Network Approaches to Diseases of the Brain


by

Matt T. Bianchi

DOI: 10.2174/97816080501781120101
eISBN: 978-1-60805-017-8, 2012
ISBN: 978-1-60805-380-3

  
  


Indexed in: Scopus

This book covers novel approaches using networks and oscillations and it will serve as a catalyst for translating these exciting advan...[view complete introduction]
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Table of Contents

Foreword , Pp. i-ii (2)

Cornelis J. Stam

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Preface , Pp. iii

Matt Bianchi, Verne Caviness and Sydney Cash

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List of Contributors , Pp. iv

Matt T. Bianchi, Verne S. Caviness and Sydney S. Cash

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Synchronizing Bench and Bedside: A Clinical Overview of Networks and Oscillations , Pp. 3-12 (10)

Matt T. Bianchi, Joshua P. Klein, Verne S. Caviness and Sydney S. Cash

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Primer on Networks in Neuroscience , Pp. 13-20 (8)

Mark A. Kramer

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Neural Networks in the Developing Human Brain , Pp. 21-31 (11)

Catherine J. Chu-Shore, Verne S. Caviness and Sydney S. Cash

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Brain Anatomy and Small-World Networks , Pp. 32-50 (19)

Danielle S. Bassett and Edward T. Bullmore

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Sleep Physiology Dynamics: Network Analysis and other Quantitative Approaches , Pp. 51-63 (13)

Matt T. Bianchi and Andrew J. Phillips

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Multimodal Imaging in Epilepsy: Combining EEG and fMRI , Pp. 64-80 (17)

Helmut Laufs

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Abnormal Synchrony and Oscillations in Neuropsychiatric Disorders , Pp. 81-99 (19)

Peter J. Uhlhaas and Wolf Singer

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Brain Stimulation Techniques and Network Studies of Brain Function , Pp. 100-123 (24)

Mouhsin Shafi and Alvaro Pascual-Leone

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Subject index , Pp. 124-125 (2)

Matt T. Bianchi, Verne S. Caviness and Sydney S. Cash

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Foreword

Is it possible to make a walk crossing each of the seven bridges of the Pregal River in Konigsberg only once? This does not sound very much like the question modern neurologists are likely to ask when dealing with their patients and the complexities of neurological disease. Surprisingly, however, this book by Drs. Bianchi, Caviness, and Cash will show how this type of question has recently become very relevant for understanding how complex brain networks develop and function, and how this enchanted loom breaks down in neuropsychiatric disease. The famous problem of the seven bridges of Konigsberg was solved by the brilliant mathematician Leonhard Euler. To do this he had to invent a completely new branch of mathematics: graph theory. Graph theory deals with complex networks by reducing them to their bare essentials: collections of network nodes or ‘vertices’ and their interconnections called ‘edges’. How could this esoteric piece of mathematics teach us something useful about the brain and its disorders?

The Hungarian writer Frigyes Karinthi may have been one of the first to hit upon some unexpected properties of large-scale networks. In a short story called Chains, one of the characters wonders whether every human being might be connected by at most six intermediate persons. This phenomenon is the basis of popular games such as the Kevin Bacon game, where one has to connect an arbitrarily chosen actor to Bacon by a series of movies in which the two actors played together. Another variant of the game is the Erdos number: this indicates how close you are to the famous and eccentric mathematician using a chain of co-authorships. The first to study this phenomenon of small distances in social networks more scientifically was a psychologist from Harvard: Stanley Milgram. With his famous letter experiment he showed that indeed distances between arbitrary persons in social networks are surprisingly small, on average close to six intermediate persons. This gave a scientific basis to the notion of six degrees of separation, but it was completely unclear how such a property of social networks could arise. We should not forget an average person has only about 150 acquaintances (Dunbar’s number), and there are close to billion people in the world.

