Lower Baseline Performance Research Articles

The effect of fampridine on working memory: a randomized controlled trial based on a genome-guided repurposing approach.

Working memory (WM), a key component of cognitive functions, is often impaired in psychiatric disorders such as schizophrenia. Through a genome-guided drug repurposing approach, we identified fampridine, a potassium channel blocker used to improve walking in multiple sclerosis, as a candidate for modulating WM. In a subsequent double-blind, randomized, placebo-controlled, crossover trial in 43 healthy young adults (ClinicalTrials.gov, NCT04652557), we assessed fampridine's impact on WM (3-back d-prime, primary outcome) after 3.5 days of repeated administration (10 mg twice daily). Independently of baseline cognitive performance, no significant main effect was observed (Wilcoxon P = 0.87, r = 0.026). However, lower baseline performance was associated with higher working memory performance after repeated intake of fampridine compared to placebo (rs = -0.37, P = 0.014, n = 43). Additionally, repeated intake of fampridine lowered resting motor threshold (F(1,37) = 5.31, P = 0.027, R2β = 0.01), the non-behavioral secondary outcome, indicating increased cortical excitability linked to cognitive function. Fampridine's capacity to enhance WM in low-performing individuals and to increase brain excitability points to its potential value for treating WM deficits.

A Virtual Breakthrough Series Collaborative for Missed Test Results

Missed test results, defined as test results not followed up within an appropriate time frame, are common and lead to delays in diagnosis and treatment. To evaluate the effect of a quality improvement collaborative, the Virtual Breakthrough Series (VBTS), on the follow-up rate of 2 types of test results prone to being missed: chest imaging suspicious for lung cancer and laboratory findings suggestive of colorectal cancer. This stepped-wedge cluster-randomized clinical trial was conducted between February 2020 and March 2022 at 12 Department of Veterans Affairs (VA) medical centers, with a predefined 3-cohort roll-out. Each cohort was exposed to 3 phases: preintervention, action, and continuous improvement. Follow-up ranged from 0 to 12 months, depending on cohort. Teams at each site were led by a project leader and included diverse interdisciplinary representation, with a mix of clinical and technical experts, senior leaders, nursing champions, and other interdisciplinary team members. Analysis was conducted per protocol, and data were analyzed from April 2022 to March 2024. All teams participated in a VBTS, which included instruction on reducing rates of missed test results at their site. The primary outcome was changes in the percentage of abnormal test result follow-up, comparing the preintervention phase with the action phase. Secondary outcomes were effects across cohorts and the intervention's effect on sites with the highest and lowest preintervention follow-up rates. Previously validated electronic algorithms measured abnormal imaging and laboratory test result follow-up rates. A total of 11 teams completed the VBTS and implemented 47 (mean, 4 per team; range, 3-8 per team; mode, 3 per team) unique interventions to improve missed test results. A total of 40 027 colorectal cancer-related tests were performed, with 5130 abnormal results, of which 1286 results were flagged by the electronic trigger (e-trigger) algorithm as being missed. For lung cancer-related studies, 376 765 tests were performed, with 7314 abnormal results and 2436 flagged by the e-trigger as being missed. There was no significant difference in the percentage of abnormal test results followed up by study phase, consistent across all 3 cohorts. The estimated mean difference between the preintervention and action phases was -0.78 (95% CI, -6.88 to 5.31) percentage points for the colorectal e-trigger and 0.36 (95% CI, -5.19 to 5.9) percentage points for the lung e-trigger. However, there was a significant effect of the intervention by site, with the site with the lowest follow-up rate at baseline increasing its follow-up rate from 27.8% in the preintervention phase to 55.6% in the action phase. In this cluster-randomized clinical trial of the VBTS intervention, there was no improvement in the percentage of test results receiving follow-up. However, the VBTS may offer benefits for sites with low baseline performance. ClinicalTrials.gov Identifier: NCT04166240.

Assessing the Impact of Transcranial Magnetic Stimulation on Speech Perception in Noise.

