Forward frontal fields: phylogeny and fundamental function

“They contribute to prospective coding[41,42]; sensory working memory[43,44]; attention to objects, places, actions and intentions[36, 45 ,46]; response inhibition[47]; the categorization of objects, sounds and event sequences[48‐50]; the selection, generation and sequencing of multiple actions[51‐53]; problemsolving s…”

“Research on the ‘granular’ prefrontal cortex of humans emphasizes such processes as updating, manipulating and strategic controlofinformationstoredinshort-termmemory[33, 67 ]; establishingtasksetsandrules[68];mediatinghierarchies of behavioral control; behavioral inhibition; cognitive control in social situations[69];…”

“Neurophysiological results that had been interpreted as memory signals[ 35 ]enabled other interpretations, usually because crucial variables remained uncontrolled and often unmonitored.”

“The idea that the knowledge stored by the ‘granular’ prefrontal cortex concerns aspects of behavior agrees with previous proposals about its role in behavioral flexibility and the diversity of its cognitive contributions, as propounded for example by Duncan and colleagues[72, 73 ,75]and by Shallice and Norman[76,77]as…”

“They contribute to prospective coding[41,42]; sensory working memory[ 43 ,44]; attention to objects, places, actions and intentions[36,45,46]; response inhibition[47]; the categorization of objects, sounds and event sequences[48‐50]; the selection, generation and sequencing of multiple actions[51‐53]; problemsolving s…”

“The idea that the knowledge stored by the ‘granular’ prefrontal cortex concerns aspects of behavior agrees with previous proposals about its role in behavioral flexibility and the diversity of its cognitive contributions, as propounded for example by Duncan and colleagues[72,73,75]and by Shallice and Norman[ 76 ,77]as…”

“They contribute to prospective coding[41,42]; sensory working memory[43,44]; attention to objects, places, actions and intentions[36,45, 46 ]; response inhibition[47]; the categorization of objects, sounds and event sequences[48‐50]; the selection, generation and sequencing of multiple actions[51‐53]; problemsolving s…”

“Figure adapted, with permission, from Ref.[27]for part (a), Ref.[26]for part (b), Ref.[ 24 ]for part (c) and Ref.[25]for part (d).”

“These concepts include the preparatory set for future actions, in addition to processing events across time gaps[58‐60], decision making[ 61 ]and goal selection[62].”

“(Please note that the letter ‘a’ has two meanings: in Ia it means agranular; in 13a it distinguishes that area from area 13b.) Architectonics are taken from Ref.[ 20 ]for part (i), Ref.[21]”

“The idea that the knowledge stored by the ‘granular’ prefrontal cortex concerns aspects of behavior agrees with previous proposals about its role in behavioral flexibility and the diversity of its cognitive contributions, as propounded for example by Duncan and colleagues[ 72 ,73,75]and by Shallice and Norman[76,77]as…”

“Orbital areas seem to function more in value- and object-based action selection[ 65 ,66].”

“Figure adapted, with permission, from Ref.[ 27 ]for part (a), Ref.[26]for part (b), Ref.[24]for part (c) and Ref.[25]for part (d).”

“Here, I take up that topic first, and at heart it involves a fundamental question: what is the prefrontal cortex? The second topic concerns the distinction between cognitive processes and knowledge, and it involves a similarly fundamental question: what does the prefrontal cortex do? Grafman and colleagues[ 2 ] have n…”

“striatum, targeting more dorsal parts of the striatum instead[23,25, 26 ].”

“The shared frontal areas For the rest of the story see Preuss[ 8 ,9], but an argument based on cortical types, topology and corticostriatal organization should suffice.”

“striatum, targeting more dorsal parts of the striatum instead[23, 25 ,26].”

“Neuroimaging[33,37‐39]and other[ 40 ]research in humans yield the same conclusion.”

“Two are especially useful in my opinion: one based mainly on neuroimaging and clinical neuropsychology, the other on neurophysiology and neuroanatomy[2, 29 ].”

“They contribute to prospective coding[ 41 ,42]; sensory working memory[43,44]; attention to objects, places, actions and intentions[36,45,46]; response inhibition[47]; the categorization of objects, sounds and event sequences[48‐50]; the selection, generation and sequencing of multiple actions[51‐53]; problemsolving s…”

“Also included are the ideas emphasized in contemporary neuroeconomics[ 63 ]such as reward expectation, the valuation and revaluation of actions and stimuli, and the effect of reinforcement history on decisions, choices and actions.”

“In another test of spatial memory, rats returned to normal performance just 60 trials after medial frontal lesions[ 19 ].”

