- Email: [email protected]
Editorial overview
Available online at www.sciencedirect.com
Editorial overview Steve Petersen and Wolf Singer Current Opinion in Neurobiology 2013, 23:159–161 For a complete overview see the Issue Available online 16 March 2013 0959-4388/$ – see front matter, # 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.conb.2013.02.011
Steve Petersen Departments of Neurology and Psychology, Washington University Medical School, 4525 Scott Avenue, Box 8111, St. Louis, MO 63130-4899, USA e-mail: [email protected] Steve Petersen received his PhD at CalTech studying monkey visual cortex, with postdoctoral work at NIH on vision and visual attention in macaques. Since 1985, he has been James S. McDonnell Professor at Washington University in the Departments of Neurology and Psychology, and is the Director of the McDonnell Center for Systems Neuroscience. His research focuses on the development of reading, attentional control systems, and large-scale functional brain networks in humans.
Wolf Singer Max Planck Institute for Brain Research, Deutschordenstrasse 46, D-60528 Frankfurt, Germany e-mail: [email protected] Wolf Singer studied Medicine in Munich and Paris, obtained his MD from the Ludwig Maximilian University in Munich, and his PhD from the Technical University in Munich.He is Director emeritus at the Max Planck Institute for Brain Research in Frankfurt and Founding Director both of the Frankfurt Institute for Advanced Studies (FIAS) and of the Ernst Stru¨ngmann Institute for Brain Research (ESI) for Neuroscience in Cooperation with Max Planck Society. His research is focused on the neuronal substrate of higher cognitive functions, and especially on the question how the distributed subprocesses in the brain are coordinated and bound together in order to give rise to coherent perception and action.
There is increasing evidence that even simple cognitive and executive functions involve the coordinated interaction of large numbers of neurons that are distributed across different, specialized cortical areas. These functional networks are determined by the layout of anatomical connections, the connectome. In addition, they are configured on the fly by selforganizing processes that dynamically gate communication between network nodes in a task and goal dependent way. In order to better understand these principles of distributed processing it is necessary to obtain comprehensive data on the brain’s connectome, to uncover basic modes of connectivity and to study the configuration of functional networks by analyzing the signatures of communication between nodes. In the past decade, novel methods have been developed for the collection of such data both from animal and human brains. These comprise: (1) advanced techniques applicable in animal studies for the tracing of connections such as trans-synaptically transported viruses and toxins and magnetic resonance-based diffusion tensor imaging for the non-invasive investigation of axonal projections in human brains; (2) optogenetic approaches to distinguish between excitatory and inhibitory projections and to identify the nature of projection and target cells; (3) application of graph theory for the analysis of network properties; (4) massive parallel recordings of neuronal activity to uncover the functional coupling among distributed neuronal populations; (5) implementation of novel mathematical and machine learning algorithms for the detection of patterns in the high dimensional time series obtained with parallel recordings from animal and human brains; and (6) development of statistical methods that allow one to assess with high temporal resolution, which nodes communicate with one another and in which direction information is conveyed. These new approaches have considerably extended our knowledge about neuronal interactions at various scales, ranging from microcircuits to subsystems and more recently to the whole brain. At the level of microcircuits available data are already considered as sufficiently detailed to warrant simulations of network dynamics. In the mammalian brain such efforts focus on columns of the neocortex, the cerebellum, the hippocampus and the olfactory bulb. However, much less is known about the anatomy and the functional properties of the macrocircuits that assure communication over larger distances, bind distributed processing structures into functionally coherent subsystems and eventually organize globally ordered states required for polymodal integration, sensory-motor coordination, the allocation of attention, decision making, goal setting and ultimately conscious awareness. The chapters in this volume summarize the latest advances in the field of macrocircuit analysis and focus on the mammalian brain.