Healthy aging is associated with reduced speech perception in noise (SPiN) abilities. The etiology of these difficulties remains elusive, which prevents the development of new strategies to optimize the speech processing network and reduce these difficulties. The objective of this study was to determine if sublexical SPiN performance can be enhanced by applying TMS to three regions involved in processing speech: the left posterior temporal sulcus, the left superior temporal gyrus, and the left ventral premotor cortex. The second objective was to assess the impact of several factors (age, baseline performance, target, brain structure, and activity) on post-TMS SPiN improvement. The results revealed that participants with lower baseline performance were more likely to improve. Moreover, in older adults, cortical thickness within the target areas was negatively associated with performance improvement, whereas this association was null in younger individuals. No differences between the targets were found. This study suggests that TMS can modulate sublexical SPiN performance, but that the strength and direction of the effects depend on a complex combination of contextual and individual factors.

Association of Racial Status and Training Language with Baseline Performance and Training Gains During Computerized Training of Technology-related Everyday Functional Skills In Older Adults

ObjectivesResearch consistently finds that lower baseline performance predicts greater gains with computerized training. Lower baseline performance can originate from many factors, including educational and environmental disadvantages, leading to reduced exposure to functional tasks. Across six computerized technology-related functional skills, baseline performance and training gains were compared across race and training language. DesignRandomized clinical trial. SettingAbout 14 community centers in New York City and Miami. ParticipantsParticipants aged 60–90 with diverse ethnic (52% Latinx) and racial (27% Black) status, trained in in English (60%) or Spanish (40%). InterventionRemotely delivered computerized cognitive and skills training (FUNSATTM) for an hour twice a week for up to 12 weeks. MeasurementsCompletion time across all 6 tests pre and post training. ResultsThe total sample included 42 Black English Speakers, 52 White English speakers, and 61 Spanish speakers. Spanish speakers had the poorest baseline performance on all tasks, underperforming English-speaking Latinx participants. However, Spanish speaking participants had the largest training gains. Lower MOCA scores predicted lower baseline performance and greater training gains across samples. Educational attainment predicted training gains only in the Spanish speakers. Despite education effects in this group, all improvements were statistically significant with large effect sizes. ImplicationsLower baseline performance of functional skills was a positive predictor of training gains and was efficiently reversed through training. Even participants who initially appeared more impaired achieved substantial gains, congruent with the results reported in psychiatric populations. Critically, low baseline competence should not be interpreted as reflecting negatively on potential training gains.

Associations of Allostatic Load with Level of and Change in Cognitive Function Among Middle-Aged and Older Hispanic/Latino Adults: The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited. To examine associations of AL with level of cognition, performance in cognition 7 years later, and change in cognition over 7 years among middle-aged and older US-based Hispanic/Latino adults. We used data (n = 5,799, 45-74 years at baseline) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation of Neurocognitive Aging (SOL-INCA). The AL score comprised 16 biomarkers representing cardiometabolic, glucose, cardiopulmonary, parasympathetic, and inflammatory systems (higher scores = greater dysregulation). Cognitive outcomes included GC and individual tests of verbal learning and memory, world fluency (WF), Digit Symbol Substitution (DSS), and Trail Making (Parts A & B). Survey-linear regressions assessed associations of AL with performance in cognition at baseline, 7 years later, and via 7-year cognitive change scores adjusting for sociodemographic characteristics, lifestyle factors, and depressive symptoms. Higher AL was associated with lower baseline performance in GC and WF; and lower 7-year follow-up performance in these same measures plus DSS and Trail Making Parts A & B. Higher AL was associated with more pronounced 7-year change (reduction) in GC and on WF and DSS tests. Findings extend previous evidence in predominantly older non-Hispanic white cohorts to show that AL is related to level of and change in GC (as well as WF and DSS) among middle-aged and older US-based Hispanic/Latino adults.

Effects of transcranial alternating current stimulation to the supplementary motor area on motor learning.