The problem was solved by Duncan Watts and Steve Strogatz in a brilliant Letter to Nature published in 1998. Using graph theory they proposed a network model that could span the whole range from fully ordered networks (each node connected to a fixed number of neighbors) to completely random networks. Networks in the intermediate regime, so-called ‘small-world’ networks, were characterized by high clustering as well as short distances between any pair of nodes. The discovery of the ‘small-world’ model, and the ‘scale-free’ networks by Barabasi and Albert one year later, revolutionized the study of complex networks. It has now been shown that high clustering, short path lengths, and scale-free properties are the typical properties of a wide range of complex networks found in nature, ranging from metabolic and gene networks to transportation systems and social networks, providing a scientific basis for Karinthi’s intuition and Milgram’s observations.

What about the brain? Neuroscientist have seized upon the new possibilities offered by modern network science to study the anatomical and functional organization of the brain, ranging form C. elegans to cats, macaques and humans. We now know that brains of all sizes and at various levels show the typical signature of small-world networks: they are highly clustered, and have very short path lengths. In addition, they are characterized by highly connected nodes called hubs, which hang together in the form of a ‘connectivity backbone’. Furthermore, complex brain networks have a delicate hierarchical structure, with modules and sub-modules. These topological features are closely related to brain function. For instance, very recently it has been shown that the path length of anatomical and functional brain networks, that is, the number of steps it takes to travel from one region of the brain to any other region, is closely related to intelligence. How our brains are wired up is strongly predictive of how smart we are.

If modern network theory is so promising for gaining a better understanding of the structure and function of complex brain networks, what does this imply for neurology and psychiatry? Can we understand neural diseases in terms of various scenarios for network breakdown? An increasing number of studies have addressed this question in recent years. Although it is too soon to make up the balance, some interesting patterns can be seen to emerge. Many degenerative disorders are characterized by a breakdown of the normal, optimal small-world structure, resulting in a more random topology of brain networks. In Alzheimer’s disease, there are indications that the disease process specifically targets the hubs of the network, which are also associated with the highest levels of amyloid deposition. In epilepsy, there is increasing evidence that certain network topologies might underlie abnormal low thresholds for network synchronization and seizure spread.

Drs. Bianchi, Caviness, and Cash have attempted to give an overview of this exciting field of network studies in neurology and psychiatry. For anyone who is not familiar with graph theory, the basic concepts are explained in various chapters, avoiding the mathematical details that would distract from the overall understanding. This book gives and excellent overview of the state of the art of network theory and oscillatory synchronization, both in relation to normal brain development, sleep and cognition, as well as with respect to a range of neurological disorders, ranging from degenerative disease to epilepsy. This book is a ‘must’ for any scientist and clinician involved with network studies. Neurologists, neurosurgeons, psychiatrists, psychologists and neuroscientists who are not familiar with these new developments will find that this book is an exciting as well as accessible introduction. Hopefully, many will get ‘hooked up’, and turn their attention to a complex network perspective of the brain.

The Harvard psychologist Stanley Milgram was one of the pioneers of the ‘small-world’ idea. Now, this book edited by neurologists and neuroscientists of Harvard and Massachusetts General Hospital continues this Boston tradition by pointing out the importance of the ‘small-world’ in our brains. Hopefully, one day, we will be able to prove network theorems about the brain, as Euler did for the seven bridges of Konigsberg.

Cornelis J. Stam
Bussum


Preface

This endeavor grew out of a reading group of neurology residents begun several years ago and based on the foundational work of Buzsaki’s Rhythms of the Brain as the centerpiece. Although many of us found the language of networks and oscillations to be somewhat unfamiliar to the parlance of our clinical training in the traditional connectionist approach to diseases of the brain, with each chapter we collectively felt the importance of these unique perspectives to understanding brain disorders. These monthly meetings brought neuro-minded individuals together for discussion, and we are deeply indebted to this group for sharing in our continued learning process across these fascinating fields. In particular, we extend our thanks and appreciation to Drs. Ali Atri, Justin Baker, James Bartscher, Adam Cohen, David Kaplan, Joshua Klein, Atul Maheshwari, Kazuma Nakagawa, Jay Pathmanathan, David Stark, Vivek Unni, Brian Wainger, Zelime Ward, Brandon Westover, and Timothy Yu. In particular we would like to thank the late Dr. Edward Bromfield for valuable discussions in the early phases of our writing.

