The rapid growth and expansion of Master of health professions education (MHPE) programs: A mixed-methods study of international curricular trends and guidelines for programs.

PURPOSE: This study explores international trends and standards of Master's degree programs through a comprehensive environmental scan and focus group interviews to understand curricular structure, content, program director expectations, educational context, and future directions. METHOD: Authors conducted a two-phase mixed-methods sequential explanatory design to conduct the environmental scan (phase 1), and subsequently conducting focus groups (phase 2) with program directors. A population list of Master's programs was used to generate a sampling frame, considering the geographic region (continent) and institution type (university, organization, public institution). Qualitative data were coded to analyze the breadth and depth of courses. Three one-hour virtual focus group interviews were conducted with ten program directors. RESULTS: The population list of 159 Masters programs worldwide was used to create a sample for analysis in the environmental scan (n = 46 Masters programs), representing programs from North America, Europe, Australia, and South Africa. Most programs (39%) delivered their courses online, with 20% exclusively offering an in-person program. Focus group participants indicated expectations of graduates, context in which they learn, as well as future directions for improving health professions education graduate programs. CONCLUSION: Program directors should consider programmatic aims, localized needs, and quality/standard of the program in designing Masters programs, with individualized growth opportunities for learners.

Tuition Costs of Master's of Health Professions Education Programs: A Cross-Sectional Analysis.

PURPOSE: The increasing professionalization of medical education during the past 2 decades has ushered in an era in which formal degrees, particularly master's of health professions education (MHPE), have become important for career advancement in medical education. Although tuition costs can pose a substantial barrier for many seeking advanced degrees in health professions education, data on tuition associated with these programs are lacking. This study examines the accessibility of pertinent cost-related information available to prospective students and the variability of costs among programs worldwide. METHOD: The authors conducted an Internet-based, cross-sectional study, augmented with emails and direct contact with educators, to extract tuition-related data for MHPE programs between March 29, 2022, and September 20, 2022. Costs were converted to an annual total within each jurisdiction's currency and converted to U.S. dollars on August 18, 2022. RESULTS: Of the 121 programs included in the final cost analysis, only 56 had publicly available cost information. Excluding programs free to local students, the mean (SD) total tuition cost was $19,169 ($16,649), and the median (interquartile range) cost was $13,784 ($9,401- $22,650) (n = 109). North America had the highest mean (SD) tuition for local students ($26,751 [$22,538]), followed by Australia and New Zealand ($19,778 [$10,514]) and Europe ($14,872 [$7,731]), whereas Africa had the lowest ($2,598 [$1,650]). The region with the highest mean (SD) tuition for international students was North America ($38,217 [$19,500]), followed by Australia and New Zealand ($36,891 [$10,397]) and Europe ($22,677 [$10,010]), whereas Africa had the lowest ($3,237 [$1,189]). CONCLUSIONS: There is substantial variability in the geographic distribution of MHPE programs and marked differences in tuition. Incomplete program websites and limited responsiveness from many programs contributed to a lack of transparency regarding potential financial implications. Greater efforts are necessary to ensure equitable access to health professions education.

Creation and Initial Validation of the Mayo Outpatient Precepting Evaluation Tool.

BACKGROUND AND OBJECTIVES: Preceptors in family medicine residencies need feedback to improve. When we found no validated, behavior-based tool to assess the outpatient precepting of family medicine residents, we sought to fill this gap by developing and initially validating the Mayo Outpatient Precepting Evaluation Tool (MOPET). METHODS: To develop the MOPET, we applied the Stanford Faculty Development Program (SFDP) theoretical framework for education, more recent work on peer review of medical teaching, and expert review of items. The residency behavioral scientist and a volunteer physician independently completed the MOPET while co-observing a precepting physician during continuity clinic sessions (N=20). We assessed the tool's validity via interrater reliability and cross-validation with the SFDP-26. RESULTS: The tool demonstrated high interrater reliability for the following effective teaching behaviors: (a) allowing the resident to present without interrupting, (b) encouraging the formulation of a goal, (c) checking in on the resident's goal, (d) using multimodal teaching aids, (e) asking to discuss the differential diagnosis, (f) asking to discuss alternative management, (g) encouraging the resident to pursue literature and/or other resources, and (h) reinforcing self-directed learning. The MOPET measures strongly correlated with most items from the SFDP-26, indicating good cross-validity. CONCLUSIONS: The MOPET is a theoretically sound, behavior-based, reliable, and initially validated tool for peer review of outpatient family medicine resident teaching. This tool can support faculty development in outpatient clinical learning environments.

