The Spiraling Cognitive-Emotional Brain: Combinatorial, Reciprocal, and Reentrant Macro-organization.

This article proposes a framework for understanding the macro-scale organization of anatomical pathways in the mammalian brain. The architecture supports flexible behavioral decisions across a spectrum of spatio-temporal scales. The proposal emphasizes the combinatorial, reciprocal, and reentrant connectivity-called CRR neuroarchitecture-between cortical, BG, thalamic, amygdala, hypothalamic, and brainstem circuits. Thalamic nuclei, especially midline/intralaminar nuclei, are proposed to act as hubs routing the flow of signals between noncortical areas and pFC. The hypothalamus also participates in multiregion circuits via its connections with cortex and thalamus. At slower timescales, long-range behaviors integrate signals across levels of the neuroaxis. At fast timescales, parallel engagement of pathways allows urgent behaviors while retaining flexibility. Overall, the proposed architecture enables context-dependent, adaptive behaviors spanning proximate to distant spatio-temporal scales. The framework promotes an integrative perspective and a distributed, heterarchical view of brain function.