How neural activity is coordinated within local microcircuits and across brain regions to drive behavior is a central open question in neuroscience. Recent advances in massively-parallel neural recording tech- nologies are producing dynamic activity maps during complex behaviors, with single-neuron granularity and single-spike resolution. To reveal fundamental dynamic features in these large-scale datasets, new principled and scalable computational methods are urgently needed. To address this need, we will de- velop a broadly applicable, non-parametric inference framework for discovering dynamic computations from large-scale neural activity recordings. Our framework seeks a dynamical model of the data, but unlike existing techniques, does not require a priori model assumptions. Existing techniques commonly ?t data with simple ad hoc models, which often miss or distort de?ning dynamic features. Instead, our non-parametric approach explores the entire space of all possible dynamics in search for the model consistent with the data, and thereby eliminates a priori guess work, ambiguous model comparisons and model-induced biases.
We aim to develop optimization algorithms to effectively search through the space of all dynamical models, implement these algorithms on GPUs to achieve maximal computational speed, and derive information-theoretic bounds to quantify reliability of our computational methods. To demonstrate how our novel methods aid scienti?c discovery, we will employ them to examine decision- related activity in parietal and premotor cortices. While different theoretical models of decision-making have been proposed, it still remains unknown how decision computations are implemented on the level of individual neurons and neural populations. Our analyses will offer the ?rst computational models of decision-making rooted directly in neural data, reconcile stability of population dynamics with hetero- geneity of single-neuron responses, reveal differences in decision-computations across cortical layers, and identify differences in decision-related dynamics of excitatory vs. inhibitory neurons.

Public Health Relevance

Neural circuits in a mammalian brain generate dynamic activity patterns that support behavioral and cognitive functions and are distorted in mental disorders such as Parkinson, schizophrenia and epilepsy. Our research will develop unbiased computational methods to extract dynamics from large-scale neural activity recordings. We will use these novel methods to discover decision-related computations in neural activity recordings from two cortical areas in two different species. We will generate a general-purpose software BrainFlow implementing our mathematical algorithms along with a suite of visualization tools, which will be made freely available on a GitHub repository.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB026949-03
Application #
10002240
Study Section
Special Emphasis Panel (ZEB1)
Program Officer
Peng, Grace
Project Start
2018-09-20
Project End
2021-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724