Quantitative architecture distinguishes prefrontal cortical systems in therhesus monkey

The prefrontal cortex encompasses a large and heterogeneous set of areas, w hose borders have been variously mapped in different architectonic studies. Differences in cortical maps present a formidable problem in comparing dat a across studies and in constructing databanks on the connections and funct ional attributes of cortical areas. Here we used quantitative approaches to cortical mapping to investigate (i) if architectonic areas of the prefront al cortex in adult rhesus monkeys have unique profiles and (ii) if groups o f architectonic areas belonging to distinct cortical types, ranging from ag ranular to eulaminate, have similar features. In addition, we used multidim ensional analyses to see if, and how, prefrontal areas form clusters when m ultiple features are considered simultaneously, We used quantitative unbias ed sampling procedures to estimate the areal and laminar density of neurons , glia and neurons positive for the calcium binding proteins parvalbumin (P V), calbindin (CB) and calretinin (CR) among 21 prefrontal areas or subdivi sions of areas. Neuronal density varied among the prefrontal cortices (rang e: 38 569 +/- 4078 to 58 708 +/- 2327 neurons/mm(3)); it was lowest in caud al orbitofrontal and medial areas (OPAII, OPro, 13, 24a, 32, M25) and highe st in lateral prefrontal areas (subdivisions of areas 46 and 8). Neurons po sitive for PV were most prevalent in lateral prefrontal areas and least pre valent in caudal orbitofrontal and medial prefrontal areas, whereas the opp osite trend was noted for neurons that expressed CB. Neurons positive for C R did not show regional differences, and the density of glia showed small v ariations among prefrontal cortices. The differences among areas, along wit h differences in the thickness of individual areas and layers, were used to establish a quantitative profile for each area. The results showed that di fferences in the density of neurons, and the preponderance of neurons posit ive for PV and CB, were related to different architectonic types of areas f ound within the prefrontal cortex. Conventional as well as multi-parameter statistical analyses distinguished at one extreme the agranular and dysgran ular (limbic) cortices, which were characterized by prominent deep layers ( V-VI), the lowest neuronal density, the highest ratio of glia/neurons, and the lowest density of PV and the highest for CB. At the other extreme, late ral eulaminate cortices were characterized by the highest density of neuron s, a prominent granular layer IV, denser supragranular (II-III) than infrag ranular (V-VI) layers, and a balanced distribution of neurons positive for PV and GB. The results provide insights into potentially different rates of development or maturation of limbic and eulaminate prefrontal areas, and t heir differential vulnerability in neurological and psychiatric diseases. T he quantitative methods used provide an objective approach to construct map s, address differences in nomenclature across studies, establish homologies in different species and provide a baseline to identify changes in patholo gic conditions.