Architecture and Organizational Principles of Broca's Region

Home , Inferior frontal gyrus, Operculum (brain)

Review

Architecture and organizational

principles of Broca’s region

1,2,3 1,2,4

Katrin Amunts and Karl Zilles

Research Centre Ju¨ lich, Institute of Neuroscience and Medicine (INM-1), Ju¨ lich, Germany

Ju¨ lich-Aachen Research Alliance (JARA), Translational Brain Medicine, Ju¨ lich, Germany

Section Structural-functional Brain Mapping, Department of Psychiatry, Psychotherapy, and Psychosomatics, Medical School,

RWTH Aachen University, Aachen, Germany

C. & O. Vogt Institute for Brain Research, University of Du¨ sseldorf, Du¨ sseldorf, Germany

Identifying cortical areas for language and speech pro-

Glossary

cessing is a prerequisite for cognitive neuroscience and

clinical research. Although Broca’s region is one of the Agranular cortex: part of the isocortex, where the internal granular layer (IV)

has been reduced during ontogeny to such a degree that it is no longer visible

essential nodes in the language network, its anatomical

as a distinct layer. For example, Brodmann areas 4 and 6 as part of the motor

constituents are ill-deﬁned and multiple deﬁnitions of

and premotor cortex.

Broca’s region exist. Sanides’ concept of microstructural Convergence zones: Binder and Desai [68] recently proposed high-level

convergence zones in the inferior parietal, lateral temporal, and ventral

gradations interpreted Broca’s region as developing

temporal cortex. They note that these zones are far from primary sensory

from neighboring motor, dorsolateral-prefrontal, and

and motor cortices, and appear to be involved in processing general rather

insular cortices. Recent mapping approaches based on than modality-specific semantic information. Other models of convergence

zones have been proposed elsewhere [91].

cytoarchitecture, transmitter receptor distribution, and

Cortical areas and cortical map: the cerebral cortex is composed of areas,

connectivity revealed a highly differentiated segregation

which are characterized by a certain microstructure, for example, cytoarchi-

of this region far beyond Brodmann’s classical scheme. tecture, connectivity, and brain function. Various cortical maps and parcella-

tion schemes have been put forward during the past century, which differ in

This novel segregational concept of structural and func-

the number of areas, their ontology, and the aspect of brain organization that

tional architecture more adequately reﬂects the various

they reflect (e.g., cytoarchitecture, myeloarchitecture, molecular architecture,

functions of Broca’s region in cognitive and/or linguistic pigmentoarchitecture).

processes. Cytoarchitecture: organizational principle of the cerebral cortex and subcortical

nuclei, which considers differences in the distribution of cell bodies, their size,

and shape between cortical areas and subcortical nuclei. Cytoarchitecture is

Introduction revealed in cell-body stained histological sections (e.g., Nissl-stain with cresyl

violet, Merker-silver stain), which are the basis of the first cortical maps, that is,

The term Broca’s region originates from a clinico-

that of Brodmann from 1909 [70] and other early maps of Broca’s region [22,23].

pathological examination of a patient, Leborgne (‘Tan’),

Dysgranular cortex: part of the isocortex, where the internal granular layer (IV)

who lost speech. The neurologist Paul Broca [1] delivered a is not clearly visible as a distinct layer due to intermingling of granular cells from

layer IV and pyramidal cells from deep layer III and superficial layer V. Brodmann

short presentation at the Anthropological Society of Paris

area 44, which is located rostrally to the premotor cortex, is an example of

in 1861 after Leborgne’s death, where he reported that the

dysgranular cortex. This area is interpreted as a core part of Broca’s region.

loss of speech, aphemia, was related to a lesion in the Gradations: streams along which cytoarchitectonic features change from one

region to another. The term and the underlying concept were introduced by

posterior part of the left third frontal convolution, later

Sanides [57,58], and based on earlier observations of the Vogt’s [27,93] and

called Broca’s region. The lesion was large and occupied Brockhaus [94]. Gradations correspond to evolutionary pathways pointing from

major parts of the inferior frontal convolution, as well as phylogenetically older to more recent cortical areas. According to this concept,

Broca’s region originates from motor precentral, opercular/insular and more

parts of the basal ganglia, the white matter, and more

dorsally located lateral-frontal areas. This complex composition makes sense

posterior regions [2,3] (Figure 1). Broca’s observation was considering the variety of brain functions associated with Broca’s region.

