Bias In Healthy Volunteers Research Articles

Comparison of Algorithms for Dementia Classification in the Survey of Health, Ageing and Retirement in Europe

AbstractBackgroundLow dementia rates, reflecting underdiagnosis in representative cohort studies, limit statistical power of etiological and preventative research. Although several algorithms for automated classification of presence or absence of dementia have been validated in the Health and Retirement Study (HRS), no such algorithm has yet been applied to the Survey of Health, Ageing and Retirement in Europe (SHARE).MethodThe Langa‐Weir classification (LW) was adapted to readily available indicators in SHARE, including immediate and delayed recall. Adapted algorithms additionally included instrumental activities of daily living (IADL) and used cut‐offs defined by either sample‐ or population‐level distributions. Performance was compared to logistic and bayesian‐logistic regression models and a gradient boosting machine (XGBoost) with the same indicators, adjusting for age groups, gender and educational level. The bayesian‐logistic regression used priors for sociodemographic indicators and global dementia incidence. Accuracy, specificity and sensitivity were compared with a train‐test split approach in SHARE wave 7 (2017).ResultIn total, N = 72,329 participants (57% female) above age 50 had no missing data on self‐reported dementia diagnosis, immediate or delayed recall and IADLs. LW based on immediate and delayed recall with a score cutoff based on dementia population‐incidence performed best overall (Accuracy = .92, Balanced Accuracy = .75, Sensitivity = .58, Specificity = .92), and showed greatest similarities to participants with self‐reported dementia diagnosis regarding risk factors and comorbidities (i.e., gripstrength, numerical performance, verbal fluency). Results from XGBoost suggested comparable performance however with risk of overfitting.ConclusionLW adaptations outperformed regression models regarding sensitivity. Comparisons of risk factor and comorbidity distributions suggest meaningful differences in comorbidities and risk factors in participants classified with and without dementia. With a lack of proxy assessments in SHARE, a suspected healthy volunteer bias and the absence of standardized cognitive assessments, probable dementia detection in SHARE necessarily comes with less confidence compared to algorithms tested in HRS. Nonetheless, performance of LW adaptations in SHARE is in line with previous validation studies in HRS. Future research should validate the algorithms through more extensive cognitive assessments once available.

Multimorbidity in a selected cohort compared to a representative sample: Does selection bias influence outcomes?

Context: UK Biobank is increasingly used to study causes, associations, and implications of multimorbidity. However, UK Biobank is criticised for lack of representativeness and 'healthy volunteer bias'. Selection bias can lead to spurious or biased estimates of associations between exposures and outcomes. Objectives: To compare association between multimorbidity and adverse health outcomes in UK Biobank and a nationally representative sample. Design: Cohorts identified from linked routine healthcare data from UK Biobank and from the Secure Anonymised Information Linkage (SAIL) databank. Setting: Community. Participants: UK Biobank participants (n=211,597, age 40-70) with linked primary care data and a sample from a nationally representative routine data source (SAIL) (n=852,055, age 40-70). Main outcome measures: Multimorbidity (n=40 long-term conditions [LTCs]) was identified from primary care Read codes and quantified using a simple count and a weighted score. Individual LTCs and LTC combinations were also assessed. Associations with all-cause mortality, unscheduled hospitalisation, and major adverse cardiovascular events (MACE) were assessed using Weibull or Poisson models and adjusted for age, sex, and socioeconomic status. Results: Multimorbidity was less common in UK Biobank than SAIL. This difference was attenuated, but persisted, after standardising by age, sex and socioeconomic status. The effect of increasing multimorbidity count on mortality, unscheduled hospitalisation, and MACE was similar between UK Biobank and SAIL at LTC counts of ≤3, however above this level UK Biobank underestimated the risk associated with multimorbidity. Absolute risk of mortality, hospitalisation and MACE, at all levels of multimorbidity, was lower in UK Biobank than SAIL (adjusting for age, sex, and socioeconomic status). Both cohorts produced similar hazard ratios for some LTCs (e.g. hypertension and coronary heart disease) but underestimated the risk for others (e.g. alcohol problems or mental health conditions). Similarly hazard ratios for some LTC combinations were similar between the cohorts (e.g. cardiovascular, respiratory conditions), UK Biobank underestimated the risk for combinations including pain or mental health conditions. Conclusions: UK Biobank accurately estimates risk of outcomes associated with LTC counts ≤3. However, for counts ≥4 estimates of magnitude of association from UK Biobank are likely to be conservative.

