Norepinephrine-mediated arousal fluctuations drive inverted U-shaped functional connectivity dynamics.

Area of Science:

• Neuroscience
• Systems Neuroscience
• Cognitive Neuroscience

Background:

• Arousal states dynamically influence brain function and behavior, a concept described by the Yerkes-Dodson law.
• The specific functional network mechanisms underlying this inverted U-shaped relationship are not well understood.

Purpose of the Study:

• To investigate the functional network substrates of arousal-modulated brain activity and behavior.
• To elucidate the causal role of the locus coeruleus-norepinephrine (LC-NE) system in shaping these dynamics.

Main Methods:

• Integrated functional magnetic resonance imaging (fMRI) with simultaneous electroencephalography (EEG) in humans and awake mice.
• Utilized invasive multimodal neural recordings and targeted manipulations of LC-NE neurons in mice.
• Combined EEG-fMRI with LC-NE system manipulations in awake mice.

Main Results:

• Found that arousal levels modulate global functional connectivity (FC) dynamics in an inverted U-shaped manner, peaking at moderate arousal.
• Demonstrated a significant correlation between these inverted U-shaped FC dynamics and arousal-modulated behavioral performance.
• Revealed the causal contribution of the LC-NE system to these arousal-dependent FC dynamics, with the inverted U-shape dependent on baseline arousal.

Conclusions:

• Uncovered the functional network basis underlying the Yerkes-Dodson law.
• Established the causal role of the norepinephrine (NE)-mediated arousal fluctuations, originating from the LC-NE system, in driving the observed inverted U-shaped brain dynamics and behavior.