Granular cortex: part of the isocortex with clearly visible internal granular layer

not without antecedents: it was preceded by studies by

(IV). Brodmann area 45 (another core part of Broca’s region), primary sensory

Franz Josef Gall, Johann Casper Spurzheim, Gustav Dax,

cortices, fronto-polar cortex, and other associational cortices are examples of

Louis P. Gratiolet, Jean Baptiste Bouillaud, Ernest Aubertin granular cortex.

Isocortex: six-layered cortex covering major parts of the lateral and medial

and others, who had published earlier observations of

aspect of the brain surface. It coincides with the phylogenetic term ‘neocortex’.

patients with aphasia after brain injury (see [4,5], for a

This type of cortex has the following layers: molecular (I), external granular (II),

historical review). external pyramidal (III), internal granular (IV), internal pyramidal (V), and

multiforme (VI). Each layer has a specific connectivity with other layers and

Broca’s case did not only provide strong arguments for

areas. The isocortex is subdivided into several dozens to hundreds of cortical

the localization of language, but also showed a hemispheric

areas in the various available maps.

specialization in the brain. Determining its anatomical Myeloarchitecture: organizational principle of the cerebral cortex and sub-

cortical nuclei, which considers differences in the intracortical distribution of

underpinnings has been the aim of a large number of

myelinated nerve fibers. This type of architecture was used to create maps of

studies. Keller and colleagues [6] provided an overview

the whole brain and Broca’s region, in particular [27,29]. It has attracted

of gross anatomical and cytoarchitectonic studies targeting increasing interest in the context of recent high-resolution MRI.

Receptorarchitecture: organizational principle of the cerebral cortex and

asymmetry. One of the strongest pieces of evidence for

subcortical nuclei, which considers differences in the distribution of receptor

anatomical asymmetry comes from studies analyzing the types of different transmitter receptors, such as glutamate, acetylcholine or

serotonin [79]. This architecture is most closely related to brain function, since

transmitter receptors are key molecules of signal transduction.

Corresponding author: Amunts, K. ([email protected]).

Review Trends in Cognitive Sciences August 2012, Vol. 16, No. 8 (a) (b)

sfs sfs ifs ifs

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Figure 1. Dorsal view of a 3D reconstruction of an MR dataset of Leborgne’s brain (a) and coronal sections through Broca’s region (ellipse) at the level of the posterior part

of the inferior frontal gyrus (b). Note the deformation of the interhemispheric fissure caused by brain fixation and the effects of the large lesion, which included not only

cortical tissue of the posterior part of the inferior frontal gyrus, but also a large portion of the white matter and basal ganglia. The MR data set was provided by Dronkers,

Plaisant, Iba-Zizen and Cabanis [3], and the figure was created in collaboration with Nina Dronkers and Odile Plaisant. Abbreviations: ifs, inferior frontal sulcus; sfs, superior

frontal sulcus.

volume of cytoarchitectonic area 44, which is larger in the analyze their relevance for recent studies, and discuss new

left than in the right hemisphere, in a proportion that is anatomical concepts of Broca’s region based on recent

similar to left-hemispheric dominance for language [7,8]; in structural, functional, and connectivity studies of the

contrast, studies of gross anatomical asymmetry of the macaque and living human brain.

anterior speech region came to more controversial conclu-

sions [6]. More recently, asymmetry has also been demon- Classical maps of Broca’s region

strated for the distribution of the cholinergic M2-receptor Cyto- and myeloarchitectonic maps are relevant for the

for the neurotransmitter acetylcholine [9] and for the deﬁnition of Broca’s region, because they represent not

underlying ﬁber tracts (see below). only topographical aspects of the cerebral cortex, but also