Incidence of Parkinson's disease in French women from the E3N cohort study over 27years of follow-up.

Parkinson's disease (PD) is an uncommon disease with a long prodromal period and higher incidence in men than women. Large cohort studies of women with a long follow-up are needed. Within the E3N French cohort study (98,995 women, 40-65years at baseline), we identified 3,584 participants who self-reported PD or used anti-parkinsonian drugs over 27years (1992-2018). We obtained medical records to validate PD diagnosis (definite, probable, possible, no). When medical records were not available, we used a validated algorithm based on drug claims to predict PD status. We retained a PD diagnosis for 1,294 women (medical records, 62%; algorithm, 38%). After exclusion of prevalent/possible cases, cases without age at diagnosis, and women lost to follow-up, our analyses included 98,069 women, of whom 1,200 had incident PD (mean age at diagnosis = 71.8years; incidence rate = 0.494/1,000 person-years). Age-adjusted incidence rates increased over the six first years of follow-up, possibly due to healthy volunteer bias, and remained stable thereafter, similar to incidence rates in women from Western Europe. Forty three percent of PD cases occurred after 20years of follow-up (2012-2018). The cumulative incidence of PD from 50 to 90years was 2.41% (95% confidence interval [CI] = 2.27-2.65). PD incidence was lower in ever than never smokers (hazard ratio = 0.86, 95% CI = 0.76-0.96). In conclusion, we estimated PD incidence rates in French women over a 27-year follow-up, and showed stable incidence between 2002 and 2018. The long follow-up and large sample size make this study a valuable resource to improve our knowledge on PD etiology in women.

A whole-population approach is required for dementia risk reduction

A whole-population approach is required for dementia risk reduction

Radio-contrast medium exposure and dialysis risk in patients with chronic kidney disease and congestive heart failure: A case-only study

BackgroundDialysis for end stage renal disease is considered a major public health challenge. Pre-existing chronic kidney disease (CKD) and congestive heart failure (CHF) may be independent risk factors for contrast-induced acute kidney injury. The aim of this study is to investigate dialysis risk in patients with CKD and CHF after radio-contrast medium exposure or coronary catheterization. MethodThis case-crossover design used the Health Insurance Database to identify incident dialysis patients with CKD and CHF. Patients themselves in 6 months ago serve as their own controls. This prevents selection bias in the control group, such as healthy volunteer bias and confounding bias. Conditional logistic regression model was used to estimate the risk of dialysis shortly after radio-contrast medium exposure. ResultsIn total, 36,709 patients with CKD and CHF underwent dialysis after radio-contrast medium exposure. At 1 week, the odds ratio (OR) for dialysis was 4.49 (95% Confidence Interval: 3.99–5.05). The ORs for acute-temporary (N = 23,418) and chronic dialysis (N = 13,291) were 5.57 (4.83–6.42) and 2.37 (1.90–2.95) after radio-contrast medium exposure, respectively. The ORs for dialysis after radio-contrast medium exposure in advanced CKD patients (N = 12,030) were 3.25 (2.53–4.19) and 4.85 (4.24–5.54) in early CKD patients (N = 24,679). The ORs for dialysis after coronary catheterization in patients with CKD and CHF was 3.75 (2.57–5.48). ConclusionsIn this study, the clinical risk for acute-temporary or chronic dialysis was significantly high when the bias was fully considered. We need strategies to reduce the subsequent risk of dialysis after radio-contrast medium exposure, especially in patients with CKD and CHF.

Reader response: Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study.

