B.J.Casey et al.Biological Psychology 54(2000)241-257 243 metaboism suggest that maturation of ocal metabolic course of overprodu ion and s equent pruning o synapses (Chugani et al.,1987)with the prefrontal cortex showing a prolonged maturation relative to visual cortex.PET studies,although informative,are typi- cally performed with clinical populations thus justifying their use with developmen- tal populations.The use of PET with pediatric patient populations to understand normal brain develop ent raises questions about the generalization of the results to truly healthy children.With the ent advances in mrico omes a whole new era in the study of the deve To ate,MRI ping huma brain in anatomica udies have revealed som interesting matura tionl chaneranuctur.The most infomative studies todater those based on carefully quantified volumetric measures and large sample sizes of 50 or more subjects (e.g.Giedd et al.,1996a,b:Reiss et al.,1996).The most consistent findings across these studies include:(1)a lack of any significant change in cerebral ofae (Giedd et a1996a;Giedd.et l 199b:Reissa ase in cortical gray matter after 12 years (Giedd et al. an ing ood ，199 Pfefferbaum et 94;C iness et al 1996 Rajapakse et al 1996;Reiss et a 996).Spec ally,subcortical gray regions (e.g basal ganglia)decrease during childhood,particularly in males(Giedd et al.,1996a Rajapakse et al.,1996;Reiss et al.,1996)while cortical gray matter in the frontal and parietal cortices does not appear to decrease until roughly puberty (Giedd et al.1999).White matter volume a opears to increase throughout childhood and well into adulthood (Caviness et al., 1996:Rajapakse et al..1996).These increases ear to be nal i na ure.Fo there appears to he ar ase in er in dors ntal cor n more ver ntal region tal cortex)(Reiss et al. 1996). l otal ter lobe volume appear relatively stable across the age range of 4 to 18 years.while hippocampal formation volume increases with age for females and amygdala volume increases with age for males (Giedd et al.,1996b).This latter finding may be consistent with the distribution of sex hormone receptors for these structures,with the amygdala having a predominance of androgen receptors (Clark et al.,1988:Sholl and Kim. 19)and the hippocampus having a predominnce of estr ogen eceptors(Morse et al,1986 Taken as a whole,th se neuroimaging rtern studies seem to sugges hat some ae-related changes are regional.One such brain region is the pref cortex.Based on the nonhuman and human primate post-mortern studies and pediatric neuroimaging studies published to date,the prefrontal cortex appears to be one of the last brain regions to mature,particularly the dorsolateral prefrontal cortex Are the last brain regions to mature the first'to go?If so,is the prefrontal cortex region mo ptible to the aging proc ss than othe ortical regions?The videnc efron al fur ion is se changes with age (Daigneault et al Braun 1993) impairment is paralleled by a disproportionate degeneration of the prefrontal cortexB.J. Casey et al. / Biological Psychology 54 (2000) 241–257 243 PET studies of glucose metabolism suggest that maturation of local metabolic rates closely parallel the time course of overproduction and subsequent pruning of synapses (Chugani et al., 1987) with the prefrontal cortex showing a prolonged maturation relative to visual cortex. PET studies, although informative, are typi￾cally performed with clinical populations thus justifying their use with developmen￾tal populations. The use of PET with pediatric patient populations to understand normal brain development raises questions about the generalization of the results to truly healthy children. With the recent advances in MRI comes a whole new era in the study of the normally developing human brain in vivo. To date, MRI-based anatomical studies have revealed some interesting matura￾tional changes in brain structure. The most informative studies to date are those based on carefully quantified volumetric measures and large sample sizes of 50 or more subjects (e.g. Giedd et al., 1996a,b; Reiss et al., 1996). The most consistent findings across these studies include: (1) a lack of any significant change in cerebral volume after five years of age (Giedd et al., 1996a; Giedd, et al., 1996b; Reiss, et al., 1996); (2) a significant decrease in cortical gray matter after 12 years (Giedd et al., 1999); and (3) an increase in cerebral white matter throughout childhood and young adulthood (Jernigan et al., 1991; Pfefferbaum et al., 1994; Caviness et al., 1996; Rajapakse et al., 1996; Reiss et al., 1996). Specifically, subcortical gray regions (e.g. basal ganglia) decrease during childhood, particularly in males (Giedd et al., 1996a; Rajapakse et al., 1996; Reiss et al., 1996) while cortical gray matter in the frontal and parietal cortices does not appear to decrease until roughly puberty (Giedd et al., 1999). White matter volume appears to increase throughout childhood and well into adulthood (Caviness et al., 1996; Rajapakse et al., 1996). These increases appear to be regional in nature. For example, there appears to be an increase in white matter in dorsal prefrontal cortex, but not in more ventral prefrontal regions (i.e. orbitofrontal cortex) (Reiss et al., 1996). Total temporal lobe volume appears relatively stable across the age range of 4 to 18 years, while hippocampal formation volume increases with age for females and amygdala volume increases with age for males (Giedd et al., 1996b). This latter finding may be consistent with the distribution of sex hormone receptors for these structures, with the amygdala having a predominance of androgen receptors (Clark et al., 1988; Sholl and Kim, 1989) and the hippocampus having a predominance of estrogen receptors (Morse et al., 1986). Taken as a whole, these neuroimaging and post-mortern studies seem to suggest that some age-related changes are regional. One such brain region is the prefrontal cortex. Based on the nonhuman and human primate post-mortern studies and pediatric neuroimaging studies published to date, the prefrontal cortex appears to be one of the last brain regions to mature, particularly the dorsolateral prefrontal cortex. Are the last brain regions to mature the first ‘to go’? If so, is the prefrontal cortex region more susceptible to the aging process than other cortical regions? There is neuropsychological evidence to suggest that prefrontal function is sensitive to changes with age (Daigneault et al., 1992; Daigneault and Braun, 1993). This impairment is paralleled by a disproportionate degeneration of the prefrontal cortex