Biomedical subjects

E A Stein

Publications and source records attributed to E A Stein.

At least 19 recordsLinked to original sources

PubMed2001

Amygdala response to both positively and negatively valenced stimuli.

Human lesion and functional imaging data suggest a central role for the amygdala in the processing of negative stimuli. To determine whether the amygdala's role in affective processing extends beyond negative stimuli, subjects viewed pictures that varied in emotional content (positive vs negative valence) and arousal level (high vs low) while undergoing functional magnetic resonance imaging. Amygdala activation, relative to a low arousal and neutral valence picture baseline, was significantly increased for both positively and negatively valenced stimuli and did not differ for the two valences. There were no laterality effects. Whereas arousal level appeared to modulate the amygdala response for negative stimuli, all positively valenced pictures (both high and low in arousal) produced significant amygdala responses. These results clearly demonstrate a role for the amygdala in processing emotional stimuli that extends beyond negative and fearful stimuli.

Adolescent↗

PubMed2001

Anesthesia alters NO-mediated functional hyperemia.

Many properties of nitric oxide, NO, (localization, diffusiveness, half-life, vasodilatory affects) have supported its potential role in mediating the link between local cerebral activity and blood flow. However, evidence that both supports and refutes a role for NO in functional hyperemia have been presented. The present study employed multiple nitric oxide synthase inhibitors, two anesthetic regimes and laser-Doppler flowmetry to test the hypothesis that NO is critically involved in mediating the functional hyperemic response within rodent whisker-barrel cortex (WBC). In urethane anesthetized animals, functional hyperemic responses were obtained both before and after 1 mg/kg atropine infusion, 30 mg/kg i.v. L-NAME (N-Nitro-L-arginine methylester) infusion, 30 mg/kg L-NA (N-Nitro-L-arginine) infusion or 25 mg/kg 7-NI (7-nitroindazole). L-NAME was also tested in a group of animals pretreated with halothane before urethane anesthesia. Neither the magnitude of the blood flow response nor its time course was altered by NO blockade or atropine administration when compared to pre-infusion controls in urethane anesthetized rats. In contrast, animals that were pretreated with halothane exhibited a 33% inhibition of functional hyperemia after L-NAME administration. Taken together, these data do not support a primary role for NO in rat WBC functional hyperemia and suggest that previous reports of inhibition may have been secondary to the anesthesia employed.

Anesthesia, General↗

PubMed2001

New statins and new doses of older statins.

The need for greater reductions in LDL cholesterol, although remaining to be proven as clinically beneficial, continues to drive the development of either higher doses of currently approved and marketed statins or the development of new, more effective agents.

Atorvastatin↗

PubMed2001

Reduction of LDL cholesterol in patients with primary hypercholesterolemia by SCH 48461: results of a multicenter dose-ranging study.

SCH 48461, an inhibitor of gastrointestinal absorption of cholesterol, was evaluated for its effects on lipid parameters in patients with primary hypercholesterolemia in a multicenter, double-blind, randomized, parallel-group study. Following the baseline phase, which consisted of a 2- to 10-week drug washout and dietary stabilization phase and a 4-week placebo lead-in (placebo baseline phase), 190 patients were randomized to an 8-week double-blind active drug (SCH 48461 1, 6.25, 25, 100, 200, or 400 mg) or 40 mg lovastatin once daily each morning or placebo treatment phase. By week 2, patients who received SCH 48461 6.25 to 400 mg or lovastatin demonstrated greater reduction from baseline in directly measured low-density lipoprotein cholesterol (LDL-C) levels than patients in the placebo group (p < or = 0.03). Overall, the percent reductions in LDL-C from baseline increased as the dose of SCH 48461 increased, with 0.6% to 15.5% reductions from the minimum dose of 1 mg to the maximum dose of 400 mg. Lovastatin 40 mg/day reduced LDL-C by 30.7% (p < 0.01). Statistically significant decreases were also seen for total cholesterol and apolipoprotein B (apo B) with doses of 25 mg to 400 mg of SCH 48461 and lovastatin. SCH 48461 was well tolerated. There was a similar incidence of adverse events in each SCH 48461- or lovastatin-treated group compared to placebo. This study demonstrated a clinically and statistically significant cholesterol-lowering effect of SCH 48461 in patients with primary hypercholesterolemia.