We read with interest the article by Kunutsor et al.,1 which describes the association of sauna bathing with the risk of stroke in a large cohort of Finnish men and women. Cohort studies comparing lifestyle factors in relation to cardiovascular risk can suffer from a specific form of selection bias, for which different terms are used throughout the literature: healthy volunteer bias or healthy user bias.2 Individuals who volunteer for a study may possess different characteristics than those in the target population. This implies that unobserved factors may explain the difference in stroke risk and not the exposure to, in this case, sauna bathing. The authors adjusted for baseline risk factors, but during the mean 14 years of follow-up, large differences in risk factors and exposure may have occurred, which could account for the observed effect. Moreover, the lack of an adequate explanation of the biological mechanism and the similar effects on conditions such as Alzheimer disease and respiratory conditions suggest healthy subject bias rather than a specific effect of sauna bathing.3,4 In view of the healthy volunteer bias and an inadequate reference group, any inferences from this study cannot be generalized to the general population.

Editors' note: Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study

In the article “Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study,” Kunutsor et al. reported a reduced risk of stroke in sauna bathers over a median follow-up of 14.9 years in middle-aged to elderly participants in the Finnish Kuopio Ischemic Heart Disease prospective cohort study. In response, Yu et al. suggest that the status of intracranial vasculature be included in the analysis as it may influence hemodynamic responses to sauna exposure. Dippel et al. highlight the risk of healthy volunteer bias and the absence of a sauna-naive reference group, and also note the lack of an adequate biological explanation for protective effects seen not only in stroke but also in other diseases. Replying to these comments, Kunutsor et al. note that they did not have vascular imaging data but contend that their Caucasian cohort was less likely to have significant asymptomatic intracranial atherosclerosis. While acknowledging potential limitations of selection bias, they emphasize relevant strengths of their study, and cite evidence on beneficial effects of sauna exposure on factors like blood pressure and inflammation that are implicated in stroke, Alzheimer disease, and respiratory conditions. In the article “Sauna bathing reduces the risk of stroke in Finnish men and women: A prospective cohort study,” Kunutsor et al. reported a reduced risk of stroke in sauna bathers over a median follow-up of 14.9 years in middle-aged to elderly participants in the Finnish Kuopio Ischemic Heart Disease prospective cohort study. In response, Yu et al. suggest that the status of intracranial vasculature be included in the analysis as it may influence hemodynamic responses to sauna exposure.

Representativeness of Medicare Participants in the Jackson Heart Study for African American Medicare Beneficiaries.

The Jackson Heart Study (JHS) assesses cardiovascular disease risk factors among African Americans in Jackson, Mississippi. Whether characteristics of JHS participants differ from those of a broader African American population are unknown. In a retrospective observational analysis, we compared characteristics and outcomes of JHS participants 65 years old and older and enrolled in Medicare (n = 1,105) to regional (n = 57,489) and national (n = 95,494) cohorts of African American Medicare beneficiaries. We weighted the regional and national cohorts to match the age and sex distributions of the JHS-Medicare cohort for pairwise baseline comparisons. Outcomes of interest included mortality and Medicare costs. We used Cox proportional hazards models to test associations between cohorts and outcomes. The JHS-Medicare cohort was younger, included more women, and had fewer beneficiaries with dual Medicare-Medicaid eligibility, compared with regional and national Medicare cohorts. The cohort also had lower risks of stroke, lung disease, heart failure, diabetes, and renal disease. Mean Medicare costs were lower ($5,066 [SD = $11,932]) than in the regional ($7,419 [SD = $17,574]) and national ($8,013 [SD = $19,378]) cohorts. The regional and national cohorts had higher mortality (adjusted hazard ratios = 1.52; 95% confidence interval [CI] = 1.31, 1.76; and 1.49; 95% CI = 1.29, 1.73, respectively). Subgroup analysis for dual Medicare-Medicaid eligibility attenuated mortality differences. JHS-Medicare participants had fewer comorbid conditions, better survival, and lower Medicare costs compared with regional and national cohorts. Observed differences may reflect healthy volunteer bias and higher socioeconomic status.See video abstract at, http://links.lww.com/EDE/B235.

Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers.

