BIOCHEMICAL MECHANISMS UNDERLYING IMPAIRED ATTENTION

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This proposal addresses potential biochemical mechanisms underlying impaired attention in children. The primary objective is to study how the components of attention and related neurobehavioral processes are affected by drugs which activate either all Dopamine (DA) receptors, just D1 receptors, D2 and D3 receptors, or just D3 receptors. We propose to investigate various components of attention and related neurobehavioral processes using a systematic, multidimensional assessment in children and adults with impaired attention due to (a) attention deficit hyperactivity disorder (ADHD), or (b) Tourettes Syndrome with and without ADHD. Such populations provide a unique opportunity to address the question of whether impaired attention in children has a similar biochemical basis regardless of its etiology. We will investigate the effects of several different drugs including: a) methylphenidate, b) pimozide, c) bromocriptine and d) pergolide. Two specific aims each with their own set of hypotheses will be addressed. Specific Aim 1 (The nature of impaired attention) addresses the relationship between the etiology of the attentional problem and the pattern of attentional deficits. We will assess different components of attention including selective and sustained attention, disinhibition as well as short term memory and fine-motor skills. It is not clear how these factors vary with different etiologies of attentional impairment. The hypotheses that will be addressed are: 1) ADHD and TS/ADHD subjects will not differ in the degree to which particular attentional skills are impaired, but they will differ in the motor skills with both TS/ADHD and TS subjects having a greater impairment in motor skills. Specific Aim 2 (The Pharmacological Basis of Impaired Attention, Fine Motor Skills and Impulsivity) addresses the relationship between DA activators and alterations in specific cognitive and motor impairments. The hypotheses that will be addressed are: 1) impaired attention is reduced by activation of D1 receptors but not by activation of D2 and/or D3 receptors; 2) fine-motor skills are affected by activation of D2 receptors, but not by activation of D1 or D3 receptors; 3) impulsivity is reduced by activation of D3 receptors, but not by the activation of D1 and/or D2 receptors. These objectives will be analyzed with a detailed comprehensive multivariate analysis. There are no studies comparing the effect of selective activation of different dopamine receptors on the various components of impaired attention. There are also no studies comparing the effect of drugs in children with impaired attention due to varying etiologies.