The 1990s were dominated by debates about postmodernism, one strand of which was concerned with the so called “aestheticization of the life world.” Wolfgang Welsch, for example, wrote in Grenzgänge der Ästhetik, “The facades get prettier, the shops more animated, the noses more perfect. But such aestheticization reaches deeper, it affects fundamental structures of reality as such.” For aestheticization means “basically that the non-aesthetic is made aesthetic or is grasped as being aesthetic.” However what counts as aestheticization and which concept of the aesthetic is presupposed can vary, as he goes on to explain:
In the context of an urban environment, aestheticization is referring to the expansion of the beautiful, the pretty, and the stylish; in advertisement as well as in self understandings it means the growing importance of performance and life style; in view of the technological determination of the objective world and the social effects of the media, “aesthetic” primarily designates virtualization. Finally, aestheticization of consciousness means: We no longer see first or last foundations, instead reality takes on a condition we formerly only knew with respect to art—a condition of being produced, changeable, non-committal, levitating etc.
Whereas Welsch, from the perspective of a somewhat generalized constructivism, affirmed these developments as a move towards the freedom of designing ever more spheres of life, others were more skeptical. Not only did they doubt that postmodern urban space should indeed be characterized by an “expansion of the beautiful and the pretty,” they also saw in the postmodern emphasis of the surface a symptom of an ugly social truth: that of a profound alienation. In their view, the postmodern cult of the surface was a symptom of a novel domination of simulacra that erodes the substance both of our ethical self understandings and our political culture. “Reality,” Rüdiger Bubner wrote, “gives up its ontological dignity in favor of an applauded semblance.” Both sides of the debate, however, assumed that aestheticization is not just a question of design, but that this question itself should be seen in a broader social context. “Aestheticization of the life-world” is thus a formulation with which both sides tried to find a tangible concept for the state of contemporary Western societies.
However, the agitated argument over the status of a supposedly obvious societal development that dominated the 1990s was soon to be deflated by sociology, for the philosophical debate remained unfounded as long as it was possible to question the actual scope of this development. As a result, attempts to empirically substantiate the thesis of the aestheticization of the life-world quickly came in for criticism, such as Gerhard Schulze’s thesis of an “experience society” brought about by affluence, who was in turn accused of falsely generalizing a phenomenon located in the more privileged part of society. Today, the parameters of this debate seem to have shifted: A much more prominent role is played by studies which show that aesthetic motifs such as creativity, spontaneity and originality are no longer signs of a sphere of freedom lying beyond the necessities of social reproduction, but have themselves become an important productive force in the capitalist economic system. According to this research, these motifs have turned into crucial social demands, representing an increase of constraints rather than freedom. In any case, sociology seems to have become the central location for serious debate on how to appropriately describe, explain and evaluate the crucial position of aesthetically connoted criteria both for individuals and for the organization of society in Western democracies.
Three examples of parliament floorplans arranged by typology: opposing benches, semicircle, and classroom. Photo: XML / www.parliamentbook.com
But as relevant as these debates are, I believe that philosophy has been wrong to retreat from them. After all, the diagnosis of aestheticization implies an assumption about the undistorted essence of both ethics and politics, which is not merely an empirical, but systematic question. The specific approach of philosophy in the context of contemporary diagnoses, however, can only become fully visible once we turn away from the business of diagnosing the present and turn to the history of philosophy. Contrary to the impression raised by recent debates, aestheticization in no way represents simply a contemporary problem; and traditionally, the concept is much more philosophical than is suggested by the largely sociological character of the current discourse. In fact, philosophical discussion of the challenges posed by certain aesthetic motifs for understanding ethics and politics even goes back to antiquity. The history of practical philosophy can even be seen as a history of crisis-diagnoses that have sought to combat the invasion of the aesthetic and its disintegrating effects into the spheres of ethics and politics. Without a reflection on the long history of this discourse the claim that the “aestheticization of the life-world” represents a new phenomenon and a new epoch will remain questionable. Without a detailed discussion of the problems that practical philosophy has historically ascribed to “the aesthetic,” our judgment of current developments will be in danger of either merely carrying over old prejudices into the present, e.g. by criticizing a supposedly novel domination of simulacra, or we will end up becoming a part of an old problem rather than a part of the solution, e.g. by becoming proponents of a supposedly new, constructivist relation to ourselves and the world. In order to clarify the philosophical assumptions that at least indirectly influence these debates, we require a historical and systematic discussion of the history of the philosophical critique of aestheticization.
As I have already indicated, this history begins in antiquity, or more precisely, with Plato’s critique of democratic culture in The Republic. Plato mistrusts the “colorful” plurality of life-forms in a democracy, as well as the “dazzling” democrats that have learned from (theatre) poets that it is possible to adopt several roles in life. He even sees a major problem in the pretty appearance of democratic culture and its privileged life-form. For according to Plato’s diagnosis, the logic of appearances constitutes the essence of democracy itself: The ethical commitment to the good gets replaced by an aesthetic stylization of existence, while good government (i.e. government that is committed to the good) gets replaced by an uncontrolled spectacle that seduces the people. For Plato, this logic is a small, dangerously subtle step on the path from democracy to tyranny. What is astounding about this diagnosis from antiquity is how familiar its central motifs are even today. Indeed, these motifs were picked up again in the philosophical discourse at the beginning of modernity (around 1800) and have continued to play an important role into the twentieth century and beyond. But why does Plato, of all thinkers, prove to be such a decisive source when it comes to naming the problems of modern democracy, or rather the problems associated with its aestheticized culture? After all, the model of democracy in antiquity cannot be applied to modern democracies; just as little can the arts of antiquity, which Plato criticized for their subversive influence on morals, be equated with modern art-forms. Nevertheless, it is no accident that modern philosophical thought on the matter draws on the work of Plato.
Plato invented a type of critique that has become so crucial for modernity that, despite the obvious differences between antiquity and modernity, a good deal of conceptual effort has been undertaken to revive it. Plato connects his analysis of various forms of government with his investigation of—to put it in modern terms—forms of subjectivization. The connection between government and self-government takes on greater significance in modernity, despite the fact that the organization of the state is no longer regarded as mirroring that of the soul, as is suggested at several points in The Republic. However, if we take a closer look at Plato’s account of this connection, we find the more complex argument that government and self-government are not merely similar to each other, but rather that they form an analogous unity via their respective relation to a value that is central to both, which in the case of democratic culture, is freedom. This thesis on the relationship between ethics and politics is what has remained crucial to the modern critique of aestheticization, and the key to the modern debate on aestheticization is likewise the problem of freedom. If the diagnosis of aestheticization sometimes more, sometimes less explicitly refers to democratic culture, then the freedom that defines this culture is the systematic problem with which it is both ethically and politically concerned.
More precisely, what is at stake is a concept of freedom associated with aesthetic motifs, namely a form of freedom that contradicts social practices, their normative orders and the corresponding identities or roles. It does so by giving private motives (moods, pleasure, taste) such a clear priority over conformity to a given social order that they come to dominate the way that individuals determine their own lives. Critics of aestheticization fear that such a private model of freedom, if successful in establishing itself in society, will have a disintegrating effect on the political community. At best, social bonds will be replaced by “aesthetic” relations; and where there are no longer any social bonds, the staging of community becomes a politically decisive force. Yet the staging of community, as critics of aestheticization go on to argue, does not create community. On the contrary, not only does it barely conceal the fact that it is only necessary because the collective has been undermined from within by the aesthetic self-understandings of its (non-)members, but it is only capable of producing a community to the degree that it simultaneously establishes a divide between those that produce the community and those who—again in the form of moods, pleasure and taste—receive it. The political community thus disintegrates into a spectacle and an audience.
Because of its disintegrating effects, the aesthetic form of freedom has been denounced as a “degenerate freedom” by Plato or as “caprice” or “arbitrariness” (Willkürfreiheit) by Hegel. In the history of the philosophical critique of aestheticization very different conceptual presuppositions have been employed in order to deliver proof, and it is here that the gap between modernity and antiquity becomes particularly visible. However, since Hegel’s objection to the romantic ironist, this critique has taken the shape of a reference to the constitutive role of social practices for the unfolding of individual freedom. Without question, this reference is still justified today. It captures extreme constructivist positions that reduce the possibility for shaping one’s own life to a question of individual ethics, as well as all those who argue that Foucault’s demand “not to be governed like that” refers to the entirety of life—just as if a life beyond all social determination were desirable or even possible. Not only is everybody always involved in social practices, but any understanding of the self requires social recognition in order to be realized.