Anticholesteremic Agents↗

PubMed2001

Aggressive treatment of dyslipidemia: a review of supporting evidence.

Clinical trial data are now sufficient to support aggressive treatment of dyslipidemia. Cholesterol-lowering therapy is known to reduce the risk of clinical events across a wide range of lipid levels, even in patients with "normal" levels. Current data support lowering low-density lipoprotein cholesterol (LDL-C) levels at least to those recommended by the National Cholesterol Education Program, but perhaps even more aggressively in some patients. Of the available cholesterol-lowering agents, statins produce the greatest reductions in LDL-C levels and coronary events and are currently the best treatment option for most patients.

Cholesterol, LDL↗

PubMed2001

Effects of statins on biomarkers of bone metabolism: a randomised trial.

BACKGROUND AND AIM: Recently, several studies have indicated there may be differences among statins regarding a possible association between therapy and a reduction in risk of fractures. No data from prospective randomised clinical trials designed to assess either biochemical or clinical effects on bone metabolism are yet available. We assayed levels of biochemical markers of bone formation in stored serum samples from a recently completed randomised clinical trial conducted to compare the effects of simvastatin and atorvastatin on the lipid profile of patients with hypercholesterolaemia. METHODS AND RESULTS: This 12-week, randomised, multicenter, open-label study was designed to compare the safety and lipid-lowering efficacy of simvastatin 40 mg or 80 mg with that of atorvastatin 20 mg or 40 mg in 846 hypercholesterolaemic patients. Stored serum samples from this study were analysed to compare the effects of simvastatin and atorvastatin on 2 biomarkers of bone turnover, bone-specific alkaline phosphatase (BSAP), a marker of bone formation, and C-teleopeptide of type 1 collagen (CTx), a marker of bone resorption. Treatment with simvastatin 40 and 80 mg/day, but not atorvastatin 20 and 40 mg/day, led to significant (p < 0.05) reductions in BSAP in both men (4.1-5.4% reduction) and women (4.2-7.4% reduction). In addition, there appeared to be a dose-dependent effect with greater reductions in BSAP seen with the 80 mg dose of simvastatin. Treatment with either 20 mg or 40 mg of atorvastatin had no significant effect on BSAP levels on the groups as a whole or in the gender-specific subgroups. CTx showed a small, but not statistically significant, decrease with simvastatin, again with an apparent dose-related trend. Atorvastatin treatment generally resulted in small, non significant increases in CTx. CONCLUSIONS: The present serum bone biomarker results show that treatment with simvastatin, but not atorvastatin, decreases BSAP and suggest that simvastatin may have a beneficial effect on bone turnover.

Adult↗

PubMed2000

Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy.

OBJECTIVES: We sought to examine the association of apolipoprotein (apo) E genotypes with baseline plasma lipid levels and severity of coronary artery disease (CAD), as well as the response to treatment with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). BACKGROUND: Apo E genotypes have been associated with plasma lipid levels and CAD. However, the influence of apo E genotypes on the response of plasma lipids and CAD progression or regression to statin treatment in patients with mildly to moderately elevated cholesterol remains unknown. METHODS: Apo E genotypes were determined by polymerase chain reaction and restriction mapping. Plasma lipids were measured at baseline and 12 weeks after therapy with fluvastatin or placebo in 320 subjects. In 287 subjects, quantitative coronary angiography was performed at baseline and after 2.5 years of treatment. RESULTS: Subjects with the 3/3 genotype had greater reductions in total cholesterol (20.4% vs. 15.4%, p = 0.01) and low density lipoprotein (LDL) cholesterol (28.8% vs. 22.7%, p = 0.03) than did the subjects with the 3/4 or 4/4 genotype. In contrast, subjects with the 2/3 genotype (n = 10) had a greater increase in high density lipoprotein cholesterol (19.1%) than did the subjects with the 3/3 genotype (4.3%, p = 0.002) and those with the 3/4 or 4/4 genotype (7.0%, p = 0.02). Subjects with the 3/4 or 4/4 genotype had an increased frequency of previous angioplasty, but other measures of baseline CAD severity and baseline lipids did not differ significantly among the genotypes, nor did CAD progression or clinical events. CONCLUSIONS: Although subjects with the epsilon4 allele had less reduction in LDL cholesterol with fluvastatin, they had similar benefit in terms of CAD progression.

