance, stimuli which simultaneously specify multiple parameter values can be used to study interactions within the parametric representation. We review an experiment, in which the representation of retinal position is probed in this way, revealing fast excitatory interactions among neurons representing similar retinal positions and slower inhibitory interactions among neurons representing dissimilar retinal positions. Similarly, DPAs can be used to analyze different sources of input that are fused within a parametric representation. We review an experiment in which the representation of the direction of goal-directed arm movements in motor and premotor cortex is studied when prior and current information about upcoming movement tasks are integrated.

Motion detection in flies: parametric control over ON-OFF pathways.

SummaryMicroscopic illumination of two neighbouring photoreceptor cells within a single ommatidium induces a strong sequence-dependent response in a directionally selective, motion-sensitive neuron. The response is characterized by a strong facilitation in the preferred direction and a weaker inhibition in the reverse direction. The data suggest that for each direction of apparent movement the signal from an ON-OFF pathway is released into the neuron via a parametric control mechanism which is activated by an adjacent channel.

Effects of preliminary perceptual output on neuronal activity of the primary motor cortex.

Observations of single neurons in the primary motor cortex of 1 monkey provided evidence that preliminary perceptual information reaches the motor system before perceptual analysis is complete. Neurons were recorded during a task in which 1 stimulus was assigned to a wrist flexion response and another was assigned to wrist extension. Two stimuli were assigned to a no-go response; each was visually similar to either the flexion or the extension stimulus. When a no-go stimulus was presented, neurons responded with weaker versions of the discharge patterns exhibited to the visually similar stimulus requiring a movement, suggesting that neurons receive partial perceptual information favoring that movement. Functionally separable neuronal populations were identified, and differences in the activations of these provide evidence about the functional effects of preliminary perceptual output on movement control processes.

Spike synchronization and firing rate in a population of motor cortical neurons in relation to movement direction and reaction time.

Abstract. We studied the dynamics of precise spike synchronization and rate modulation in a population of neurons recorded in monkey motor cortex during performance of a delayed multidirectional pointing task and determined their relation to behavior. We showed that at the population level neurons coherently synchronized their activity at various moments during the trial in relation to relevant task events. The comparison of the time course of the modulation of synchronous activity with that of the firing rate of the same neurons revealed a considerable difference. Indeed, when synchronous activity was highest, at the end of the preparatory period, firing rate was low, and, conversely, when the firing rate was highest, at movement onset, synchronous activity was almost absent. There was a clear tendency for synchrony to precede firing rate, suggesting that the coherent activation of cell assemblies may trigger the increase in firing rate in large groups of neurons, although it appeared that there was no simple parallel shifting in time of these two activity measures. Interestingly, there was a systematic relationship between the amount of significant synchronous activity within the population of neurons and movement direction at the end of the preparatory period. Furthermore, about 400 ms later, at movement onset, the mean firing rate of the same population was also significantly tuned to movement direction, having roughly the same preferred direction as synchronous activity. Finally, reaction time measurements revealed a directional preference of the monkey with, once again, the same preferred direction as synchronous activity and firing rate. These results lead us to speculate that synchronous activity and firing rate are cooperative neuronal processes and that the directional matching of our three measures – firing rate, synchronicity, and reaction times – might be an effect of behaviorally induced network cooperativity acquired during learning.