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 Previous Article
Volume 16, Number 15,
Issue of August 1, 1996
pp. 4816-4822
Copyright ©1996 Society for Neuroscience
Dextroamphetamine Enhances ``Neural Network-Specific''
Physiological Signals: A Positron-Emission Tomography rCBF
Study
Received Jan. 17, 1996; revised May 13, 1996; accepted May 15, 1996.
Venkata S. Mattay,
Karen Faith Berman,
Jill L. Ostrem,
Giuseppe Esposito,
John D. Van
Horn,
Llewellyn B. Bigelow, and
Daniel R. Weinberger
Clinical Brain Disorders Branch, Intramural Research Program,
National Institute of Mental Health, National Institutes of Health
Neuroscience Center at Saint Elizabeth's, Washington, DC 20032
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 systemsand
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.
Key words:
dextroamphetamine;
rCBF;
PET;
monoamines;
dopamine;
working memory;
hippocampus;
dorsolateral prefrontal cortex
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