General problem:
When we observe the world, we do not merely act upon our observations. Rather, we use our prior experience with the environment to make decisions that are statistically optimal in most cases. Nowhere is this phenomenon more true than it is for timing. We have strong prior expectations of the speed of cars on the highway, or of the timing of a ball falling under the influence of gravity, or the time a tennis serve will reach our racket. These anecdotal ideas have been studied by decades of psychophysical experiments and formalized for human timing behaviors through mathematical modeling. However, until now, we do not understand how the brain stores and processes these sophisticated behaviors. The goal of this project, PredOpt, was to investigate neural mechanisms of such behaviors that involve rapid timing movements.
Benefits for society:
Cognitive psychology has studied the interplay of memory and sensation in timing for many decades and has developed a good understanding of these behaviors. However, in the clinic, loss of cognition related to temporal skills is complex and it is virtually impossible to concretely diagnose symptoms arising from loss of such functions. This is why in PredOpt we aimed to make steps towards uncovering the neural circuitry behind cognitive aspects of timing, where the memory of temporal experiences is stored and acquired. We aimed to develop mathematical models of these neural pathways so that we could test loss of function and make predictions for what consequences may arise. This has two benefits. 1) It helps us understand how the healthy brain utilizes memory and cognition to perform skillful and well-timed movements. 2) By understanding neural mechanisms that underlie rapid anticipation and prediction during well-timed movements, clinicians can establish better links between symptoms and potential pathways that are causing specific loss of function.
Overall objections:
We had the following overall objectives for PredOpt:
1) To identify a neural pathway where the memory of sub-second time intervals is acquired, stored and processed.
2) To manipulate the experience of the animal and test whether the pathway reflects this change in experience
3) To develop a mathematical model of the neural mechanism by which this experience is acquired and generate predictions for future clinical and neuroscientific investigations.
This work is performed in the mouse model because the expected pathways responsible for these behaviors lie in the cerebellum, which is a structure that is phylogenetically preserved in all mammals and therefore we expect a basis for clinical translation to primate models.
