Neurophysiology

Contains reports on one research projectNational Institutes of Health (Grant 5 PO1 GM14940-07

Effect of the subjective intensity of fatigue and interoception on perceptual regulation and performance during sustained physical activity

BACKGROUND: The subjective experience of fatigue impairs an individual’s ability to sustain physical endurance performance. However, precise understanding of the specific role perceived fatigue plays in the central regulation of performance remains unclear. Here, we examined whether the subjective intensity of a perceived state of fatigue, pre-induced through prior upper body activity, differentially impacted performance and altered perceived effort and affect experienced during a sustained, isometric contraction in lower body. We also explored whether (cardiac) interoception predicted the intensity of experienced perceptual and affective responses and moderated the relationships between constructs during physical activity. METHODS: Using a repeated-measures study design, thirty male participants completed three experimental conditions, with the intensity of a pre-induced state of fatigue manipulated to evoke moderate (MOD), severe (SEV) and minimal (control; CON) intensity of perceptions prior to performance of the sustained contraction. RESULTS: Performance of the sustained contraction was significantly impaired under a perceived state of fatigue, with reductions of 10% and 14% observed in the MOD and SEV conditions, respectively. Performance impairment was accompanied by greater perceived effort and more negative affective valence reported during the contraction. However, effects were limited to comparisons to CON, with no difference evident between the two experimental trials (i.e. MOD vs. SEV). Individuals’ awareness of their accuracy in judging resting heartbeats was shown to predict the subjective intensity of fatigue experienced during the endurance task. However, interoception did not moderate the relationships evident between fatigue and both perceived effort and affective valence. CONCLUSIONS: A perceived state of fatigue limits endurance performance, influencing both how effortful activity is perceived to be and the affective experience of activity. Though awareness of interoceptive representations of bodily states may be important to the subjective experience of fatigue, interoception does not modulate the relationships between perceived fatigue and other perceptual (i.e. effort) and affective constructs

The Neon Nova. III. The Infrared Light Curves of Nova QU Vulpeculae (Nova Vul 1984 #2)

We report 1.25 to 19.5 µm broadband infrared (IR) photometric measurements acquired during an eight year period on the prototypical ONeMg “neon nova” QU Vulpeculae (Nova Vul 1984 #2). The energy distribution of the ejecta evolved through several phases. An early free-free emission phase was followed by an IR coronal phase characterized by the appearance of strong emission lines from forbidden atomic transitions. The lines of [Ne Vi] at 7.6 /xm, and [Ne il] at 12.8 µm were especially strong during the coronal phase. A small amount of silicate dust condensed in the ejecta after about a year. The evidence provided by our IR observations for high abundances of metals in the ejecta of QU Vul is reviewed. We present the IR light curves of QU Vul, and show that the temporal development of its persistent IR coronal emission phase was evident in the broadband K (2.3 µm) and L (3.6 µm) photometry. Using data from our previous studies of classical novae, we suggest that K and L photometry can distinguish between the slower ONeMg novae with persistent IR coronal activity and CO novae that produce copious quantities of circumstellar dust. The most striking signature is produced in the L band, which contains emission from [Mg Vlll] at 3.02 µm, [A1 Vi] at 3.66 µm, and [Si ix] at 3.92 µm. We comment on the peculiar tendency of the IR light curves of novae to decay exponentially

Factors associated with malaria parasitemia, anemia and serological responses in a spectrum of epidemiological settings in Uganda.

BACKGROUND: Understanding the current epidemiology of malaria and the relationship between intervention coverage, transmission intensity, and burden of disease is important to guide control activities. We aimed to determine the prevalence of anemia, parasitemia, and serological responses to P. falciparum antigens, and factors associated with these indicators, in three different epidemiological settings in Uganda. METHODS AND FINDINGS: In 2012, cross-sectional surveys were conducted in 200 randomly selected households from each of three sites: Walukuba, Jinja district (peri-urban); Kihihi, Kanungu district (rural); and Nagongera, Tororo district (rural) with corresponding estimates of annual entomologic inoculation rates (aEIR) of 3.8, 26.6, and 125.0, respectively. Of 2737 participants, laboratory testing was done in 2227 (81.4%), including measurement of hemoglobin, parasitemia using microscopy, and serological responses to P. falciparum apical membrane antigen 1 (AMA-1) and merozoite surface protein 1, 19 kilodalton fragment (MSP-119). Analysis of laboratory results was restricted to 1949 (87.5%) participants aged ≤ 40 years. Prevalence of anemia (hemoglobin < 11.0 g/dL) was significantly higher in Walukuba (18.9%) and Nagongera (17.4%) than in Kihihi (13.1%), and was strongly associated with decreasing age for those ≤ 5 years at all sites. Parasite prevalence was significantly higher in Nagongera (48.3%) than in Walukuba (12.2%) and Kihihi (12.8%), and significantly increased with age to 11 years, and then significantly decreased at all sites. Seropositivity to AMA-1 was 53.3% in Walukuba, 63.0% in Kihihi, and 83.7% in Nagongera and was associated with increasing age at all sites. AMA-1 seroconversion rates strongly correlated with transmission intensity, while serological responses to MSP-119 did not. CONCLUSION: Anemia was predominant in young children and parasitemia peaked by 11 years across 3 sites with varied transmission intensity. Serological responses to AMA-1 appeared to best reflect transmission intensity, and may be a more accurate indicator for malaria surveillance than anemia or parasitemia

Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.

At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings

Estimating malaria parasite prevalence from community surveys in Uganda: a comparison of microscopy, rapid diagnostic tests and polymerase chain reaction.

