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 a
ction 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.
In this paper, a nonparametric maximum likelihood (ML) estimator for band-limited (BL) probability density functions (pdfs) is proposed. The BLML estimator is consistent and computationally efficient. To compute the BLML estimator, three approximate
algorithms are presented: a binary quadratic programming (BQP) algorithm for medium scale problems, a Trivial algorithm for large-scale problems that yields a consistent estimate if the underlying pdf is strictly positive and BL, and a fast implementation of the Trivial algorithm that exploits the band-limited assumption and the Nyquist sampling theorem (BLMLQuick). All three BLML estimators outperform kernel density estimation (KDE) algorithms (adaptive and higher order KDEs) with respect to the mean integrated squared error for data generated from both BL and infinite-band pdfs. Further, the BLMLQuick estimate is remarkably faster than the KD algorithms. Finally, the BLML method is applied to estimate the conditional intensity function of a neuronal spike train (point process) recorded from a rats entorhinal cortex grid cell, for which it outperforms state-of-the-art estimators used in neuroscience.