Leborgne’s brain was never subjected to any histological reﬂect organizational principles, connectivity, cellular

analysis, and thus, the extent of the lesion site could be composition, comparative neuroanatomical concepts, as

assigned only to surface landmarks. This is a severe well as physiological and pathological aspects. Each archi-

restriction for further analysis of structural-functional tectonic area is a unique part of the brain, comprising

correlations, since non-primary sulci and borders of micro- correlated structural and functional properties. Korbinian

structurally deﬁned areas vary to a considerable degree Brodmann, a pioneer of cytoarchitectonics, was convinced

and independently from each other [8,10]. Moreover, they that each of his more than forty cytoarchitectonic areas

differ between hemispheres [6]. Signiﬁcant variability is has a unique function and evolutionary position [14]. For

also found in the localization and extent of brain lesions in example, he proposed area 4 as the anatomical equivalent

different cases [11,12]. As a consequence, we can only of the primary motor cortex, which guides voluntary

speculate about the cortical areas (see Glossary) contribut- movements [15]. This concept was already supported by

ing to the speech deﬁcit in the patients described by Broca electrophysiological observations at that time. Brodmann

and others, since the deﬁnition of Broca’s region remains viewed Broca’s region as the anatomical correlate of the

vague in anatomical terms. functionally deﬁned anterior center of speech. However,

Presently, different deﬁnitions of Broca’s region co-exist the relationship between microscopic structure, for

[6]. Here, we use the term ‘Broca’s region’ for a region on instance, cytoarchitecture, and function had never been

the inferior frontal gyrus, including parts of surrounding rigorously tested in this region during Brodmann’s time. A

cortices. We will argue that there are also no robust precise anatomical, that is, microstructurally based, map

functional criteria to deﬁne Broca’s region unambiguously. is therefore a necessary prerequisite for any topographi-

There is an ongoing debate about the selective engagement cally speciﬁc interpretation of (language-related) brain

of this region in language versus a multifunctional involve- activity and for a common structural and functional

ment in cognition [13]. conceptualization of brain and language.

The solution to such controversies requires a clear Many attempts to map Broca’s region and surrounding

concept of the neuroanatomical organization of Broca’s cortices were made at the beginning of the 20 century by

region and other regions involved in language. To address using different methods, theoretical concepts of cortical

this point, we will brieﬂy review the literature concerning parcellation, and different nomenclature (Table 1). Some

the architecture of Broca’s region, compare existing maps of these maps addressed the whole cerebral cortex, for

and parcellation schemes with their underlying concepts, example, the cytoarchitectonic maps of Brodmann [14],

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Table 1. Approximate correspondences of areas in the historical maps. Correspondences are largely based on descriptions by von

Economo and Koskinas [16]

Brain macroscopy opercular part triangular part orbital part

Maps by: Areas

Brodmann [14] 44 45 Part of 47

Kononova [26]

Sarkisov et al. [17]

Vogt and Vogt [27] 56,(57) (57),58,59 60–66

Riegele [23]

Ngowyang [25]

Kreth [24]

Strasburger [29]

Hopf [30]

Sanides [57,58] 56,57 58,59 60–66

von Economo and Koskinas [16] FCBm FDG FDop FCDop FFF(Pars praetriangularis)

Stengel [22]

von Economo and Koskinas [16], and the Russian school Different ﬁber pathways have been demonstrated in Broca’s

including Sarkisov, Kononova, Filimonov, Blinkov and region [43,44]. Recently, Catani et al. identiﬁed ﬁber tracts

others [17], the pigmentoarchitectonic map of Braak connecting the posterior part of Broca’s region with the

[18], Campbells cyto- and myeloarchitectonic maps [19], supplementary motor area (SMA), and the more rostral

Elliot Smith’s map of unstained thin brain sections [20], part with the middle frontal gyrus; additionally, both parts

and Flechsig’s map based on studies of the developing were interconnected through U-ﬁbers [45].

brain [21]. In addition, detailed cytoarchitectonic [22–26] Evidence for two auditory processing pathways, similar

and myeloarchitectonic [27–30] maps of the frontal lobe to those in the visual cortex [46,47], has been provided. The

and/or Broca’s region have been published. Figure 2 and dual stream model proposes a ventral stream, which is

Box 1 illustrate similarities and discrepancies between the involved in mapping sound onto meaning, and a dorsal

maps. A major disadvantage of these efforts is the lack of stream, which is involved in mapping sound onto articula-

quantitative, statistically testable criteria for parcellation tory-based representations [48]. Parker and colleagues

in nearly all cases. The measurement of architectonic have identiﬁed a dorsal pathway from Wernicke’s to

differences became feasible only with the development of

modern image analyzers and statistical tools (e.g., [31]). Box 1. Historical maps

