THE MACAQUE CLAUSTRUM HUB: HOW INTRINSIC AND EXTRINSIC CLAUSTRAL CONNNECTIVITY SHAPE WHOLE-BRAIN NETWORKS

A publication describing transcriptomics and connectomics of the macaque claustrum defined four compartments (PSZs) where cell-type and connectivity profiles were highly correlated (Lei et al., 2025). Here, we define connection weight (via FLN) and hierarchical position (via SLN) to characterize the intrinsic and extrinsic connectivity of these four compartments. This indicates the individual centralities of each PSZ and reveals how each contributes to shaping whole-brain networks. Earlier models show cortical networks obey a wire minimization rule, formalized as the Exponential Distance Rule (EDR; Markov et al., 2013). Tracer injections suggest that claustral-cortical and claustral-claustral projections do not obey the EDR. Further, injections reveal pronounced regional differences: (i) regional differences in the reciprocity of cortico-claustral connectivity, while all cortical regions receive input from the claustrum, cortico-claustral reciprocity is much sparser in sensory areas; (ii) laminar origins show strong asymmetries, with a predominant supragranular origin from frontal regions to rostral, cognitively related PSZs, and a predominantly infragranular origin from caudal sensory regions to sensory-related PSZs. This indicates an inverted hierarchy relative to cortico-cortical networks. We examine whether intrinsic claustral connectivity reflects relations with cognitive and sensory regions. Analysis reveals regional variation in the contribution of each compartment as a major cortical hub. These results indicate the claustrum is not a homogeneous hub; its intrinsic connectivity organizes it into a structured system with an inverted hierarchical relationship with cortical networks. This architecture provides a structural basis for understanding the claustrum as a hub orchestrating cortical activity and a contributor to global brain-state regulation.