Naturally occurring phenylethanoid glycosides: potential leads for new therapeutics.

Natural products have long been regarded as excellent sources for drug discovery given their structure diversity and wide variety of biological activities. Phenylethanoid glycosides are naturally occurring compounds of plant origin and are structurally characterized with a hydroxyphenylethyl moiety to which a glucopyranose is linked through a glycosidic bond. To date several hundred compounds of this type have been isolated from medicinal plants and further pharmacological studies in vitro or in vivo have shown that these compounds possess a broad array of biological activities including antibacterial, antitumor, antiviral, anti-inflammatory, neuro-protective, antioxidant, hepatoprotective, immunomodulatory, and tyrosinase inhibitory actions. Given their extensive activity profile, structure-activity relationships analyses of these compounds have been performed in a number of studies to reveal potential leads for future drug design. This article will summarize the major developments in phenylethanoid glycosides-based research in the past decade. The progresses made in phytochemistry and biological activity studies of these compounds will be reviewed. Particular attention will be given to the novel structures identified to date and the prominent therapeutic values associated with these molecules.

Effects of neuroleptic treatment on cortisol and 3-methoxy-4-hydroxyphenylethyl glycol levels in blood.

Plasma cortisol and serum 3-methoxy-4-hydroxyphenylethyl glycol (MHPG) were determined before and after 5-6 weeks of neuroleptic treatment in patients with schizophrenia. Following drug treatment both plasma cortisol and serum MHPG levels in patients decreased and plasma cortisol levels were also lower than in unmedicated healthy controls. Indications of a relationship between the reduction of cortisol and MHPG levels were found. The data show that neuroleptic drug treatment inhibits cortisol secretion. It is speculated that this inhibition could be related to reduced noradrenergic activity.

Excretion of catecholamines and their metabolites in transplantable rat phaeochromocytoma.

The urinary excretion pattern of catecholamines and their metabolites was studied in rats bearing a subcutaneous transplantable phaeochromocytoma. Compared with normal rats, tumour-bearing animals showed a markedly raised excretion of dopamine, noradrenaline and adrenaline, together with certain of their major acidic and alcoholic metabolites. No evidence of increased octopamine production could be obtained. There was a significant correlation between the output of dopamine and its metabolites, allowing accurate assessment of dopamine turnover rates which were comparable with those observed in human phaeochromocytoma. Tumour development, as determined by tumour weight, also correlated significantly with urinary excretion of noradrenaline and dopamine. Rat phaeochromocytoma appears to be a useful model for the human tumour.

Effects of debrisoquin on the excretion of catecholamine and octopamine metabolites in the rat and guinea pig.

The effects of debrisoquin, administered daily for 4 days to rats (40 mg/kg, i.p.) and guinea pigs (4 mg/kg, i.p.), were determined for urinary excretion of several acidic and neutral amine metabolites, including the norepinephrine metabolites, 3-methoxy-4-hydroxyphenethylene glycol (MHPG) and vanillylmandelic acid (VMA), the dopamine metabolites, 3,4-dihydroxyphenethanol (DHPE), 3-methoxy-4-hydroxyphenethanol (MHPE), and homovanillic acid (HVA), and the octopamine metabolite, p-hydroxyphenylglycol (pHPG). The excretion of MHPG was reduced to 32% of control in rats and to 46% in guinea pigs, HVA was reduced to 64 and 80% in these two species, respectively, and MHPE was lowered to 59% of control in the rat but was not affected in the guinea pig. DHPE and pHPG were not altered significantly in either species. VMA was a minor metabolite in both species, being less than 6% of MHPG, and its formation was blocked only partially (rat) or not at all (guinea pig) by debrisoquin. The data refute the idea based on previous in vitro studies that VMA is a major metabolite of norepinephrine in the periphery of the guinea pig as it is in man.

Effects of intraventricular injections of 6-hydroxydopamine on amine metabolites in rat brain and urine.