In contrast to recent 3D electronic atlases [32], the

Broca’s region was mapped several times in the past. Maps,

presentation of schematic drawings made comparisons

however, differ between each other with respect to size, extent,

between the maps difﬁcult and sometimes impossible. and the number of areas and other features (Figure 2). For example,

Furthermore, schematic maps do not enable reliable com- the followers of Vogt, Strasburger [29], and Riegele [23] included

areas of the triangular and opercular parts of the inferior frontal

parisons between cytoarchitectonic areas and their func-

gyrus, ventrally adjacent cortex and parts of the orbitofrontal cortex.

tional correlates as obtained in recent neuroimaging

Other authors restricted the region to areas 44 and 45 (i.e., opercular

studies of healthy volunteers. Such observations add

and triangular parts exclusively; Figure 2). Vogt interpreted Broca’s

important information about functional segregation in the region as a correlate of his areas 57–59, as well as 65 [96], whereas

healthy human brain, and, therefore, supplement lesion von Economo and Koskinas considered FCBm to represent Broca’s

area [16]. All authors largely agreed that the insula would not be part

studies in aphasics, electrophysiological recordings during

of Broca’s region and that the dorsal border is approximately

surgery, as well as comparative studies. Neuroimaging can

represented by the inferior frontal sulcus.

also reveal the structural and functional connectivity of

Maps also differed in terms of the underlying concepts of cyto- or

Broca’s region with surrounding and distant regions of myeloarchitectonic borders. For example, Stengel [22] indicated

the brain. Finally, developmental studies further improve sharp borders as dashed lines and contrasted them to unsharp

transitions labeled by a series of short horizontal lines (Figure 2).

our understanding of Broca’s region and its organizational

Vogt and his scholars disagreed and highlighted the sharpness of

principles [33,34].

the borders between two areas as a general principle, including

borders of so called ‘local modifications’[23]. The question whether

Pathways to Broca’s region a border is ‘sharp’ or ‘unsharp’ goes beyond a pure academic

discussion, since it has consequences for connectivity within an

The classical view of the arcuate fascicle as the pathway

area and between areas, and finally brain function. Combined

connecting the posterior language region (Wernicke’s re-

electrophysiological and histological studies on one and the same

gion) with the anterior one (Broca’s region), as proposed by

brain have demonstrated that neurons with similar receptive fields

Wernicke and Lichtheim [35] and Dejerine [36], has domi- and response properties are located within the same cytoarchitec-

nated the concepts of language circuitries for a long time. tonic area; response properties of neurons change suddenly when

crossing the border between two areas [27,92,97–99].

For example, several studies have been published during

Another matter of disagreement concerned the question whether

the past few years revealing a leftward asymmetry in the

an area may be present in one brain, but absent in another (for

arcuate fascicle with respect to fractional anisotropy, vol-

example, compare the three individual maps of Strasburger with

ume, relative ﬁber density and/or number of streamlines as respect to the presence of subareas of 58 and 59 in Figure 2). Von

a putative correlate of lateralization for language [37–42]. Economo and Koskinas distinguished 54 ground areas with 76

variants and 107 modifications, which may or may not be present

Tractography data in the human brain provide, however,

depending on the actual brain [16].

a more differentiated pattern of relevant ﬁber pathways.

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Review Trends in Cognitive Sciences August 2012, Vol. 16, No. 8 Brodmann, 1909 Sarkisov, 1949 Vogt, 1910 Vogt, 1951

Sanides, 1962 Riegele, 1931 Ngowyang, 1934

Strasburger, 1938

von Economo and Koskinas, 1925

Stengel, 1930 Hopf, 1956 Kreht, 1935

TRENDS in Cognitive Sciences

Figure 2. Overview of historical architectonic maps of the cerebral cortex with a focus on Broca’s region. In order to compare the different maps more easily with each

other, Brodmann areas 44 and 45 and the corresponding areas in the other maps were colored in red and yellow, respectively. The equivalence of Brodmann areas 44 and

45 to areas of researchers applying a different nomenclature and parcellation is based on von Economo and Koskinas, who carefully compared the different architectonic

descriptions and illustrations found in the literature [16]. Other authors sometimes assumed slightly different correspondences, for example, with respect to Vogt’s area 57:

Riegele [23] emphasizes the similarity of area 57 with 58 as compared to 56, whereas Ngowyang [25] interprets 56 as the caudal area 44 of Brodmann, and 57 its rostral part.

