Neuropharmacological studies of acquired aphasia have suggested that the outcome of speech/language therapy, the primary form of rehabilitation for aphasia, can be enhanced by adjuvant treatment with low doses (10 mg) of dextroamphetamine (DEX). The nature of the effect and its physiological basis are unclear. The PIs propose that one important contributory factor relates to DEX's enhancement of attentional mechanisms involved in speech and language processing. The overarching aim of the proposal is to characterize DEX's influence on attentive processing of speech, which is a likely nexus point for interactions between attentional and language systems. Utilizing a double-blind placebo-controlled crossover design, the PIs will compare the influence of two dose levels of DEX (10 mg, 20 mg) and placebo on neuropsychological measures and on neurophysiological responses recorded while subjects with aphasia selectively attend to speech and nonspeech sounds. The major objectives of the project are to: 1) ascertain whether DEX results in systematic changes in cortical responses in subjects with aphasia compared to placebo and identify the level of processing at which these effects occur; 2) compare responses using speech and nonspeech stimuli to examine whether effects may vary depending on whether auditory information is linguistic in nature; 3) delineate possible dose dependencies in DEX effects by comparing the low dose used in adjuvant neuropharmacological treatment studies of aphasia (10 mg.) with an average range dose (20 mg.) for treatment of adults with attention deficit hyperactivity disorder; and 4) document through correlational analyses the extent to which neurophysiological changes are coupled to variations in performance on neuropsychological measures of attention and speech processing. The broad objective is to advance our understanding of the electrophysiological and behavioral correlates of DEX treatment effects in aphasia. The proposed short term controlled assessment of DEX utilizes a highly efficient approach to evaluating medication effects that could potentially accelerate progress in clinical trials research in aphasia. ? ?