The effects in rats of intraventricular injections of 6-hydroxydopamine (6-OHDA) on the urinary excretion 1-3 weeks later of 3-methoxy-4-hydroxyphenethylene glycol (MHPG), 3,4-dihydroxyphenethanol (DHPE), 3-methoxy-4-hydroxyphenethanol (MHPE), p-hydroxyphenylglycol (pHPG), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were examined. The excretion of MHPG was decreased to 63 and 71% of control on days 7 and 14, respectively, but had returned to control levels by day 23, even though the brain levels were decreased by 87%. Free and total HVA excretion was reduced on both days 7 and 23, but free and total DOPAC was reduced only on day 7. Based on these data, it can be estimated that about 39% of the free and 46% of the total HVA in urine originates in the CNS. The excretion of conjugated HVA was decreased by 70-80%, but this decrease does not support the notion that the conjugated form of HVA is derived principally from the brain and thus serves as a better marker of brain dopamine metabolism, since the level of this metabolite in the brain was not correspondingly decreased but was instead increased. Urinary DOPAC levels were generally more variable and derived to a greater extent from the periphery; therefore, DOPAC appears to be less suitable than HVA as a marker of brain dopamine. The results also indicate that as much as 35% of the urinary MHPG may originate in the CNS, although compensatory changes in catecholamine metabolism in either the brain or in the periphery may have somewhat influenced this estimate. The results also suggest that at least as much pHPG as MHPG in urine derives from the CNS. The data are consistent with the idea that the neutral dopamine metabolites largely derive from the brain, but the relatively small depletion in their brain levels produced by 6-OHDA prevented the exact proportion being determined accurately.

Effects of continuous and intermittent cold (SART) stress on sympathoadrenal system activity in rats.

We compared sympathoadrenal responses to intermittent cold (SART) stress (in which cold exposure is interrupted by 4-hourly intervals daily at room temperature) with those to continuous cold (-3 degrees C) stress. Plasma levels of dihydroxyphenylalanine (DOPA), catecholamines and their metabolites as well as tyrosine hydroxylase (TH) activities in sympathetically innervated tissues were examined in rats exposed to each stressor for 1 day or for 5 days. Neither SART nor continuous exposure to cold for 1 day or 5 days altered plasma epinephrine (EPI) levels. However, norepinephrine (NE) and dihydroxyphenylglycol (DHPG) levels increased markedly during exposure to these stressors. On the first day of SART or continuous cold stress, NE levels were increased similarly, but the increments in DHPG levels were greater during SART stress. Since DHPG is formed in neurons, neural reuptake of NE may be more enhanced on the first day of SART stress than on the first day of continuous cold stress. After 5 days of SART stress plasma NE levels were significantly higher than those found after 5 days of continuous cold exposure. Plasma levels of DHPG were elevated to the same extent in both 5 days SART- and continuously cold-stressed rats, whereas plasma levels of methoxyhydroxyphenylglycol (MHPG) increased only by 5 days SART stress. Even at 1 h after the removal from 5 days SART stress, increased plasma levels of NE, DHPG and MHPG were still evident. These results suggest that 5 days SART stress elevates extraneuronal O-methylation of DHPG, and that NE turnover is more greatly increased by SART stress than by continuous cold stress. Plasma levels of DOPA, dopamine, dihydroxyphenylacetic acid and homovanillic acid also increased after either SART or continuous cold stress for 1 day and 5 days. Adrenal TH activities were significantly increased in rats exposed to SART or continuous cold stress for 1 day and 5 days, but in brown fat TH activity was elevated only in rats exposed to 5 days of continuous cold. Both SART and continuous cold stress are selective and potent stimuli for activation of the sympathoneural system, apparently without significant adrenomedullary EPI release. The increase of TH activity in the brown fat pad as well as of plasma NE and its metabolites is probably a result of adaptation to cold. It appears that even short intervals of return to a normal environmental temperature, as in SART, are sufficient to diminish sympathetic adaptation to cold.

In vivo analysis of dopamine and its metabolites in the caudate nucleus during euthermia and hibernation.