In other words, in his understanding the similarity of 57 to 56 is higher than to 58 (which belongs to Brodmann area 45). The map of Sarkisov [17] is, with respect to the

frontal lobe, very much based on the work of Kononova [26].

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Broca’s region that includes the arcuate fascicle and con- authors of this study concluded that precursor circuits

nectivity to Brodmann area 40, lateral superior and middle have been identiﬁed in the nonlinguistic human primate

temporal gyri, and a ventral pathway that runs via the brain, which help to understand the circuits, mechanisms,

external capsule/uncinate fascicle [41]. A recent review and evolutionary development of language processing in

discusses four major streams: dorsal pathway I connects the human brain. Is such an evolutionary perspective also

the superior temporal gyrus to the premotor cortex via the inherent in the architectonic segregation of Broca’s region?

arcuate fascicle and the superior longitudinal fascicle; Does the architectonic segregation of the human cerebral

dorsal pathway II connects the superior temporal gyrus cortex enable the identiﬁcation of developmental lines,

to Brodmann area 44 via the arcuate and superior longi- along which evolutionarily more recent areas differentiated

tudinal fascicles; ventral pathway I connects Brodmann from older ones?

area 45 and the temporal cortex via the extreme capsule,

whereas ventral pathway II connects the frontal opercu- Sanides’ gradations and Broca’s region

lum and the anterior parts of the superior temporal gyrus Sanides contributed a new view on principles of

and sulcus via the uncinate fascicle [49]. Most importantly, cytoarchitectonic segregation of the cortex, the concept

these models do not only distinguish ﬁber pathways con- of ‘gradations’ [57,58] (Box 2). Gradations are spatially

necting brain regions with each other, but explicitly ascribe directed sequences of cortical areas, which originate, in

roles to these regions in speech processing and language most cases, in phylogenetically old regions of the cortex.

[43]. For example, dorsal pathway I subserves auditory- The gradation theory provides a framework for the identi-

motor integration, whereas dorsal pathway II seems to be ﬁcation of the source region, from which language-related

functionally related to higher-level semantic and syntactic cortical areas originated. Three gradation streams arrive at

language functions [49]. Broca’s region (Figure 3 and Box 2):

Limitations with respect to the interpretation of DTI (a) Caudo-rostrally directed gradation from the fronto-

data arise from the following facts: (i) the directionality of motor zone to Broca’s region. The close topographical

ﬁber tracts cannot be obtained from DTI studies; (ii) the and functional relationship between motor and

spatial resolution is in the range of millimeters, and track-

ing results, therefore, refer to gross macroscopical units

such as gyri, but not cortical areas; and (iii) connectivity in Box 2. Sanides’ concept of gradations

a strict sense requires veriﬁcation at the synaptic level.

The concept is based on earlier short notes by the Vogt’s [27,93] and

These are reasons why studies in experimental animals,

later Brockhaus [94]. They observed that certain architectonic

in particular the macaque brain, are highly important, features change from area to area along well-defined developmental

lines in a stepwise manner (Figure 2). Brockhaus called them

although the open question of homologies between ma-

directions of differentiation, but did not yet interpret them as a

caque and human brain areas involved in language is

developmental principle. Gradations, according to Sanides [57,58],

particularly relevant [50]. Similarities in connectivity be-

reflect architectonic similarities of a stream of neighboring areas,

tween macaque and human brains have been demonstrat- which change in a stepwise manner. Sanides subdivided the frontal

ed, for example, the presence of an anterior and posterior lobe into different zones and identified gradations for each of them.

