Neuromodulatory Influences on Integration and Segregation in the Brain.

Cognitive function relies on the dynamic cooperation of specialized regions of the brain; however, the elements of the system responsible for coordinating this interaction remain poorly understood. In this Opinion article I argue that this capacity is mediated in part by competitive and cooperative dynamic interactions between two prominent metabotropic neuromodulatory systems – the cholinergic basal forebrain and the noradrenergic locus coeruleus (LC). I assert that activity in these projection nuclei regulates the amount of segregation and integration within the whole brain network by modulating the activity of a diverse set of specialized regions of the brain on a timescale relevant for cognition and attention. The dynamic balance between segregation and integration in the brain is crucial for cognitive function. The ascending arousal system is ideally placed to modulate dynamic network topology over time. The cholinergic basal forebrain facilitates segregation through the targeted alteration of multiplicative gain. The noradrenergic LC facilitates integration through the diffuse alteration of response gain. Coordinated activity between the cholinergic and noradrenergic system sets the balance between segregation and integration in the brain. [ABSTRACT FROM AUTHOR]