“Petrides[ 34 ]did an especially crucial experiment in macaque monkeys.”

“They contribute to prospective coding[41,42]; sensory working memory[43, 44 ]; attention to objects, places, actions and intentions[36,45,46]; response inhibition[47]; the categorization of objects, sounds and event sequences[48‐50]; the selection, generation and sequencing of multiple actions[51‐53]; problemsolving s…”

“highest activity when the monkey remembered the R location (top row), regardless of where the monkey attended (columns).(c)Most cells in the dorsolateral prefrontal cortex are like the blue one in B. Data from Ref.[ 36 ].”

“By contrast, rats trained after medial frontal lesions reached 90% correct performance at a median interval of 2 s, and they did so in just 140 trials: a respectable, if subpar, achievement[ 18 ].”

“Monkeys trained after prefrontal lesions failed to learn the DR task at all, even after 500 trials with a brief 1-s interval[ 17 ].”

“In a study that used a 5-s delay interval, two of four monkeys performed at chance level for 1000 trials, when testing stopped[ 15 ].”

“This task, thus, required the processes invoked by several theories of the ‘granular’ prefrontal cortex: the maintenance of information in working memory[71], adaptive coding, which confers the ability to guide behavior whenever problems exceed routine levels of difficulty[72,73], and attentional selection[37,74], inc…”

“They contribute to prospective coding[41,42]; sensory working memory[43,44]; attention to objects, places, actions and intentions[36,45,46]; response inhibition[47]; the categorization of objects, sounds and event sequences[48‐50]; the selection, generation and sequencing of multiple actions[51‐53]; problemsolving str…”

“This task, thus, required the processes invoked by several theories of the ‘granular’ prefrontal cortex: the maintenance of information in working memory[71], adaptive coding, which confers the ability to guide behavior whenever problems exceed routine levels of difficulty[72,73], and attentional selection[ 37 ,74], i…”

“Although some experts held more nuanced views, very few studies tested the working-memory theory of prefrontal cortex critically, and one that did contradicted it fairly convincingly[ 30 ].”

“In accord with this idea, neuroanatomists have recognized a ‘ventral shift’ of corticostriatal projections (from a given area) in primates relative to rodents[ 28 ].”

“Specifically, neuroimaging experiments pitting attentional selection against the maintenance of information in working memory showed a predominance of attentional functions for the dorsolateral prefrontal cortex [32], and other studies also stressed attentional functions, such as monitoring items in short-term memory[…”

“Orbital areas seem to function more in value- and object-based action selection[65, 66 ].”

“Neuroimaging studies at first emphasized working memory, then other ideas began to intrude[ 31 ].”

“In the spirit of e pluribus unum, the strategy task (Figure 6a) that we devised might help us to understand how several kinds of knowledge combine to produce a sophisticated behavior[54, 62 ,70].”

“Research on the ‘granular’ prefrontal cortex of humans emphasizes such processes as updating, manipulating and strategic controlofinformationstoredinshort-termmemory[33,67]; establishingtasksetsandrules[68];mediatinghierarchies of behavioral control; behavioral inhibition; cognitive control in social situations[ 69 ];…”

“Research on the ‘granular’ prefrontal cortex of humans emphasizes such processes as updating, manipulating and strategic controlofinformationstoredinshort-termmemory[33,67]; establishingtasksetsandrules[ 68 ];mediatinghierarchies of behavioral control; behavioral inhibition; cognitive control in social situations[69];…”

“They contribute to prospective coding[41,42]; sensory working memory[43,44]; attention to objects, places, actions and intentions[36,45,46]; response inhibition[ 47 ]; the categorization of objects, sounds and event sequences[48‐50]; the selection, generation and sequencing of multiple actions[51‐53]; problemsolving s…”

“They contribute to prospective coding[41, 42 ]; sensory working memory[43,44]; attention to objects, places, actions and intentions[36,45,46]; response inhibition[47]; the categorization of objects, sounds and event sequences[48‐50]; the selection, generation and sequencing of multiple actions[51‐53]; problemsolving s…”

“This complete failure persisted in subsequent testing with 2-s intervals [ 16 ].”

“In the spirit of e pluribus unum, the strategy task (Figure 6a) that we devised might help us to understand how several kinds of knowledge combine to produce a sophisticated behavior[54,62, 70 ].”

“…(Figure 7A), a region that has been implicated in cognitive functions such as attentional search, working memory, cognitive control, and decision making between motivational outcomes (Williams and Castner, 2006; Lee and Seo, 2007; Wise, 2008; Kable and Glimcher, 2009; Wallis and Kennerley, 2010).”

