Pharmacopsychiatry 2013; 46(S 01): S10-S21
DOI: 10.1055/s-0033-1337922
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Network Organization in Health and Disease: On Being a Reductionist and a Systems Biologist Too

W. Bechtel
1   Department of Philosophy, Center for Chronobiology, and Interdisciplinary Program in Cognitive Science, University of California, San Diego, CA, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
18 April 2013 (online)

Abstract

Whereas the challenge for traditional mechanistic science was to identify parts and operations, the current challenge in many fields of biology is to understand how the many parts of mechanisms are organized in networks and their operations coordinated across these networks. This paper explores how tools from graph theory are enabling analysis of organization at both macro- and micro-levels. In applying these approaches to brain regions, systems neuroscientists are identifying both small-world organization with hubs at the macro-scale and frequently occurring subgraphs that link specific brain regions at a more micro-scale. This has lead to the discovery of networks in which activity in multiple brain regions exhibits coherent oscillations and demonstrations that these networks are disrupted in various mental disorders.·

 
  • References

  • 1 Bechtel W, Richardson RC. Discovering complexity: Decomposition and localization as strategies in scientific research. Cambridge, MA: MIT Press; 2010
  • 2 Bechtel W, Abrahamsen A. Explanation: A mechanist alternative. Stud Hist Phil Biol Biomed Sci 2005; 36: 421-441
  • 3 Bechtel W. Mechanism and biological explanation. Philosophy of Science 2011;
  • 4 Craver CF. Explaining the brain: Mechanisms and the mosaic unity of neuroscience. New York: Oxford University Press; 2007
  • 5 Hempel CG. Aspects of scientific explanation, in Aspects of scientific explanation and other essays in the philosophy of science. Hempel CG. ed. New York: Macmillan; 1965: 331-496
  • 6 Glennan S. Mechanisms and the nature of causation. Erkenntnis 1996; 44: 50-71
  • 7 Machamer P, Darden L, Craver CF. Thinking about mechanisms. Phil Sci 2000; 67: 1-25
  • 8 Buchner E. Alkoholische Gärung ohne Hefezellen (Vorläufige Mittheilung). Ber dtsch chem Ges 1897; 30: 117-124
  • 9 Embden G, Deuticke HJ, Kraft G. Über die intermediaren Vorgänge bei der Glykolyse in der Muskulatur. Klin Wschr 1933; 12: 213-215
  • 10 Bechtel W. Discovering cell mechanisms: The creation of modern cell biology. Cambridge: Cambridge University Press; 2006
  • 11 Hubel DH, Wiesel TN. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J Physiol 1962; 160: 106-154
  • 12 Hubel DH, Wiesel TN. Receptive fields and functional architecture of monkey striate cortex. J Physiol 1968; 195: 215-243
  • 13 Felleman DJ, van Essen DC. Distributed hierarchical processing in the primate cerebral cortex. Cereb Cortex 1991; 1: 1-47
  • 14 Bechtel W. Mental mechanisms. London: Routledge; 2008
  • 15 O’Keefe JA, Dostrovsky J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely moving rat. Brain Res 1971; 34: 171-175
  • 16 O’Keefe JA, Nadel L. The hippocampus as a cognitive map. Oxford: Oxford University Press; 1978
  • 17 Bliss TVP, Lømo T. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaesthetized rabbit following stimulation of the perforant path. J Physiol 1973; 232: 331-356
  • 18 Craver CF. The making of a memory mechanism. J History Biol 2003; 36: 153-195
  • 19 Craver CF. Interlevel experiments and multilevel mechanisms in the neuroscience of memory. Phil Sci 2002; 69: S83-S97
  • 20 Krebs HA. Cyclic processes in living matter. Enzymologia 1946; 8 12: 88-100
  • 21 Levy A, Bechtel W. Abstraction and the organizaton of mechanisms. Phil Sci (in press)
  • 22 Jones N, Wolkenhauer O. Diagrams as locality aids for explanation and model construction in cell biology. Biol Philosophy 2012; 27: 705-721
  • 23 Erdös P, Rényi A. On the evolution of random graphs. Proc Math Inst Hungarian Acad Sci 1960; 5: 17-61