Certainly our own conceptual framework has drawn profoundly from the growing literature spanning basic and clinical neurosciences. While the translation of these techniques and perspectives into clinically relevant diagnostic, prognostic, and treatment strategies are in their infancy, the trajectory of the learning curve appears already quite steep. Adding these facets to the clinician’s conceptual armamentarium promises to rapidly narrow the gap between the theoretical and the practical implications for individual patient care.

The text is not meant to be a specialized compendium reference, nor a highly technical niche review, but rather a linking “edge” between the nodes of basic and clinical researchers and practitioners - and with any such attempts, sharing a common language is a crucial first step. We hope that these chapters will shed light bi-directionally, as the basic scientists and clinicians who study and treat disorders of the brain have much to learn from one another.

Whether one cares about the brain from the perspective of neurology, psychiatry, or philosophy, there is a certain shared sense of awe inspired, perhaps equally, by the careful observation of normal and pathological brain function. It is therefore with humble appreciation that we thank those who contributed to the current collection. On behalf of all of the authors, we hope that our attempt to capture the excitement of this field will inspire further collaborations and development of novel approaches, with a keen eye towards the clinical relevance of these exciting endeavors.

Matt Bianchi
Verne Caviness
Sydney Cash

List of Contributors

Editor(s):
Matt T. Bianchi
Massachusetts General Hospital
USA




Contributor(s):
Bassett Danielle S.
Brain Mapping Unit Department of Psychiatry
University of Cambridge
UK


Bianchi Matt T.
Sleep Division, Neurology Department
Massachusetts General Hospital
55 Fruit Street Wang 7
MA , 02114
USA


Bullmore Edward T.
Brain Mapping Unit Department of Psychiatry, University of Cambridge
University of Cambridge
UK


Cash Sydney S.
Neurology Department
Massachusetts General Hospital
55 Fruit Street Wang 7
Boston
MA, 02114
USA


Caviness Verne S
Neurology Department
Massachusetts General Hospital
55 Fruit Street Wang 7
Boston
MA, 02114
USA


Chu-Shore Catherine J.
Divisions of Pediatric Neurology and Neurophysiology, Department of Neurology
Massachusetts General Hospital
175 Cambridge Street Suite 340
Boston
MA , 02114



Klein Joshua P.
Neurology Department
Brigham and Women’s Hospital
75 Francis Street
Boston
MA , 02115
USA


Kramer Mark A.
Department of Mathematics and Statistics
Boston University
111 Cummington St
Boston
MA, 02215
USA


Laufs Helmut
Department of Neurology and Brain Imaging Center, Goethe-University Frankfurt am Main
Theodor-Stern-Kai 2-16
Frankfurt am Main, 60590
Germany


Pascual-Leone Alvaro
Department of Neurology
330 Brookline Ave KS 454 Boston
Boston
MA , 02215
USA


Phillips Andrew J.
Division of Sleep Medicine
Brigham & Women’s Hospital, Harvard Medical School
221 Longwood Avenue
Boston
MA , 02115
USA


Shafi Moushin
Neurology Department
Massachusetts General Hospital
55 Fruit Street, Wang 8
Boston
MA , 02114
USA


Singer Wolf
Department of Neurophysiology
Max Planck Institute for Brain Research
Deutschordenstrasse 46
Max-von-Laue-Strasse 1
Frankfurt am Main, 60528
Germany


Uhlhaas Peter J.
Frankfurt am Main, Department of Neurophysiology
Max Planck Institute for Brain Research
Deutschordenstrasse 46
Heinrich-Hoffmann-Strasse 10
Frankfurt am Main, 60528
Germany




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