Ls. In contrast, juvenile MAM exposed rats with mild PNH did

Ls. In contrast, juvenile MAM exposed rats with mild PNH did not show significant deficits in processing the oddball cue as compared to controls. These results parallel previous findings with regard to the behavioral effects of cerebral cortical microgyria, wherein the severity or extent of postnatal day one (P1) freeze-lesion-induced microgyria (double-bilateral versus single-bilateral pair) was related to degree of deficits seen for rapid acoustic processing [15]. In adulthood (P60+), subjects were again tested for basic pre-pulse inhibition (NST), as well as oddball tone-pair detection (i.e., detection of a tone-pair reversal). Unlike severe PNH juvenile subjects, adult MAM subjects did notshow any impairment in the detection of a single tone (NST). These findings may reflect a developmental delay of PPI circuitry in rats with severe cortical developmental disruption, one that may "catch up" with typically developing rats by adulthood. In fact, additional work will be needed to determine if the initial PPI deficit in juvenile MAM-treated rats is a product of abnormal or maturationally delayed startle circuitry. Nonetheless, given that juvenile MAM-treated rats were able to significantly detect silent gaps in white noise at a performance level comparable to controls, the interpretation of a general developmental delay in PPI (as opposed to any deficits in hearing or gross startle response) seems the most likely cause of altered NST scores in MAM-treated juveniles. Interestingly, combined adult oddball results also indicated that juvenile oddball two-tone processing deficits ameliorate over time Pyridine, 2-amino-5-methoxy- in the moderate PNH condition-- either as a result of previous experience, or normal maturation. This is in contrast to the persistent oddball deficits seen in the severe PNH condition. The contrast between improved performance in mild PNH subjects, andJ Neurodevelop Disord (2009) 1:237?Fig. 7 Graphs showing: (a) significant difference between MAM treated and control adult subjects on the 225 and 175 ms FM sweep conditions; and (b) combined adult FM sweep performance for the three PNH severity groups (mild, moderate and severe) and control rats, showing significant deficits in all PNH conditions (*p<.05, **p<.01)Fig. 8 Graphs showing: (a) MAM treated rats with a significant spatial learning deficit on the Morris water maze as compared to controls (*p=.05); and (b) no difference between the two Treatment groups on the non-spatial water mazepersistent oddball deficits in subjects with severe PNH, supports the notion of a deficit spectrum--one in which severity of processing impairments is directly related to the severity of neurodevelopmental disruption. With regard to the improved performance of mild PNH subjects in adulthood, we have previously reported that both maturation and experience can improve long-term acoustic processing. Specifically, Peiffer and colleagues [39] reported that juvenile rats with bilateral microgyria exhibited deficits in detecting short silent gaps (2?0 ms) in broadband white noise as compared to adults with no prior experience, suggesting that auditory temporal acuity improves with developmental maturation. We also reported that adult microgyric rats with prior acoustic experience show significantly better acoustic processing than adult rats with no prior experience [45]. These cumulative studiessuggest that both maturation and experience may have contributed to the improvement of MAM treated rats with moderate PNH on.