Transcranial alternating current stimulation (tACS) is a noninvasive method for brain stimulation that artificially modulates oscillatory brain activity in the cortical region directly beneath the electrodes by applying a weak alternating current. Beta (β) oscillatory activity in the supplementary motor area (SMA) is involved in motor planning and maintenance, whereas gamma (γ) oscillatory activity is involved in the updating of motor plans. However, the effect of applying tACS to the SMA on motor learning has not yet been investigated. This study assessed the effects of applying tACS to the SMA on motor learning. Forty-two right-handed healthy adults (age 20.6 ± 0.5 years, 24 men and 18 women) were included. Motor learning was assessed using a visuomotor tracking task with pinch tension of the right thumb and right forefinger. Each trial lasted 60 s, and the error rates were measured. Conductive rubber electrodes were attached to the SMA and the left shoulder for tACS. Stimulation was applied at an intensity of 1.0 mA and frequencies of 70 and 20 Hz in the γ-tACS and β-tACS treatment groups, respectively. The sham group was only administered a fade-in/out. The visuomotor tracking task was performed for 10 trials before tACS and 10 trials after tACS. Two trials were conducted on the following day to determine motor skill retention. The average deviation measured during 60 s was considered the error value. Pre-stimulation learning rate was calculated as the change in error rate. Post-stimulation learning rate and retention rate were calculated as the change in error rate after stimulation and on the day after stimulation, respectively. In both the stimulation groups, differences in pre-stimulation learning, post-stimulation learning, and retention rates were not significant. However, in the γ-tACS group, baseline performance and pre-stimulation learning rate were positively correlated with post-stimulation learning rate. Therefore, applying γ-tACS to the SMA can increase post-stimulation learning rate in participants exhibiting low baseline performance and high pre-stimulation learning rate. Our findings suggest that motor learning can be effectively enhanced by applying γ-tACS to the SMA based on an individual's motor and learning abilities.

Successful modulation of temporoparietal junction activity and stimulus-driven attention by fNIRS-based neurofeedback—A randomized controlled proof-of-concept study

Abstract The right temporoparietal junction (rTPJ) is a core hub in neural networks associated with reorienting of attention and social cognition. However, it remains unknown whether participants can learn to actively modulate their rTPJ activity via neurofeedback. Here, we explored the feasibility of functional near-infrared spectroscopy (fNIRS)-based neurofeedback in modulating rTPJ activity and its effect on rTPJ functions such as reorienting of attention and visual perspective taking. In a bidirectional regulation control group design, 50 healthy participants were reinforced to either up- or downregulate rTPJ activation over 4 days of training. Both groups showed an increase in rTPJ activity right from the beginning of the training but only the upregulation group maintained this effect, while the downregulation group showed a decline from the initial rTPJ activation. This suggests a learning effect in the downregulation exclusively, making it challenging to draw definitive conclusions about the effectiveness of rTPJ upregulation training. However, we observed group-specific effects on the behavioral level. We found a significant group x time interaction effect in the performance of the reorienting of attention task and group-specific changes, with decreased reaction times (RTs) in the upregulation group and increased RTs in the downregulation group across all conditions after the neurofeedback training. Those with low baseline performance showed greater improvements. In the perspective-taking task, however, only time effects were observed that were non-group-specific. These findings demonstrate that fNIRS-based neurofeedback is a feasible method to modulate rTPJ functions with preliminary evidence of neurophysiologically specific effects, thus paving the way for future applications of non-invasive rTPJ modulation in neuropsychiatric disorders.

The effect of incentivization on the conjunction fallacy in judgments: a meta-analysis.

The conjunction fallacy is a classical judgment bias that was argued to be a robust cognitive illusion insensitive to the positive effect of incentivization. We conducted a meta-analysis of the literature (n = 3276) and found that although most studies did not report a significant effect of incentivization, the results across studies show a significant positive effect for incentivization, d = 0.19, with an odds ratio of 1.40 for answering correctly when incentivized. There was no moderating effect of payoff size despite the differences in incentive value between studies. Additionally, the effect was relatively smaller when examining absolute differences in the probability of correct judgment instead of odds ratios, suggesting that it may be partly driven by studies with low baseline performance. These findings join those of other judgment-bias studies to suggest a small but nevertheless robust debiasing effect of incentivization.

