Causal evidence for cholinergic stabilization of attractor landscape dynamics

Area of Science:

• Neuroscience
• Systems Neuroscience
• Cognitive Neuroscience

Background:

• Neuromodulatory systems significantly impact brain state dynamics.
• Previous research has largely been descriptive, lacking causal evidence.

Purpose of the Study:

• To causally investigate the role of cholinergic input from the basal forebrain in stabilizing cortical brain states.
• To quantify the impact of nucleus basalis of Meynert (nbM) inactivation on resting-state fMRI dynamics.

Main Methods:

• Combined local inactivation of the basal forebrain (nbM) with simultaneous resting-state fMRI in macaques.
• Analyzed changes in fMRI state transition energy barriers and information transfer.
• Utilized a neurodynamical model to simulate cholinergic effects on neuronal firing and adaptation.

Main Results:

• Inactivation of the nbM decreased energy barriers for fMRI state transitions in cortical activity.
• Specific nbM sub-region inactivation selectively affected information transfer in connected cortical areas.
• Neurodynamical modeling supported the experimental findings.

Conclusions:

• The cholinergic system, particularly input from the nbM, plays a critical causal role in stabilizing macroscale brain state dynamics.
• Cholinergic projections are essential for maintaining the stability of ongoing cortical activity patterns.