RationaleThere is now compelling evidence for a link between enteric microbiota and brain function. The ingestion of probiotics modulates the processing of information that is strongly linked to anxiety and depression, and influences the neuroendocrine stress response. We have recently demonstrated that prebiotics (soluble fibres that augment the growth of indigenous microbiota) have significant neurobiological effects in rats, but their action in humans has not been reported.ObjectivesThe present study explored the effects of two prebiotics on the secretion of the stress hormone, cortisol and emotional processing in healthy volunteers.MethodsForty-five healthy volunteers received one of two prebiotics (fructooligosaccharides, FOS, or Bimuno®-galactooligosaccharides, B-GOS) or a placebo (maltodextrin) daily for 3 weeks. The salivary cortisol awakening response was sampled before and after prebiotic/placebo administration. On the final day of treatment, participants completed a computerised task battery assessing the processing of emotionally salient information.ResultsThe salivary cortisol awakening response was significantly lower after B-GOS intake compared with placebo. Participants also showed decreased attentional vigilance to negative versus positive information in a dot-probe task after B-GOS compared to placebo intake. No effects were found after the administration of FOS.ConclusionThe suppression of the neuroendocrine stress response and the increase in the processing of positive versus negative attentional vigilance in subjects supplemented with B-GOS are consistent with previous findings of endocrine and anxiolytic effects of microbiota proliferation. Further studies are therefore needed to test the utility of B-GOS supplementation in the treatment of stress-related disorders.

P.1.e.003 Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers

P.1.e.003 Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers

Predicted Death Counts in the German National Cohort 2014 – 2110

Based on the study protocol of the German National Cohort (n = 200.000 between 20 and 69 years of age, recruited 2014 – 2018), one of the largest observational studies ever, and the model population data in the generation/cohort life tables of the German National Statistical Office, we deterministically predict total number of deaths of males and females from 2014 up to the last year 2110, when the youngest age group recruited – the birth cohort of 1998, recruited in 2018 – reaches age 112, the ultimate age in the generation life tables used here. We predict the death counts at any given calendar year that is approximately attributable to the birth cohorts of the five age groups at recruitment (20 – 29, 30 – 39, 40 – 49, 50 – 59, 60 – 69), namely 1945 – 1956, 1957 – 1966, 1967 – 1976, 1977 – 1986, 1987 – 1998. We furthermore differentiate by age group at death of 20 – 64, 65 – 74, 75 – 84, 85 – 99, 100+, 105+, 110+. The health care quality parameter „avoidable deaths” or „mortality amenable to medical/health care” referring to deaths which by most definitions occur before age 49, 65 or 75, can be observed from the onset of the survey until 2063 or 2073. On the other hand, the German National Cohort, from 2045 onwards, can be expected to generate 10.352 centenarians (100+), from 2050 onwards, 1442 semisupercentenarians (105+) and from 2055 onwards 73 supercentenarians (110+). Possibly these latter projections will even prove to be too low. We further differentiate between participants and non-participants in order to estimate the effects of the „healthy volunteer bias”, and find even under strong assumptions that such an effect will cause only minor bias. We finally show, how well period-, cohort- and life-cycle-effects may be distinguished in the death counts in the study population, broken down by age, sex and year of death. These predictions may serve practical policy purposes as well as an infrastructure for research.

P.3.023 Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers

The N2 subcomponents of event-related potentials are known to reflect early attentional processes. The anterior N2 may reflect conflict monitoring, whereas the posterior N2 may be involved in target detection. The aim of this study was to identify the brain areas involved in the generation of the N2 subcomponents, in order to define the spatiotemporal dynamics of these attentional processes. We recorded 128-channel electroencephalograms in 15 healthy controls performing a three-stimulus visual oddball task and identified standard-, distracter- and target-elicited N2 components. Individual N2 sources were localized using standardized-weighted-low-resolution-electromagnetic-tomography (swLORETA). Comparative analyses were performed with a non-parametric permutation technique. Common N2 generators were observed in the Brodmann area (BA) 24 of the anterior cingulate cortex (ACC). The posterior cingulate cortex and the central precuneus were more involved in distracter processing, whereas the anterior precuneus and BA 32 of the ACC were target-specific. In accordance with previous demonstration of the frontoparietal cortex’s critical role in attentional processes, these new data shed light on the ACC’s role in conflict monitoring and its interaction with other median and frontoparietal structures in early attentional processes.

