A Simple Stimulatory Device for Evoking Point-like Tactile Stimuli: A Searchlight for LFP to Spike Transitions
Summary
To elucidate the complex transition from Local Field Potentials (LFPs) to spikes a suitable stimulator for light mechanical peripheral stimuli was built. As an application, the spiking activities recorded from somatosensory cortex were analyzed by a multi-objective optimization strategy. The results demonstrated that the proposed stimulator was able to deliver tactile stimuli with millisecond and millimeter precisions.
Abstract
Current neurophysiological research has the aim to develop methodologies to investigate the signal route from neuron to neuron, namely in the transitions from spikes to Local Field Potentials (LFPs) and from LFPs to spikes.
LFPs have a complex dependence on spike activity and their relation is still poorly understood1. The elucidation of these signal relations would be helpful both for clinical diagnostics (e.g. stimulation paradigms for Deep Brain Stimulation) and for a deeper comprehension of neural coding strategies in normal and pathological conditions (e.g. epilepsy, Parkinson disease, chronic pain). To this aim, one has to solve technical issues related to stimulation devices, stimulation paradigms and computational analyses. Therefore, a custom-made stimulation device was developed in order to deliver stimuli well regulated in space and time that does not incur in mechanical resonance. Subsequently, as an exemplification, a set of reliable LFP-spike relationships was extracted.
The performance of the device was investigated by extracellular recordings, jointly spikes and LFP responses to the applied stimuli, from the rat Primary Somatosensory cortex. Then, by means of a multi-objective optimization strategy, a predictive model for spike occurrence based on LFPs was estimated.
The application of this paradigm shows that the device is adequately suited to deliver high frequency tactile stimulation, outperforming common piezoelectric actuators. As a proof of the efficacy of the device, the following results were presented: 1) the timing and reliability of LFP responses well match the spike responses, 2) LFPs are sensitive to the stimulation history and capture not only the average response but also the trial-to-trial fluctuations in the spike activity and, finally, 3) by using the LFP signal it is possible to estimate a range of predictive models that capture different aspects of the spike activity.
Introduction
In the context of signal processing the impulse response provides a fundamental characterization of the behavior of a dynamical system.
Although the ideal impulse stimulus is practically not achievable, it is possible to obtain a reasonable approximation of it by using an actuator element that generates high frequency displacements. This type of light tactile-vibratory stimulation is known to target both deep skin (e.g. fast responding, fast adapting Pacinian corpuscles)2 and superficial receptors (e.g. low-threshold slowly adapting Merkel discoid structures)2.
Current stimulation devices, mainly piezoelectric actuators, are charged with a number of drawbacks, not least resonances and small displacements. To overcome these flaws, an alternative implementation of impulse-like stimulation is proposed by using a blunted tip (a cactus smoothed tip in our case) vertically mounted on the membrane center of a mid-range speaker cone. This provides the advantage of larger displacements and broader frequency spectrum.
An effective application of such a device was the study of the relevant neurophysiological problem of the LFPs to spikes dependency. Because of the subtle temporal association between these electrical events a finely regulated device was needed for delivering peripheral stimuli. The stimuli had to be as fast and spatially selective as possible in order to reduce the "background noise" and sharpen the signals of interest. To this purpose, the stimulation device and the stimulus delivery protocol were jointly optimized for the task. In this paper, we describe the technique and present some representative results.
A stimulation protocol based on randomized paired-pulses has been designed and optimized in order to avoid habituation. This protocol offered the advantage of classical paired pulses and reduced the possibility of spurious locking between stimuli and spontaneous periodical bursts of neuronal activity.
By using this randomized paired pulse it was possible to obtain fast and reliable LFP and spike responses and to capture the special feature of these responses related to the dependence of both LFPs and spikes on the stimulation history. Indeed, from the raw LFP responses, a set of three LFP features (the LFP itself, the LFP first derivative and phase of the first derivative) strongly correlating with the average spike response, was also extracted.
Few methods have been proposed to fit models that predict spikes from LFPs3,4. In general a critical point of the model fitting process, common also to the prediction of spike event from the stimulus signal, is constituted by the appropriate choice of the objective function to maximize/minimize. While a range of objective functions has been proposed (e.g. correlation and coherence)5 none of these jointly captures the whole complexity of spike responses. Accordingly, a novel framework based on multi-objective optimization is introduced. We show that by using the proposed devised and this computational framework it is possible to estimate a set of predictive models based on strong LFP to spike relationships.
Protocol
Representative Results
Discussion
This work firstly presented a new, simple and low-cost device enabling to deliver fast and spatially point-like sensory stimuli. Then a randomized paired pulse stimulation protocol and a set of computational analyses were validated. The overall aim was to establish a framework for the estimation of LFP-spike relations in electrophysiological recordings during tactile stimulation.
The device, the protocol and the analytical approach have jointly contributed to the result, namely the first demon…
Declarações
The authors have nothing to disclose.
Acknowledgements
SN and AGZ were supported by the PON 01-01297 VIRTUALAB funds.
Materials
| Microstepper | AB Transvertex (Stockholm, Sweden) | The microstepper used to pull down the electrode matrix | |
| 32 channels Cheetah System | Neuralynx (MT, USA) | The electrophysiological recording system | |
| L293D h-bridge | RS Components (Cinisello Balsamo, Italy) | The bridge used to connect the microcontroller to the speaker | |
| H21A3 Optical Interrupter Switch | Fairchild Semiconductor Corporation (San Jose, California) | The phototransistor used to estabilish the tip displacement | |
| Arduino Uno | Arduino (Duemilanove, Italy) | The microcontroller used to deliver current pulse to the speaker | |
| Microelectrode Matrices GB1 | FHC | ||
| Isoflurane | Rhodia Organique Fine Ltd. | The anaestetic used to prepare animals | |
| Stereotaxic apparatus | Narishighe (Tokyo, Japan) | ||
| Sprague-Dawley male rats | Charles River (Calco, LC, Italy) | ||
| Gallamine thriethiodide | Sigma-Aldrich | The compound used to curarize the animals | |
| Cresyl violet | Sigma-Aldrich | ||
| Topical antiseptics (Betadine 10%) | Meda Pharma (Milanm Italy) | ||
| Heparine | Sigma-Aldrich | ||
| Formaldehyde | Carlo Erba Reagents (Pomigliano Milanese, Milan, Italy) |
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