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Register a new userElectrical neurostimulation for chronic pain: on selective relay of sensory neural activities in myelinated nerve fibers
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Chronic pain affects about 100 million adults in the US. Despite their great need, neuropharmacology and neurostimulation therapies for chronic pain have been associated with suboptimal efficacy and limited long-term success, as their mechanisms of action are unclear. Yet current computational models of pain transmission suffer from several limitations. In particular, dorsal column models do not include the fundamental underlying sensory activity traveling in these nerve fibers. We developed a (simple) simulation test bed of electrical neurostimulation of myelinated nerve fibers with underlying sensory activity. This paper reports our findings so far. Interactions between stimulation-evoked and underlying activities are mainly due to collisions of action potentials and losses of excitability due to the refractory period following an action potential. In addition, intuitively, the reliability of sensory activity decreases as the stimulation frequency increases. This first step opens the door to a better understanding of pain transmission and its modulation by neurostimulation therapies.
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Pain is a multidimensional process, which can be modulated by emotions, however, the mechanisms underlying this modulation are unknown. We used pictures with different emotional valence (negative, positive, neutral) as primes and applied electrical painful stimuli as targets to healthy participants. We assessed pain intensity and unpleasantness ratings and recorded electroencephalograms (EEG). We found that pain unpleasantness, and not pain intensity ratings were modulated by emotion, with increased ratings for negative and decreased for positive pictures. We also found two consecutive gamma band oscillations (GBOs) related to pain processing from time frequency analyses of the EEG signals. An early GBO had a cortical distribution contralateral to the painful stimulus, and its amplitude was positively correlated with intensity and unpleasantness ratings, but not with prime valence. The late GBO had a centroparietal distribution and its amplitude was larger for negative compared to neutral and positive pictures. The emotional modulation effect (negative versus positive) of the late GBO amplitude was positively correlated with pain unpleasantness. The early GBO might reflect the overall pain perception, possibly involving the thalamocortical circuit, while the late GBO might be related to the affective dimension of pain and top-down related processes.
Model-based studies of auditory nerve responses to electrical stimulation can provide insight into the functioning of cochlear implants. Ideally, these studies can identify limitations in sound processing strategies and lead to improved methods for providing sound information to cochlear implant users. To accomplish this, models must accurately describe auditory nerve spiking while avoiding excessive complexity that would preclude large-scale simulations of populations of auditory nerve fibers and obscure insight into the mechanisms that influence neural encoding of sound information. In this spirit, we develop a point process model of the auditory nerve that provides a compact and accurate description of neural responses to electric stimulation. Inspired by the framework of generalized linear models, the proposed model consists of a cascade of linear and nonlinear stages. We show how each of these stages can be associated with biophysical mechanisms and related to models of neuronal dynamics. Moreover, we derive a semi-analytical procedure that uniquely determines each parameter in the model on the basis of fundamental statistics from recordings of single fiber responses to electric stimulation, including threshold, relative spread, jitter, and chronaxie. The model also accounts for refractory and summation effects that influence the responses of auditory nerve fibers to high pulse rate stimulation. Throughout, we compare model predictions to published physiological data and explain differences in auditory nerve responses to high and low pulse rate stimulation. We close by performing an ideal observer analysis of simulated spike trains in response to sinusoidally amplitude modulated stimuli and find that carrier pulse rate does not affect modulation detection thresholds.
Determining how much of the sensory information carried by a neural code contributes to behavioral performance is key to understand sensory function and neural information flow. However, there are as yet no analytical tools to compute this information that lies at the intersection between sensory coding and behavioral readout. Here we develop a novel measure, termed the information-theoretic intersection information $I_{II}(S;R;C)$, that quantifies how much of the sensory information carried by a neural response R is used for behavior during perceptual discrimination tasks. Building on the Partial Information Decomposition framework, we define $I_{II}(S;R;C)$ as the part of the mutual information between the stimulus S and the response R that also informs the consequent behavioral choice C. We compute $I_{II}(S;R;C)$ in the analysis of two experimental cortical datasets, to show how this measure can be used to compare quantitatively the contributions of spike timing and spike rates to task performance, and to identify brain areas or neural populations that specifically transform sensory information into choice.
Current neuroscience focused approaches for evaluating the effectiveness of a design do not use direct visualisation of mental activity. A recurrent neural network is used as the encoder to learn latent representation from electroencephalogram (EEG) signals, recorded while subjects looked at 50 categories of images. A generative adversarial network (GAN) conditioned on the EEG latent representation is trained for reconstructing these images. After training, the neural network is able to reconstruct images from brain activity recordings. To demonstrate the proposed method in the context of the mental association with a design, we performed a study that indicates an iconic design image could inspire the subject to create cognitive associations with branding and valued products. The proposed method could have the potential in verifying designs by visualizing the cognitive understanding of underlying brain activity.
The generation of action potential brings into play specific mechanosensory stimuli manifest in the variation of membrane capacitance, resulting from the selective membrane permeability to ions exchanges and testifying to the central role of electromechanical processes in the buildup mechanism of nerve impulse. As well established [See e.g. D. Gross et al, Cellular and Molecular Neurobiology vol. 3, p. 89 (1983)], in these electromechanical processes the net instantaneous charge stored in the membrane is regulated by the rate of change of the net fluid density through the membrane, orresponding to the difference in densities of extacellular and intracellular fluids. An electromechanical model is proposed for which mechanical forces are assumed to result from the flow of ionic liquids through the nerve membrane, generating pressure waves stimulating the membrane and hence controlling the net charge stored in the membrane capacitor. The model features coupled nonlinear partial differential equations: the familiar Hodgkin-Huxleys cable equation for the transmembrane voltage in which the membrane capacitor is now a capacitive diode, and the Heimburg-Jacksons nonlinear hydrodynamic equation for the pressure wave controlling the total charge in the membrane capacitor. In the stationary regime, the Hodgkin-Huxley cable equation with variable capacitance reduces to a linear operator problem with zero eigenvalue, the bound states of which can be obtained exactly for specific values of characteristic parameters of the model. In the dynamical regime, numerical simulations of the modified Hodgkin-Huxley equation lead to a variety of typical figures for the transmembrane voltage, reminiscent of action potentials observed in real physiological contexts.
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