But by exclusively associating “aesthetic” freedom with freedom from the social in toto, the critique of aestheticization conceals another, more productive interpretation: Distance from the social does not necessarily entail a distance from all social determinacy—a distance that would be as abstract as indeed imaginary. We could also grasp this distance in a different way: not as a model for the life of the subject, but as a productive element of it. Referring to aesthetic existence, to “dazzling” life-forms, does not mean demonstrating and defending abstract freedom from the social, but rather the mutability of the social itself. The aestheticization of freedom would then no longer stand for the misunderstanding of a kind of freedom from the social, in a kind of non-dialectic opposition, to freedom in the social. Rather, it would express the tension at the heart of the life of every individual. Changes of the self are not brought about by a pseudo-superior subject standing above all social identity. Instead, such changes are rooted in experiences of self-difference, which compel the subject to reconceive of itself, its self-understanding, and the meaning of its subjectivity from a distance. I do not distance myself from an overly disciplined self-understanding, for example, by placing myself over this understanding—as if I were the sovereign of my own sovereignty—but, to the contrary, by experiencing desires that counter them in such a way that I (by laughing about myself) become free for new, probably more appropriate self-images. Whoever lives within the misunderstanding of solipsistic self-production is thus just as unfree as those who have never had the experience of distance from themselves, their social roles and its corresponding expectations. It is only possible to mediate between both sides of this tense relationship if we grasp them as elements in a process in which we can change both ourselves and the social practices of which we are a part. Indeed we would misunderstand the changes in ourselves if we took them to be merely private changes. Through these changes we change the practices of which we too are a part. Occasionally this can occur without our noticing, while in other cases it can lead to collisions between ourselves and existing practices, a collision that can only be removed by making explicit changes to either ourselves or the world. That I now choose to understand myself differently can also mean that in order to be able to live out my new self-understanding I must enter into a struggle for recognition.
To defend the possibility of such change, however, means to defend the possibility of changing given determinations of the good as a good in itself. The form of government that has integrated the possibility of questioning given determinations of the good into the concept of the good itself is—as Plato already clearly recognized—democracy. It is the only form of government in which it is allowed to publicly criticize everything, to publicly call everything into question—including the shape of democracy itself. Because it remains open, despite all the risk involved, to re-determinations of the good, and thus to the possibility of a more just order, democracy remains—to cite the now famous formulation employed by Jacques Derrida—“to come.” Yet this is not meant, as Derrida is often misunderstood, as an eternal suspension until the arrival of a coming messiah of democracy. On the contrary, our determinations of the good are all that we have for realizing our freedom in the here and now. Democratic openness to future events neither means openness for the sake of openness, nor is this a fundamental criticism of normative determinations in general. Rather, it emphasizes the possibility of historical revision. For precisely this reason, democracy, to cite Claude Lefort, is the “historical society par excellence.” Yet due to its insight into the historicity of the good, democracy indeed has an internal connection to what has been criticized as the “aestheticization of the political.” We can make plausible that participants in social practices are always potential non-participants, and thus also that members of society are potential non-members, such that the meaning of social practices can be called into question at any time. If this is the case, then the immediate result will be a critique of pre-political conceptions of the order and unity of the political collective. Neither the order nor the unity of the community can simply be presupposed; rather its character is revealed to be a political determination. Furthermore, this means that the unity of the community, along with the order within which it is grasped, must be politically created, produced, staged. Because democracy knows neither order nor unity beyond political representation, it not only stands in clear opposition to Plato’s anti-democratic conception of the natural political order, but also concerns the idea of collective self-government, an idea that is central to the modern understanding of democracy. This latter point has far-reaching consequences, for if it is true that the self of collective self-government cannot be assumed to be a unified will and that it must first be brought forth by political representation, then this means that the demos of democracy can never exist beyond the separation thereby established between representatives and the represented, producers and receivers, the rulers and the ruled, performers and the audience. The demos can therefore never exist outside of relations of power and domination; it never exists as such. In fact, sovereign power and authority are presumed the moment someone steps forward and claims to speak for everyone, yet the people being spoken for are helpless against this presumption of power only to the extent that they are blinded by measures designed to conceal the elements of sovereignty and rhetoric entailed by this act. The democratic answer to the problem of sovereign power does not consist in concealing the latter, but in exhibiting it and thus exposing it to an examination of its legitimacy. For it is precisely through this democratically understood “aestheticization of the political” that democracy preserves its openness to the future. On the democratic political stage, the representatives of the demos must justify themselves before those whose will they represent; they must face a heterogeneous audience whose members always potentially have or develop alternative conceptions of the democratic general will, which can ultimately be asserted publicly as a (counter) power in opposition to the currently prevailing conception.
A view of Le Corbusier's Palace of Assembly (1963), a legislative assembly designed by the noted architect and part of his The Capitol Complex, Chandigarh, India. Photo: XML
Such a defense of an aesthetic, even theatrical dimension of democracy, of the necessity of representation (and the sovereignty that comes with it) does not mark the end of a critique of representation but its beginning. Contrary to the generalized critique of all forms of political stagings or “the media,” we now need a critique in the original sense of the term, i.e. as differentiation. First of all, we must distinguish the aesthetic of totalitarian stagings of unity and of post-democratic disintegration from the political stagings in which democratic power justifies itself before the demos that it claims to represent. Within the framework of totalitarian mass spectacles, for example, everything serves the ideological expression of unity. However, the realization of such a totality, which excludes any kind of division, can only be had at an extraordinarily high price. To the degree that power succumbs to the “madness,” as Claude Lefort and Marcel Gauchet write, of embodying the position of universality and articulating the true general will, power necessarily passes over into the particular: “Instead of the universality to which it lays claim, we only perceive the arbitrariness of rules and decisions, the narrow bias of judgment and the constant resort to brute force”. The contradiction of totalitarianism consists of the fact that “the sought-for elimination of all divisions within society requires a power that separates itself from this society and thereby divides itself between the claim of its transcendence and its factual social immanence.” The fact that totalitarian rule is “doomed” in spite of “all the compulsory measures at its disposal” does not eliminate the possibility that the totalitarian vision can succeed in reality—even if only for a certain time, which history has shown to be necessarily too long.
Italian police officers covered in pink paint by students protesting a school reform plan in Milan, Italy, March 12, 2015.
In its own way, post-democracy, too, is determined, like totalitarianism, by the ideological conception of a complete accordance of power and society. Only this time the idea of accordance is accompanied by a visual culture that is not shaped by an aesthetic of unity, but by an aesthetic of disintegration; it is precisely the endless openness of this culture which proves to be especially inclusive. Post-democratic power denies itself up to a point at which it negates its own sovereignty to define the common good and instead merely claims to manage economic necessities and constraints. To the degree that power legitimates its actions by invoking its own powerlessness, the responsibility for the state of society and the situation of each individual is pushed onto the governed (and no longer onto the government), thereby equating itself with the image of a (neoliberal) classless society that embraces even the poorest of the poor by according them the potential for creative self-realization. Each individual should see himself “as his own militant,” as a bundle of energy that can be molded to fit into continuously new contexts with new contracts, all the while viewing themselves as being in pursuit of their own pleasures. You just have to want it. In terms of a politics of representation this corresponds to a “regime of the all-visible” which eliminates the distinction between image and reality; all citizens are granted the opportunity to present themselves and their individual particularity, but they are no longer met with the expectation of a demand for political representation. By granting each person the possibility of individual visibility, post-democracy claims that it has given each person his or her just due. In both aesthetic and political terms, this recalls the nightmare of a society that has taken on the form of an afternoon talk show.