The ‘fronto-opercular zone’ (FoZ; Figure 59 in Sanides [57]; Figure 2

part of area 45 [51,52]. (Dis-)similarities between human

in the present review) roughly corresponds to Broca’s region. It

and macaque brains have been discussed, as well [53].

represents a zone where several gradations converge (Figure 3):

Differences between human brains and those of non-hu-

(a) in caudo-rostral direction: from the frontomotor zone (FmZ;

man primates concern, for instance, the ability to process agranular motor and premotor cortex (Vogt area 40/41) to Vogt

complex sentence structures. This difference seems to be dysgranular area 56 and granular area 58;

(b) in ventro-dorsal direction: from the insula via the opercular

neuroanatomically linked to the dorsal pathway connect-

cortex to Vogt areas 56 and 58;

ing the posterior part of Broca’s area and the posterior

superior temporal gyrus/sulcus [54,55].

cortex of the paraopercular zone (PoZ) to Vogt area 58.

Petrides and Pandya [51] have shown that area 44 of the To provide an example of a cytoarchitectonic gradation – the

macaque brain receives strong input from area PFG of the gradation from the motor cortex towards the more rostrally located

frontal areas (a) was characterized by an increasing visibility of the

inferior parietal lobule, an area that corresponds to a

laminar pattern, a decrease in thickness of layers III and V, an

region in the caudal human supramarginal gyrus. By

increasing subdivision of layer V into 2 sublayers, and an increasing

contrast, the caudally adjacent premotor area 6 mainly

granularity in layer IV. These cytoarchitectonic changes are

has connections with area PF, which is located more accompanied by myeloarchitectonic changes. Interestingly, the

FoZ does not receive any gradations from more rostrally located

rostrally in the inferior parietal lobule [56], and seems

areas. Arrows of gradation seem to stop area 53 v, belonging to the

to control orofacial muscles. In addition, area 44 receives

most ventral part of the para-opercular zone (PoZ) (Figure 2).

input from the caudal inferior parietal lobule, primarily

In addition to the embedding of Broca’s region into neighboring

area PG, which is located at the angular gyrus in the areas, Sanides’ concept of gradations represents a framework for

human brain [56]. Both subdivisions of area 45 receive understanding the internal organization of Broca’s region. However,

Sanides did not quantify these observations, including the definition

parietal input from PFG and PG via the second and third

of architectonic borders. Moreover, if gradations are a general

superior longitudinal fascicles (SLF II and SLF III). Some

principle of cortical organization, it can be hypothesized that other

of the axons originating from the most ventral part of area

aspects of cortical structure follow similar streams of gradations.

PG belong to the arcuate fascicle. In contrast to this dorsal Sanides explained the cortical development and areal specialization

stream, the ventral pathway is linked to the extreme from an evolutionary perspective, and he introduced hierarchical

aspects of cortical organization as compared to the mosaic-like

capsule, originates from areas of the superolateral tempo-

maps of his predecessors (e.g., Brodmann).

ral cortex, and terminates primarily in area 45 [51]. The

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opercular cortex during language tasks. A functional

subdivision with respect to the opercular and triangu-

lar parts, on the one hand, and the ventrally adjacent

frontal operculum, on the other hand, was recently

proposed [54]. The authors of this study argued for the

(c)

representation of evolutionarily more ancient proces-

(a)

sing of sequential grammars in the frontal operculum

as compared to the more complex grammars in the

opercular part of the inferior frontal gyrus (Brodmann

(b)

area 44). The closely related, but functionally increas-

ing differentiation of these two regions could be

explained by the parallel sequence in structural

differentiation along the ventro-dorsal gradation

stream of Sanides (Figure 3b), originating in the

insula.

TRENDS in Cognitive Sciences located prefrontal cortex into Broca’s region

(Figure 3c). Functional imaging studies of sentence

Figure 3. Gradation streams relevant for Broca’s regions. Three main gradation

comprehension and verbal working memory or task

streams can be identified based on Sanides’ map [58]: from the motor/premotor

region (a), the dorsally located prefrontal cortex (c), and the insula/frontal switching demonstrate activations in the inferior

operculum (b) (see also Figure 2).

