Recent whole-brain calcium imaging recordings of the nematode C. elegans have demonstrated that the neural activity associated with behavior is dominated by dynamics on a low-dimensional manifold that can be clustered according to behavioral states. Previous models of C. elegans dynamics have either been linear models, which cannot support the existence of multiple fixed points in the system, or Markov-switching models, which do not describe how control signals in C. elegans neural dynamics can produce switches between stable states. It remains unclear how a network of neurons can produce fast and slow timescale dynamics that control transitions between stable states in a single model. We propose a global, nonlinear control model which is minimally parameterized and captures the state transitions described by Markov-switching models with a single dynamical system. The model is fit by reproducing the timeseries of the dominant PCA mode in the calcium imaging data. Long and short time-scale changes in transition statistics can be characterized via changes in a single parameter in the control model. Some of these macro-scale transitions have experimental correlates to single neuro-modulators that seem to act as biological controls, allowing this model to generate testable hypotheses about the effect of these neuro-modulators on the global dynamics. The theory provides an elegant characterization of control in the neuron population dynamics in C. elegans. Moreover, the mathematical structure of the nonlinear control framework provides a paradigm that can be generalized to more complex systems with an arbitrary number of behavioral states.

We develop a principled mathematical framework for controlling nonlinear, networked dynamical systems. Our method integrates dimensionality reduction, bifurcation theory and emerging model discovery tools to find low-dimensional subspaces where feed-forward control can be used to manipulate a system to a desired outcome. The method leverages the fact that many high-dimensional networked systems have many fixed points, allowing for the computation of control signals that will move the system between any pair of fixed points. The sparse identification of nonlinear dynamics (SINDy) algorithm is used to fit a nonlinear dynamical system to the evolution on the dominant, low-rank subspace. This then allows us to use bifurcation theory to find collections of constant control signals that will produce the desired objective path for a prescribed outcome. Specifically, we can destabilize a given fixed point while making the target fixed point an attractor. The discovered control signals can be easily projected back to the original high-dimensional state and control space. We illustrate our nonlinear control procedure on established bistable, low-dimensional biological systems, showing how control signals are found that generate switches between the fixed points. We then demonstrate our control procedure for high-dimensional systems on random high-dimensional networks and Hopfield memory networks.

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