This project is a maturational study of startle modulation during childhood and an application of the normative data to the syndrome of attention-deficit hyperactivity disorder (ADHD). The major aim of this proposal is to continue our studies of startle modulation in ADHD along lines suggested by current literature and our own data, namely that pathophysiology in ADHD is likely to be located in structures rostral to brainstem regions. To explore this hypothesis, startle will be used as a probe to evaluate the sustained attention of ADHD during a continuous performance task (CPT). ADHD children have shown attentional deficits on the CPT, and startle attenuation can reflect the degree of attentional engagement and downstream cortical control of brainstem sensory processing mechanism. Additionally this proposal continues our normative maturational studies, extending them to CPT attenuation of startle, by studying this type of startle modulation in preschool children. Since 30 percent of our ADHD subjects had primary nocturnal enuresis, and it was those ADHD boys with enuresis who showed significantly reduced inhibitory prestimulation modulation of startle (PMS), a new aim of this proposal is to study PMS in definitive groups of boys with ADHD with and without nocturnal enuresis and boys with pure nocturnal enuresis. These groups will be large enough so that their dimensional characteristics (severity of ADHD, and frequency of nocturnal enuresis) and expected comorbidity (oppositional defiant disorder in ADHD, daytime wetting and encopresis in nocturnal enuretics, and specific development disorders in both groups can be evaluated. Because there is a strong familial component to primary nocturnal enuresis, both parents of each pure enuretic boy will be tested for PMS. Hence, this proposal will explore the possibility of a familial neurophysiologic marker in enuresis. A feature of this proposal is the evaluation of diagnostic and functional neuroanatomic specificity. This will be achieved by comparing the enuretic and ADHD populations not only with normal controls but also with each other on both the PMS and CPT attenuation of startle experiments. It is anticipated that the enuretics will show deficient inhibitory PMS and normal CPT attenuation of startle, suggesting a primary brainstem dysfunction, while ADHD boys will show the opposite, suggesting cortical dysfunction, with downstream effects on startle modulation.
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