frontal sulcus [64,65]. Language-related processes,

for instance, Chinese logograph reading, semantic

language processes has been demonstrated in several processes, and syntactic binding, cause activation even

experiments. The concept of mirror neurons interprets in the left middle frontal gyrus [66–68], dorsal to the

action observation and performance as the starting classical Broca region. Brodmann’s map does not allow

point for the evolution of language [59,60]. Motor an unambiguous deﬁnition of this particular brain

imagery and imitation have been associated with the region to either areas 44/45 or dorsally adjacent areas

posterior part of Broca’s region [61,62]. Orofacial 9 and 46. Moreover, recent maps have suggested a

responses in the macaque homologue of Broca’s area more complex segregation of this region than proposed

suggested that area 44 might have evolved originally by Brodmann [9,69]. Thus, the identiﬁcation of a

as an area exercising high-level motor control over sharply delineated ‘language domain’ in contrast to

orofacial actions, including those related to communi- ‘non-language’ cortex seems to be problematic in this

cation [63]. Consequently, Sanides’ caudo-rostral region as well. Some scientists emphasized general

gradation stream coincides with the evolution of regulatory mechanism, which might operate across

language-related cortical areas of ‘motor’ origin multiple domains like working memory and sentence

(Figure 3a). comprehension [68,71,72] in contrast to more domain-

Due to the complex anatomy of the transition between speciﬁc approaches.

Broca’s region and premotor cortices, it is often not

clear whether the observed activity in neuroimaging Following the streams of gradation to Broca’s region, the

studies comes from premotor area 6, or from the more frontopercular zone with Broca’s region may be interpreted

rostral area 44. As discussed above, both areas differ in as a higher-level convergence zone, in analogy to those

their microstructure, connectivity, and function [51], discussed recently by Binder and Desai for semantics [68].

which makes the distinction highly relevant. However, Thus, gradations would be streams not only for cytoarch-

the spatial resolution of most fMRI studies is itectonic changes, but also for cognitive functions. In that

approximately 2 mm, which is not sufﬁcient for sense, the fronto-opercular zone is the anatomical correlate

assigning brain activation either to the rostral or of the anterior language region. Such a view could poten-

the caudal bank of the precentral sulcus, where areas tially integrate ﬁndings of linguistic and non-linguistic

44 and 6, are located in most cases. Thus, many studies functions associated with Broca’s region [73,74]. It would

label their ﬁndings as 44/6, and leave an ambiguity in also allow for a functional segregation within this region,

localization, which is neurobiologically not satisfacto- matching the structurally distinct areas.

ry. Moreover, a recent receptorarchitectonic study has

identiﬁed several new areas on the ventral precentral New topography of Broca’s region

gyrus (6v1, 6v2, 6r1), and area 44 has been further Are there any new aspects of the segregation of Broca’s

subdivided [9]. This new segregation further increases region into areas 44 and 45 as compared to the classical

the number of areas along the rostro-caudal axis, maps, beyond the fact that there is now a computerized 3D

which have to be considered as potentially involved in version [75]? Does the Brodmann map from 1909 still

language. represent an appropriate tool for understanding the locali-

(b) Ventro-dorsally directed gradation from the insula to zation of function? We are convinced that the recent maps

Broca’s region. The opercular cortex is usually not differ principally from the historical attempts for the

included in Broca’s region as deﬁned in a strict sense, following reasons. First, historical maps relied on observa-

although many fMRI studies report activations in tions in only one or a few brains. By contrast, recent

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(a) ifs (b) ifj2 47

ifj1 4 6v2 cs 6r1

6v1 44d op9 ifs2 Cortical area ds prcs op8 ifs1 6v1 4 45 44 45p ifs 0.2 0.3 0.4 0.5 0.6 0.7 0.8 44v Distance 6r1 (c) 45a ab

hb op6 op4 47 op8 Amunts et al., 2010 op9 45

Amunts et al., 1999

TRENDS in Cognitive Sciences

Figure 4. (a) The map of Broca’s region based on the distribution of receptors of neurotransmitters and modulators shows a complex segregation of the inferior frontal

gyrus and adjacent cortices [9]. In particular, it shows the presence of a series of new areas in the inferior frontal sulcus (ifs) labeled as areas ifs1, ifs2, ifj1 and ifj2, as well in

the frontal operculum (‘op’-areas). The areas of this region can be clustered based on their receptorarchitectonic pattern as shown in (b). Transmitter receptors are key

molecules for neurotransmission, and therefore, indicative of function. Areas 44 and 45 of the classical Broca region are most similar to each other and they cluster with

areas op8 and op9 of the frontal operculum. Interestingly, area 47 is the most different of all analyzed areas, suggesting distinct function [9]. (c) Cytoarchitectonic

probabilistic map of right area 45 [8] in the standard reference space of the single subject template from the MNI [95]. The color indicates the overlap of individually mapped

area 45 in common reference space. Note the high intersubject variability (labeled in blue and green) of area 45 in regions outside the free surface of the triangular part

