Attention deficits are frequently reported after traumatic brain injury (TBI) and have significant consequence for the rehabilitation process as well as for subsequent education or vocational pursuits. However, controversy exists regarding the precise components of the distributed arousal and attentional system that are impaired by TBI, and the most effective treatment. Multiple neurotransmitter systems, including norepinephrine, dopamine, serotonin, and acetylcholine, are known to be affected by TBI, and uncontrolled trials of drugs which manipulate these systems are thought to be potentially beneficial. The proposed research makes use of drugs which manipulate the dopaminergic (bromocriptine) and noradrenergic (desipramine) systems, as well as those which affect both of these systems (methylphenidate), to clarify theoretical questions about the nature of attentional systems and their impairment, as well as to derive practically useful therapeutic efficacy data. Subjects with subacute or chronic TBI will be administered one of the above medications in a double-blind, placebo-controlled, cross-over design. Dependent variables will include a wide range of measures ranging from laboratory tasks focusing on single facets of the arousal and attention system, to ecologically valid complex measures of attention-related performance. A pilot group of 10 subjects will be tested initially to identify dependent variables likely to be sensitive to drug effects. A larger follow-up study will confirm the drug benefits in multivariate analysis. Additional analyses will assess the factor structure of the arousal and attention system and individual subject variables that predict impairment and response to treatment. The factor structure will also be compared to that obtained from a control sample.
