Cytoarchitectonic, receptor distribution and functional connectivity analyses of the macaque frontal lobe

Abstract

Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas, including novel subdivisions of Walker’s areas 10, 9, 8B, and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Indeed, structural and functional organization of subdivisions encompassing areas 46 and 12 demonstrated significant differences in the interareal levels of α2 receptors. Furthermore, multivariate analysis included receptor fingerprints of previously identified 16 motor areas in the same macaque brains and revealed 5 clusters encompassing frontal lobe areas. We used the MRI datasets from the non-human primate data sharing consortium PRIME-DE to perform functional connectivity analyses using the resulting frontal maps as seed regions. In general, rostrally located frontal areas were characterized by bigger fingerprints, that is, higher receptor densities, and stronger regional interconnections. Whereas more caudal areas had smaller fingerprints, but showed a widespread connectivity pattern with distant cortical regions. Taken together, this study provides a comprehensive insight into the molecular structure underlying the functional organization of the cortex and, thus, reconcile the discrepancies between the structural and functional hierarchical organization of the primate frontal lobe. Finally, our data are publicly available via the EBRAINS and BALSA repositories for the entire scientific community.

Different subregions of monkey lateral prefrontal cortex respond to abstract sequences and their components

“…Our main goals were to 1) test anatomical specificity in whether sequence related responses previously observed in area 46 of DLPFC were unique to a specific subregion of area 46; 2) test functional specificity in whether similar responses would be observed in the absence of a visual sequential rule; and 3) to determine if there is anatomical and functional specificity in sequence related dynamics that parallel those in humans (ramping). A growing body of literature has highlighted both anatomical and functional distinctions across DLPFC subregions (Rapan et al 2023). Further, previous work has identified networks in the frontal cortex that are involved in processing timing structures (Onoe et al 2001;Genovesio et al 2006;Chiba et al 2021), raising the possibility that the structured timing could be a component of the neural response in the DLPFC.…”

“…To address the first question, of anatomical specificity and whether sequence representations were unique to subregions of area 46 within the DLPFC, we used new regions of interest (ROI) that tiled area 46 and replicated previous analyses during the SEQ task (Yusif Rodriguez, et al, 2023). First, to tile area 46 we used the MEBRAINS Multilevel Macaque Brain Atlas (Rapan et al 2023;Balan et al 2024)that parcellated area 46 according to cytoarchitectonic divisions augmented by functional connectivity and neurochemical data. This atlas divides area 46 into eight distinct regions (four anterior and four posterior) that are then divided into dorsal and ventral shoulder and fundus regions (Figure 2A,B).…”

“…Our next goal was to determine the anatomical specificity of the onset deviant responses in right p46f. Previous work has demonstrated that area 46 contains anatomical and functional subdivisions (Tanji and Hoshi 2008;Sallet et al 2013;Saleem et al 2014;Ahuja and Yusif Rodriguez 2022;Jung et al 2022;Xu et al 2022;Rapan et al 2023). The involvement of these subregions in abstract visual sequence representation was previously unstudied, leaving the specificity of these responses an open question.…”

“…15 mm) along with its dorsal and ventral banks. Though seminal studies have identified subdivisions within this region (Petrides and Pandya 1984;Petrides 2005), the exact borders and subdivisions of monkey area 46, along with its relation to human area 46, have been debated and revised for decades (e.g., Walker 1940;Petrides and Pandya 1984Petrides 2005;Petrides et al 2012;Rapan et al 2023) Functional evidence has also indicated that there are subdivisions within area 46 (Tanji and Hoshi 2008;Sallet et al 2013;Saleem et al 2014;Ahuja and Yusif Rodriguez 2022;Jung et al 2022;Xu et al 2022;Rapan et al 2023). Together, these anatomical and functional mappings indicate that there are meaningful subdivisions within monkey area 46 and thus, raise the question of how particular functional responses, such as abstract visual sequence representation, may correspond to these mappings.…”

“…To investigate the anatomical and functional specificity of abstract visual sequence responses in monkey LPFC, we took a two-fold approach. First, we took advantage of a recent parcellation of monkey LPFC that accounted for both anatomical and functional differences across the region (Rapan et al 2023). We used this parcellation as the basis for mapping regions of interest (ROIs) that tiled area 46 within the LPFC.…”