  • 24 Yook S-H, Oltvai ZN, Barabási A-L. Functional and topological characterization of protein interaction networks. PROTEOMICS 2004; 4: 928-942
  • 25 Ermentrout GB, Kopell N. Frequency plateaus in a chain of weakly coupled oscillators. 1. Siam J Math Anal 1984; 15: 215-237
  • 26 Watts D, Strogratz S. Collective dynamics of small worlds. Nature 1998; 393: 440-442
  • 27 Pool IdS, Kochen M. Contacts and influence. Social Networks 1978; 1: 5-51
  • 28 Milgram S. The small world problem. Psychol Today 1967; 2: 60-67
  • 29 White JG, Southgate E, Thomson JN et al. The structure of the nervous system of the nematode Caenorhabditis elegans. Phil Trans Sec B 1986; 314: 1-340
  • 30 Varshney LR, Chen BL, Paniagua E et al. Structural properties of the Caenorhabditis elegans neuronal network. PLoS Comput Biol 2011; 7: e1001066
  • 31 Sohn Y, Choi MK, Ahn YY et al. Topological cluster analysis reveals the systemic organization of the Caenorhabditis elegans connectome. PLoS Comput Biol 2011; 7: e1001139
  • 32 Barabási A-L, Albert R. Emergence of scaling in random networks. Science 1999; 286: 509-512
  • 33 Maxwell JC. On governors. Proc Roy Soc Lond 1868; 16: 270-283
  • 34 Wiener N. Cybernetics: Or, control and communication in the animal and the machine. New York: Wiley; 1948
  • 35 Goodwin BC. Temporal organization in cells; a dynamic theory of cellular control processes. London: Academic; 1963
  • 36 White JG. Neuronal connectivity in Caenorhabditis elegans. Trends Neurosci 1985; 8: 277-283
  • 37 Shen-Orr SS, Milo R, Mangan S et al. Network motifs in the transcriptional regulation network of Escherichia coli. Nature Genets 2002; 31: 64-68
  • 38 Mangan S, Zaslaver A, Alon U. The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks. J Mol Biol 2003; 334: 197-204
  • 39 Alon U. An introduction to systems biology: Design principles of biological circuits. Boca Raton, FL: Chapman & Hall/CRC; 2007
  • 40 Tyson JJ, Novák B. Functional Motifs in Biochemical Reaction Networks. Ann Rev Phys Chem 2010; 61: 219-240
  • 41 Tyson JJ, Chen KC, Novák B. Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr Opin Cell Biol 2003; 15: 221-231
  • 42 Sporns O, Zwi JD. The small world of the cerebral cortex. Neuroinformatics 2004; 2: 145-162
  • 43 Chen ZJ, He Y, Rosa-Neto P et al. Revealing modular architecture of human brain structural networks by using cortical thickness from MRI. Cereb Cortex 2008; 18: 2374-2381
  • 44 Sporns O, Tononi G, Kötter R. The human connectome: A structural description of the human brain. PLoS Comput Biol 2005; 1: e42
  • 45 Hagmann P. From diffusion MRI to brain connectomics. 2005 EPFL
  • 46 Chiang A-S, Lin CY, Chuang CC et al. Three-dimensional reconstruction of brain-wide wiring networks in drosophila at single-cell resolution. Curr Biol 2011; 21: 1-11
  • 47 Gong G, He Y, Concha L et al. Mapping anatomical connectivity patterns of human cerebral cortex using in vivo diffusion tensor imaging tractography. Cereb Cortex 2009; 19: 524-536
  • 48 Hagmann P, Kurant M, Gigandet X et al. Mapping human whole-brain structural networks with diffusion MRI. PLoS ONE 2007; 2: e597
  • 49 Hagmann P, Cammoun L, Gigandet X et al. Mapping the structural core of human cerebral cortex. PLoS Biol 2008; 6: e159
  • 50 Sporns O. The human connectome: a complex network. Ann N Y Acad Sci 2011; 1224: 109-125
  • 51 Biswal B, Yetkin FZ, Haughton VM et al. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med 1995; 34: 537-541
  • 52 Shulman GL, Corbetta M, Buckner RL et al. Common blood flow changes across visual tasks: I. increases in subcortical structures and cerebellum but not in nonvisual cortex. J Cogn Neurosci 1997; 9: 624-647
  • 53 Cordes D, Haughton VM, Arfanakis K et al. Mapping functionally related regions of brain with functional connectivity MR imaging. Am J Neuroradiol 2000; 21: 1636-1644
  • 54 Greicius MD, Krasnow B, Reiss AL et al. Functional connectivity in the resting brain: A network analysis of the default mode hypothesis. Proc Natl Acad Sci USA 2003; 100: 253-258