Both extremes demonstrate the urgency to not only defend a democratic setting in which power appears and must legitimize itself as such, but also the many stages on which arguments about the appropriate representation of the demos, about the respective version of the general will, can be carried out. These are the different, partially interlocking dimensions of democratic life on which the self-difference of the demos can occur: it not only appears in the relation between the government and the non-parliamentary opposition, but also in the relation between the government and the parliamentary opposition; between politics and the media; between the media and the citizens; and finally, between citizen and man, the limit of democratic community. Those cases in which one or more of these differences are absorbed or ignored should appear to be a problem, such as whenever human rights are equated with the civil rights granted by nation-states, or when the relationship between the government and the opposition is eliminated in favor of a one-party state; when free speech and the right to protest are restricted, or when the influence of economic and/or political power blurs the line between politics and the media. Within this perspective, discussions about different formats and strategies of political communications, or the role of new technologies and media for the formation of publics and counter-publics, gain critical relevance.
Defending the levels of democratic life that bear witness to a conflict over various views of what is publicly relevant, of what constitutes the common will, means abandoning the conception of democracy as the final, good form of rule in which the problem of sovereignty has been overcome, just because “the people” itself takes up the position of the sovereign, for this conception presupposes the problematic fiction of an identity of the demos with itself. Given the unforeseeable heterogeneity of its (non-)members, this notion of democracy is a structurally totalitarian one. The insight that the demos never exists outside its representation implies, as we have seen, the recognition of an element of sovereignty at the very foundation of democratic societies. However, this is not the unfortunate death, but the beginning of democratic politics. For this is the kind of politics whose dynamic derives from the experience of the self-difference of the demos, in which democracy is realized only by means of a constant struggle over the nature of its very concept.
Superhumanity, a project by e-flux Architecture at the 3rd Istanbul Design Biennial, is produced in cooperation with the Istanbul Design Biennial, the National Museum of Modern and Contemporary Art, Korea, the Govett-Brewster Art Gallery, New Zealand, and the Ernst Schering Foundation.
The text documents a lecture in which the author summarized some of the theses from her book The Art of Freedom. On the Dialectics of Democratic Existence (Cambridge: Polity Press, 2016) for discussion.
Juliane Rebentisch is Professor of Philosophy and Aesthetics at the University of Arts and Design in Offenbach/Main, Germany.
Visual information is largely processed through two pathways in the primate brain: an object pathway from the primary visual cortex to the temporal cortex (ventral stream) and a spatial pathway to the parietal cortex (dorsal stream). Whether and to what extent dissociation exists in the human prefrontal cortex (PFC) has long been debated. We examined anatomical connections from functionally defined areas in the temporal and parietal cortices to the PFC, using noninvasive functional and diffusion-weighted magnetic resonance imaging. The right inferior frontal gyrus (IFG) received converging input from both streams, while the right superior frontal gyrus received input only from the dorsal stream. Interstream functional connectivity to the IFG was dynamically recruited only when both object and spatial information were processed. These results suggest that the human PFC receives dissociated and converging visual pathways, and that the right IFG region serves as an integrator of the two types of information.
Keywords: Visual Streams, Prefrontal Cortex, Short-term Memory, Functional Magnetic Resonance Imaging, Diffusion Tractography, Functional Connectivity
In the primate brain, visual information is conveyed from retina to primary visual cortex by three pathways: the magnocellular, parvocellular and koniocellular pathways (Livingstone and Hubel, 1988). Although recent studies have found significant intermixing of different pathways in the early primary visual cortex (Lechica et al., 1992; Yabuta and Callaway, 1998), and in V2 (Sincich and Horton, 2002), it has also been suggested that such intermixing follows a specific pattern, such that new parallel streams of information are conveyed to the extrastriate cortex (Nassi and Callaway, 2009). After leaving the primary visual cortex, visual information is largely processed through two pathways that involve different cortical regions: the object pathway extending from the primary visual cortex to the temporal cortex (ventral stream) and the spatial navigation pathway to the parietal cortex (dorsal stream). Despite extensive connections between the dorsal stream and ventral stream (Felleman and Van Essen, 1991), each represents different features.
The existence of these two separate visual processing pathways was first proposed by Schneider (1969) followed by Ungerleider and Mishkin (1982) who, based on their lesion studies, suggested that the dorsal stream is involved in the processing of visual spatial information, such as object localization (where), and the ventral stream is involved in the processing of visual object identification information (what) (Ungerleider and Mishkin, 1982). Since this initial proposal, it has been alternatively suggested that the dorsal pathway should be known as the ‘How’ pathway, as the visual spatial information processed here provides us with information about how to interact with objects (Goodale and Milner, 1992). For the purpose of object recognition, the neural focus is on the ventral stream.
This concept of separate representation of different features has been further supported by lesion studies (Goodale and Milner, 1992; Ungerleider and Haxby, 1994), electrophysiology studies (Gross et al., 1972; Sato et al., 1980; Bruce et al., 1981; Fuster and Jervey, 1981; Desimone et al., 1984; Miyashita and Chang, 1988; Miller et al., 1991; Batuev et al., 1985; Gnadt and Andersen, 1988; Koch and Fuster, 1989; Barash et al., 1991a, b; Chafee and Goldman-Rakic, 1998), and histological tracer studies (Andersen et al., 1985; Felleman and Van Essen, 1991; Kaas 2004; Lyon 2007) in non-human primates.
But how are object and spatial information represented in the prefrontal cortex (PFC), which is positioned at the end of the sensory processing stream (Levy and Goldman-Rakic 2000; Courtney 2004)? This question has long been debated in non-human primate studies of the PFC, and there continue to be varying viewpoints about whether these types of information are processed in the same or different regions of the PFC (Fuster and Alexander, 1971; Kubota and Niki, 1971; Funahashi et al., 1989; Wilson et al., 1993; Rao et al., 1997; O’Scalaidhe et al., 1997).
Functional magnetic resonance imaging (fMRI) studies in humans have suggested that object (what) information is supported by the inferior frontal gyrus (IFG) or ventrolateral PFC (VLPFC), and that spatial (where) information is supported by the superior frontal gyrus (SFG) (Wilson et al., 1993; Courtney et al., 1996; Courtney et al., 1998a; Belger et al., 1998; Courtney et al., 1998b; Mohr et al., 2006; Sala and Courtney 2007; Volle et al., 2008). Another model suggests a hierarchical organization of the PFC, with short-term maintenance functions ascribed to the IFG/VLPFC, and higher order non-mnemonic functions (e.g., manipulation of items in memory) ascribed to the dorsolateral PFC (DLPFC), which is located anterior to the SFG (Petit et al., 1996; Owen et al., 1996; D’Esposito et al., 1998; Mohr et al., 2006). Although these models do not necessarily exclude one another, questions remain about how the posterior cortices and the PFC interact, and how the information from the posterior cortices is represented within the PFC. The goal of the current study was to explore whether there is an area in the PFC in which the information from the two streams converges, and/or whether there is no such area but connections underlying the two streams dynamically combine the information from the two streams.
In the macaque or rhesus monkey, the terms “VLPFC” and “DLPFC” are often used for the upper and lower bank of the principal sulcus respectively, and the term “IFG” is used for an area located posterior to the arcuate sulcus in the inferior prefrontal region. However, it is more elusive in humans how to term multiple areas in the prefrontal cortex. In this paper, we used the term “VLPFC” in the human brain to mention a broad area lower to the inferior frontal sulcus where in part the inferior frontal gyrus is located (e.g. Gilbert and Burgess 2008), and used the term “IFG” as a part of the VLPFC. We intended to use the term “IFG” only in the context of the human study and in the description of the current human study (e.g. activity in the IFG).
The anatomical connections to the PFC in the non-human primate have provided essential information about functional localization. A number of anatomical studies have shown that the VLPFC and DLPFC regions receive different connections from posterior association cortices. The VLPFC is connected to the inferotemporal cortex (Kawamura and Naito, 1984; Barbas, 1988; Barbas and Pandya 1989), a region involved in the representation of visual objects. In contrast, the DLPFC receives dense projections from the parietal cortex (Mesulam, et al., 1977; Petrides and Pandya, 1984; Andersen et al., 1985; Barbas and Mesulam, 1985; Cavada and Goldman-Rakic, 1989), a region involved in visuo-spatial processing. Findings showing that the DLPFC and VLPFC in non-human primates are the recipients of different projections (object versus spatial) have suggested a parallel organization of functional dissociation within the PFC, and it would therefore be reasonable to expect that regions receiving these different visual inputs are functionally related to the ventral and dorsal visual-processing streams with which they are selectively connected (Goldman-Rakic, 1988). However, our understanding of human brain connections has not advanced at the same level as our understanding of connections in the non-human primate brain, because studies involving invasive tracer techniques cannot be conducted in living human subjects. Furthermore, in postmortem human brains, the current tracer techniques permit definition if only short-range connections.