Golden-mantled ground squirrels (Citellus lateralis) were chronically implanted with a unilateral push-pull cannula in the caudate nucleus. Perfusates obtained in these unanesthetized, unrestrained animals during the euthermic (non-hibernating) and hibernating states were analyzed for dopamine (DA) and its metabolites (homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methoxy-4-hydroxyphenethanol (MOPET) using high performance liquid chromatography with electrochemical detection. The data revealed clear differences in the performance of the caudate DA system in the two states. During the euthermic state, DA metabolism was indicative of a constant and high turnover rate. Free DA was not detectable in the majority of samples, HVA was detected at consistently high levels, and DOPAC and conjugated DA were present at low levels. By contrast, DA metabolism was sharply altered during hibernation. Free DA was present at high concentrations and HVA concentrations were low. DOPAC was not detected in any sample whereas MOPET was present in all samples. Conjugated DA was present at high concentrations during the second half of the hibernation bout. The shift in the post-release disposition of DA could enhance the stability of DA receptors (i.e. prevent supersensitivity) during the prolonged periods of reduced neural activity typical of hibernation.

Enhancement of [3H]dopamine release and its [3H]metabolites in rat striatum by nicotinic drugs.

Recent evidence has identified directly muscarinic acetylcholine receptor (m-ACh R) and nicotinic acetylcholine receptor (n-ACh R) in the brain utilizing receptor binding assay. Several studies suggest that release of dopamine (DA) in the striatum is regulated by presynaptic receptors present on dopaminergic terminals. In the present study, the effects of cholinergic drugs on [3H]DA release were examined using micropunched tissue and synaptosomes obtained from rat striatum. ACh (5 x 10(-4) M) significantly increased spontaneous [3H]DA release, and the overflow was partially inhibited by D-tubocurarine (1 mM) but not atropine. Nicotine, lobeline, coniine and spartein, nicotinic agonists, significantly increased spontaneous and 25 mM K + evoked [3H]DA release almost in a dose-dependent manner. In contrast, oxotremorine (2 x 10(-4) M), muscarinic agonist, did not any change in [3H]DA efflux. Furthermore, the metabolites of [3H]DA were separated by column chromatography. The main metabolite of [3H]DA in the spontaneous release from rat striatal synaptosomes was [3H]DOPAC (3,4-dihydroxyphenylacetic acid). Lobeline (5 x 10(-5) M) accelerated the outflow of [3H]DOPAC and [3H]OMDA metabolites (O-methylated and deaminated metabolites). These results could give rise to the suggestion that there was n-ACh R on the dopaminergic nerve terminals in the striatum and n-ACh R might have related to a directly excitatory effect on the DA release.

Effects of amphetamine and amfonelic acid on the disposition of striatal newly synthesized dopamine.

A comparison of the in vivo biochemical actions of the psychotomimetic central stimulants, d-amphetamine (d-AMPH) and amfonelic acid (AFA), on the metabolism of rat striatal newly synthesized [3H]dopamine (DA) was made by pulse labeling with [3H]tyrosine. No evidence for the formation of the alcoholic DA metabolites [3H]3-methoxy-4-hydroxyphenylethanol (MOPET) or [3H]3,4-dihydroxyphenylethanol (DOPET) was found in control or drug-treated animals. Both [3H]3,4-dihydroxyphenylacetic acid (DOPAC) and [3H]homovanillic acid (HVA) concentrations were increased by AFA in the presence of haloperidol, while [3H]DA content was decreased. In contrast, d-AMPH, in the presence of haloperidol, decreased [3H]DOPAC and increased [3H]DA, even in monoamine oxidase-blocked rats. Thus monoamine oxidase inhibition did not appear to be a major factor in the action of amphetamine to increase [3H]DA, but cannot be excluded as a contributing factor to the lowering of [3H]DOPAC. Similar actions of d-AMPH were seen on preformed DA. Amphetamine may release newly synthesized DA in such a way that some of the released DA enters the neuronal storage system.

Effect of theophylline on monoamine metabolism in the rat brain.