Alpha 2B Adrenoceptor Genotype Moderates Effect of Reboxetine on Negative Emotional Memory Bias in Healthy Volunteers

Evidence suggests that emotional memory plays a role in the pathophysiology of depression/anxiety disorders. Noradrenaline crucially modulates emotional memory. Genetic variants involved in noradrenergic signaling contribute to individual differences in emotional memory and vulnerability to psychopathology. A functional deletion polymorphism in the α-2B adrenoceptor gene (ADRA2B) has been linked to emotional memory and post-traumatic stress disorder. The noradrenaline reuptake inhibitor reboxetine attenuates enhanced memory for negative stimuli in healthy and depressed individuals. We examined whether the effect of reboxetine on emotional memory in healthy individuals would be moderated by ADRA2B genotype. ADRA2B deletion carriers demonstrated enhanced emotional memory for negative stimuli compared with deletion noncarriers, consistent with prior studies. Reboxetine attenuated enhanced memory for negative stimuli in deletion noncarriers but had no significant effect in deletion carriers. This is the first demonstration of genetic variation influencing antidepressant drug effects on emotional processing in healthy humans.

Extinguishing Extinction: Hemispheric Differences in the Modulation of TMS-induced Visual Extinction by Directing Covert Spatial Attention

The topic of spatial attention is of great relevance for researchers in various fields, including neuropsychology, cognitive neuroscience, and cognitive psychology, as well as for clinical practice. Deficits of spatial attentional arising from parietal brain damage remain largely confined to the left visual field. The mechanisms underlying this hemispheric asymmetry are still elusive. We mimicked the neuropsychological syndrome of contralesional extinction by temporarily inducing a spatial attentional bias in healthy volunteers with TMS. We investigated whether directing covert spatial attention could enhance or, more importantly, counteract the resulting behavioral deficits. Although both the left and right parietal TMS induced contralateral extinction, only left hemifield extinction following right parietal TMS was severely aggravated by a competing stimulus in the ipsilesional (right) hemifield. We put forward the hypothesis that an asymmetry with respect to the ability of detaching attention from a distractor is contributing to the right hemispheric lateralization with regard to extinction. On a broader level, we suggest that "virtual patients" might be used for evaluating neuropsychological treatment in an early stage of development, reducing the burden on actual patients.

Imaging the neural mechanisms of TMS neglect-like bias in healthy volunteers with the interleaved TMS/fMRI technique: preliminary evidence.

Applying a precisely timed pulse of transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC) can produce temporary visuo-spatial neglect-like effects. Although the TMS is applied over PPC, it is not clear what other brain regions are involved. We applied TMS within a functional magnetic resonance imaging (fMRI) scanner to investigate brain activity during TMS induction of neglect-like bias in three healthy volunteers, while they performed a line bisection judgment task (i.e., the landmark task). Single-pulse TMS at 115% of motor threshold was applied 150 ms after the visual stimulus onset. Participants completed two different TMS/fMRI sessions while performing this task: one session while single-pulse TMS was intermittently and time-locked applied to the right PPC and a control session with TMS positioned over the vertex. Perceptual rightward bias was observed when TMS was delivered over the right PPC. During neglect-like behavior, the fMRI maps showed decreased neural activity within parieto-frontal areas, which are often lesioned or dysfunctional in patients with left neglect. Vertex TMS induced behavioral effects compatible with leftward response bias and increased BOLD signal in the left caudate (a site which has been linked to response bias). These results are discussed in relation to recent findings on neural networks subserving attention in space.

Adjusting a cancer mortality-prediction model for disease status-related eligibility criteria

BackgroundVolunteering participants in disease studies tend to be healthier than the general population partially due to specific enrollment criteria. Using modeling to accurately predict outcomes of cohort studies enrolling volunteers requires adjusting for the bias introduced in this way. Here we propose a new method to account for the effect of a specific form of healthy volunteer bias resulting from imposing disease status-related eligibility criteria, on disease-specific mortality, by explicitly modeling the length of the time interval between the moment when the subject becomes ineligible for the study, and the outcome.MethodsUsing survival time data from 1190 newly diagnosed lung cancer patients at MD Anderson Cancer Center, we model the time from clinical lung cancer diagnosis to death using an exponential distribution to approximate the length of this interval for a study where lung cancer death serves as the outcome. Incorporating this interval into our previously developed lung cancer risk model, we adjust for the effect of disease status-related eligibility criteria in predicting the number of lung cancer deaths in the control arm of CARET. The effect of the adjustment using the MD Anderson-derived approximation is compared to that based on SEER data.ResultsUsing the adjustment developed in conjunction with our existing lung cancer model, we are able to accurately predict the number of lung cancer deaths observed in the control arm of CARET.ConclusionsThe resulting adjustment was accurate in predicting the lower rates of disease observed in the early years while still maintaining reasonable prediction ability in the later years of the trial. This method could be used to adjust for, or predict the duration and relative effect of any possible biases related to disease-specific eligibility criteria in modeling studies of volunteer-based cohorts.