Recent technical advances in diffusion tensor imaging (DTI) (Basser et al., 1994) have allowed us to look at long-range white matter connections in the human brain (Mori et al., 1999; Jones et al., 1999; Conturo et al., 1999). The process of reconstructing the 3-dimensional pathways is called diffusion tractography. An increasing number of studies have used DTI to show anatomical connections in the human brain (Conturo et al. 1999; Basser et al. 2000; Stieltjes et al. 2001; Xu et al. 2002; Behrens et al. 2003; Lehericy et al. 2004; Powell et al. 2004; for review, see Johansen-Berg and Rushworth, 2009; Catani and Thiebaut de Schotten, 2009), and recent studies have used DTI to assess connectivity between functionally defined regions of interest (ROIs) (Guye et al. 2003; Toosy et al. 2004; Dougherty et al. 2005; Kim et al. 2006; Takahashi et al. 2007, 2008). In this study, we use a boot-trac algorithm (Lazar and Alexander 2005; Takahashi et al. 2007, 2008) to create probabilistic maps of DTI tractography.
Given that a cortical area can be characterized by its pattern of connections to other areas (Schmahmann and Pandya, 2006), and that brain functions rely on anatomical connectivity, studying connectivity patterns between posterior cortices and the PFC in humans may provide an important clue to understanding the interactions between them. Toward this end, we used diffusion tractography to examine whether anatomical connections from the parietal and temporal cortices project to distinct areas in the PFC, or if they converge on the same areas in the PFC. Although DTI provides information about anatomical pathways in vivo, there is no functional interpretation in the reconstructed fibers themselves. We performed a whole-brain functional connectivity analysis, looking at the functional coupling between functionally identified ROIs.
Materials and Methods
We tested fifteen healthy, normally sighted subjects (7 males and 8 females, aged 21-39, mean age 26), all of whom reported themselves to be native speakers of English, right handed, with no neurological or psychiatric history. Written informed consent, in accordance with the Declaration of Helsinki, was obtained from each subject after the nature and possible outcomes of the study were explained. Image acquisition was completed at Boston University School of Medicine, and the scanning procedures were approved by the BU Institutional Review Board.
All stimuli were presented on a tangential screen positioned 1.1 m from the subjects. Thirty-six face stimuli from the Max Planck Institute, Tübingen, Germany (http://www.kyb.mpg.de/) were used for the ‘face’ condition The faces were framed by ovals so that hair was not visible. Faces and control stimuli were grayscale on a black background, and occupied a visual angle of 3.20° × 3.60°; they were presented at the center of the screen during the face run, and at one of nine peripheral locations during the combined run, in the encoding and judgment periods (Fig. 1). Control stimuli for faces were generated by randomizing phases of original face images in Fourier domains, to preserve spatial frequency components.
Experimental design for functional imaging.
White dot stimuli for the ‘spatial’ condition were generated using Matlab software (The Mathworks Inc., Natick, MA, USA). The dot stimuli were presented on a black background, at one of the 8 positions located 2.50° visual angle away from the center in the encoding and judgment periods. The same white dots served as control dot stimuli, and were presented at the center of the screen.
Between the encoding and judgment periods, white crosshairs appeared at the center of the screen, while red crosshairs appeared during inter-trial periods. All stimuli were presented using presentation software from Neurobehavioral Systems Inc., Albany, CA, USA.
The functional experiment consisted of three independent runs: ‘face’, ‘spatial’, and ‘combined’ runs. fMRI data were acquired during all runs. There were 4 blocks in each run, and one block consisted of 4 trials. Each trial lasted 18 seconds, consisting of a 6 sec encoding period followed by 6 sec maintenance, 2 sec judgment, and 4 sec inter-trial periods (Fig. 1). In each encoding period, 3 stimuli were displayed for 2 sec each. Each face was presented only once throughout all of the encoding periods. Subjects were asked to keep their eyes on the center of the screen as much as possible, and to remember the stimuli they had seen (faces in the ‘face’ run, locations of the dots in the ‘spatial’ run, and faces and locations in the ‘combined’ run) for the maintenance period. In the judgment period that followed, only one stimulus was displayed, and subjects were asked to indicate by pressing one of the two buttons on a box held in the right hand whether or not the same stimulus was shown in the encoding period of the same trial.
In the control blocks in the ‘face’ and ‘combined’ condition, noise ovals were displayed to replace the face stimuli. In the control blocks in the ‘spatial’ condition, a white dot appeared at the center of the screen. For the control blocks, subjects pressed either one of the two buttons randomly after the target stimuli appeared. This task protocol has been used in many studies to localize face and spatial representation in the brain (Courtney et al., 1996; Haxby et al., 1995; Courtney et al., 1998a). We used these short-term memory tasks to enforce stimulus encoding, and to ensure that both the posterior cortices and PFC were recruited to complete the tasks. The ordering of the ‘face’, ‘spatial’, and ‘combined’ runs were counterbalanced across subjects. We used face stimuli because we wanted to study object recognition that has a direct link to the real life (not abstract objects etc.). Among the objects in the real life (e.g. real objects, animals etc.), activation in the ventral pathway was most reliably identified by using human face stimuli. The functional experiment lasted approximately 18 minutes. Eye movements were not measured. However, subjects were instructed to fixate their eye movements at the center of the screen during the task. Subjects reported their response by pressing one of two buttons.
We used a 3 Tesla whole-body scanner (Intera, Philips) to acquire gradient-echo echo-planar (GE-EPI) T2*-weighted BOLD-sensitive images and diffusion-weighted images based on spin-echo echo-planar imaging (SE-EPI). Conventional T1-weighted structural images were also obtained to provide anatomical information for each subject. We used the following parameters for BOLD functional image acquisition: repetition time (TR) = 2.6 sec, echo time (TE) = 35 ms flip angle = 90°, in-plane matrix size 128 × 128, field of view (FOV) = 230 mm × 230 mm, voxel resolution = 1.8 mm × 1.8 mm, number of slices 36, slice thickness 4 mm. Slice orientation was axial, and the imaging volume was aligned to cover the whole brain. Each scanning run commenced with the acquisition of 5 dummy volumes, allowing tissue magnetization to achieve a steady state, after which functional volumes were acquired (115 volumes for each run).
We used the following parameters for DWI acquisition: TR = 17.1 sec, TE = 80 msec, in-plane matrix size 128 × 128, FOV 230 mm × 230 mm, voxel resolution 1.8 mm × 1.8 mm, number of slices = 96, slice thickness = 1.5 mm, with fat suppression, b = 1,000 sec/mm2, 15 directions, gradient strength = 0.2 G/mm, p reduction = 2.0. For each subject we acquired 16 data sets (15 diffusion weighted + 1 non-diffusion weighted images). A total of 4 signal averages were collected to ensure sufficient signal-to-noise ratio (SNR) for high-quality tensor mapping. From these data we calculated diffusion tensors for all imaged pixels. To compensate for motion, scans were acquired separately and then co-registered with others before averaging. Use of the sensitivity encoding (SENSE) technique reduced susceptibility artifacts significantly. Diffusion-weighted data were acquired in the same FOV with BOLD images to simplify post hoc spatial registration. Subsequently, the foci of the BOLD activations were used as seeding points for diffusion tractography. The same procedures were previously applied to dissociate anatomical pathways related to specific cognitive function (Takahashi et al., 2007, 2008).