The effect of theophylline on brain monoamine metabolism was studied in rats. Single doses of theophylline caused a striking and dose-related increase in the levels of 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MOPEG-SO4) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain. The level of brain homovanillic acid was only slightly affected. No appreciable change occurred, however, in the levels of brain norepinephrine, serotonin and dopamine. The increased level of brain MOPEG-SO4 or 5-HIAA after theophylline does not appear to result from its interference with the transport system for the acids in the brain since the rate of decline of the acid levels following pargyline was not affected. Under the conditions of brain monoamine oxidase inhibition, theophylline enhanced the increase in brain normetanephrine level without causing any change in 3-methoxytyramine level. The enhancement of brain normetanephrine level by theophylline became more pronounced when rats were pretreated with imipramine in addition to pargyline. These results suggest that, in the brain, theophylline may cause a release of serotonin leading to its increased turnover. The results also confirm the previous conclusion that the methylxanthine causes a release of norepinephrine and a concomitant increase in its turnover in the brain.

Effects of morphine on the turnover of brain catecholamines and serotonin in rats-acute morphine administration.

Morphine increased the rate of brain dopamine (DA) depletion when given before alpha-methyl-p-tyrosine (AMT) or alpha-propyl-dopacetamide, but not when given after AMT. No effect of morphine was found on the rate of depletion of brain noradrenaline (NA) or serotonin (5-HT) after the two synthesis inhibitors. The accumulation of homovanillic acid and 5-hydroxy-indoleacetic acid induced by probenecid was significantly increased by morphine pretreatment, whereas the accumulation of 3-methoxy-4-hydroxy-phenylglycol sulphate was not changed. These findings can be best explained by the hypothesis that morphine increases the non-functional intraneuronal catabolism of newly synthesized DA and 5-HT, without much effect on the monoamines already taken up in the synaptic vesicles. NA turnover does not seem to be changed by acute morphine administration.

Effects of morphine on the turnover of brain catecholamines and serotonin in rats-chronic morphine administration.

The turnover of brain monoamine was studied in rats in which different degrees of tolerance to and dependence on morphine were induced by pellet implantation. The degree of tolerance to morphine was assessed by measuring the increase in effective dose for an antinociceptive effect (vocalization test). The rate of depletion of brain dopamine (DA) and serotonin (5-ht) after alpha-methyl-p-tyrosine (AMT) or alpha-propyl-dopacetamide (dopacetamide) was not changed by chronic morphine treatment. In contrast, the accumulation of brain homovanillic acid HVA) and 5-hydroxyindoleacetic acid (5-HIAA) after probenecid was significantly increased, but there was no correlation between the biochemical changes and the degree of tolerance/dependence of the animals; at a very high degree of dependence 5-HIAA accumulation even became normal. In rats in which smaller amounts of morphine were repeatedly injected every 8 hr for 1 week the increased accumulation of HVA and 5-HIAA persisted in spite of complete tolerance to the antinociceptive effect. The rate of depletion of brain noradrenaline (NA) after AMT or dopacetamide was not changed and the accumulation of brain 3-methoxy-4-hydroxy-phenylglycol sulphate (MHPG-SO4) after probenecid was not affected in most chronic morphine groups. In the group with the highest degree of tolerance/dependence NA depletion after AMT was even retarded. The results suggest that chronic morphine treatment increases the synthesis and the intraneuronal destruction of newly synthesized DA and 5-HT without changing the rate of functional utilization of the monoamines. It is unlikely that the changes in monoamine metabolism are causally related to processes leading to morphine tolerance/dependence.

The role of cytoplasmic (newly synthesized) dopamine for the spontaneous and electrically evoked release of dopamine and its metabolites from the isolated neurointermediate lobe of the rat pituitary gland in vitro.

