AD 1 Networks in the brain

Abstract

Marcus E Raichle, a neurologist, is a Professor of Radiology, Neurology, Neurobiology and Biomedical Engineering at Washington University in St Louis. He is a member of the National Academy of Sciences, The Institute of Medicine and the American Academy of Arts and Sciences and a Fellow of the American Association for the Advancement of Science. He and his colleagues have made outstanding contributions to the study of human brain function through the development and use of positron emission tomography (PET) and functional MRI (fMRI). Their landmark study (Nature, 1988) described the first integrated strategy for the design, execution and interpretation of functional brain images. It represented 17 years of work developing the components of this strategy (eg, rapid, repeat measurements of blood flow with PET; stereotaxic localisation; imaging averaging; and, a cognitive subtraction strategy). Another seminal study led to the discovery that blood flow and glucose utilisation change more than oxygen consumption in the active brain (Science, 1988) causing tissue oxygen to vary with brain activity. This discovery provided the physiological basis for subsequent development fMRI and caused researchers to reconsider the dogma that brain uses oxidative phosphorylation exclusively to fuel its functional activities. Finally seeking to explain task-induced activity decreases in functional brain images they employed an innovative strategy to define a physiological baseline (PNAS, 2001; Nature Reviews Neuroscience, 2001). This has led to the concept of a default mode of brain function and invigorated studies of intrinsic functional activity, an issue largely dormant for more than a century. An important facet of this work was the discovery of a unique fronto-parietal network in the brain that has come to be known as the default network. This network is now the focus of work on brain function in health and disease worldwide. In summary, the Raichle group has consistently led in defining the frontiers of cognitive neuroscience through the development and use of functional brain imaging techniques. Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive it ignores the alternative possibility that brain functions are mainly intrinsic involving information processing for interpreting, responding to and predicting environmental demands. I shall argue that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain9s energy resources. Remarkably this intrinsic activity exhibits spatial patterns of coherence that emerge from the analysis of spontaneous fluctuations in fMRI BOLD signal. From these fluctuations it is possible to delineate the cortical systems of the human brain and their subcortical connections. We have dubbed this activity a ‘default mode of brain function’. Of particular interest is one system that resides at the top of this organisation and has come to be known as the brain9s default mode network. It has received much attention with regard to psychiatric conditions because of the self-referential nature of its putative functions. Taken together, these surprising advances in our understanding of human brain function offer a rich opportunity to more fully understand psychiatric diseases.