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R Miletich

Publications and source records attributed to R Miletich.

5 recordsLinked to original sources

Where the brain appreciates the moral of a story.

To identify the distributed brain regions used for appreciating the grammatical, semantic and thematic aspects of a story, regional cerebral blood flow was measured with positron emission tomography in nine normal volunteers during the reading of Aesop's fables. In four conditions, subjects had to monitor the fables for font changes, grammatical errors, a semantic feature associated with a fable character, and the moral of the fable. Both right and left prefrontal cortices were consistently, but selectively, activated across the grammatical, semantic, and moral conditions. In particular, appreciating the moral of a story required activating a distributed set of brain regions in the right hemisphere which included the temporal and prefrontal cortices. These findings emphasize that story processing engages a widely distributed network of brain regions, a subset of which become preferentially active during the processing of a specific aspect of the text.

Attention

Positron emission tomographic imaging of cardiac sympathetic innervation and function.

Sites of uptake, storage, and metabolism of [18F]fluorodopamine and excretion of [18F]fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of [18F]-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of [18F]fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function.

Animals

Neuronal uptake and metabolism of 2- and 6-fluorodopamine: false neurotransmitters for positron emission tomographic imaging of sympathetically innervated tissues.

The neuronal uptake and metabolism of 2-fluorodopamine (2F-dopamine), 6-fluorodopamine (6F-dopamine) and tritium-labeled dopamine were compared in heart, submaxillary gland and spleen of rats to assess the utility of 18F-labeled 2F- or 6F-dopamine for positron emission tomographic imaging of sympathetically innervated tissues. Tritiated dopamine with and without 2F- or 6F-dopamine, or tritiated 2F-dopamine alone, were injected i.v. into rats that were or were not pretreated with desipramine to block catecholamine neuronal uptake or with reserpine to block vesicular translocation of catecholamines. Tissue and plasma samples were obtained at intervals up to 1 hr after injections. At 1 hr after injection of tritiated dopamine, tritium-labeled norepinephrine, dopamine, dihydroxyphenylacetic acid and dihydroxyphenylglucol accounted for less than 2% of the tritium in plasma but up to 92% of that in tissues; tritiated norepinephrine accounted for 70% or more of the tritium in tissues. In contrast, at 1 hr after injection of tritiated 2F-dopamine, tritiated 2F-norepinephrine accounted for 30 to 46% of the tritium in tissues. Desipramine and reserpine pretreatment blocked the tissue accumulation of tritiated and fluorinated dopamine as well as their dihydroxy-metabolites, indicating that accumulation of exogenous norepinephrine and dopamine analogs was within sympathetic storage vesicles. Relative to the doses of dopamine precursors, less 2F- and 6F-norepinephrine accumulated in tissues than tritiated norepinephrine, due largely to inefficient beta-hydroxylation of fluorinated dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Elimination of REM sleep rebound in rats by alpha-adrenoreceptor blockers, phentolamine and phenoxybenzamine.

Two alpha-adrenoreceptor blocking agents, phentolamine (5 mg/kg, IP) and phenoxybenzamine (10 mg/kg IP) were administered to rats deprived of rapid eye movement (REM) sleep for 24 hours to test the hypothesis that reduced noradrenergic transmission may abolish REM sleep rebound. The hypothesis was based on results from our previous studies which showed that administration to rats of diethyldithiocarbamate (DDC), a dopamine beta hydroxylase inhibitor, decreased the concentration of brain norepinephrine and reduced REM sleep permanently without the subsequent appearance of REM sleep rebound. Present results show that administration of both alpha-adrenoreceptor blockers abolished REM sleep rebound. At the time of maximum reduction of REM sleep, the concentration of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MOPEGSO4), a final product of norepinephrine metabolism in the brain, was found increased in the whole brains of rats suggesting that the selected doses of the drugs were sufficient to produce effective central alpha-adrenergic receptor blockade. These data indicate that the action of both alpha-adrenoreceptor blocking agents in noradrenergic system was paralleled by the permanent loss of REM sleep and support the hypothesis implicating reduced noradrenergic transmission in elimination of REM sleep rebound.

Animals