title: Stochastic optimal control of single neuron spike trains.
abstract: OBJECTIVE
  External control of spike times in single neurons can reveal important information about a neuron's sub-threshold dynamics that lead to spiking, and has the potential to improve brain-machine interfaces and neural prostheses. The goal of this paper is the design of optimal electrical stimulation of a neuron to achieve a target spike train under the physiological constraint to not damage tissue.
  
  
  METHODS
  We pose a stochastic optimal control problem to precisely specify the spike times in a leaky integrate-and-fire (LIF) model of a neuron with noise assumed to be of intrinsic or synaptic origin. In particular, we allow for the noise to be of arbitrary intensity. The optimal control problem is solved using dynamic programming when the controller has access to the voltage (closed-loop control), and using a maximum principle for the transition density when the controller only has access to the spike times (open-loop control).
  
  
  RESULTS
  We have developed a stochastic optimal control algorithm to obtain precise spike times. It is applicable in both the supra-threshold and sub-threshold regimes, under open-loop and closed-loop conditions and with an arbitrary noise intensity; the accuracy of control degrades with increasing intensity of the noise. Simulations show that our algorithms produce the desired results for the LIF model, but also for the case where the neuron dynamics are given by more complex models than the LIF model. This is illustrated explicitly using the Morris-Lecar spiking neuron model, for which an LIF approximation is first obtained from a spike sequence using a previously published method. We further show that a related control strategy based on the assumption that there is no noise performs poorly in comparison to our noise-based strategies. The algorithms are numerically intensive and may require efficiency refinements to achieve real-time control; in particular, the open-loop context is more numerically demanding than the closed-loop one.
  
  
  CONCLUSIONS
  Our main contribution is the online feedback control of a noisy neuron through modulation of the input, taking into account physiological constraints on the control. A precise and robust targeting of neural activity based on stochastic optimal control has great potential for regulating neural activity in e.g. prosthetic applications and to improve our understanding of the basic mechanisms by which neuronal firing patterns can be controlled in vivo.
authors.affiliation: Department of Mathematics and Statistics, University of Ottawa, Ottawa, ON K1N 6N5, Canada. Department of Mathematical Sciences, University of Copenhagen, DK-1165 Copenhagen, Denmark.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Iolov
authors.forename: Susanne
authors.initials: S
authors.lastname: Ditlevsen
authors.forename: André
authors.initials: A
authors.lastname: Longtin
mesh_terms: D000465:Algorithms; D055592:Biophysical Phenomena; D003198:Computer Simulation; D055724:Electrophysiological Phenomena; D025461:Feedback, Physiological; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D012984:Software; D013269:Stochastic Processes; D009435:Synaptic Transmission / Q000502:physiology