Cranial nerve clock. Part II: functional MR imaging of brain activation during a declarative memory task.

RATIONALE AND OBJECTIVES: The authors performed this study to assess brain activation during encoding and successful recall with a declarative memory paradigm that has previously been demonstrated to be effective for teaching students about the cranial nerves. MATERIALS AND METHODS: Twenty-four students underwent functional magnetic resonance (MR) imaging during encoding and recall of the name, number, and function of the 12 cranial nerves. The students viewed mnemonic graphic and text slides related to individual nerves, as well as their respective control slides. For the recall paradigm, students were prompted with the numbers 1-12 (test condition) intermixed with the number 14 (control condition). Subjects were tested about their knowledge of cranial nerves outside the MR unit before and after functional MR imaging. RESULTS: Students learned about the cranial nerves while undergoing functional MR imaging (mean post- vs preparadigm score, 8.1 +/- 3.4 [of a possible 12] vs 0.75 +/- 0.94, bilateral prefrontal cortex, left greater than right; P < 2.0 x 10(-12)) and maintained this knowledge at I week. The encoding and recall paradigms elicited distributed networks of brain activation. Encoding revealed statistically significant activation in the bilateral prefrontal cortex, left greater than right [corrected]; bilateral occipital and parietal associative cortices, parahippocampus region, fusiform gyri, and cerebellum. Successful recall activated the left much more than the right prefrontal, parietal associative, and anterior cingulate cortices; bilateral precuneus and cerebellum; and right more than the left posterior cingulate. CONCLUSION: A predictable pattern of brain activation at functional MR imaging accompanies the encoding and successful recall of the cranial nerves with this declarative memory paradigm.

Noradrenergic modulation of cognitive flexibility in problem solving.

Stress causes impaired performance on tests of creativity. Drugs that block beta-adrenergic receptors improve test performance in patients with test anxiety. Furthermore, catecholamine precursors (L-DOPA) reduce the flexibility of semantic networks. Our study investigated the effect of noradrenergic system modulation on cognitive flexibility in problem solving. Eighteen normal subjects undertook three problem solving tasks (number series, shape manipulation and anagrams) 45 min after propranolol, placebo and ephedrine. On the task that appeared to rely most heavily on cognitive flexibility (anagrams), subjects who were most able to solve these problems demonstrated significantly shorter solution times (logarithmic scores) after propranolol than after ephedrine. This suggested that the noradrenergic system exerts a modulatory effect on cognitive flexibility in problem solving.

Behavioral, anatomical, and physiological aspects of recovery of motor function following stroke.

Restoration of motor function is relatively common in humans and non-human primates. Studies of the behavioral aspects of recovery indicate that responses re-emerge in a fixed sequence that resembles initial acquisition. The extent to which this occurs depends on factors unique to the subject. Research suggests that the traditional view of a hierarchically organized brain is inaccurate. Instead, the brain is comprised of parallel circuits which may be disinhibited and/or recruited when damage occurs. In some cases, damage leads to reorganization of cerebral cortical maps. Available data point to the utility of interventions to promote recovery. Research suggests that recovery from other forms of impairment (e.g., non-vascular lesions or impairment in language) involves similar processes.

Use of WIN 51711 to prevent echovirus type 9-induced paralysis in suckling mice.

The systemic efficacy of the antipicornavirus agent WIN 51711 was assessed in suckling mice infected with echovirus type 9 (Barty strain). Single, daily intraperitoneal doses of WIN 51711 as low as 10 mg/kg significantly (P less than .01) slowed the rate of onset of echovirus-induced paralysis and reduced the number of paralyzed animals. Intraperitoneal administration beginning 2 hr before infection or 48 hr after infection was equally effective in preventing paralysis. Oral administration of WIN 51711 twice daily beginning 72 hr after infection was the most-effective dosage regimen, with doses as low as 3 mg/kg preventing paralysis in 75% of the animals. Titers of virus in asymptomatic mice on day 6 after infection were reduced by up to 4.75 log pfu in WIN 51711-medicated mice when compared with placebo. Maximal concentrations of WIN 51711 in adult mice after oral medication with a 100 mg/kg dose were 24.3, 21.5, 10.4, 9.8, 6.9, and 4.1 micrograms/g in heart, kidney, brain, liver, serum (micrograms/ml), and muscle, respectively at 0.5-1.0 hr after medication.

