Cortical Computations Underlying Planning, Generating, and Orchestrating Complex Cognitive-Motor Sequences - Project Summary Activities of daily living (e.g., brushing one’s teeth) require a slew of brain regions to rapidly coordinate their responses to drive sequences of movements over long timescales. Recent progress resulting from applying classical tools from physical science and engineering to develop theories regarding how neural activity evolves across time has led to a number of new treatment options for movement disorders (e.g., motor prosthetics, deep brain stimulation, etc.). Activities of daily living, however, require production of complex cognitive-motor sequences. For example, motor cortex, which is the primary site for a large number of investigations for neural prosthetics applications, is only sensitive to the upcoming movement. Even a simple movement involving two arm reaches performed in succession, requires input from upstream brain regions. Thus, if we hope to restore the ability to orchestrate long timescale actions, we need to expand our scientific focus to study network-level interactions between brain regions. Relevant upstream areas include the supplementary motor area (SMA), which has been implicated in tracking and coordinating action sequences, and dorsolateral prefrontal cortex (dlPFC), which has been hypothesized to specify the correct order in which movements should be performed. Despite decades of research in the function of these areas, we still lack a concrete theory that describes the computations of these areas, characterizes their interactions, and proposes a mechanism of how they work together to orchestrate movement sequences. This project will attempt to fill this gap. This project will test the central hypothesis that movement sequences arise from the coordinated action of cortical regions that divide computational labor in specific ways. In particular, this project will investigate two fundamental questions. First, how does the brain (hypothesis: dlPFC) choose the right order in which to perform a movement sequence. Second, how does a brain area upstream of motor cortex (hypothesis: SMA) convert an abstract sequence of actions into movement commands that can be transmitted downstream in the right way at the right time. This project will test these hypotheses through a combination of developing a complex cognitive- motor task, acquiring large-scale simultaneously recorded measurements of neural activity using state-of-the-art electrophysiology tools, performing high-dimensional data analysis, and developing sophisticated neural network models of interacting brain regions. This project will facilitate direct interdisciplinary interactions between experimental motor neurophysiologist and theoretical neuroscientists at Columbia University. Moreover, the long-term objectives of this proposal will contribute to the core goal of NINDS by acquiring fundamental knowledge about movement control as it relates to development of therapeutics. The outcome of this project will result in key computational principles that underlie how the interaction between cortical regions gives rise to our ability to plan, orchestrate, and guide movements over long timescales.
