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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The Brain's Default Network Anatomy, Function, and Relevance to Disease

— A method has been developed for the simultaneous measurement of the rates of glucose consumption in the various structural and functional components of the brain in vivo. The method can be applied to most laboratory animals in the conscious state. It is based on the use of 2-deoxy-D-[14C]glucose ([14C]DG) as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissues. [14C]DG is used because the label in its product, [14C]deoxyglucose-6-phosphate, is essentially trapped in the tissue over the time course of the measurement. A model has been designed based on the assumptions of a steady state for glucose consumption, a first order equilibration of the free [14C]DG pool in the tissue with the plasma level, and relative rates of phosphorylation of [14C]DG and glucose determined by their relative concentrations in the precursor pools and their respective kinetic constants for the hexokinase reaction. An operational equation based on this model has been derived in terms of determinable variables. A pulse of [14C]DG is administered intravenously and the arterial plasma [14C]DG and glucose concentrations monitored for a preset time between 30 and 45min. At the prescribed time, the head is removed and frozen in liquid N2-chilled Freon XII, and the brain sectioned for autoradiography. Local tissue concentrations of [14C]DG are determined by quantitative autoradiography. Local cerebral glucose consumption is calculated by the equation on the basis of these measured values.

The method has been applied to normal albino rats in the conscious state and under thiopental anesthesia. The results demonstrate that the local rates of glucose consumption in the brain fall into two distinct distributions, one for gray matter and the other for white matter. In the conscious rat the values in the gray matter vary widely from structure to structure (54-197 μmol/100 g/min) with the highest values in structures related to auditory function, e.g. medial geniculate body, superior olive, inferior colliculus, and auditory cortex. The values in white matter are more uniform (i.e. 33–40 μmo1/100 g/min) at levels approximately one-fourth to one-half those of gray matter. Heterogeneous rates of glucose consumption are frequently seen within specific structures, often revealing a pattern of cytoarchitecture. Thiopental anesthesia markedly depresses the rates of glucose utilization throughout the brain, particularly in gray matter, and metabolic rate throughout gray matter becomes more uniform at a lower level.

The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat.

The scope and purpose of this work is 2-fold: to synthesize the available evidence and to translate it into recommendations. This document provides recommendations only when there is evidence to support them. As such, they do not constitute a complete protocol for clinical use. Our intention is that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient. We think it is important to have evidence-based recommendations to clarify what aspects of practice currently can and cannot be supported by evidence, to encourage use of evidence-based treatments that exist, and to encourage creativity in treatment and research in areas where evidence does not exist. The communities of neurosurgery and neuro-intensive care have been early pioneers and supporters of evidence-based medicine and plan to continue in this endeavor. The complete guideline document, which summarizes and evaluates the literature for each topic, and supplemental appendices (A-I) are available online at https://www.braintrauma.org/coma/guidelines.

Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition

The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

The structural and functional integrity of the brain depends on the delicate balance between substrate delivery through blood flow and energy demands imposed by neural activity. Complex cerebrovascular control mechanisms ensure that active brain regions receive an adequate amount of blood, but the nature of these mechanisms remains elusive. Recent findings implicate perivascular neurons, gliovascular interactions and intramural vascular signalling in the control of the cerebral microcirculation. Neurons, astrocytes and vascular cells seem to constitute a functional unit, the primary purpose of which is to maintain the homeostasis of the brain's microenvironment. Alterations of these vascular regulatory mechanisms lead to brain dysfunction and disease. The emerging view is that cerebrovascular dysregulation is a feature not only of cerebrovascular pathologies, such as stroke, but also of neurodegenerative conditions, such as Alzheimer's disease.

Neurovascular regulation in the normal brain and in Alzheimer's disease.

In 1945 the authors reported the determination of cerebral blood. flow in man by the use of nitrous oxide in low concentration, a technique which permitted for the first time quantitative clinical measurement of this important physiologic function (1). Since that time numerous modifications have been made in the procedure (2) and the underlying theory has been subjected to extensive experimental evaluation. The present report constitutes a description of the technique as we have now employed it in over 300 determinations, an examination of its underlying theory and validity, and values obtained with its use in 34 studies on 14 normal young men.

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The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure and normal values

A method for measuring quantitatively the volume of cerebral blood flow in man by inhalation of nitrous oxide (1) found its first application in a study of the cerebral circulatory effects of low CO2 tension achieved by hyperventilation; of high CO2 tension, and of high and low 02 tensions obtained by inhalation of appropriate gas mixtures (2). Only the first part of this study, the effects of active and passive hyperventilation, has been published in detail (3). The purpose of the present paper is to present the remainder of these findings and to derive from them, together with those of the hyperventilation experiments, evidence bearing on the intrinsic control of the human cerebral circulation as revealed by quantitative measurements.

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The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men

Quantitative measurements of the total blood flow to the brain of man have not previously been reported and the few procedures which have been used for the purpose of obtaining relative or qualitative values have recently been subjected to considerable criticism (1). The method to be described is based on the principle that the rate at which the cerebral venous blood content of an inert gas approaches the arterial blood content depends upon the volume of blood flowing through the brain. Certain aspects of this principle were recognized by Haggard (2) who postulated that the rate at which an anesthetic gas is taken up by the brain depends in part on the rate of blood flow to that organ, and similarly by Ferris, Molle a,nd Ryder (3) who stated that the clearance of nitrogen from the brain during the inhalation of 100 per cent oxygen may be markedly influenced by the magnitude of cerebral blood flow. As far as we are aware, however, the principle has not previously been subjected to mathematical analysis and applied to actual measurements of cerebral blood flow in animals or man. The experiments described in the preceding report (4) a,fforded an opportunity for calibrating this procedure against direct measurements of cerebral blood flow and thus for refining the technical and theoretical fact,ors to a degree that would not otherwise have been possible. METHODS. The specific substance which is employed is not of consequence provided that it is physiologically inert in the concentrations employed, capable of diffusing rapidly across the blood-brain barrier, and susceptible of accurate analysis in the blood. It need not$ even be a gas if it meets all these requirements. In the present experimentIs nitrous oxide has been employed although ot#her gases may be found to be more suittable. Radioact,ive gases offer certain unique advantages and their use is being considered. In the animal experiments t,he inhaled gas consisted of 40 per cent! nitrous oxide in oxygen which was inhaled through the inspiratory valve attached to the tracheal cannula. In the early experiments on man 15 per cent nitrous oxide and 85 per cent oxygen was employed and was inhaled tlhrough the inlet, t,ube of an anesthesia mask. Because the presence of nit,rogen in t/he blood imroduces cer-

The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations

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The effects of active and passive hyperventilation on cerebral blood flow, cerebral oxygen consumption, cardiac output, and blood pressure of normal young men

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Carl F. Schmidt

Papers

The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure and normal values

The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men

The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations

The effects of active and passive hyperventilation on cerebral blood flow, cerebral oxygen consumption, cardiac output, and blood pressure of normal young men

The blood flow and oxygen consumption of the human brain in diabetic acidosis and coma.