Neuromodulatory control of brain network dynamics

Introduction

Spontaneous brain activity, the most expensive metabolic process of the human brain, is highly dynamic and continually evolves over timescales of seconds. Human neuroimaging has made it possible to map dynamic patterns of spontaneous network activity with increasing precision. However, our understanding of the origin, function, and organization of this phenomenon remains alarmingly limited.

Project Aim

This project aims to elucidate the physiological mechanisms and operational principles that govern spontaneous network dynamics (termed here "brain network dynamics" - BND). To achieve these goals, I will establish an integrated research platform that combines advanced manipulations and recordings of BND in the awake mouse brain.

Research Approach

To comprehensively probe the mechanisms that operate BND, I will carry out two complementary sets of causal manipulations that are conceptualized as:

1. Exogenous neuromodulation - synthetic (optogenetically generated, Aim 1)
2. Endogenous neuromodulation - intrinsic (neurotransmitter related, Aim 2)

Using this approach, I will:

a. Uncover the rhythms that causally sustain BND and establish how BND causally responds to (and can be controlled by) mechanistically precise exogenous neuromodulation.

b. Empirically test the hypothesis that cholinergic and noradrenergic transmission cooperatively control the intrinsic organization of BND, as well as the selective engagement of higher-order cortical systems relevant for attention and cognition.

Theoretical Framework

Crucially, multiscale network activity will be theoretically linked to dynamical regimes (brain states) of translational relevance via quantitative analyses.

Implications

This research will address fundamental questions regarding the neural mechanisms governing BND and the possibility of controlling its organization via targeted exogenous modulation, with important implications for basic, theoretical, and translational neuroscience.