Isolated rat NILs were incubated in Krebs-HEPES solution. The release of dopamine and its metabolites (DOPAC, HVA and MOPET) was determined by HPLC with electrochemical detection. The spontaneous release of the sum of metabolites was about 40 times that of dopamine. The spontaneous outflow of dopamine metabolites was unaffected after inhibition of dopamine uptake (by GBR 12921) or after pretreatment with reserpine (5 mg/kg, 12 h before the experiments), but it was reduced by 50% after preincubation with the irreversible DOPA decarboxylase inhibitor, (MFMD, 10 microM, for 10 min). The combination of pretreatment with reserpine and preincubation with MFMD resulted in an 80% inhibition of the spontaneous outflow of dopamine metabolites. Treatment with reserpine caused a 98% depletion of the dopamine tissue content, whereas 60 min after exposure to MFMD the dopamine tissue content was decreased by 40%. Electrical stimulation of the pituitary stalk (3-15 Hz, in the presence of GBR 12921) caused a frequency-dependent release of dopamine. Stimulation at 7 or 15 Hz caused also a significant release of dopamine metabolites. After pretreatment with reserpine, the release of dopamine evoked by stimulation at 15 Hz was abolished, whereas the evoked release of the metabolites was only reduced by about 55%. After MFMD, the evoked release of dopamine decreased by a percentage similar to that of dopamine tissue content, but the reduction of the evoked release of metabolites was more pronounced. In conclusion, the spontaneous release of dopamine metabolites from the dopaminergic nerve endings in the NIL largely reflects the catabolism of newly synthesized dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of autoreceptor mediated regulation of the spontaneous dopamine turnover in the isolated neurointermediate lobe of the rat pituitary gland in vitro.

Isolated neurointermediate lobes of the rat pituitary gland were incubated in Krebs-HEPES solution and the spontaneous outflow of endogenous dopamine and its metabolites (DOPAC, HVA and MOPET) was determined by HPLC with electrochemical detection. The spontaneous outflow of dopamine metabolites (about 1500 fmol/10 min) largely exceeded that of dopamine (about 60 fmol/10 min). Apomorphine concentration-dependently (IC50, 205 nmol/l) reduced the spontaneous outflow of the dopamine metabolites. The effect of apomorphine developed slowly and was progressive over an observation period of 70 min. After 1 h of exposure to a maximall effective concentration of apomorphine (10 mumol/l), the outflow of metabolites was inhibited by 43%. The effect of apomorphine was not affected by the dopamine D2 receptor antagonist (-)-sulpiride nor by the dopamine D1 receptor antagonist SCH 23390. Neither quinpirole nor fenoldopam significantly affected the spontaneous outflow of dopamine metabolites. It was previously shown that the high rate of spontaneous outflow of dopamine metabolites from the dopaminergic nerves in the neurointermediate lobe reflects largely the immediate catabolism of newly synthesized dopamine. This high rate of spontaneous dopamine synthesis in the neurointermediate lobe is not controlled by dopamine autoreceptors. Apomorphine appears to inhibit the spontaneous dopamine turnover by an inhibition not mediated by dopamine receptors.

Determination of 3,4-dihydroxyphenylethyleneglycol in urine by gas chromatography with a flame ionization detector: a new rapid method.

3,4-Dihydroxyphenylethyleneglycol, a major metabolite of noradrenaline in rat brain, is estimated alone or with 4-hydroxy-3-methoxyphenylethyleneglycol in rat and human urine by gas chromatography with a flame ionization detector. The samples are hydrolyzed and extracted at pH 2 with ethyl acetate. Then, to analyze only 3,4-dihydroxyphenylethyleneglycol the reaction with n-butaneboronic acid is carried out directly; if 4-hydroxy-3-methoxyphenylethyleneglycol also has to be estimated, preliminary acetylation in alkaline aqueous solution is performed. The advantages of the specificity due to the reagents used is discussed.

Changes in the metabolism of hypothalamic norepinephrine associated with the onset of maternal behavior in the nulliparous rat.

Both norepinephrine (NE) and its major metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were assayed both in the hypothalamus of nulliparous rats that had behaved maternally toward foster young and in the hypothalamus of those that had failed to behave maternally. It was found that the maternally-behaving animals had both lower concentrations of NE and higher concentrations of MHPG as compared with their nonresponding counterparts. These data parallel those reported for the puerperal female and suggest that the onset of maternal behavior may be mediated by increased transmission across hypothalamic noradrenergic synapses.

Correlations between P300 components and neurotransmitters in the cerebrospinal fluid.

P300 and cerebrospinal fluid neurotransmitter metabolites and amino acids were examined in 10 patients with Alzheimer's disease, 9 patients with vascular dementia and 10 healthy controls. A negative correlation between P300 amplitude and MHPG concentration, negative correlation between P200 and N200 latencies and norepinephrine concentration, positive correlation between N200 latency and lysine concentration and positive correlation between N100 amplitude and tyrosine concentration were statistically significant. These findings suggest that the noradrenergic system influences P300 amplitude, and that multiple systems may influence P300 components.