  • 55 Honey CJ, Sporns O, Cammoun L et al. Predicting human resting-state functional connectivity from structural connectivity. Proc Natl Acad Sci USA 2009; 106: 2035-2040
  • 56 Greicius MD, Supekar K, Menon V et al. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex 2009; 19: 72-78
  • 57 van den Heuvel MP, Mandi RC, Kahn RS et al. Functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain. Hum Brain Map 2009; 30: 3127-3141
  • 58 He Y, Wang J, Wang L et al. uncovering intrinsic modular organization of spontaneous brain activity in humans. PLoS ONE 2009; 4: e5226
  • 59 Buckner RL, Sepulcre J, Talukdar T et al. Cortical hubs revealed by intrinsic functional connectivity: Mapping, assessment of stability, and relation to Alzheimer’s disease. J Neurosci 2009; 29: 1860-1873
  • 60 Sporns O, Kötter R. Motifs in brain networks. PLoS Biol 2004; 2: e369
  • 61 Sporns O. Networks of the brain. Cambridge, MA: MIT Press; 2010
  • 62 Vicente R, Gollo LL, Mirasso CR et al. Dynamical relaying can yield zero time lag neuronal synchrony despite long conduction delays. Proc Natl Acad Sci USA 2008; 105: 17157-17162
  • 63 Sporns O, Honey CJ, Kötter R. Identification and classification of hubs in brain networks. PLoS ONE 2007; 2: e1049
  • 64 Bechtel W. The endogenously active brain: The need for an alternative cognitive architecture. Philosophia Scientia (in press)
  • 65 Andreasen NC, O’Leary DS, Cizadlo T et al. Remembering the past: two facets of episodic memory explored with positron emission tomography. Am J Psychiatry 1995; 152: 1576-1585
  • 66 Antrobus JS, Singer JL, Goldstein S et al. Mindwandering and cognitive structure. Trans N Y Acad Sci 1970; 32: 242-252
  • 67 Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: Anatomy, function, and relevance to disease. Ann N Y Acad Sci 2008; 1124 (The Year in Cognitive Neuroscience 2008) 1-38
  • 68 Broyd SJ, Demanuele C, Debener S et al. Default-mode brain dysfunction in mental disorders: a systematic review. Neurosci Biobehav Rev 2009; 33: 279-296
  • 69 Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci 2011; 15: 483-506
  • 70 Buckner RL, Synder AZ, Shannon BJ et al. Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci 2005; 25: 7709-7717
  • 71 Lustig C, Synder AZ, Bhakta M et al. Functional deactivations: change with age and dementia of the Alzheimer type. Proc Natl Acad Sci USA 2003; 100: 14504-14509
  • 72 Greicius MD, Srivastava G, Reiss AL et al. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci USA 2004; 101: 4637-4642
  • 73 Supekar K, Menon V, Rubin D et al. Network analysis of intrinsic functional brain connectivity in Alzheimer's disease. PLoS Comput Biol 2008; 4: e1000100
  • 74 Yao Z, Zhang Y, Lin L et al. Abnormal cortical networks in mild cognitive impairment and Alzheimer’s disease. PLoS Comput Biol 2010; 6: e1001006
  • 75 Garrity AG, Pearlson GD, McKiernan K et al. Aberrant “default mode” functional connectivity in schizophrenia. Am J Psychiatry 2007; 164: 450-457
  • 76 Bassett DS, Bullmore E, Verchinski BA et al. Hierarchical organization of human cortical networks in health and schizophrenia. J Neurosci 2008; 28: 9239-9248
  • 77 van den Heuvel MP, Mandi RC, Stam CJ et al. Aberrant frontal and temporal complex network structure in schizophrenia: a graph theoretical analysis. J Neurosci 2010; 30: 15915-15926
  • 78 White TP, Joseph V, Francis ST et al. Aberrant salience network (bilateral insula and anterior cingulate cortex) connectivity during information processing in schizophrenia. Schizophr Res 2010; 123: 105-115
  • 79 Kennedy DP, Redcay E, Courchesne E. Failing to deactivate: resting functional abnormalities in autism. Proc Natl Acad Sci USA 2006; 103: 8275-8280
  • 80 Iacoboni M. Failure to deactivate in autism: the co-constitution of self and other. Trends Cogn Sci 2006; 10: 431-433
  • 81 Greicius MD, Flores BH, Menon V et al. Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry 2007; 62: 429-437