Hall lab HallRichardW@uams.edu

Survival of extremely premature neonates has improved greatly, requiring prolonged neonatal intensive care that is associated with repetitive pain, stress, and maternal separation.  These infants, however, develop a high prevalence of cognitive deficits and abnormal behaviors during their early childhood and school years.  Multiple follow-up studies of ex-preterm children have reported major developmental deficits, with lifetime needs for special assistance, and increasing burdens on the health care budget.  Early repetitive pain or maternal separation, both occurring routinely in preterm babies, lead to permanent changes in brainstem and spinal cord circuitry, neuroendocrine function, or cognition.  These changes are later manifested as abnormal pain processing, increased anxiety/stress disorders, attention deficit disorder, and other atypical behaviors.

We hypothesize that repetitive pain paradigms lead to attention deficit disorder and poor cognition resulting from an abnormal regulation of preattentional mechanisms (arousal, sensorimotor gating) in older children.  To examine pre-attentional mechanisms in human adolescents we have been recording the sleep state-dependent midlatency auditory evoked P50 potential, as well as attentional processes using a psychomotor vigilance task.  Our results suggest that adolescents who were born pre-term (PT) become equally segregated into three groups of patients, one with low P50 potential amplitude (decreased level of arousal- LO), one with normal level of arousal (MED), and one with exaggerated level of arousal (hypervigilant- HI).  All three groups show marked decreases in reaction time.  These results suggest that both arousal and attentional deficits are evident in ex-pre-term adolescents.  However, the differential electrophysiological profiles suggest different forms of therapy may be required.  Interestingly, major differences in habituation to repetitive stimulation were not observed.  Moreover, the changes in P50 potential amplitude were not correlated with weight at birth or weeks of gestation at birth.  This suggests that we may be able to identify the potential direction of benefits in order to tailor treatment.