Functional MRI Analyses
All functional images were initially analyzed with the SPM99 software for statistical parametirc mapping (Wellcome Department of Neurology, UK), and later with custom-made Matlab programs that were previously used in our studies (Takahashi et al., 2007, 2008). For each subject, we realigned the acquired images to the first volume to correct for head movement. Differences in acquisition timing between each slice were corrected for by using sinc interpolation. We spatially normalized each volume to a standard EPI template of 2 mm cubic voxels in the Talairach and Tournoux space (Talairach et al., 1988), using nonlinear basis functions. Each image was smoothed spatially with a Gaussian kernel of 8 mm full-width half-maximum (FWHM), and the time series was smoothed temporally with a 4-sec FWHM Gaussian kernel. Slow signal drifts were removed by high-pass filtering using cut-off periods of 170 sec. For each voxel, data were best-fitted (least squares) using a linear combination of regressors. The regressors were constructed to correspond to each trial type for each subject, and then convolved with the standard hemodynamic response function (HRF). We analyzed all trials with three regressors that corresponded to encoding, maintenance, and judgment periods, respectively. We did not separate correct and incorrect trials within blocks. Contrasts were examined first at the single subject level; then the resulting images were analyzed at the group level using t-tests (random effect analysis).
We set an initial height threshold of p < 0.001, and then used a threshold of p < 0.01 corrected for whole-brain multiple comparisons at the cluster level, according to the SPM standard procedures (Friston et al., 1994). The reason why we did not perform the correction for non-sphericity of the data was based on published suggestions by Friston et al. (2005) in which they reported that the two-stage procedure (SPM standard procedure) with sphericity assumptions about the impact of first level variance components on second-level parameter estimates is a very reasonable approximation in the vast majority of experimental situations. In addition, all of the subjects who participate on our study completed tasks of the same duration; hence, first-level error variance can be considered to be the same across subjects.
The location of each cluster was indicated by peak voxels in the normalized structural images, and labeled using the Talairach and Tournoux nomenclature (Talairach et al., 1988). Table 1 lists all of the activated clusters that passed the threshold (p < 0.01, corrected for multiple comparisons at the cluster level). If the cluster extended into multiple Brodmann’s areas, we separately noted the peak voxels in different areas. Because activated regions in the FG and IPS were bilateral and continuous across the midline, we separated them at the midline to create regions of interest for diffusion tractography analyses.
Regions activated to face stimuli (a) and to spatial stimuli (b).
We realigned the DWI images using the diffusion toolbox in SPM2. The first images of each run were realigned to the first image of the first run to remove eddy current-induced distortions. All of the images were then averaged across the 4 runs. For each voxel, diffusion tensor and fractional anisotropy (FA) were calculated using standard procedures (Mori et al., 1999). After fitting the 15 DWIs by an ellipsoid tensor we removed voxels that had very large residuals; i.e., those voxels with residuals exceeding 35% of the value of the apparent diffusion coefficients (ADC) averaged across the whole brain. In all, approximately 15% of voxels distributed along the edge of the brain were removed. We defined the starting points for diffusion tractography using the T maps generated by SPM99, which resulted from random effect analysis of 15 subjects, as described in the “Functional MRI analyses” section. We used p < 0.001 (uncorrected) as an initial height threshold and p < 0.01 (corrected at the cluster-level) as the starting point criteria (Takahashi et al., 2007, 2008).
The starting points for tractography were set at intervals of 1 mm in the foci of fMRI activation clusters. The coordinates of the activated clusters in the Talairach space were reverse-normalized into each subject’s native space, and were used as the basis for fiber tracking. We then transformed the coordinates of the end points in the native space to the Talirach space, averaged the data across all subjects, and superimposed the resulting maps onto the normalized T1-weighted images in Talairach space. We did sub-voxel seeding without grid shift, and after each 0.5mm step, an interpolated value was calculated for each DWI. For reverse normalization and normalization of the coordinates we used T1 and DWI scans in the same FOV. We have previously used this approach to define major white matter pathways (Takahashi et al., 2007, 2008); this method provides greater accuracy than direct spatial normalization of DWIs, in which resampling reduces image resolution.
We used a tractography algorithm based on the method described in Lazar et al. (Lazar et al., 2003), a tensor deflection approach, developed to overcome crossing fiber problem (Alexander et al. 2001), that uses the entire tensor information instead of a single eigenvector (Lazar et al. 2003). Tractography was not terminated in voxels where the minor eigenvalue was minimal and therefore the reconstructed 3-dimensional tensor model was in a “pancake” shape. When a tractography pathway encountered such a voxel, we let tractography continue to the adjacent voxel following the direction in the previous voxel. We have previously applied this method, showing many examples of known fiber bundles for validation (Takahashi et al. 2007, 2008). At every position along the fiber trajectory a diffusion tensor was interpolated (linear) and eigenvectors were computed. The eigenvector associated with the greatest eigenvalue indicates the principal direction of water diffusion. Fiber tracts were propagated along this direction over a small distance (0.5 mm) to the next point, where a new diffusion tensor was interpolated. Tractography was terminated when the angle between two consecutive eigenvectors was greater than a given threshold (60°), or when the FA value was smaller than a given threshold (0.14). FA < 0.14-0.15 has been reported to provide the best tradeoff between fewer erroneous tracts and penetration into the white matter (Thottakara et al. 2006); we used this same criterion in our previous studies (Takahashi et al., 2007, 2008). Although the tensor deflection algorithm is suggested to overcome the crossing fiber problem, and 15 directions that we used is more than double of the minimum number of the diffusion gradient directions, having more diffusion gradient directions would give more accurate tractography results.
Group analysis in diffusion tractography – Population map
For Figure 2A and 2C, we performed diffusion tractography for all voxels in each activated cluster. To establish dissociation and convergence of the anatomical connectivity of the dorsal and ventral pathways, we used a heuristic algorithm that propagated tensorlines from both regions. We determined the terminal points of the tensorlines by calculating across subjects the probability that an end point from a particular seed region would fall within a voxel (Takahashi et al., 2007, 2008). The resulting map was superimposed onto normalized T1-weighted anatomical images. The maps, which we defined as “population maps,” were reported as the percentage of subjects in whom connections were found.
(Upper panel) Activation maps superimposed on a three-dimensional brain. Areas in green were active to spatial stimuli, while areas in red were active to face stimuli during the encoding phase. The image on the left side represents the right hemisphere,...
Estimation of tractography error by the bootstrap method – BOOT-TRAC probabilistic map
To ensure the reliability of tractography and we estimated the dispersion errors in diffusion tractography using a statistical nonparametric bootstrap method (BOOT-TRAC) (Lazar and Alexander, 2005) to evaluate intra- and inter-subject variability (Figure 2B and 2D). For each gradient direction, we randomly selected and averaged two of four datasets (volumes), and obtained an averaged 15-direction dataset, diffusion tensors, and reconstructed fibers. To obtain a BOOT-TRAC probabilistic map from multiple seeds we first performed fiber tracking from all seed points, for each bootstrap sample. We repeated this procedure 100 times and created probabilistic maps based on how many times, out of 100, fibers passed each voxel in the brain. We assigned a value of “1” to voxels that were passed by at one or more fibers, and “0” to voxels not passed by any fiber. We repeated this procedures for 100 bootstrap samples and determined probabilities for each “1” voxel; we refer to the resulting maps as “BOOT-TRAC probabilistic maps” (Takahashi et al., 2007, 2008).
Estimation of anatomical convergence
For display purposes, we projected the population maps onto a 3-dimensional template brain (Fig. 3A). This procedure was done by modifying one of the programs in the SPM package that is used to project activated regions onto the 3-dimensional template brain. Instead of activation maps, we used the population maps after thresholding them at 5. The threshold of 5 was set for the population analyses only for a visualization purpose. We displayed the terminal points of tractography from the activated areas in the right IPS (terminal areas are shown in green) and in the right FG (terminal areas shown in red). Overlap areas are shown in yellow.
(A) Population maps of the dorsal and ventral pathways projected onto a three-dimensional template brain. Terminal points of tractography (n > 5) from the activated area in the right IPS are shown in green, and terminal points of tractography...
To further estimate anatomical convergence in a quantitative way, we examined whether the anatomical pathways from the dorsal stream (right IPS) and ventral stream (right FG) converged on the same voxels. We noted areas that were continuous across more than 100 voxels, and that showed more than 50% BOOT-TRAC probabilities in both pathways from the right IPS and the right FG (Supplementary Table S1). Only peak voxels located more than 16 mm apart are listed.