“Dorsolateral prefrontal cortex, a key component of the cognitive workspace, is lacking in most other mammals, and is less developed in nonhuman primates than in humans (Reep, 1984; Braak, 1980; Preuss, 1995; Wise, 2008).”

“This kind of selection may have been made possible by the dramatic elaboration of the prefrontal cortex (Hauser 1999), especially the granular frontal cortex, which does not appear to have a homolog in rodents (Wise 2008).”

“The degree to which the rat neocortex contains structural and functional homologs of areas in primate dlPFC, such as area 46, remains controversial (Wise, 2008).”

“However, it is important to note that there are large differences in anatomy across species, and OFC in rats has a very different cytoarchitecture than OFC in monkeys and humans (Wise, 2008; Wallis, 2012).”

“Such a dissociation is in line with the cytoarchitectonic properties of the OFC, showing that the anterior part, characterized by a granular cell layer, is phylogenetically more recent than the posterior part consisting in agranular and dysgranular cortices (Ongür and Price, 2000; Wise, 2008).”

“In the course of evolution, the PFC has expanded considerably in primates: new areas have appeared (medial and lateral PFC), and older areas such as the cingulate regions have become rewired with connections to both subcortical regions and the new PFC regions (Passingham & Wise, 2012; Wise, 2008).”

“In rodents, prefrontal cortex is entirely agranular (Murray 2008, Preuss 1995, Price 2007, Wise 2008).”

“The agranular areas that constitute rodent OFC resemble the most posterior OFC and adjacent insula in primates (Preuss, 1995; Wise, 2008).”

“In addition, primates developed a distinct mesoprefrontal dopamine system originating from dorsolateral and lateral substantia nigra (SN) to project to the evolutionarily novel and granular dorsal and lateral areas of the PFC (areas 12/47, 9/46, and 9) [21 – 23].”

“Evolutionary Influences on Deep Layer III Microcircuitry The dlPFC expands greatly over evolution, with no exact counterpart in rodents, and an enormous extension from nonhuman to human primates (Elston, 2003; Elston et al., 2006; Preuss, 1995; Wise, 2008).”

“For example, lesions of the ACC gyrus (BA 32 and 24) disrupt social interest and valuation in macaques (Rudebeck et al., 2006; Noonan et al., 2010).”

“And if we were to focus more on the evolutionary aspects of prefrontal development in terms of structural organization and function, should we not include longitudinal neurodevelopmental studies on more species [18, 19]? Although the basic principles of cortical development may be similar in all mammals, the modificat…”

“Just as in research using humans and non-human primates (see Wise, 2008), the regional specialization of the PFC in rats remains an area of active debate.”

“The anterior part of the OFC, especially well developed in humans and characterized by a granular cell layer, is thought to be phylogenetically and ontogenetically more recent than the posterior and medial parts, which consist of agranular and dysgranular cortices (Ongür and Price, 2000; Wise, 2008).”

“Moreover, Hampton et al. [83 ] use functional imaging to demonstrate that lesions of the amygdala disrupt reward expectation signals in ventromedial PFC, implying that a representation of stimulus value in PFC may be ‘downstream’ from the value signal in the amygdala.”

“The orbitofrontal cortex is much less well developed in rodents, which has only an agranular orbitofrontal cortex which corresponds to a small posterior part of the primate orbitofrontal cortex (Passingham and Wise, 2012; Rolls, 2014a; Wise, 2008), and that is why the rodent orbitofrontal cortex is not considered here.”

“Different investigators consider PL to be homologous to NHP a32 (10,48,49), lateral PFC (9,50), or a24 (51); the homologue of rodent Cg is similarly contentious (8,10,48).”

“(In primates, most of the orbitofrontal cortex is granular cortex, and the rat may have no equivalent to this Wise 2008; Small and Scott 2009; Passingham and Wise 2012; Rolls 2014b, 2015).”

“According to this last view the ACC, which exists albeit in different forms in all mammals, might guide foraging, a key behaviour for all mammals, while vmPFC, a primate specialization [49] might be especially important when decisions are made between simultaneously available options.”

“, 24aa and 24ap, respectively) based on descriptions of area 24 as dysgranular anteriorly with associated cognitive-related function transitioning to an agranular cytoarchitecture posteriorly associated with motor function (30, 40, 41).”

“, 2008), although there are notable differences between rodents and primates (Feierstein et al., 2006; Zald, 2006; Wise, 2008).”

“with the rat having only agranular regions (Wise, 2008), see Fig.”

“These specializations include prominent expansion of the frontal cortex, parts of which are implicated in psychiatric disorders and have no homolog in other mammals (Wise, 2008).”