Oral efficacy of WIN 51711 in mice infected with human poliovirus.

WIN 51711, a new broad-spectrum anti-picornavirus agent, prevented the development of paralysis and subsequent death in mice infected intracerebrally with a lethal dose of human poliovirus type 2 (MEF strain). The prophylactic efficacy of intragastrically administered WIN 51711 was dose dependent over the 3.9- to 62.5-mg/kg (twice daily) dose range, with a minimal significantly effective dose of less than 15.6 mg/kg per dose (twice daily) (P less than 0.008). An oral four times a day dosage regimen initiated 48 h postinfection with WIN 51711 doses as low as 12.5 mg/kg was effective in significantly reducing poliovirus-induced paralysis and death compared with a placebo. Viral titers in the brains and spines of mice infected intracerebrally with 200 50% lethal doses of poliovirus were reduced by 3 to 5 log10 PFU/g in the WIN 51711-medicated group compared with placebo-medicated animals. The potent in vitro and in vivo anti-picornavirus activity of WIN 51711 makes it a potentially useful drug for the treatment of enterovirus infections in humans.

Antiviral activity of Win 41258-3, a pyrazole compound, against herpes simplex virus in mouse genital infection and in guinea pig skin infection.

Win 41258-3 (4-[6-(2-chloro-4-methoxyphenoxy)hexyl]-3,5-diethyl-1H-pyrazole methane sulfonate) has in vitro and in vivo activity against herpes simplex virus types 1 and 2. In cell culture, a concentration of 2 microgram/ml produced a greater than 50% inhibition of plaque formation of herpes simplex virus type 2, and 3 microgram/ml produced a 100% reduction of herpes simplex virus type 1. Win 41258-3 was effective against herpes simplex virus types 1 and 2 in mouse genital infection after intravaginal administration. Win 41258-3 was administered to mice at 4 h postinfection with solutions containing 1.25, 2.5, 5, or 10% of the compound in saturated tampons. Therapy resulted in a high survival rate (80 to 100%) of treated animals versus 20 to 30% of placebo-treated controls. Win 41258-3 was also effective in guinea pig skin infection produced by herpes simplex virus type 1. Solutions of 2.5, 5, and 10% Win 41258-3, applied to the skin starting 24 h postinfection, resulted in rapid suppression of development of herpetic vesicles and significant reduction of the virus titers in the lesion sites.

Antiviral activity of some beta-diketones. 3. Aryl bis(beta-diketones). Antiherpetic activity.

A series of bis(beta-diketones) was synthesized and tested in vitro for antiviral actitity against herpes simplex type 2. Two parameters which were studied in an effort to optimize activity were the nature of the aryl group and the length of the alkyl bridge. One of the more active compounds, 4,4'-[(1,4-phenylenedioxy)bis(6,1-hexanediyl)]-bis[3,5-heptanedione] (6), was evaluated more extensively and found to inhibit the cytopathic effect in tissue culture of herpes simplex virus type 1 as well as type 2. Compound 6 was evaluated in vivo topically against herpes simplex type 1 in experimentally induced skin infections in guinea pigs. A topical treatment with 2% of 6 in a vanishing cream base, administered 24 h postinfection applied five times daily for 4 days, significantly reduced the number and size of herpetic vesicles.

Method for determining antineuraminidase activity.

A test was developed to screen drugs for antineuraminidase (influenza sialidase) activity in vitro. Neuraminidase prepared from Vibrio cholerae was added to a substrate containing ganglioside, prepared from calf brain. Sialic acid is a split product in the reaction. The presence of sialic acid was detected colorimetrically by use of Warren's Thiobarbituric Acid Assay after drugs had been added to inhibit the action of neuraminidase on the calf brain substrate.