Neuromodulatory processing in the bi-pathway brain architecture

The brain is inherently a complex and parallel system that processes both external and internal sensory cues to generate adaptive responses. Sensory cues encapsulate not only objective information about their physical and chemical properties but also subjective information related to their ecological significance. Objective information is processed and conveyed through relatively stereotyped sensorimotor pathways to drive behaviors, while subjective information is received and transmitted through relatively flexible neuromodulatory systems. These neuromodulatory pathways influence signal processing of the sensorimotor pathways at multiple stages by modulating neuronal excitability and the efficiency of synaptic transmission, thereby endowing animals with flexibility. This sophisticated neuromodulatory processing is finely tuned by the spatiotemporal dynamics of various neuromodulators released from specialized neuromodulatory neurons that encode sensory, motor as well as cognitive variables. Dysfunctions in neuromodulatory pathways disrupt spatiotemporal patterns of neuromodulators, which in turn compromise sensorimotor transformation and cognitive functions. This review aims to delineate the mechanisms and roles of neuromodulatory processing within the bi-pathway brain architecture and propose prospective research topics along with innovative experimental paradigms.