Anticholesteremic Agents↗

PubMed2000

Practice-related functional activation changes in a working memory task.

The effects of practice on the functional anatomy of a visuospatial working memory (VSWM) task were studied using functional Magnetic Resonance Imaging (fMRI). Functional imaging was conducted as subjects completed a moderate (Experiment 1) or extensive (Experiment 2) amount of practice on a delayed-match-to-sample task. While improvement in task performance was seen with practice, the task's dependence upon VSWM did not change. Activations in frontal (inferior, middle, and precentral gyri and superior frontal sulcus), parietal (intra-parietal sulcus, inferior parietal lobule, and precuneus) and cingulate (anterior and posterior) regions were observed as were bilateral insular and occipital activations. With the exception of the posterior cingulate, practice produced activation decreases in these regions, thus providing little evidence for a re-organization of the functional neuroanatomy. Fewer regions passing statistical criteria were observed at the end of practice relative to early in practice. Regions that were lost were mostly posterior (occipital and precuneus) but also included the left middle frontal gyrus, left precentral gyrus, and right insula suggesting that a more precise VSWM functional map can be observed once processes specific to encountering a novel task are removed. Little further activation changes were observed after extensive practice. These results suggest, minimally, that practice effects should be considered so as to avoid incorrectly attributing functional activation to a cognitive process of interest. Further, these data show that the dynamics of functional change can be tracked while a task is being learned and as an important cognitive process becomes more skilled.

Adult↗

PubMed2000

Regional cerebral blood flow responses to variable frequency whisker stimulation: an autoradiographic analysis.

Activation of the rat primary somatosensory barrel field (S1BF) is a commonly used model to study the mechanisms of evoked coupled cortical blood flow changes. However, the relationship between these blood flow changes and variable whisker movement has not been completely characterized. We have previously shown that in urethane anesthetized rats, the magnitude of laser-Doppler measured cortical blood flow changes increase linearly with the frequency of full pad whisker movement over the physiological range of 1.5 to 10.5 s. To further test the hypothesis that local cortical blood flow increases with frequency of whisker movement and underlying neuronal activity, regional cerebral blood flow (rCBF) was determined autoradiographically in seven urethane anesthetized SD rats. Selected rows of whiskers (rows C, D, E) were stimulated at 3 s on the right side of the rat's face and simultaneously at 10 s on the left side for 2 min prior to radioactive tracer administration. Subregions of somatosensory cortex were identified with the aid of thionin and cytochrome oxidase stained sections. Mean rCBF (ml/100 g/min) for S1BF were: S1BF [0 s] left cortex, 146+/-13; S1BF [0 s] right cortex, 158+/-15; S1BF[3 s], 160+/-13; S1BF [10 s] 178+/-14. In both stimulated and nonstimulated regions, the profile of blood flow increased across cortex laminae, peaking in layer IV and decreasing through deeper layers. Maximal blood flow increases elicited by whisker movement occurred in cortical layers I-IV. These data support the hypothesis that whisker movement elicited rCBF changes are input frequency dependent and are most pronounced in cortical layers I though IV. These data provide a strong framework in which to study the mechanisms of neuronal activity-blood flow coupling.

Animals↗

PubMed2000

Heroin-induced neuronal activation in rat brain assessed by functional MRI.

The present study demonstrates the application of fMRI technology to neuropharmacology and the interaction of drug/receptor in the rat brain. Specifically, we have observed two different types of fMRI signal changes induced by acute i.v. heroin administration in rat brains under conditions of spontaneous and artificial respiration. Under spontaneous respiration, a global decrease in fMRI signal was observed; under artificial respiration, a region-specific increase in fMRI signal was identified and the activation sites are consistent with the distribution of opiate mu-receptors in rat brain as previously reported by autoradiography. Both heroin-induced fMRI signal changes were suppressed by pretreatment of naloxone, an opiate mu-receptor antagonist, and reversed by injection of naloxone following heroin infusion. These results suggest that fMRI has specific advantages in spatial and temporal resolution for studies of neuropharmacology and drugs of abuse.

Analgesics, Opioid↗

PubMed2000

Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS).

