Early cortical folding and the emergence of structural brain asymmetries have been previously analyzed by neuropathology as well as qualitative analysis of magnetic resonance imaging (MRI) of fetuses and preterm neonates. In this study, we present a dedicated image analysis framework and its application for the detection of folding patterns during the critical period for the formation of many primary sulci (20-28 gestational weeks). Using structural information from in utero MRI, we perform morphometric analysis of cortical plate surface development and modeling of early folding in the normal fetal brain. First, we identify regions of the fetal brain surface that undergo significant folding changes during this developmental period and provide precise temporal staging of these changes for each region of interest. Then, we highlight the emergence of interhemispheric structural asymmetries that may be related to future functional specialization of cortical areas. Our findings complement previous descriptions of early sulcogenesis based on neuropathology and qualitative evaluation of 2D in utero MRI by accurate spatial and temporal mapping of the emergence of individual sulci as well as structural brain asymmetries. The study provides the missing starting point for their developmental trajectories and extends our understanding of normal cortical folding.

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Existing knowledge of growth patterns in the living fetal human brain is based upon in utero imaging studies by magnetic resonance imaging (MRI) and ultrasound, which describe overall growth and provide mainly qualitative findings. However, formation of the complex folded cortical structure of the adult brain requires, in part, differential rates of regional tissue growth. To better understand these local tissue growth patterns, we applied recent advances in fetal MRI motion correction and computational image analysis techniques to 40 normal fetal human brains covering a period of primary sulcal formation (20 -28 gestational weeks). Growth patterns were mapped by quantifying tissue locations that were expanding more or less quickly than the overall cerebral growth rate, which reveal increasing structural complexity. We detected increased local relative growth rates in the formation of the precentral and postcentral gyri, right superior temporal gyrus, and opercula, which differentiated between the constant growth rate in underlying cerebral mantle and the accelerating rate in the cortical plate undergoing folding. Analysis focused on the cortical plate revealed greater volume increases in parietal and occipital regions compared to the frontal lobe. Cortical plate growth patterns constrained to narrower age ranges showed that gyrification, reflected by greater growth rates, was more pronounced after 24 gestational weeks. Local hemispheric volume asymmetry was located in the posterior peri-Sylvian area associated with structural lateralization in the mature brain. These maps of fetal brain growth patterns construct a spatially specific baseline of developmental biomarkers with which to correlate abnormal development in the human.

Systemic glucose utilization declines during sleep in man. We tested the hypothesis that this decline in utilization is largely accounted for by reduced brain glucose metabolism. 10 normal subjects underwent internal jugular and radial artery cannulation to determine cerebral blood flow by N20 equilibrium technique and to quantitate cross-brain glucose and oxygen differences before and every 3 h during sleep. Sleep stage was graded by continuous electroencephalogram, and systemic glucose turnover was estimated by isotope dilution. Brain glucose metabolism fell from 33.6±2.2 ,gmol/100 g per min (mean±SE) before sleep (2300 h) to a mean nadir of 24.3±1.1 gmol/100 g per min at 0300 h during sleep (P = 0.001). Corresponding rates of systemic glucose utilization fell from 13.2±0.8 to 11.0±0.5 gmol/ kg per min (P = 0.003). Diminished brain glucose metabolism was the product of a reduced arteriovenous glucose difference, 0.643±0.024 to 0.546±0.020 mmol/liter (P = 0.002), and cerebral blood flow, 50.3±2.8 to 44.6±1.4 cc/ 100 g per min (P = 0.021). Brain oxygen metabolism fell commensurately from 153.4±11.8 to 128.0±8.4 Mmol/100 g per min (P = 0.045). The observed reduction in brain metabolism occurred independent of stage of central nervous system electrical activity (electroencephalographic data), and was more closely linked to duration of sleep. We conclude that a decline in brain glucose metabolism is a significant determinant of falling rates of systemic glucose utilization during sleep. (J. Clin. Invest. 1994. 93:529-535.) Key words: brain * glucose metabolism * oxygen metabolism , sleep * electroencephalogram

community study ͉ developing country ͉ diarrheal disease ͉ environment ͉ humans

BackgroundDiscoveries that emerging and re-emerging pathogens have their origin in environmental change has created an urgent need to understand how these environmental changes impact disease burden. In this article we present a framework that provides a context from which to examine the relationship between environmental changes and disease transmission and a structure from which to unite disparate pieces of information from a variety of disciplines.MethodsThe framework integrates three interrelated characteristics of environment–disease relationships: a) Environmental change manifests in a complex web of ecologic and social factors that may ultimately impact disease; these factors are represented as those more distally related and those more proximally related to disease. b) Transmission dynamics of infectious pathogens mediate the effects that environmental changes have on disease. c) Disease burden is the outcome of the interplay between environmental change and the transmission cycle of a pathogen.ResultsTo put this framework into operation, we present a matrix formulation as a means to define important elements of this system and to summarize what is known and unknown about the these elements and their relationships. The framework explicitly expresses the problem at a systems level that goes beyond the traditional risk factor analysis used in public health, and the matrix provides a means to explicitly express the coupling of different system components.ConclusionThis coupling of environmental and disease transmission processes provides a much-needed construct for furthering our understanding of both specific and general relationships between environmental change and infectious disease.

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Our findings provide guidance in understanding how to best reduce and eliminate diarrheal disease through integrated control strategies.