Supervisor beware: Contemptuous feedback harms low performers and taxes working memory of rejection sensitive persons

In this independent constructive replication and generalizability study, we revisit Melwani and Barsade’s laboratory study on receiving contempt in a work context. They found that recipients of contempt had better task performance than the recipients of neutral, angry, or no failure feedback. They also found social status moderates this link, such that the low-status recipients of contempt performed significantly better than high-status recipients. The present study revisits the emotional feedback and performance link by focusing on objective task performance in a supervisor–subordinate setting. Participants ( N = 124) were randomly assigned to one of three scripted negative feedback conditions (neutral, anger, and contempt) and interacted with the team using an online messenger platform. Participants completed three copyediting tasks and received three rounds of negative written feedback. Results indicated that contempt led to a distinct pattern: subjects with low baseline performance on copyediting tasks consistently performed worse in the contempt condition than those in other conditions. We also extend the replication by showing how working memory is taxed differentially across feedback conditions. We found that rejection-sensitive participants incurred greater working memory deficits when receiving contempt. Our results inform research on Golem and Underdog effects and can also have implications for inclusive management practices in online work.

Are facet-specific task trainings efficient in improving children’s executive functions and why (they might not be)? A multi-facet latent change score approach

It currently remains unclear how facet-specific trainings of three core modules of executive function (EF; updating, switching, and inhibition) directly compare regarding efficacy, whether improvements on trained tasks transfer to nontrained EF tasks, and which factors predict children’s improvements. The current study systematically investigated three separate EF trainings in 6- to 11-year-old children (N = 229) using EF-specific trainings that were similar in structure, design, and intensity. Children participated in pre- and posttest assessments of the three EFs and were randomly allocated to one of three EF trainings or to an active or passive control group. Multivariate latent change score models revealed that only the updating group showed training-specific improvements in task performance that were larger compared with active controls as well as passive controls. In contrast, there were no training-specific benefits of training switching or inhibition. Latent changes in the three EF tasks were largely independent, and there was no evidence of transfer effects to nontrained EF tasks. Lower baseline performance and older age predicted larger changes in EF performance. These seemingly opposing effects support compensation accounts as well as developmental theories of EF, and they highlight the importance of simultaneously accounting for multiple predictors within one model. In line with recent theoretical proposals of EF development, we provide new systematic evidence that questions whether modular task trainings represent an efficient approach to improve performance in narrow or in broader indicators of EF. Thereby, this evidence ultimately highlights the need for more comprehensive assessments of EF and, subsequently, the development of new training approaches.

Spatial‐temporal subtypes of amyloid deposition show distinct baseline and longitudinal cognitive profiles

