Dextroamphetamine enhances "neural network-specific" physiological signals: a positron-emission tomography rCBF study

Abstract

Previous studies in animals and humans suggest that monoamines enhance behavior-evoked neural activity relative to nonspecific background activity (i.e., increase signal-to-noise ratio). We studied the effects of dextroamphetamine, an indirect monoaminergic agonist, on cognitively evoked neural activity in eight healthy subjects using positron-emission tomography and the O15 water intravenous bolus method to measure regional cerebral blood flow (rCBF). Dextroamphetamine (0.25 mg/kg) or placebo was administered in a double-blind, counterbalanced design 2 hr before the rCBF study in sessions separated by 1-2 weeks. rCBF was measured while subjects performed four different tasks: two abstract reasoning tasks--the Wisconsin Card Sorting Task (WCST), a neuropsychological test linked to a cortical network involving dorsolateral prefrontal cortex and other association cortices, and Ravens Progressive Matrices (RPM), a nonverbal intelligence test linked to posterior cortical systems--and two corresponding sensorimotor control tasks. There were no significant drug or task effects on pCO2 or on global blood flow. However, the effect of dextroamphetamine (i.e., dextroamphetamine vs placebo) on task-dependent rCBF activation (i.e., task - control task) showed double dissociations with respect to task and region in the very brain areas that most distinctly differentiate the tasks. In the superior portion of the left inferior frontal gyrus, dextroamphetamine increased rCBF during WCST but decreased it during RPM (ANOVA F (1,7) = 16.72, p < 0.0046). In right hippocampus, blood flow decreased during WCST but increased during RPM (ANOVA F(1,7) = 18.7, p < 0.0035). These findings illustrate that dextroamphetamine tends to "focus" neural activity, to highlight the neural network that is specific for a particular cognitive task. This capacity of dextroamphetamine to induce cognitively specific signal augmentation may provide a neurobiological explanation for improved cognitive efficiency with dextroamphetamine.

Figures

Fig. 1.

An example of the individualized ROI templates that were drawn on the MRI of each subject. Locations of regions in which overall repeated-measures ANOVA (Drug × Task interaction) reached statistical significance are shown in solid whiteand are indicated by asterisks. For statistical analysis, area-weighted averages were calculated across several slices for like structures including (1) superior portion of the inferior frontal gyrus in slices indicated by a single asterisk, and (2) hippocampal area in the slice indicated by a double asteriskand in the next most inferior slice (data not shown).

Fig. 2.

Region-by-task interaction effect of dextroamphetamine. Double dissociations were seen (1) in the superior portion of the left inferior frontal gyrus, where rCBF increased during WCST but decreased during RPM, and (2) in the right hippocampal area, where rCBF increased during RPM but decreased during WCST.