BACKGROUND: Household surveys are important tools for monitoring the malaria disease burden and measuring impact of malaria control interventions with parasite prevalence as the primary metric. However, estimates of parasite prevalence are dependent on a number of factors including the method used to detect parasites, age of the population sampled, and level of immunity. To better understand the influence of diagnostics, age, and endemicity on estimates of parasite prevalence and how these change over time, community-based surveys were performed for two consecutive years in three settings and the sensitivities of microscopy and immunochromatographic rapid diagnostic tests (RDTs) were assessed, considering polymerase chain reaction (PCR) as the gold standard. METHODS: Surveys were conducted over the same two-month period in 2012 and 2013 in each of three sub-counties in Uganda: Nagongera in Tororo District (January-February), Walukuba in Jinja District (March-April), and Kihihi in Kanungu District (May-June). In each sub-county, 200 households were randomly enrolled and a household questionnaire capturing information on demographics, use of malaria prevention methods, and proxy indicators of wealth was administered to the head of the household. Finger-prick blood samples were obtained for RDTs, measurement of hemoglobin, thick and thin blood smears, and to store samples on filter paper. RESULTS: A total of 1200 households were surveyed and 4433 participants were included in the analysis. Compared to PCR, the sensitivity of microscopy was low (65.3% in Nagongera, 49.6% in Walukuba and 40.9% in Kihihi) and decreased with increasing age. The specificity of microscopy was over 98% at all sites and did not vary with age or year. Relative differences in parasite prevalence across different age groups, study sites, and years were similar for microscopy and PCR. The sensitivity of RDTs was similar across the three sites (range 77.2-82.8%), was consistently higher than microscopy (p < 0.001 for all pairwise comparisons), and decreased with increasing age. The specificity of RDTs was lower than microscopy (76.3% in Nagongera, 86.3% in Walukuba, and 83.5% in Kihihi) and varied significantly by year and age. Relative differences in parasite prevalence across age groups and study years differed for RDTs compared to microscopy and PCR. CONCLUSION: Malaria prevalence estimates varied with diagnostic test, age, and transmission intensity. It is important to consider the effects of these parameters when designing and interpreting community-based surveys

Incidence of Malaria and Efficacy of Combination Antimalarial Therapies over 4 Years in an Urban Cohort of Ugandan Children

Combination therapies are now recommended to treat uncomplicated malaria. We used a longitudinal design to assess the incidence of malaria and compare the efficacies of 3 combination regimens in Kampala, Uganda.Children aged 1-10 years were enrolled from randomly selected households in 2004-05 and 2007, and were followed at least monthly through 2008. Insecticide-treated bednets (ITNs) were provided in 2006. Children were randomized upon their first episode, and then treated for all episodes of uncomplicated malaria with amodiaquine/sulfadoxine-pyrimethamine (AQ/SP), artesunate/amodiaquine (AS/AQ), or artemether/lumefantrine (AL). Risks of parasitological failure were determined for each episode of uncomplicated malaria and clinical parameters were followed. A total of 690 children experienced 1464 episodes of malaria. 96% of these episodes were uncomplicated malaria and treated with study drugs; 94% were due to Plasmodium falciparum. The rank order of treatment efficacy was AL > AS/AQ > AQ/SP. Failure rates increased over time for AQ/SP, but not the artemisinin-based regimens. Over the 4-year course of the study the prevalence of asymptomatic parasitemia decreased from 11.8% to 1.4%, the incidence of malaria decreased from 1.55 to 0.32 per person year, and the prevalence of anemia (hemoglobin <10 gm/dL) decreased from 5.9% to 1.0%. No episodes of severe malaria (based on WHO criteria) and no deaths were seen.With ready access to combination therapies and distribution of ITNs, responses were excellent for artemisinin-containing regimens, severe malaria was not seen, and the incidence of malaria and prevalence of parasitemia and anemia decreased steadily over time.isrctn.org ISRCTN37517549

The Early Spectrophotometric Evolution of V1186 Scorpii (Nova Scorpii 2004 #1)

We report optical photometry and optical through mid-infrared spectroscopy of the classical nova V1186 Sco. This slowly developing nova had an complex light curve with multiple secondary peaks similar to those seen in PW Vul. The time to decline 2 magnitudes, t$_2$, was 20 days but the erratic nature of the light curve makes determination of intrinsic properties based on the decline time (e.g., luminosity) problematic, and the often cited MMRD relationship of Della Valle and Livio (1995) fails to yield a plausible distance. Spectra covering 0.35 to 35 $\mu$m were obtained in two separate epochs during the first year of outburst. The first set of spectra, taken about 2 months after visible maximum, are typical of a CO-type nova with narrow line emission from \ion{H}{1}, \ion{Fe}{2}, \ion{O}{1} and \ion{He}{1}. Later data, obtained between 260 and 380 days after maximum, reveal an emerging nebular spectrum. \textit{Spitzer} spectra show weakening hydrogen recombination emission with the emergence of [\ion{Ne}{2}] (12.81 $\mu$m) as the strongest line. Strong emission from [\ion{Ne}{3}] (15.56 $\mu$m) is also detected. Photoionization models with low effective temperature sources and only marginal neon enhancement (Ne $\sim$ 1.3 Ne$_{\odot}$) are consistent with these IR fine-structure neon lines indicating that V1186 Sco did not occur on a ONeMg white dwarf. In contrast, the slow and erratic light curve evolution, spectral development, and photoionization analysis of the ejecta imply the outburst occurred on a low mass CO white dwarf. We note that this is the first time strong [\ion{Ne}{2}] lines have been detected so early in the outburst of a CO nova and suggests that the presence of mid-infrared neon lines is not directly indicative of a ONeMg nova event.Comment: 7 figures, 37 pages. Astronimocal Journal accepte