BACKGROUND: The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) is the first primary-prevention study in a cohort with average total cholesterol (TC) and LDL cholesterol (LDL-C) and below-average HDL cholesterol (HDL-C). Treatment with lovastatin (20 to 40 mg/d) resulted in a 25% reduction in LDL-C and a 6% increase in HDL-C, as well as a 37% reduction in risk for first acute major coronary event (AMCE), defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. This article describes the relation between baseline and on-treatment lipid and apolipoprotein (apo) parameters and subsequent risk for AMCEs. METHODS AND RESULTS: With all available data from the entire 6605-patient cohort, a prespecified Cox backward stepwise regression model identified outcome predictors, and logistic regression models examined the relation between lipid variables and AMCE risk. Baseline LDL-C, HDL-C, and apoB were significant predictors of AMCE; only on-treatment apoB and the ratio of apoB to apoAI were predictive of subsequent risk; on-treatment LDL-C was not. When event rates were examined across tertiles of baseline lipids, a consistent benefit of treatment with lovastatin was observed. CONCLUSIONS: Persons with average TC and LDL-C levels and below-average HDL-C may obtain significant clinical benefit from primary-prevention lipid modification. On-treatment apoB, especially when combined with apoAI to form the apoB/AI ratio, may be a more accurate predictor than LDL-C of risk for first AMCE.

Acute Disease↗

PubMed2000

Cocaine administration decreases functional connectivity in human primary visual and motor cortex as detected by functional MRI.

Functional magnetic resonance imaging (fMRI) was conducted to observe the effects of cocaine administration on the physiological fluctuations of fMRI signal in two brain regions. Seven long-term cocaine users with an average age of 32 years and 8 years of cocaine use history were recruited for the study. A T2*-weighted fast echo-planar imaging (EPI) pulse sequence was employed at 1.5 T to acquire three sets of brain images for each subject under three conditions (at rest, after saline injection, and after cocaine injection [0.57 mg/kg]). Cross-correlation maps were constructed using the synchronous, low frequency signal from voxel time courses after filtering respiratory, cardiac, and other physiological noise. A quantitative evaluation of the changes in functional connectivity was made using spatial correlation coefficient (SCC) analysis. A marked 50% reduction in SCC values in the region of primary visual cortex and 43% reduction in SCC values in the region of primary motor cortex were observed after cocaine administration. This significant reduction in SCC values in these cortical regions is a reflection of changes in neuronal activity. It is suggested that the observed changes in low frequency components after acute cocaine administration during a resting, no-task situation may be used as a baseline reference source when assessing the effects of cocaine on task-driven activation or on mesolimbic dopamine pathways.

Adolescent↗

PubMed2000

Lipid-altering efficacy and safety of simvastatin 80 mg/day: long-term experience in a large group of patients with hypercholesterolemia. World Wide Expanded Dose Simvastatin Study Group.

BACKGROUND: Elevated levels of low-density lipoprotein (LDL) cholesterol promote the development of atherosclerosis and coronary heart disease. HYPOTHESIS: Simvastatin 80 mg/day will be more effective than simvastatin 40 mg/day at reducing LDL cholesterol and will be well tolerated. METHODS: Two similar, randomized, multicenter, controlled, double-blind, parallel-group, 48-week studies were performed to evaluate the long-term lipid-altering efficacy and safety of simvastatin 80 mg/day in patients with hypercholesterolemia. One study conducted in the US enrolled patients meeting the National Cholesterol Education Program (NCEP) LDL cholesterol criteria for pharmacologic treatment. In the other multinational study, patients with LDL cholesterol levels > or = 4.2 mmol/l were enrolled. At 20 centers in the US and 19 countries world-wide, 1,105 hypercholesterolemic patients, while on a lipid-lowering diet, were randomly assigned at a ratio of 2:3 to receive simvastatin 40 mg (n = 436) or 80 mg (n = 669) once daily for 24 weeks. Those patients completing an initial 24-week base study were enrolled in a 24-week blinded extension. Patients who had started on the 80 mg dose in the base study continued on the same dose in the extension, while those who had started on the 40 mg dose were rerandomized at a 1:1 ratio to simvastatin 40 or 80 mg in the extension. RESULTS: There was a significant advantage in the LDL cholesterol-lowering effect of the 80 mg dose compared with that of the 40 mg dose, which was maintained over the 48 weeks of treatment. The mean percentage reductions (95% confidence intervals) from baseline in LDL cholesterol for the 40 and 80 mg groups were 41% (42, 39) and 47% (48, 46), respectively, for the 24-week base study, and 41% (43, 39) and 46% (47, 45), respectively, after 48 weeks of treatment (p < 0.001 between groups). Larger reductions in total cholesterol and triglycerides were also observed with the 80 mg dose compared with the 40 mg dose at Weeks 24 and 48. Both doses were well tolerated, with close to 95% of patients enrolled completing the entire 48 weeks of treatment. Myopathy (muscle symptoms plus creatine kinase increase > 10 fold upper limit of normal) and clinically significant hepatic transaminase increases (> 3 times the upper limit of normal) occurred infrequently with both doses. There was no significant difference between the groups in the number of patients with such increases, although there were more cases for both with the 80 mg dose. CONCLUSIONS: Compared with the 40 mg dose, simvastatin 80 mg produced greater reductions in LDL cholesterol, total cholesterol, and triglycerides. Both doses were well tolerated.

