From: Metabolic activity in the brain

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Matthew Wood
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1 From: Metabolic activity in the brain The cerebral cortex is not the most metabolically active part of the brain; this is not intuitive and may not seem to make sense. The cerebral cortex can be seen on functional MRI images (fmri) to be selectively activated in areas responsive to particular sensory stimuli for example the fusiform gyrus responds to familiar faces, but a diminished response in people with autism may be one more sign of underconnectivity or derailed maturation [1, 2]. Activity at a continuously high level is not needed in the cerebral cortex, anymore than computer memory locations need to be constantly active they are activated only when accessed to store or retrieve data. Brainstem sensory pathways are more likely to be constantly active, especially the auditory system, which often provides the first alert or even a startle reaction for things we need to pay attention to. The brainstem nuclei damaged by asphyxia at birth are metabolically the most active centers of the brain [3, 4]; they may function as multiplexing gates that handle the flood of sensory stimuli to which we are constantly exposed. As Fisch (1970) noted, the auditory system is continuously active, even while we sleep, and remains constantly vigilant of what goes on in our environment [5]. Sokoloff (1981) concluded from measurements of glucose uptake that the inferior colliculus is clearly the most metabolically active structure in the brain [4]. During a period of asphyxia such as that inflicted in the experiments with newborn monkeys, brainstem nuclei sustain damage; the cerebral cortex may not be affected at all [6]. Ronald Myers (who had worked with Windle) later found that partial hypoxia or circulatory insufficiency late in gestation is damaging to the cortex, and produces the pattern of damage responsible for cerebral palsy [7]. Protective mechanisms that preserve activity in the brainstem areas of high metabolic rate appear to go into action during periods of oxygen insufficiency; the cortex then becomes vulnerable and is damaged. Figure 8 is an autoradiogram from the experiments on cerebral blood flow in cats [3]. A radioactive tracer was injected and its distribution one minute later shows the greatest amounts (darkest areas) in nuclei of the auditory pathway. This autoradiogram picture was included in the published proceedings of a symposium, as part of a presentation by Seymour Kety, who was the principal investigator of the experiments with radioactive tracers used to measure blood flow [8]. The blood flow data from the same research is shown in table 3. Sokoloff et al. (1977) substituted carbon 14 labeled deoxyglucose for the inert tracer used by Landau et al. (1955) to measure blood flow [9]. Deoxyglucose is an analogue of glucose that enters the brain but then is not further metabolized. Uptake of deoxyglucose provides a measure of glucose utilization that can differ from blood flow in some circumstances. Normally glucose uptake is greatest in the same brain areas with the highest rate of circulation. Baseline values for blood flow and deoxyglucose uptake can both be used as estimates of metabolic rate, and these methods are now revealing more and more the often surprising effects of drugs and other factors that alter homeostasis in the brain. Eileen Nicole Simon,

2 Table 4 below is adapted from data presented by Sokoloff (1981). As in the measurements of blood flow, baseline uptake of deoxyglucose is highest in the inferior colliculus. High levels of glucose transport proteins and enzymes that drive aerobic metabolism match high blood flow and deoxyglucose uptake in the inferior colliculus. Table 5 below (adapted from Zeller et al., 1997) shows that glucose transport protein (GLUT1) and capillary density are also highest in the inferior colliculus of laboratory rats. References 1. Schultz RT et al. (2003) The role of the fusiform face area in social cognition: implications for the pathobiology of autism. 2. Pelphrey KA et al. (2007) Perception of dynamic changes in facial affect and identity in autism. 3. Landau WM et al. (1955) The local circulation of the living brain; values in the unanesthetized and anesthetized cat. 4. Sokoloff L (1981) Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. 5. Fisch L (1970) The selective and differential vulnerability of the auditory system. 6. Windle WF (1969) Brain damage by asphyxia at birth. 7. Myers RE (1972) Two patterns of perinatal brain damage and their conditions of occurrence. 8. Kety SS (1962) Regional neurochemistry and its application to brain function. 9. Sokoloff L et al. (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. 10. Zeller K et al. (1997) Distribution of Glut1 glucose transporters in different brain structures compared to glucose utilization and capillary density of adult rat brains. Eileen Nicole Simon,

Figure 8: Autoradiograph showing distribution of a radioactive tracer in the brain of a cat one minute following injection of the tracer (from Kety 1962).

3 Figure 8: Autoradiograph showing distribution of a radioactive tracer in the brain of a cat one minute following injection of the tracer (from Kety 1962). This technique has revealed that the highest blood flow in the brain is to structures in the auditory pathway in several other mammalian species, including monkeys. Eileen Nicole Simon,

4 Table 3: Cerebral Blood Flow in Cats, from Landau et al. (1955) Brain Structure cc/gm/min Brain System Inferior colliculus 1.80 auditory Sensory-motor cortex 1.38 Auditory cortex 1.30 Visual cortex 1.25 Medial geniculate 1.22 auditory Lateral geniculate 1.21 visual Superior colliculus 1.15 visual Caudate 1.10 subcortical motor Thalamus 1.03 Association cortex 0.88 Cerebellar nuclei 0.87 Cerebellar white matter 0.24 Cerebral white matter 0.23 Spinal cord white matter 0.14 Eileen Nicole Simon,

5 Table 4: Deoxyglucose uptake in brain structures. From Sokoloff (1981) Brain Structure Monkey Albino Rat Brain System SD 1-4 SD 2-7 Inferior colliculus auditory Auditory cortex Vestibular nucleus Medial geniculate auditory Superior olivary nucleus auditory Visual cortex Mammillary body limbic Superior colliculus auditory Thalamus, lateral nucleus Caudate-putamen subcortical motor Cochlear nucleus auditory Cerebellar nuclei Sensorimotor cortex Lateral geniculate visual Hippocampus limbic Cerebellar cortex Cerebellar white matter Eileen Nicole Simon,

6 Table 5: Glucose transport protein (GLUT1) and capillary density in rats, From Zeller et al. (1997) Brain Structure GLUT1 Density Capillary Density Brain System SD SD Inferior colliculus auditory Posterior cortex Frontal cortex Superior colliculus visual Visual cortex Anterior olfactory nucleus smell Medial Geniculate body auditory Hippocampus CA1 region limbic Caudate nucleus subcortical motor Auditory cortex Eileen Nicole Simon,

PSY 302: CHAPTER 3 NOTES THE BRAIN (PART II) - 9/5/17. By: Joseline

PSY 302: CHAPTER 3 NOTES THE BRAIN (PART II) - 9/5/17 By: Joseline Left 3 MAJOR FISSURES : 2HEMISPHERES Right Lateral Ventricle Central Fissure Third Ventricle Sulcus Lateral Fissure Gyros Fissure- Fissures