www.sciencedirect.com
Current Opinion in Neurobiology 2013, 23:159–161
160 Macrocircuits
Methodological and conceptual contributions Olaf Sporns concentrates on graph theoretical analyses of the cortical connectome and discusses the principles allowing both for the functional segregation of subsystems and their integration. The reviewed evidence indicates segregation of functions in densely interconnected ‘communities’ and integration by strategic connections between the ‘hubs’ of such communities. Complementing these structural considerations, Friston, Moran and Seth introduce methods for the functional identification of large-scale networks and the analysis of information flow. They compare the virtues of assessing directed connectivity either with measurements of Granger Causality or with Dynamic Causal Modeling and also discuss the question of how functional segregation and integration can coexist and be dynamically adjusted, emphasizing that a distinction needs to be made between functional and effective connectivity. Because it has long been held that long-range connections are exclusively excitatory and that the action of inhibitory ‘interneurons’ is only local, most analyses of large-scale networks have focussed exclusively on excitatory interactions. The results reviewed in the chapter by Caputi, Melzer, Michael and Monyer indicate that these classical concepts on long-distance communication have to be extended because of the growing evidence for long-range inhibitory projections. These link both subcortical and cortical structures, often reciprocally, and are likely to play an important role in the temporal coordination of network activity by synchronization. Markov and Kennedy review the seminal studies on the connectome of the neocortex that suggest a hierarchical organization of processing stages, a clear separation of feed-forward and feed-back connections and a functional dichotomy of driving and modulatory projections. Subsequently they present recent evidence that indicates a more complex organization of interareal communication that emphasizes more symmetrical reciprocal interactions for which they coin the term of ‘counter-stream’. Two chapters, one by Muckli and Petro, the other by Katzner and Weigelt, discuss the embedding of the primary visual cortex (V1) in the system of the multiple, densely interconnected cortical areas of the visual system. On the basis of morphological — V1 receives many more top down than bottom up projections — and functional considerations — V1 is activated by imagery in the absence of retinal stimulation — Muckli and Petro discuss the role of V1 as target of higher cognitive functions such as attention, predictive coding and imagination. Because the visual system is one of the best explored subsystems of the primate brain and because the best performing methods for the anatomical and functional analysis of macrocircuits exploit mouse genetics, Katzner Current Opinion in Neurobiology 2013, 23:159–161
and Weigelt analyze the differences and similarities between the visual systems of the two species. They conclude that basic principles appear to be similar, including the susceptibility of mouse V1 to top down effects. Jbabdi, Sotiropoulos and Behrens present a conceptual argument that many current approaches to understanding brain networks underappreciate the fact that brain networks, unlike, for example, the Internet are under spatial constraint. They argue that including spatial arrangements and topographic organizations then should provide a deeper understanding of the function of macrocircuits.
Domains of study One of the first subsystems identified as exerting top down control in sensory processing has been the attentional system. It is now established that it consists of a wide network of cortical areas and subcortical structures, raising the question of how these distributed regions can agree on a single focus of attention and propagate this decision to other subsystems. Miller and Buschman concentrate in their review on the fronto-parietal attention network and discuss data suggesting that coherent oscillatory activity plays a major role in the coordination of attention and the gating of sensory signals. Another executive function, closely related to attention is task control, the goal-specific and task-specific allocations of neuronal processing resources and their coordination. Power and Petersen survey evidence that this function is also achieved by self-organization in distributed networks. On the basis of whole brain functional mapping data acquired both during resting state and different tasks, the authors conclude that there are at least two distinct task control systems that coexist as partly overlapping networks comprising cortical areas involved in sustained and adaptive cognitive control, respectively. Both allocation of attention and task or goal selection are strongly influenced by value assigning systems. With respect to the number of target areas and the globality of their effects, these value assigning systems differ from the other networks discussed in this volume. They originate in distinct nuclei in the brain stem and innervate with massively bifurcating axons a large number of subcortical centers and in a graded fashion virtually all cortical areas. Schultz, who pioneered the investigations of the reward function of the dopaminergic projections, reviews the evidence that this system is functionally more heterogeneous than previously assumed and plays a crucial role in bidirectional signaling of reward prediction errors, thereby gating synaptic plasticity and learning. www.sciencedirect.com