Adult↗

PubMed2000

Lipid modulation and atherosclerotic events: extending the clinical spectrum with fibrates and statins.

Two recently published clinical endpoint trials, Veterans Affairs Cooperative Studies Program High-density Lipoprotein Intervention Trial (VA-HIT) and Atorvastatin Versus Revascularization Treatment (AVERT), studied lipid populations and clinical subgroups not previously evaluated in prior trials. VA-HIT, which used gemfibrozil, resurrected the potential benefits of fibrates in atherosclerotic subjects after previous trials either showed nonsignificant reductions in coronary artery disease (CAD) events or raised questions regarding non-CAD events. This study also raised intriguing questions about mechanisms and reinvigorated the triglyceride-atherothrombotic debate. The latest statin trial, AVERT, helped move the potential use of statins in two directions, addressing whether more LDL-cholesterol reduction is better, and whether lipid lowering offers an alternative to revascularization in certain subgroups. Finally, the design or initiation of a number of innovative and potentially landmark statin, fibrate, or combination studies has been published, or their results made public. The focus is on current gaps in our knowledge as we move toward evidence-based medicine. These include primary and secondary prevention of CAD in the elderly, primary prevention of CAD in persons with diabetes, and primary prevention of stroke.

Adult↗

PubMed2000

Hepatitis C virus infection in cocaine users--a silent epidemic.

Over a recent three year period, approximately 600 individuals responded to newspaper advertisements for research studies requiring healthy, cocaine using subjects. These subjects were screened using a standard phone interview in order to eliminate individuals with known medical or psychiatric illnesses that would exclude them from ongoing neuroimaging studies of drug abuse. Individuals were specifically asked about their hepatitis and HIV status. Of these, 170 subjects passed the phone screen, having no known medical or psychiatric illness outside of cocaine abuse/dependence and were willing to be further evaluated for the studies. These subjects were brought to the Medical College of Wisconsin's General Clinical Research Center and tested for, among other measures, hepatitis B, hepatitis C, and HIV. Of these, 144 completed the examination and all testing. In this cohort of assumed healthy subjects, 47 (33%) tested positive for antibodies to the hepatitis C virus (HCV). Only 7 (5%) tested positive for the hepatitis B surface antigen and 2 (1.4%) to HIV. The demographics of this cohort are 56% African-American, 81% male, 75% never-married, 55% unemployed with a mean age of 36 years. The percentage of subjects reporting any lifetime intravenous drug use among the HCV(+) and the HCV(-) cohorts was 77% vs. 29% respectively. Some routes of HCV transmission are still unclear and may reflect lifestyle or other factors related to cocaine use outside of parenteral drug use. Since almost all HCV infections become chronic, and many progress to chronic active hepatitis, cirrhosis, and ultimately hepatocellular carcinoma, these observations suggest a significant epidemic in an unsuspecting population with little regular access to health care. These individuals also form a large pool for the continued transmission of HCV to the general population. Additional public health interventions are suggested.

Adult↗

PubMed2000

Application of the National Cholesterol Education Program and joint European treatment criteria and clinical benefit in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS).