The effects of high frequency rTMS on negative attentional bias are influenced by baseline state anxiety

High frequency (HF) repetitive Transcranial Magnetic Stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) has been shown to induce an attentional bias towards threatening information in healthy adults, associated with decreased activation in the right DLPFC and increased activation in the right amygdala. Additionally, it has been shown that healthy individuals with higher state anxiety portray similar negative attentional biases and cortico-subcortical activation patterns to those induced by HF-rTMS of the right DLPFC. Therefore, the aim of this study is to investigate whether inter-individual differences in state anxiety levels prior to the administration of HF-rTMS of the right DLPFC might be related to the degree to which rTMS induces such a negative attentional bias in healthy volunteers. We administered HF-rTMS of the right DLPFC to a group of 28 healthy female individuals. In line with previous research, a single session of HF-rTMS of the right DLPFC induced an attentional bias towards threatening information. Moreover, self-report measures of state anxiety (STAI-State) prior to stimulation correlated positively with the magnitude of the induced attentional bias. More specifically, we found that healthy individuals who scored higher on self-reports of state anxiety acquired more attentional bias towards negative information after HF-rTMS. Therefore, the effects of a single placebo-controlled rTMS session of the right DLPFC is consistent with the effects of a disrupted prefrontal-amygdala circuitry. The effects on attentional bias are largest in those participants reporting higher state anxiety scores, possibly because underlying amygdala activation is highest.

Principles of Cancer Screening: Lessons From History and Study Design Issues

Early detection of cancer has held great promise and intuitive appeal in the medical community for well over a century. Its history developed in tandem with that of the periodic health examination, in which any deviations--subtle or glaring--from a clearly demarcated "normal" were to be rooted out, given the underlying hypothesis that diseases develop along progressive linear paths of increasing abnormalities. This model of disease development drove the logical deduction that early detection, by "breaking the chain" of cancer development, must be of benefit to affected individuals. In the latter half of the 20th century, researchers and guidelines organizations began to explicitly challenge the core assumptions underpinning many clinical practices. A move away from intuitive thinking began with the development of evidence-based medicine. One key method developed to explicitly quantify the overall risk-benefit profile of a given procedure was the analytic framework. The shift away from pure deductive reasoning and reliance on personal observation was driven, in part, by a rising awareness of critical biases in cancer screening that can mislead clinicians, including healthy volunteer bias, length-biased sampling, lead-time bias, and overdiagnosis. A new focus on the net balance of both benefits and harms when determining the overall worth of an intervention also arose: it was recognized that the potential downsides of early detection were frequently overlooked or discounted because screening is performed on basically healthy persons and initially involves relatively noninvasive methods. Although still inconsistently applied to early detection programs, policies, and belief systems in the United States, an evidence-based approach is essential to counteract the misleading--even potentially harmful--allure of intuition and individual observation.

The effects of time-on-task and concurrent cognitive load on normal visuospatial bias.

Research suggests that the severity of left spatial neglect can be modulated by changes in general alertness. Analogous effects in healthy volunteers now suggest that this may reflect an amplified form of a normal pattern. Recent neuropsychological studies also suggest that concurrent cognitive load may exacerbate rightward bias. In this study, for the first time, the authors examined the effect of both factors on spatial bias in healthy volunteers. Participants performed a task in which as many letters as possible needed to be reported from a briefly presented visual array under three conditions (alone, with a syllable-discrimination secondary task and with a pitch-discrimination secondary task). The results confirmed a significant rightward shift associated with time-on-task across all conditions--the first demonstration of such an effect within a fixation controlled, brief presentation task. While the secondary tasks influenced overall visual performance, there was no discernable effect on bias.