Editorial overview Petersen and Singer 161
Demertzi, Soddu, and Laureys examine the provocative issue of conscious utilizing patients with apparent impairments of conscious. They present a framework for thinking about different forms of impairment and provide a hypothesized set of circuit breakdowns that would lead to these differences. Dum and Strick discuss the ways in which neurotropic viruses can be used to reveal multi-synaptic pathways in the brain. These techniques are invaluable in describing larger scale anatomical circuits, and examples are presented from motor, ‘cognitive’, and autonomic circuits. Friederici and Gierhan present an integrative review of imaging studies suggesting a fractionation of function among four separate long-range pathways that subserve production, semantics and levels of syntactic processing. Rugg and Vilberg extend the focus on medial temporal lobe (MTL) in memory retrieval to include a network of related cortical regions, arguing that there are separate content-independent and content-carrying regions that support conscious accessible memory representations. Relatedly, Wandell and Yeatman provide a comprehensive review of the development of white matter pathways in reading, including a dual-process account of why pathways may deviate from normal. These measures may
www.sciencedirect.com
prove useful in identifying children at risk for reading problems, and lead to treatment options. Schall presents a review of primarily non-human primate electrophysiological studies that outline the large-scale circuitry of decision-making. This includes regions that primarily contribute to categorization and stimulus selection, those affiliated with response selection, and regions related to performance monitoring and adjustment. Engen and Singer move to the level of social interaction by examining macro-circuitry related to empathy. The arguments presented here include observations that many circuits related to first-hand experience are also engaged in social, or empathetic responses. Uhlhaas proposes, and provides evidence, that future research in schizophrenia could be stronger by including a focus on neuronal dynamics in large-scale networks. In particular, neural synchrony may be impaired in patients with the disease with implications for translational research. We believe that each of these articles is interesting on its own. As a group they encourage excitement about understanding interactions beyond the local circuitry and provide methods, concepts and examples of how to approach the questions raised at this level.
Current Opinion in Neurobiology 2013, 23:159–161
Editorial overview Steve Petersen and Wolf Singer Current Opinion in Neurobiology 2013, 23:159–161 For a complete overview see the Issue Available online 16 March 2013 0959-4388/$ – see front matter, # 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.conb.2013.02.011
Steve Petersen Departments of Neurology and Psychology, Washington University Medical School, 4525 Scott Avenue, Box 8111, St. Louis, MO 63130-4899, USA e-mail: [email protected] Steve Petersen received his PhD at CalTech studying monkey visual cortex, with postdoctoral work at NIH on vision and visual attention in macaques. Since 1985, he has been James S. McDonnell Professor at Washington University in the Departments of Neurology and Psychology, and is the Director of the McDonnell Center for Systems Neuroscience. His research focuses on the development of reading, attentional control systems, and large-scale functional brain networks in humans.
Wolf Singer Max Planck Institute for Brain Research, Deutschordenstrasse 46, D-60528 Frankfurt, Germany e-mail: [email protected] Wolf Singer studied Medicine in Munich and Paris, obtained his MD from the Ludwig Maximilian University in Munich, and his PhD from the Technical University in Munich.He is Director emeritus at the Max Planck Institute for Brain Research in Frankfurt and Founding Director both of the Frankfurt Institute for Advanced Studies (FIAS) and of the Ernst Stru¨ngmann Institute for Brain Research (ESI) for Neuroscience in Cooperation with Max Planck Society. His research is focused on the neuronal substrate of higher cognitive functions, and especially on the question how the distributed subprocesses in the brain are coordinated and bound together in order to give rise to coherent perception and action.