AbstractBackgroundWe recently identified three distinct spatial‐temporal trajectories of amyloid deposition through the application of a machine‐learning model (i.e., Subtype and Stage Inference [SuStaIn]) to amyloid positron emission tomography (PET) data. These included Frontal, Parietal, and Occipital subtypes, defined by the earliest regions to show abnormality. The current study aimed to determine whether these subtypes of amyloid accumulation hold value in predicting baseline and longitudinal cognitive functioning in addition to a validated measure of global amyloid burden, i.e. Centiloid (CL) units.MethodThe Frontal, Parietal, and Occipital subtypes were applied to the amyloid‐PET standard uptake value ratios (SUVr) of 2,510 subjects from 3 cohorts (ADNI, EMIF‐AD, OASIS‐3). Of these, 570 subjects with a high subtype probability assignment (>50%), assigned stage ≥ 1, and available cognition were included in the analyses. Subtypes were compared on global cognition and several cognitive domains including memory, attention, executive functioning, language, and visuospatial functioning. To assess whether subtype assignment added to baseline CL in predicting baseline and longitudinal cognition (range follow‐up=0.4‐11 years), linear models (predictors: subtype and CL) and linear mixed models (predictors: subtype*time and CL*time) were performed, respectively. All models were adjusted for baseline age, sex, education, and baseline cognitive stage.ResultParticipant characteristics are shown in Table‐1. The majority was assigned to the Frontal subtype (57%), followed by Occipital (22%) and Parietal (20%). After adjusting for baseline CL, the Occipital subtype showed lower baseline language scores than the Parietal subtype (β=‐0.34, p=.046) (Fig‐1A) and lower baseline attention scores than both Frontal (β=‐0.39, p=.047) and Parietal (β=‐0.73, p=.002) subtypes (Fig‐1B, Table‐2). In addition, the Occipital subtype declined faster over time on global cognition (Fig‐2A) and language (Fig‐2B) as compared to the Frontal (βglobal cognition=‐0.35, pglobal cognition=.007; βlanguage=‐0.10, planguage=.015) and Parietal (βglobal cognition=‐0.50, pglobal cognition=.002; βlanguage=‐0.13, planguage=.015) subtypes.ConclusionOur results show the added value of amyloid subtype assignment on top of CL measures on baseline and longitudinal cognition. Specifically, the Occipital subtype was associated with lower baseline performance and showed faster rates of cognitive decline. These findings suggest that subtype assignment based on amyloid PET might improve prognosis and patient stratification in clinical trials.

Amyloid‐ß aggregation, APOE‐e genotype, and the trajectory of cognitive decline in persons without dementia

AbstractBackgroundThe association of amyloid abnormality with cognitive decline in persons with normal cognition (NC) and mild cognitive impairment (MCI) is important to guide AD trial design and understand prognoses. We examined the relation between amyloid abnormality and decline over time in several cognitive domains, and tested whether apolipoprotein (APOE)‐e genotype modified this association.MethodWe included 3,820 persons (2,599 NC, 1,221 all‐cause MCI) from 22 Amyloid Biomarker Study cohorts, with baseline PET (n = 846) or CSF (n = 2,974) amyloid measurements available. Amyloid abnormality on PET was based on visual read or cohort‐specific cutoffs, and for CSF on cohort‐specific or data‐driven cutoffs. Global cognition was assessed by Mini‐Mental State Examination (MMSE), functional performance by Clinical Dementia Rating global scale (CDR), and memory immediate and delayed recall by verbal learning tests. We examined baseline amyloid abnormality associations with cognitive performance over time and potential modification by APOE‐e (up to 3‐way interactions) using random‐slope/random‐intercept linear mixed‐models corrected for age, sex, education with random cohort effects.ResultMean follow‐up duration was 2.1 (range 0.5‐8) years. Baseline MMSE was worse in persons with abnormal‐amyloid compared with normal‐amyloid (NC mean difference = 0.2, p = 0.04, MCI mean difference = 2.4, p<0.001). In NC, amyloid abnormality was not associated with decline in any domain (Table 1), nor was the association influenced by APOE‐e4. In MCI, amyloid abnormality was associated with lower baseline performance and steeper decline on all domains (Table 1). In APOE‐e4‐carriers with MCI, MMSE decline was steeper than in non‐carriers (p<0.001, 1.5x steeper in amyloid‐abnormal, 3x steeper in amyloid‐normal). The rate of decline on immediate/delayed recall in MCI was higher in APOE‐e4‐carriers than non‐carriers, independent of amyloid status (p<0.001). For both NC and MCI, decline was steepest in persons with e4e4, followed by e3e4, e3e3, e2e4, and e2e3 (p = 0.001, Figure 1), independent of amyloid status.ConclusionAmyloid abnormality was not associated with cognitive decline in persons with NC after a short‐term follow‐up. In MCI, amyloid abnormality was closely associated with cognitive decline in several domains, with an additive effect of APOE‐e on decline. These results may be relevant for future trial recruitment strategies. Future studies should examine long‐term outcomes in NC.