“Rodent mPFC clearly differs from primate PFC in several aspects; it lacks a granular layer, has a different topological organization, and contains a reduced version of the corticostriatal network [79].”

“The dorsolateral granular prefrontal cortex is a unique primate specialization (Preuss, 1995; Wise, 2008) and has features in the human brain that are lacking in other primates (Semendeferi et al.”

“However, these effects contrast with the severe and permanent effects seen after lesions of the periprincipal cortex in macaques (reviewed in [48, 92]).”

“Notwithstanding neuroanatomical differences in cytoarchitecture, topology and connectivity across specie”

“The prefrontal cortex of rodents is largely agranular (Krettek and Price 1977; Wise 2008).”

“In addition, the anatomical and functional properties of cortical areas projecting to the DS and VS show substantial differences between rodents and primates (Seamans et al., 2008; Wise, 2008).”

“A discussion of this evidence and an illustration of rodent frontal cortex appear in Wise (15).”

“Primates have a more developed OFC than rodents, with extensive granular and dysgranular cortex, including area 13; in contrast, rodent OFC is entirely agranular (Preuss, 1995; Ongür and Price, 2000; Barbas, 2007; Wise, 2008).”

“There is some controversy about the existence of an anatomically comparable PFC structure in rodents (Preuss, 1995; Dalley et al., 2004; Wise, 2008).”

“More generally, however, the vPFC is among the brain regions that have encountered the greatest evolutionary changes between macaques and humans (Wise, 2008).”

“A BRIEF REVIEW OF PFC TOPOGRAPHY The large, highly differentiated primate PFC is topographically organized along multiple dimensions, with more newly evolved areas situated more rostrally, and more primitive areas and functions situated more caudally [3].”

“Reprinted with permission from [65].”

“Taking into account their anatomical connectivity, projection patterns of the rat medial OFC (mOFC) and lateral OFC (lOFC) to striatum and amygdala are similar to those of areas 14 and 12/13 of the primate OFC (Ongür and Price, 2000; Schilman et al., 2008; Wise, 2008; Hoover and Vertes, 2011).”

“Neuroanatomists like Preuss [46] and Wise [47] argue that only primates have a prefrontal cortex in the strict sense, together with its specific functions like control of attention, action planning and action selection and decision-making.”

“, object features and/or location, categories, rules), suggesting LPFC’s encoding of value information may support allocation of attentional resources or cognitive control toward behaviorally relevant information (Hare et al., 2009; Kennerley & Wallis, 2009c; Lebedev et al., 2004; Miller & Cohen, 2001; Wise, 2008).”

“the rat may have no equivalent to this (Passingham & Wise, 2012; Rolls, 2014, 2015c; Small & Scott, 2009; Wise, 2008).”

“The granular PFC was added newly to the anterior pole of the frontal lobe during the evolution of primates [53,54].”

“, 2007), although large parts of the monkey PFC appear to be functionally and anatomically unique to primates (Wise, 2008).”

“First, although the homology between human and monkey cingulate areas is strong, the homology between primate and rodent is not straightforward (Rushworth et al., 2004; Wise, 2008).”

“…feature of primate neuroanatomy is an expansion of prefrontal areas such as OFC, involving the emergence of dysgranular and granular cortex that are absent in rodents, and concomitant elaboration of interconnectivity with the amygdala (Ghashghaei et al., 2007; Ongü r and Price, 2000; Wise, 2008 ).”

“However, we note that there is arguably no rodent homolog to the medial PFC cluster we identified (Wise, 2008).”

“Whereas most studies focus on one region at a time, and conclusions are drawn based on different paradigms and from different species, these two regions form a two-way dense-projections network that is extensively evolved in the primate (Ghashghaei et al., 2007; Wise, 2008).”

“Another factor that complicates the interpretation of data gathered from various species is that, despite important similarities, the anatomy of these regions differs between rodents and primates [10 ].”

“Primate evolution produced an increased capacity to respond flexibly to varying social contexts as well as expansion of the prefrontal cortex [1, 2].”

“For example, encoding of the main task plan (across a series of behavioral paradigms) was best represented by activity in AINS and dACC (Dos-enbach et al., 2006, 2007, 2008; Nelson et al., 2010).”

“This is in contrast 53 to granular dorsomedial areas involved in mental state inference, which appear 54 to have evolved more recently (Wise, 2008).”

“Such is the case made for the prefrontal cortex of primates (Preuss, 1995; Wise, 2008).”

“Some have argued that primate-rodent OFC homologies are limited, particularly given the absence of dysgranular and granular cortex which makes up the rostral extent of the OFC in primates (Passingham and Wise, 2012; Wise, 2008).”