There is increasing evidence that even simple cognitive and executive functions involve the coordinated interaction of large numbers of neurons that are distributed across different, specialized cortical areas. These functional networks are determined by the layout of anatomical connections, the connectome. In addition, they are configured on the fly by selforganizing processes that dynamically gate communication between network nodes in a task and goal dependent way. In order to better understand these principles of distributed processing it is necessary to obtain comprehensive data on the brain’s connectome, to uncover basic modes of connectivity and to study the configuration of functional networks by analyzing the signatures of communication between nodes. In the past decade, novel methods have been developed for the collection of such data both from animal and human brains. These comprise: (1) advanced techniques applicable in animal studies for the tracing of connections such as trans-synaptically transported viruses and toxins and magnetic resonance-based diffusion tensor imaging for the non-invasive investigation of axonal projections in human brains; (2) optogenetic approaches to distinguish between excitatory and inhibitory projections and to identify the nature of projection and target cells; (3) application of graph theory for the analysis of network properties; (4) massive parallel recordings of neuronal activity to uncover the functional coupling among distributed neuronal populations; (5) implementation of novel mathematical and machine learning algorithms for the detection of patterns in the high dimensional time series obtained with parallel recordings from animal and human brains; and (6) development of statistical methods that allow one to assess with high temporal resolution, which nodes communicate with one another and in which direction information is conveyed. These new approaches have considerably extended our knowledge about neuronal interactions at various scales, ranging from microcircuits to subsystems and more recently to the whole brain. At the level of microcircuits available data are already considered as sufficiently detailed to warrant simulations of network dynamics. In the mammalian brain such efforts focus on columns of the neocortex, the cerebellum, the hippocampus and the olfactory bulb. However, much less is known about the anatomy and the functional properties of the macrocircuits that assure communication over larger distances, bind distributed processing structures into functionally coherent subsystems and eventually organize globally ordered states required for polymodal integration, sensory-motor coordination, the allocation of attention, decision making, goal setting and ultimately conscious awareness. The chapters in this volume summarize the latest advances in the field of macrocircuit analysis and focus on the mammalian brain.
www.sciencedirect.com
Current Opinion in Neurobiology 2013, 23:159–161
160 Macrocircuits
Methodological and conceptual contributions Olaf Sporns concentrates on graph theoretical analyses of the cortical connectome and discusses the principles allowing both for the functional segregation of subsystems and their integration. The reviewed evidence indicates segregation of functions in densely interconnected ‘communities’ and integration by strategic connections between the ‘hubs’ of such communities. Complementing these structural considerations, Friston, Moran and Seth introduce methods for the functional identification of large-scale networks and the analysis of information flow. They compare the virtues of assessing directed connectivity either with measurements of Granger Causality or with Dynamic Causal Modeling and also discuss the question of how functional segregation and integration can coexist and be dynamically adjusted, emphasizing that a distinction needs to be made between functional and effective connectivity. Because it has long been held that long-range connections are exclusively excitatory and that the action of inhibitory ‘interneurons’ is only local, most analyses of large-scale networks have focussed exclusively on excitatory interactions. The results reviewed in the chapter by Caputi, Melzer, Michael and Monyer indicate that these classical concepts on long-distance communication have to be extended because of the growing evidence for long-range inhibitory projections. These link both subcortical and cortical structures, often reciprocally, and are likely to play an important role in the temporal coordination of network activity by synchronization. Markov and Kennedy review the seminal studies on the connectome of the neocortex that suggest a hierarchical organization of processing stages, a clear separation of feed-forward and feed-back connections and a functional dichotomy of driving and modulatory projections. Subsequently they present recent evidence that indicates a more complex organization of interareal communication that emphasizes more symmetrical reciprocal interactions for which they coin the term of ‘counter-stream’. Two chapters, one by Muckli and Petro, the other by Katzner and Weigelt, discuss the embedding of the primary visual cortex (V1) in the system of the multiple, densely interconnected cortical areas of the visual system. On the basis of morphological — V1 receives many more top down than bottom up projections — and functional considerations — V1 is activated by imagery in the absence of retinal stimulation — Muckli and Petro discuss the role of V1 as target of higher cognitive functions such as attention, predictive coding and imagination. Because the visual system is one of the best explored subsystems of the primate brain and because the best performing methods for the anatomical and functional analysis of macrocircuits exploit mouse genetics, Katzner Current Opinion in Neurobiology 2013, 23:159–161
and Weigelt analyze the differences and similarities between the visual systems of the two species. They conclude that basic principles appear to be similar, including the susceptibility of mouse V1 to top down effects. Jbabdi, Sotiropoulos and Behrens present a conceptual argument that many current approaches to understanding brain networks underappreciate the fact that brain networks, unlike, for example, the Internet are under spatial constraint. They argue that including spatial arrangements and topographic organizations then should provide a deeper understanding of the function of macrocircuits.
