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 and introduced a novel subdivision of Walker’s areas 10, 9, 8B and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Since 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 five clusters encompassing frontal lobe areas. Based on the functional connectivity analysis, clustered areas showed similar connectivity distribution pattern. In particular, rostrally located areas (in clusters 1-2) were characterized by bigger fingerprints, i.e., higher receptor densities, and stronger regional interconnections. Whereas, more caudal areas (in clusters 3-5) had smaller fingerprints, but showed a widespread connectivity pattern with distant cortical regions. Taken together, present study provides a comprehensive insight into the molecular structure underlying the functional organization of the cortex and, thus, reconcile 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.

Dissociable representations of decision variables within subdivisions of macaque orbitofrontal and ventrolateral frontal cortex

“…These trajectories were then mapped to immunohistology stained sections and neurons were assigned to one of eight distinct ventral frontal cortex subdivisions based on the depth of each electrode at the time of recording (Tables 1 and 2). These subdivisions followed the detailed parcellations of this part of the frontal lobe reported by Price, Palomero-Gallagher, and colleagues (Carmichael and Price, 1994;Rapan et al, 2023).…”

“…7 and 9). Compared to other vlPFC subregions, 12l is more strongly connected, anatomically and functionally, to lateral prefrontal cortex, notably area 45 and 46v (Saleem et al, 2014;Rapan et al, 2023). These more dorsal parts of lateral frontal cortex are more closely associated with guiding attention and actions towards the goal of a decision and are directly connected to premotor areas (Miller and Cohen, 2001;Cai and Padoa-Schioppa, 2014).…”

“…Subdivisions of OFC and vlPFC are also distinct based on the connections that they send and receive from other parts of the prefrontal cortex, temporal, premotor, subcortical, and sensory areas (Carmichael and Price, 1995a, 1995b, 1996. Such distinct connectivity between dissociable subdivisions of ventral frontal is also observable at the level of fMRI functional connectivity in both human and monkeys (Kahnt et al, 2012;Rapan et al, 2023). Despite these clear differences, it is less clear if such anatomical distinctions are associated with variation in function across these subdivisions of OFC and vlPFC.…”

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

“…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).…”

M1 selective muscarinic allosteric modulation enhances cognitive flexibility and effective salience in nonhuman primates

“…One key open question from these insights is to what extent are attentional subcomponent processes supported by muscarinic signaling and whether there are sub-receptors of the muscarinic receptor family that differentially support separable subcomponent processes underlying attention, such as filtering of distracting information, enhancing the flexible updating and shifting of attention sets, or supporting robust goal representations during goal-directed behavior. Each of these diverse subcomponent processes has been associated in prior studies with the muscarinic M 1 muscarinic receptor, which is widely expressed in the cortex, striatum and hippocampus (19, 20) and may thus mediate some of these muscarinic pro-cognitive effects (2, 21).…”