Functional connectivity analyses
We performed functional connectivity analysis of the activated regions (McIntosh et al., 1994) using the same procedure we used in our previous study (Takahashi et al., 2008). The fMRI signals were preprocessed for realignment, slice timing correction, normalization and spatial smoothing, in the same way as described above (fMRI Analyses section). We then removed low-frequency drifts in the time course in each voxel. We did not include the realignment parameters in the design matrix for the functional connectivity analyses. Power et al. (2012) reported that many long-distance correlations are decreased by subject motion, whereas many short-distance correlations are increased. In the current study, we focused on long-distance anatomical connections and functional correlation, so the subject motion could decrease the correlations but we may not falsely detect the long-distance correlations.
Given the spatial smoothing of the fMRI data, the activity of a single voxel can also be considered representative of the activity of the region around the voxel. Peak voxels were used for functional connectivity analysis (Talairach coordinates 34, -58, -14 in the right FG and 20, -66, 60 in the right IPS). We obtained maps of the correlation coefficients between time courses in the peak voxel (either the right FG or right IPS) and calculated other voxels for individual subjects. To make inferences about the functional connectivity encoded by these correlation coefficients at the between-subject level, we transformed them into summary statistics using Fisher’s Z Transform. The resulting within-subject maps were then passed to a second-level or between-subject one-sample t-test to generate SPMs, using standard methods. T values were corrected for multiple comparisons for a whole brain at the cluster level (p < 0.01), using p < 0.001 (uncorrected) as an initial height threshold, to be comparable to the fMRI analyses.
Reaction times were 2250±158 msec for the face task, 2120±183 msec for the spatial task, and 2428±384 msec for the combined task. The percentages of correct response in the total judgments were 100% in the face and spatial tasks, and 86.0±4.6% for the combined task.
Dissociation of activation to face and spatial stimuli
In response to face presentation, blood-oxygen level-dependent (BOLD) activity was observed in the bilateral fusiform gyri (FG; Brodmann’s Area [BA] 37), and in two regions in the right inferior frontal gyrus (IFG; BA 45/46 (dorsal IFG) and BA 44/9 (ventral IFG)) (Fig. 2, upper panel, Table 1a; n = 15; p < 0.01, corrected for whole-brain multiple comparisons at cluster level, according to the SPM standard procedures (Friston et al., 1994)). We note that although we use IFG in this results section, where we discuss only human data, when comparing across species in the introduction and discussion sections, we used IFG/VLPFC in reference to humans and VLPFC in reference to non-human primates. We also observed activation in the right anterior cingulate cortices (ACC; BA 32), a region in the left medial frontal cortex (MFC; BA 6), the right MFC (BA 9), and the right inferior parietal lobe (IPL; BA 40).
In contrast, activation in response to spatial stimuli was observed in the bilateral intraparietal sulcus (IPS; BA 7) extending to left visual areas (BA 19/39), and in the right SFG (BA 6) (Fig. 2, upper panel, Table 1b). The activated region in the right SFG (BA 6; Talairach coordinate 34, 6, 66) was located more dorsal from the frontal eye field (FEF; BA 8), which suggested that SFG activity was not due to subjects’ eye movements. We noted weak activation in the left SFG region in response to the spatial stimuli, below the threshold (p > 0.01 corrected for multiple comparisons). Significant functional activation in response to face and spatial stimuli was clearly dissociated in both hemispheres. The right IPS region activated by spatial stimuli was located dorsal to the right IPL region activated by the face stimuli, and there was no overlap (at threshold of p < 0.01 corrected for whole-brain multiple comparisons at the cluster level).
Anatomical connectivity from the posterior cortices to the PFC
We next examined how the dorsal (parietal cortex) and ventral (temporal cortex) streams anatomically project to the PFC. We performed diffusion tractography to explore anatomical connections from the activated regions. Supplementary Figure S1 shows all of the tractography fibers in one subject, from the right FG activated by face stimuli (red) and from the right IPS activated by spatial stimuli (green). The tractography pathways from the right FG were restricted primarily to the ventral areas, projecting to the right temporal cortex and the right IFG. In contrast, the right IPS activated by spatial stimuli projected to both dorsal and ventral areas: the right SFG, the right temporal cortex, and the right IFG.
The lower panels of Figure 2 (2A and 2C) show the percentage of subjects in whom we found connections from the right FG (Fig. 2 A) and the right IPS (Fig. 2 C) to each voxel (“population map”; see Materials and Methods section for more details). We found a high probability of connections from the right FG in the right temporal pole and in the right IFG; similarly, we found high probability of connections from the right IPS in the right SFG and IFG. Figure 2B and 2D show the result of the BOOT-TRAC averaged across all subjects. These BOOT-TRAC probabilistic maps evaluate both intra- and inter-subject variability on final reconstructed fibers. The results were very similar to what we observed in the “population map” (Fig. 2A and 2C), confirming that our results are reliable even when accounting for dispersion error.
The population maps of tractography from the right FG (Fig. 2A) and the right IPS (Fig. 2C) were projected on a 3-dimensional template brain (Fig. 3A). As described above, the ventral pathways (Fig. 3A red) remained mainly in the ventral areas, and the dorsal pathways (Fig. 3A green) projected to the right SFG (an arrowhead in dark blue) as well as to the right IFG (arrowheads in light blue). Overlap areas (Fig. 3A yellow) were located in areas from the right posterior parieto-occipital junction to the right middle temporal gyrus, the right parahippocampal gyrus and hippocampus, and the right IFG. The right IFG was the only PFC area where the two streams showed convergence. In the left hemisphere, pathways from the left FG and left IPS projected to similar areas in the right hemisphere, but there was no converging area in the left PFC (Fig. 3A, see also Supplementary Fig. S2).
Intra- and inter-stream anatomical connectivity
To address connectivity within streams (dorsal to dorsal or ventral to ventral) and across streams (dorsal to ventral or ventral to dorsal), we examined connections between activated areas, across all subjects. We first focused on five areas: right IPS and right SFG regions activated by spatial stimuli (dorsal stream), and right FG and two right IFG regions activated by face stimuli (ventral stream). We refer to the two right IFG regions activated by face stimuli as right dorsal IFG (BA 44/9) and right ventral IFG (BA 45/46). Intra-stream anatomical connections within the ventral stream were found between the right FG and right ventral IFG in 14 subjects (93.3 %), and between the right FG and right dorsal IFG in 10 subjects (66.7 %). Intra-stream connections within the dorsal stream were found between the right IPS and the right SFG in 12 subjects (80.0 %). Overall, we found very consistent intra-stream connections with high probability, which likely support the functional dissociation in the PFC during the timeframe of our study. Interestingly, we also found a high probability of some inter-stream connections. The right IPS was anatomically connected to the right dorsal IFG in 12 subjects (80.0 %), and to the right ventral IFG in 12 subjects (80.0 %). In contrast, the right FG was connected to the right SFG in only 1 subject (6.70 %). We also found inter-stream connections between posterior areas: the right FG and right IPS were connected in 15 subjects (100 %). Connectivity among all activated areas is reported in Supplementary Table S2.
Examination of voxel-level convergence of anatomical connectivity
We examined for projection overlaps from the dorsal stream (right IPS) and ventral stream (right FG). In the PFC, we found that projection overlap was highly probable (more than 50 %) only in the right ventral IFG (BA 47/10, Talairach coordinate 48, 48, -8), even though we found overlapping projections in other posterior areas (Supplementary Table S1a). In the left hemisphere, we saw no convergence area in the left PFC (Supplementary Table S1b), consistent with the results shown in the previous section (Fig. 3A and Supplementary Fig. S2).
As described above, the right dorsal IFG region activated by face stimuli received anatomical connections from both the FG and IPS (Supplementary Table S2), but was not found to have overlapping projections at the voxel level from the FG and IPS (Supplementary Table S1). This was because projections from the IPS and FG terminated at different places in these areas.
Intra- and inter-stream functional connectivity
We found that two regions in the right IFG were connected to both the dorsal stream (IPS) and ventral stream (FG). The right SFG activated by spatial stimuli was connected to the right IPS only, not to the right FG. The inter-stream anatomical connectivity between the right IPS (dorsal) and the right IFG (ventral) seemed to disagree with the functional dissociation in the PFC that we observed in this study, although it may be in line with previous observations of IFG activation in response to both spatial and object short-term memory tasks (Smith et al. 1995; Owen, 1996; Rao et al., 1997; D’Esposito, 1998; Postle et al., 2000; Nystrom et al., 2000).
