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78 CHARACTERISTICS OF BRAIN AND BEHAVIORbilaterally (see figure 3-13). The prefrontal, lateral temporal, and inferior parietalcortices we have shown to be affected in ADHD are strongly interconnected withone another anatomically (Cavada & Goldman-Rakic, 1989a, 1989b; Goldman-Rakic, 1987; Pandya & Barnes, 1987; Petrides & Pandya, 2002), suggesting thatthis action-attentional network is anatomically disrupted in children who haveADHD.A Note About Cortical Thicknessand Gray Matter DensityAs one interprets the findings described above regarding “gray” matter changesas a function of normal adolescent development, prenatal exposure to alcohol, andADHD, some methodological issues must be taken into account. Regardless ofthe method used, VBM or CPM, measurement of gray matter at the cortical surfaceis limited by the resolution of the imaging techniques used. In normal development,for example, we speculated that cortical gray matter density reductioncould in part be due to increased proliferation of myelin into the periphery of thecortical neuropil, which would change the MR signal value from gray matter inthe younger subjects to white matter in the older subjects. Apparent cortical “thinning”during childhood is probably not entirely due to a reduction in the size ornumber of neuron cell bodies or their synaptic processes (for a discussion seeSowell et al., 2003a; Sowell et al., 2004b), but rather by an increase in the myelincoating of fibers in the lower cortical layers. The same may be true in the ALC(Sowell et al., 2002a) and ADHD (Sowell et al., 2003b) samples in which increasesin perisylvian gray matter density could be due to myelination abnormalities, andnot abnormalities in the gray matter itself. Thus, the changes observed in ourmeasurements of “gray matter” may actually be due to growth, or a lack thereof,in the underlying white matter. Given this, “gray matter” thinning or changes in“gray matter” density may not be the best terms to describe the anatomical changeswe observe with VBM and CPM in these developmental populations. However,with normal development, data from ourselves and others using volumetric methodssuggests that gray matter is replaced by white given that white matter volumesincrease, and gray matter volumes decline (Courchesne et al., 2000; Gieddet al., 1999; Jernigan et al., 1991).Further, our CPM studies have shown brain growth in spatial and temporalconcordance with gray matter thinning (Sowell et al., 2001c; Sowell et al., 2004a).One would necessarily conclude that if only regressive changes, such as synapticpruning, were accounting for the cortical thinning, brain growth would notbe observed simultaneously. Even in histological data, the boundary betweengray and white matter is not always distinct (Annese et al., 2004). Of course,MRI cannot be used to measure cell packing, myelin per se, or synaptic density.