Domains of study One of the first subsystems identified as exerting top down control in sensory processing has been the attentional system. It is now established that it consists of a wide network of cortical areas and subcortical structures, raising the question of how these distributed regions can agree on a single focus of attention and propagate this decision to other subsystems. Miller and Buschman concentrate in their review on the fronto-parietal attention network and discuss data suggesting that coherent oscillatory activity plays a major role in the coordination of attention and the gating of sensory signals. Another executive function, closely related to attention is task control, the goal-specific and task-specific allocations of neuronal processing resources and their coordination. Power and Petersen survey evidence that this function is also achieved by self-organization in distributed networks. On the basis of whole brain functional mapping data acquired both during resting state and different tasks, the authors conclude that there are at least two distinct task control systems that coexist as partly overlapping networks comprising cortical areas involved in sustained and adaptive cognitive control, respectively. Both allocation of attention and task or goal selection are strongly influenced by value assigning systems. With respect to the number of target areas and the globality of their effects, these value assigning systems differ from the other networks discussed in this volume. They originate in distinct nuclei in the brain stem and innervate with massively bifurcating axons a large number of subcortical centers and in a graded fashion virtually all cortical areas. Schultz, who pioneered the investigations of the reward function of the dopaminergic projections, reviews the evidence that this system is functionally more heterogeneous than previously assumed and plays a crucial role in bidirectional signaling of reward prediction errors, thereby gating synaptic plasticity and learning. www.sciencedirect.com
Editorial overview Petersen and Singer 161
Demertzi, Soddu, and Laureys examine the provocative issue of conscious utilizing patients with apparent impairments of conscious. They present a framework for thinking about different forms of impairment and provide a hypothesized set of circuit breakdowns that would lead to these differences. Dum and Strick discuss the ways in which neurotropic viruses can be used to reveal multi-synaptic pathways in the brain. These techniques are invaluable in describing larger scale anatomical circuits, and examples are presented from motor, ‘cognitive’, and autonomic circuits. Friederici and Gierhan present an integrative review of imaging studies suggesting a fractionation of function among four separate long-range pathways that subserve production, semantics and levels of syntactic processing. Rugg and Vilberg extend the focus on medial temporal lobe (MTL) in memory retrieval to include a network of related cortical regions, arguing that there are separate content-independent and content-carrying regions that support conscious accessible memory representations. Relatedly, Wandell and Yeatman provide a comprehensive review of the development of white matter pathways in reading, including a dual-process account of why pathways may deviate from normal. These measures may
www.sciencedirect.com
prove useful in identifying children at risk for reading problems, and lead to treatment options. Schall presents a review of primarily non-human primate electrophysiological studies that outline the large-scale circuitry of decision-making. This includes regions that primarily contribute to categorization and stimulus selection, those affiliated with response selection, and regions related to performance monitoring and adjustment. Engen and Singer move to the level of social interaction by examining macro-circuitry related to empathy. The arguments presented here include observations that many circuits related to first-hand experience are also engaged in social, or empathetic responses. Uhlhaas proposes, and provides evidence, that future research in schizophrenia could be stronger by including a focus on neuronal dynamics in large-scale networks. In particular, neural synchrony may be impaired in patients with the disease with implications for translational research. We believe that each of these articles is interesting on its own. As a group they encourage excitement about understanding interactions beyond the local circuitry and provide methods, concepts and examples of how to approach the questions raised at this level.
Current Opinion in Neurobiology 2013, 23:159–161