To evaluate the functional strength of connectivity between these areas, we examined functional correlation among these areas during both the face task and the spatial task. In agreement with anatomical connectivity results, intra-stream functional connectivity from the right FG to the right ventral IFG, and from the right IPS to the right SFG were found during both face and spatial tasks (Table 2). We found that inter-stream functional connectivity between the right IPS and the right ventral IFG was not significant in either the object-only or the spatial-only conditions (Table 3).
Magnitude of functional connectivity along intra-stream connections observed from diffusion tractography.
Magnitude of functional connectivity along inter-stream connections observed from diffusion tractography.
Interstream functional connectivity during integration of two streams
Here, we hypothesized that the interstream connectivity between the right IPS and the right ventral IFG is important only when combined object and spatial information is processed in the brain. To test this hypothesis, we asked subjects to remember both the positions and identities of faces in combination (see Materials and Methods). We found that the right IFG region was specifically active during the maintenance phase, not during the perception or retrieval phases of the combined condition (Figure 3B). More interestingly, we found that functional connectivity along this interstream pathway became significant during the combined condition (Table 3). These results suggest that the interstream pathway is dynamically recruited only when combined object and spatial information is processed in the brain.
In this study, two parallel pathways between the posterior cortices to the PFC were observed from the right FG to the right ventral IFG/VLPFC, and from the right IPS to the right SFG. The dorsal pathway was activated by spatial information, while the ventral pathway was activated by object (face) information. The right SFG was connected only to the right IPS, not to the right FG. This suggested that the right SFG receives mainly spatial information from the right IPS. We also identified pathways from the right IPS to the right ventral IFG/VLPFC across the dorsal and ventral pathways. The right ventral IFG/VLPFC region received anatomical connections from both the right FG and right IPS. Interestingly, we found that functional connectivity along this interstream pathway became significant during the combined condition. These results suggest that the right ventral IFG region serves as an integrator of the two types of information during short-term memory. In summary, our results suggest that the right ventral IFG is one prefrontal area in the human brain to receive converging long-range anatomical pathways from both the dorsal and ventral visual streams, and the right ventral IFG region may incorporate spatial information from the right IPS with object information from the right FG, so as to combine and maintain both types of information.
Intra-stream long-range anatomical connectivity - Comparisons with non-human primate studies
Although anatomical connections in non-human primates have been well characterized between the posterior cortices and the PFC, evidence for connectivity in humans is still limited, in part by technilogical limits. Our tractography results that showed pathways running from the right IPS to the right SFG likely correspond to the human homologue of the second branch of the superior longitudinal fasciculus (SLF II), as described in the human brain (Thiebaut de Schotten et al., 2005) and monkey brain (Schmahmann, and Pandya, 2006). In the monkey, the SLF II originates in the caudal inferior parietal lobe (corresponding to the human angular gyrus) and the occipito-parietal area, and projects to the dorsolateral prefrontal cortex (Schmahmann, and Pandya, 2006); these results mirror our tractography results showing connections between the right IPS and the right SFG, originating from broad areas around the parieto-occipital junction that includes the ventral end of the right IPS and dorsal edge of the right FG.
Our results on the pathway from the right FG to the right ventral IFG/VLPFC also showed strong agreement with previous observations in the ventral course of the inferior fronto-occipital fasciculus (IFOF) in the human brain, which connects the occipital/posterior temporal lobes and the inferior frontal lobe (Mori et al., 2007; Catani and Thiebaut de Schotten, 2009). In non-human primates, the uncinate fasciculus is the major connection from the temporal lobe to the frontal lobe, while in humans, diffusion tractography studies have repeatedly revealed that the ventral pathway of the IFOF originates from the occipital and posterior temporal lobe and courses directly to the ventral frontal lobe (Mori et al., 2007; Takahashi et al., 2007), and that the uncinate fasciculus originates from the anterior temporal lobe and courses to the ventral frontal lobe (Mori et al., 2007). The ventral pathways of the IFOF seem to be unique to the human brain; previous studies have led researchers to suspect that the IFOF is related to visual processing (Catani and Thiebaut de Schotten, 2009), and that its disconnection differentiates the ventral frontal cortex from more posterior sources of visual input related to object identification (Urbanski et al., 2008).
Inter-stream long-range anatomical connectivity - Comparisons with non-human primate studies
Interestingly, we identified inter-stream anatomical pathways from the right IPS to the right ventral IFG/VLPFC region. Based on the available literature, this pathway may correspond to a branch of the IFOF in humans that courses from the parietal lobe to the frontal lobe (Mori et al., 2007). In non-human primates, the DLPFC receives dense connections particularly from the IPS and the superior parietal cortex, less so from the inferior parietal cortex. The IFG that is located posterior to the VLPFC (posterior to the arcuate sulcus), is connected not only to infero-temporal cortex, but also to the inferior parietal cortex (Schmahmann and Pandya, 2006). The third branch of the SLF (SLF III) originates from the posterior parieto-occipital junction and surrounding areas, and courses to the VLPFC; tracer studies (Schmahmann and Pandya, 2006) and tractography studies (Schmahmann et al., 2007) demonstrating the monkey SLF III pathway may be related to our tractography results showing connections from the right IPS to the right ventral IFG. However, it is still not clear whether the SLF III in monkeys correlates to a branch of the IFOF in humans. The anatomical converging region that we observed in the ventral IFG/VLPFC (BA 47/10 in humans) seems to be located more anterior ventral than the terminal areas of the SLF III in monkeys (ventral BA 6, ventral BA 9/46, and BA 44 in monkeys), and more anterior ventral than suggested possible human frontal areas that receive pathways from the inferior parietal lobe (Petrides et al., 2012). Further comparative examinations between humans and monkeys will be necessary in order to conclude whether monkeys have an anatomical converging area in the PFC, and if they do, how that area correlates to the ventral IFG/VLPFC area in humans.
Role of the right ventral IFG/VLPFC
The right ventral IFG/VLPFC in humans may represent a convergence zone of the two streams of visual processing: (1) the occipito-temporo-frontal stream, which is dedicated to object processing and passes through the IFOF and the uncinate fasciculus, and (2) the parieto-frontal network, which is presumably connected by the human homologue of the third branch of the SLF. We speculate that this area may play an important role in integrating object and spatial information. Indeed, in monkeys, neurons in the lateral PFC respond to both the location and identity of previously presented visual objects, which allows the integration of “what” and “where” information (Rao et al., 1997). IFG/VLPFC is, however, strongly involved in processing of working memory, and we are not able to completely exclude the possibility that the connectivity between the IPS and IFG was recruited because our study involved working memory tasks. Given that the combination of multiple features is an important aspect of working memory processing, it is difficult to dissociate those features—this remains a challenge for future studies. Further correlation studies for functional and anatomical connectivity in humans and monkeys will be important to clarify the role of the IFG/VLPFC in integrating the information from the posterior cortices. A possible way to separate these two processes is to use a working memory task that needs the combined object and spatial information for completing the task, and to compare activated regions by another working memory task that can be completed without combining the two types of information but by other strategies.
We observed activation in response to face stimuli in two right IFG/VLPFC regions: the right dorsal IFG/VLPFC (BA 44/9) and the right ventral IFG/VLPFC (BA 45/47); thee results are consistent with previous reports (Courtney et al., 1996; Haxby et al., 1995; Courtney et al., 1997; Fiez et al., 1996; McCarthy et al., 1996; Cohen et al., 1997) that referred to these regions as the posterior mid-frontal cortex and inferior frontal cortex. These studies also found activation in the anterior mid-frontal cortex (BA 46)/DLPFC, which was more active during a memory delay period (Courtney et al., 1997). We did not find this activation, probably because our study included a relatively small number of items (3 locations) and short delay (6 sec). Courtney and colleagues reported that such a short delay period with low memory load results in right hemisphere-dominant activation (Courtney et al., 1996), which is consistent with our results. We also found right hemispere-dominant activation in response to spatial stimuli in a right SFG region, as has also been seen in previous reports (Courtney et al., 1996; Courtney et al., 1998a; Petit et al., 1996; Mellet et al., 1996; Mohr et al., 2006).