Enhancing national audit through addressing the quality improvement capabilities of feedback recipients: a multi-phase intervention development study

BackgroundNational audits are a common, but variably effective, intervention to improve services. This study aimed to design an intervention to increase the effectiveness of national audit.MethodsWe used interviews, documentary analysis, observations, co-design and stakeholder engagement methods. The intervention was described in an intervention manual and illustrated using a logic model. Phase 1 described the current hospital response to a national audit. Phase 2 identified potential enhancements. Phase 3 developed a strategy to implement the enhancements. Phase 4 explored the feasibility of the intervention alongside the National Audit of Dementia and refined the intervention. Phase 5 adapted the intervention to a second national audit (National Diabetes Audit). Phase 6 explored the feasibility and fidelity of the intervention alongside the National Diabetes Audit and used the findings to further refine the intervention.ResultsThe developed intervention is a quality improvement collaborative (QIC), containing virtual educational workshop, virtual outreach for local team leads and virtual facilitation of a learning collaborative delivered after feedback has been received. The QIC aims to support national audit recipients to undertake improvement actions tailored to their local context. The target audience is clinical and clinical governance leaders. We found that actions from national audit were constrained by what the clinical lead perceived they deliver personally, these actions were not aligned to identified influences upon performance. We found that the hospital response could be enhanced by targeting low baseline performance, identifying and addressing influences upon to performance, developing trust and credibility, addressing recipient priorities, presenting meaningful comparisons, developing a conceptual model, involving stakeholders and considering the opportunity cost. Phase 3 found that an educational workshop and outreach strategy could support implementation of the enhancements through developing coherence and cognitive participation. We found feasibility could be increased by revising the content, re-naming the intervention, amending activities to address time commitment, incorporating a more structured analysis of influences, supporting collaboration and developing local feedback mechanisms. Phase 5 found adaptation to a second national audit involved reflecting differences in the clinical topic, context and contractual requirements. We found that the behaviour change techniques identified in the manual were delivered by facilitators. Participants reported positive attitudes towards the intervention and that the intervention was appropriate.ConclusionsThe QIC supports local teams to tailor their actions to local context and develop change commitment. Future work will evaluate the effectiveness of the intervention as an adjunct to the National Diabetes Audit.

Effect of Transcranial Electrical Stimulation over the Posterior Parietal Cortex on Tactile Spatial Discrimination Performance

The intraparietal sulcus region, which is part of the posterior parietal cortex (PPC), has been shown to play an important role in discriminating object shapes using the fingers. Transcranial random noise stimulation (tRNS) and anodal transcranial pulsed current stimulation (tPCS) are noninvasive strategies widely used to modulate neural activity in cortical regions. Therefore, we investigated the effects of tRNS and anodal tPCS applied to left or right PPC on the tactile discrimination performance of the right index finger in 20 neurologically healthy subjects. A grating orientation task (GOT) was performed before and immediately after delivering tRNS (stimulus frequency 0.1–640 Hz) in Experiment 1 or anodal tPCS (pulse width 50 ms and inter-pulse interval 5 ms) in Experiment 2. Performing tRNS over the right PPC significantly improved discrimination performance on the GOT. Subjects were classified into low and high baseline performance groups. Conducting tRNS over the left PPC significantly reduced the GOT discrimination performance in the high-performance group. By contrast, anodal tPCS delivered to the PPC of the left and right hemispheres had no significant effect on the tactile GOT discrimination performance of the right hand. We show that transcranial electric stimulation over the PPC may improve tactile perception but the effect depends on stimulus modality, parameters, and on the stimulated hemisphere.

Intranasal Oxytocin Improves Social Behavior in Laboratory Beagle Dogs (Canis familiaris) Using a Custom-Made Social Test Battery.