AIMS: The Air Force/Texas Coronary Atherosclerosis Prevention Study reported that diet with lovastatin, 20-40 mg daily, reduced the risk for a first coronary event by 37%. Because only 17% of this cohort would have qualified for drug therapy according to current U.S. guidelines, we assessed clinical benefit by risk categories. METHODS AND RESULTS: The main outcome measures were event rates of first acute major coronary events stratified by National Cholesterol Education Program and European criteria and target goal. Both those who would and would not be eligible for drug therapy, according to National Cholesterol Education Program guidelines, benefited from intervention. As expected, drug-eligible participants (event rate: lovastatin 1%/year, placebo 1.87%/year [relative risk 0.53, 95% confidence interval: 0.33, 0.84]) were at greater absolute risk for acute major coronary events than non-eligible participants (lovastatin 0.62%/year, placebo 0.93%/year [relative risk 0.67, 95% confidence interval: 0.51, 0.88]). Similar results were found using European guidelines for coronary risk management. Treatment to a target goal suggested a non-significant trend to greater benefit. CONCLUSIONS: The consistent relative benefit across risk categories suggests that it may be possible to improve identification of at-risk persons who would benefit from primary prevention, and to recommend appropriate goals of such treatment.

Aged↗

PubMed2000

Effects of high-dose simvastatin on adrenal and gonadal steroidogenesis in men with hypercholesterolemia.

In view of the role of both the de novo biosynthesis and receptor-mediated uptake of cholesterol for normal steroidogenesis, we evaluated whether extending the therapeutic dose of the hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, to 80 mg/d would affect adrenal and gonadal steroid synthesis in men with hypercholesterolemia. To evaluate this question, we enrolled men into a multicenter randomized, placebo-controlled study lasting 12 weeks. Men with serum low-density lipoprotein cholesterol (LDL-C) more than 145 mg/dL after 6 weeks of a lipid-lowering diet were randomized to 80 mg simvastatin or placebo. Half of the subjects were asked to undergo a 6-hour infusion of corticotropin (ACTH) to evaluate cortisol synthesis, and the entire cohort received a human chorionic gonadotropin (hCG) stimulation test to assess gonadal hormone secretion using pooled serum samples taken 15 minutes apart. A total of 81 men (age, 45 +/- 11 years; 93% Caucasian) with baseline serum LDL-C of 197 mg/dL (placebo, n = 39) and 184 mg/dL (simvastatin 80 mg, n = 42) completed the study. After 12 weeks, serum LDL-C, triglycerides, and high-density lipoprotein cholesterol (HDL-C) in the simvastatin group changed by -43%, -25%, and 8%, respectively (all P < .001). The basal cortisol level and the peak serum cortisol and area under the curve response to the 6-hour ACTH infusion were comparable between the two treatment groups at baseline and after 12 weeks. The pooled total testosterone level at baseline was 541 and 513 ng/dL in the placebo and simvastatin-treated groups, respectively, which declined to 536 +/- 20.5 ng/dL (-1.5%) and 474 +/- 30.4 ng/dL (-13.6%, P = .09) after treatment (mean +/- SD). The pooled free testosterone declined by 6.3% in the simvastatin group, versus a 4.9% increase in the placebo group (P = .588), while pooled bioavailable testosterone declined 10.2% in the simvastatin group and increased 1.4% in the placebo group (P = .035). There were no changes in serum gonadotropin levels or sex hormone-binding globulin (SHBG). After administration of hCG, there were no differences in the peak total pooled testosterone level before or after 12 weeks of treatment. Simvastatin 80 mg was well tolerated compared with placebo. In conclusion, basal and stimulated cortisol production was unaffected by the use of simvastatin 80 mg versus placebo. As reported with other statins and cholestyramine, there were small declines in the simvastatin-treated group for pooled total, free, and bioavailable testosterone after 12 weeks, although there was no compensatory increase in serum follicle-stimulating hormone (FSH) or luteinizing hormone (LH) levels.

Adrenal Cortex↗

PubMed2000

A parametric manipulation of central executive functioning.

The central executive is both an important and poorly understood construct that is invoked in current theoretical models of human cognition and in various dysexecutive clinical syndromes. We report a task designed to isolate one elementary executive function, namely the allocation of attentional resources within working memory. The frequency with which attention was switched between items in working memory was varied across different trials, while storage and rehearsal demands were held constant. Functional magnetic resonance imaging revealed widespread areas, both prefrontal and more posterior, that differentially activated as a function of a trial's executive demands. Furthermore, areas that differed as a function of executive demands tended to lie adjacent to areas that were activated during the task but that did not so differ. Together, these data suggest that a distributed neuroanatomy, rather than a specific and unique locus, underlies this attention switching executive function.

Adult↗