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      Revisiting the Functional Anatomy of the Human Brain: Toward a Meta-Networking Theory of Cerebral Functions

      1 , 1
      Physiological Reviews
      American Physiological Society

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          Abstract

          For more than one century, brain processing was mainly thought in a localizationist framework, in which one given function was underpinned by a discrete, isolated cortical area, and with a similar cerebral organization across individuals. However, advances in brain mapping techniques in humans have provided new insights into the organizational principles of anatomo-functional architecture. Here, we review recent findings gained from neuroimaging, electrophysiological, as well as lesion studies. Based on these recent data on brain connectome, we challenge the traditional, outdated localizationist view and propose an alternative meta-networking theory. This model holds that complex cognitions and behaviors arise from the spatiotemporal integration of distributed but relatively specialized networks underlying conation and cognition (e.g., language, spatial cognition). Dynamic interactions between such circuits result in a perpetual succession of new equilibrium states, opening the door to considerable interindividual behavioral variability and to neuroplastic phenomena. Indeed, a meta-networking organization underlies the uniquely human propensity to learn complex abilities, and also explains how postlesional reshaping can lead to some degrees of functional compensation in brain-damaged patients. We discuss the major implications of this approach in fundamental neurosciences as well as for clinical developments, especially in neurology, psychiatry, neurorehabilitation, and restorative neurosurgery.

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          The organization of the human cerebral cortex estimated by intrinsic functional connectivity.

          Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.
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            A default mode of brain function.

            A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.
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              The brain's default network: anatomy, function, and relevance to disease.

              Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.
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                Author and article information

                Journal
                Physiological Reviews
                Physiological Reviews
                American Physiological Society
                0031-9333
                1522-1210
                July 01 2020
                July 01 2020
                : 100
                : 3
                : 1181-1228
                Affiliations
                [1 ]Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Center, Montpellier, France; Team “Plasticity of Central Nervous System, Stem Cells and Glial Tumors,” INSERM U1191, Institute of Functional Genomics, Montpellier, France; and University of Montpellier, Montpellier, France
                Article
                10.1152/physrev.00033.2019
                32078778
                675dbc25-c942-4243-9d7e-9040ca6f8cf5
                © 2020
                History

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