(orange and red colors).

cytoarchitectonic probabilistic maps are based on an for the access of prefrontal and rostral opercular frontal

observer-independent mapping in a sample of ten brains; inputs to the ventral premotor cortex [78], and may corre-

they provide population-based information of an area in spond to human area 6r1 [9]; the complete homology of

standard reference space, enabling a reliable comparison of areas in human and macaque brains, however, is still

the cytoarchitectonic areas with language function (e.g., unresolved.

[76]) in different brains. This is relevant, since (i) inter- Apart from the mapping aspect, receptorachitectonic

subject variability in brain anatomy is signiﬁcant, and studies also demonstrated that Broca’s region is organized

adds to variability in behavior and brain function, and in a hierarchical way (Figure 4), similar to other cortical

(ii) relating microstructural areas to speciﬁc functions is regions [79–81]. Hierarchical organization has also been

crucial for understanding brain organization. found for other aspects of organization at a systemic level,

Regional differences in connectivity and cytoarchitec- including cytoarchitecture [82], connectivity [83,84], and

tonics of Broca’s region have been ampliﬁed by differences genetic topography [85]. Sanides’ concept of architectonic

in molecular organization, leading to new parcellation gradation is in line with these arguments [86]. Speech

schemes. A recent study on the distribution of receptors production, planning behavior, and executive control have

of different neurotransmitters and modulators has shown been conceptualized as hierarchically organized, to provide

that Broca’s region can be subdivided into more than a only a few examples [87–89]. These ﬁndings support the

dozen areas [9]. These areas include subdivisions of area 44 notion of nested, hierarchical levels of organization [90].

and 45, a series of areas located in the depth of the inferior At the same time, the model does not exclude parallel

frontal sulcus, the frontal operculum, and at the point of processing and constant modiﬁcation [88,90].

transition to the premotor cortex (Figure 4). The degree of

detail of the parcellation of human inferior frontal gyrus Concluding remarks

and adjacent sulci matches that of the macaque brain [77], The data reviewed in this article indicate a complex segre-

and goes beyond that in other maps [51]. Area F5a of gation of Broca’s region. Its areas are unique with respect

Belmalih and co-authors seems to be a privileged gateway to their cellular architecture, myeloarchitecture, molecular

424

Review Trends in Cognitive Sciences August 2012, Vol. 16, No. 8

18 Braak, H. (ed.) (1980) Architectonics of the Human Telencephalic

signature, connectivity, and function. In addition to the

Cortex, Springer

subdivision of ‘classical’ constituents of Broca’s region, that

19 Campbell, A.W. (ed.) (1905) Histological Studies on the Localisation of

is, areas 44 and 45, further areas of inferior frontal sulcus,

Cerebral Function, Cambridge University Press

frontal operculum and ventral premotor cortex have to be 20 Elliot Smith, G. (1907) A new topographical survey of the human

taken into account when searching for the anatomical cerebral cortex, being an account of the distribution of the

anatomically distinct cortical areas and their relationship to the

correlates of language processing. Area 47, which occupies

cerebral sulci. J. Anat. 41, 237–254

the orbital part of the inferior frontal gyrus and adjacent

21 Flechsig, P. (ed.) (1927) Meine Myelogenetische Hirnlehre mit

orbitofrontal gyri, is receptorarchitectonically remarkably

Biographischer Einleitung, Springer (in German)

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Angew. Psychol. 130, 630–677 (in German)

belong to one of the newly identiﬁed areas of the frontal

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it does not reﬂect the richness of functional segregation as Zeitschrift fu¨ r mikroskopisch-anatomische Forschung 39, 331–354 (in

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seen in functional imaging studies of language. The novel

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Stirnhirns. I. Teil. Cytoarchitektonische Felderung der Regio

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