Positron emission tomography study of human brain functional development

Abstract

From over 100 children studied with 2-deoxy-2[18F]fluoro-D-glucose and positron emission tomography we selected 29 children (aged 5 days to 15.1 years) who had suffered transient neurological events not significantly affecting normal neurodevelopment. These 29 children were reasonably representative of normal children and provided an otherwise unobtainable population in which to study developmental changes in local cerebral metabolic rates for glucose (lCMRGlc). In infants less than 5 weeks old lCMRGlc was highest in sensorimotor cortex, thalamus, brainstem, and cerebellar vermis. By 3 months, lCMRGlc had increased in parietal, temporal, and occipital cortices; basal ganglia; and cerebellar cortex. Frontal and dorsolateral occipital cortical regions displayed a maturational rise in lCMRGlc by approximately 6 to 8 months. Absolute values of lCMRGlc for various grey matter regions were low at birth (13 to 25 mumol/min/100 gm), and rapidly rose to reach adult values (19 to 33 mumol/min/100 gm) by 2 years. lCMRGlc continued to rise until, by 3 to 4 years, it reached values of 49 to 65 mumol/min/100 gm in most regions. These high rates were maintained until approximately 9 years, when they began to decline, and reached adult rates again by the latter part of the second decade. The highest increases of lCMRGlc over adult values occurred in cerebral cortical structures; lesser increases were seen in subcortical structures and in the cerebellum. This time course of lCMRGlc changes matches that describing the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. The determination of changing metabolic patterns accompanying normal brain development is a necessary prelude to the study of abnormal brain development with positron emission tomography.

Metabolic Maturation of the Brain: A Study of Local Cerebral Glucose Utilization in the Developing Cat

“…Previous studies in monkeys (Kennedy et al, 1982), humans (Chugani and Phelps, 1986;Chugani et al, 1987), and rats (Nehlig et al, 1988) have found a relationship between a developmental in crease of lCMRglc in a particular brain structure and the emergence of behavior mediated by that struc ture. In the present studies, we also find a general relationship between metabolic and behavioral de velopment in the kitten, as discussed below.…”

“…This developmental period (15 to 60 days) corresponds to the time of rapid synaptic proliferation known to occur in the cat. At 90 and 120 days, a slight decline in lCMRglc Using positron emission tomography (PET), we have previously described the distribution and ab solute rates of local cerebral glucose utilization in the normal human brain from birth to adulthood (Chugani and Phelps, 1986;Chugani et al, 1987 Abbreviations used: BHB, f3-hydroxybutyrate ; 2DG, 2-deoxyglucose; PET, positron emission tomography . …”

“…This developmental period (15 to 60 days) corresponds to the time of rapid synaptic proliferation known to occur in the cat. At 90 and 120 days, a slight decline in lCMRglc Using positron emission tomography (PET), we have previously described the distribution and ab solute rates of local cerebral glucose utilization in the normal human brain from birth to adulthood (Chugani and Phelps, 1986;Chugani et al, 1987). Our findings indicated that although the adult pat tern in the distribution of cerebral glucose utiliza tion is reached by about 1 year of age, local cerebral was observed, but this was followed by a second, larger peak occurring at about 180 days, when sexual matura tion occurs in the cat.…”

Associative and strategic components of episodic memory: A life-span dissociation.

“…H. Johnson, 2001;Paus, 2005), whereas MTL regions mature at relatively faster rates (Casey, Giedd, & Thomas, 2000;Gogtay et al, 2004;Ofen et al, 2007;Sowell et al, 2003; but see Gogtay et al, 2006). The differential developmental trajectories of brain regions suggest that the zone of maximum functional development progresses from MTL to neocortical PFC areas (Chugani, Phelps, & Mazziotta, 1987; for computational modeling, see Shrager & Johnson, 1996). With respect to brain aging, PFC regions are among the first to show signs of senescence-related deterioration during adulthood (Hedden & Gabrieli, 2004;Park & Gutchess, 2005;Raz et al, 2005).…”

Social outcomes in childhood brain disorder: A heuristic integration of social neuroscience and developmental psychology.

“…Similarly, the prefrontal cortex is not fully myelinated until mid-to-late adolescence (Giedd et al, 1999;Klingberg et al, 1999;Sowell et al, 1999;Yakovlev, 1962;Yakovlev & Lecours, 1967). Synaptogenesis occurs at the same rate in most cortical regions (Rakic, Bourgeois, Eckenhoff, Zecevic, & Goldman-Rakic, 1986), although the prefrontal cortex may lag behind the rest of the brain (Chugani, Phelps, & Mazziotta, 1987;Huttenlocher, 1979). White matter may also undergo protracted development within anterior brain regions (Klingberg et al, 1999;Sowell et al, 1999).…”