Hemispheric asymmetry of brain function and anatomical connectivity
In this study, we focused mainly on activation and connectivity in the right hemisphere, because activation to face or spatial stimuli occurs predominantly in the right hemisphere. In the left hemisphere, we found somewhat different results. While we found no anatomical convergence area in the left PFC, the right ventral IFG/VLPFC was a convergence area. Several factors may explain this hemispheric asymmetry. One possibility is that the observed hemispheric asymmetry was influenced by handedness. For example, recent imaging studies have reported the relationships between handedness and brain activity during motor, memory, and language tasks (e.g. Cuzzocreo et al., 2009; Propper et al., 2010; for review, Hatta 2007) and some of them suggested that handedness reflects the laterality of hemispheric brain activity in task-related brain regions. However, some other studies did not show such clear relationships (Hatta 2007), and further examination should be done to clarify the relationships between the degree of handedness and deviation of functional organization in each cognitive event.
The other possibilities could be related to the way of our data processing. First, the sizes of the activated areas in the IPS and FG were larger in the right hemisphere than in the left hemisphere. Since we explored pathways from regions of interests (activated areas), the observed laterality of the pathways could be largely due to the locations and sizes of the activated areas. Larger activated areas in the right hemisphere are likely to be related to larger numbers of connections from the activated regions, which could result in a more comprehensive network. Second, the sizes of the activated areas depend on the threshold used in this study. It is possible that outer regions in the activated area in the left IPS might be weakly activated at a sub-threshold. These outer regions might have anatomical connections with the left ventral IFG/VLPFC. Third, anatomical connection patterns themselves may have hemispheric asymmetry. Given that functional hemispheric asymmetry has been repeatedly found in the human brain, it is not surprising to observe such asymmetry in anatomical connections in humans. However, it may not be very likely that the major anatomical bundles would have such large hemispheric asymmetry to the extent we observed between the IPS and the ventral IFG/VLPFC in this study.
Activation in the right parietal lobe
In the right parietal lobe, we found activation to spatial stimuli in the right IPS, and activation to face stimuli in the right IPL although their activated regions did not overlap at the threshold of p < 0.01 (corrected). This does not necessarily go against the idea of representation of spatial information in the parietal cortex. The right IPL region may process some kind of spatial properties of face stimuli, or may process detailed features of the face stimuli themselves. Our experimental design does not explicitly distinguish these two possibilities, but if the right IPL processes spatial properties of the face stimuli, spatial information together with the information in the right IPS may be transferred via the IPS-IFG/VLPFC pathway. If the right IPL itself processes face information, the two modalities of information could converge to some extent in the local connections within the right parietal lobe before they are further processed in the PFC (Konen and Kastner, 2008).
The hierarchical model represents non-mnemonic higher order functions in the PFC, such that manipulation of items in memory is ascribed to anterior mid-frontal cortex (BA46), and short-term maintenance functions are ascribed to the IFG (BA 45/47) (Petit et al., 1996; Owen et al., 1996; D’Esposito et al., 1998; Mohr et al., 2006). In our previous study, we found anatomical connectivity between these areas, as well as two parallel pathways between these two PFC areas and the FG (Takahashi et al., 2007). Although we did not find activation in the anterior mid-frontal cortex/DLPFC in this study, these connections would be important for manipulating information maintained in the IFG/VLPFC (Petit et al., 1996).
Our findings on the existence of the inter-stream anatomical connectivity between the right IPS and right ventral IFG/VLPFC may be in line with previous observations that both spatial and object short-term memory tasks activated the IFG/VLPFC (e.g., Owen, 1997; D’Esposito et al., 1998). In this study, however, we did not find activation to spatial stimuli in the right IFG/VLPFC, probably because of our relatively small number of items (3 locations) and short delay (6 sec). Indeed, in previous studies, direct comparison of activity during face and spatial stimuli revealed functional dissociation between ventral and dorsal frontal cortices; with face information processed in the IFG/VLPFC and spatial information in the SFG (e.g., Courtney et al., 1998a). Thus, the functional dissociation of the dorsal and ventral frontal areas might not be absolute, but relative, particularly in the ventral regions.
Functional connectivity along anatomical connectivity
In agreement with the functional dissociation, we found that the inter-stream functional connectivity along this pathway was weak during the object-only and spatial-only conditions. This result suggests that anatomical inter-stream connectivity exists between the right IPS and right ventral IFG/VLPFC, but its functional strength is weak during tasks that require only one type of information, that is, either face or spatial information. This may explain why the ventral IFG/VLPFC regions were preferentially activated by face stimuli, but were also sometimes activated by spatial stimuli. Thus, the functional dissociation in the PFC may be mutually supported by anatomical connectivity and functional connectivity. Interestingly, we found that functional connectivity along this interstream pathway is dynamically recruited only when both object and spatial information are processed in the brain. Thus, the functional connections together with the anatomical connections form a flexible network for supporting both segregation and integration of the dorsal and ventral visual streams.
Limitation of the current study
In the current study design, it was possible that the spatial task could have induced micro saccades. Micro saccades have been reported to cause similar activation patterns as small visually guided saccades (e.g. Tse et al., 2010), and therefore we cannot exclude the possibility that the activated regions in the spatial task in the current study could have related to the induced micro saccades. However, as we showed in the result section, we did not find activation in the eye movement related areas. Therefore we suspect that the effect of eye-movement to the results of working memory was minimal in this study.
We presented visual stimuli in a block design, because it seemed to be confusing for subjects to challenge randomized types of trials that would require set-shifting when the trial types changed, and because set-shifting would in turn require preparation. Even though it would be possible to subtract post hoc the component of set-shifting related activation, the task itself would be confusing to the subjects, and the error rate would likely increase as a direct result of set-shifting, which is not a focus of this study. The correct trials were 100% for the simple face and spatial tasks, and we only used the activated areas in the tasks with 100% performance as seed regions to initiate tractography. Therefore, the error did not affect our main results (tractography). However, the activation in the combined task would contain not only working memory but also an error-monitoring component.
The spatial and object tasks differ not only in spatial versus object (face) processing but also in the eccentricity of the stimuli, and thus, in principle it is possible that this eccentricity difference is partially responsible for the differential activation. However, the spatial stimuli used in this study were located at a visual angle 2.5 degrees away from the center, which was within the foveal representation (2.6 degrees), and could drive ventral streams in the temporal cortex, as well as dorsal streams in the parietal cortex (Levy et al., 2001; Hasson et al., 2002). The nature of the stimuli was also different between tasks: a simple dot versus a face. However, we used the matched stimuli in control tasks, and therefore the effect of the stimulus difference should be mostly removed by control tasks that we used for each condition.
We thank Nichole Eusemann for editorial support. This work was supported by National Institutes of Health (NS44825); the Human Frontiers Science Program; and the Uehara Memorial Foundation (Japan).
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
- Alexander AL, Hasan KM, Lazar M, Tsuruda JS, Parker DL. Analysis of partial volume effects in diffusion-tensor MRI. Magn Reson Med. 2001;45:770–780.[PubMed]
- Andersen RA, Asanuma C, Cowan WM. Callosal and prefrontal associational projecting cell populations in area 7A of the macaque monkey: a study using retrogradely transported fluorescent dyes. J Comp Neurol. 1985;232:443–455.[PubMed]
- Basser PJ, Mattiello J, LeBihan D. Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson Med. 1994;103:247–254.[PubMed]
- Basser PJ, Pajevic S, Pierpaoli C, Duda J, Aldroubi A. In vivo fiber tractography using DT-MRI data. Magn Reson Med. 2000;44:625–632.[PubMed]
- Barash S, Bracewell RM, Fogassi L, Gnadt JW, Andersen RA. Saccade-related activity in the lateral intraparietal area. I. Temporal properties; comparison with area 7a. J Neurophysiol. 1991a;66:1095–1108.[PubMed]
- Barash S, Bracewell RM, Fogassi L, Gnadt JW, Andersen RA. Saccade-related activity in the lateral intraparietal area. II. Spatial properties. J Neurophysiol. 1991b;66:1109–1124.[PubMed]