For a long time, oxytocin has been thought to have a generally positive effect on social cognition and prosocial behavior; however, recent results suggested that oxytocin has beneficial effects only under certain conditions. The aim of the present study was to explore potential associations between social competence and the effect of intranasal oxytocin on the social behavior of laboratory beagle dogs. We expected oxytocin treatment to have a more pronounced positive effect on dogs with lower baseline performance in a social test battery. Thirty-six adult dogs of both sexes received 32 IU intranasal oxytocin and physiological saline (placebo) treatment in a double-blind, cross-over design, with 17–20 days between the two sessions. Forty minutes after the treatment, dogs participated in a social test battery consisting of eight situations. The situations were carried out within one session and took 20–30 min to complete. Principal component analysis on the coded behaviors identified four components (Willingness to interact, Preference for social contact, Non-aversive response to nonsocial threat, and Non-aversive response to social threat). The subjects' behavior during the placebo condition was used to assess their baseline performance. We found that oxytocin treatment had a differential effect on the behavior depending on the baseline performance of the individuals in all components, but only two treatment × baseline performance interactions remained significant in a less sensitive analysis. In accordance with our hypothesis, oxytocin administration increased dogs' contact seeking and affiliative behaviors toward humans but only for those with low baseline performance. Dogs with low baseline performance also showed significantly more positive (friendly) reactions to social threat after oxytocin administration than after placebo, while for dogs with high baseline performance, oxytocin administration led to a more negative (fearful) reaction. These results indicate that similar to those on humans, the effects of oxytocin on dogs' social behavior are not universally positive but are constrained by individual characteristics and the context. Nevertheless, oxytocin administration has the potential to improve the social behavior of laboratory beagle dogs that are socially less proficient when interacting with humans, which could have both applied and animal welfare implications.

The Quality of Primary Care in Cambodia: An Assessment of Knowledge and Effort of Public Sector Maternal and Child Care Providers

ABSTRACT Improving the quality of primary care is essential for achieving universal health coverage in low- and middle-income countries. This study examined the level and variation in primary care provider knowledge and effort in Cambodia, using cross-sectional data collected in 2014–2015 from public sector health centers in nine provinces. The data included clinical vignettes and direct observations of processes of antenatal care, postnatal care, and well-child visits and covered between 290–495 health centers and 370–847 individual providers for each service and type of data. The results indicate that provider knowledge and observed effort were generally low and varied across health centers and across individual providers. In addition, providers’ effort scores were generally lower than their knowledge scores, indicating the presence of a “know-do gap.” Although higher provider knowledge was correlated with higher levels of effort during patient encounters, knowledge only explained a limited fraction of the provider-level variation in effort. Due to low baseline performance and the know-do gap, improving provider adherence to clinical guidelines through training and practice standardization alone may have limited impact. Overall, the findings suggest that raising the low quality of care provided by Cambodia’s public sector will require multidimensional interventions that involve training, strategies that increase provider motivation, and improved health center management. The authors reported there is no funding associated with the work presented in this article.

Haplogroups of Mitochondrial DNA Differentiate Patterns of Cognitive Change Over 7 Years

Mitochondrial DNA (mtDNA) may play an important role in Alzheimer’s disease (AD) and cognitive decline. A particular haplogroup of mtDNA (haplogroup J), has been observed more commonly in patients with AD than in cognitively normal controls. We used mtDNA haplogroups to predict change in cognitive performance over seven years. We hypothesized that haplogroup J would predict poorer cognitive function and steeper cognitive decline. We analyzed data from 140 cognitively normal older adults (age 65+) who participated in the University of Kansas Alzheimer’s Disease Center annual registry. We used factor analysis to create three composite scores (verbal memory, attention, executive function) from 11 individual cognitive tests. We performed latent growth curve modeling to describe trajectories of cognitive performance and change. We compared haplogroup H, the most common, to haplogroup J, the potential risk group. Results indicated haplogroup J carriers had significantly lower baseline performance (B=-.049, p< .01) and slower rates of improvement (B=-.046, p < .05) on tests of verbal memory compared to haplogroup H. For executive function, groups did not differ at baseline (B=.065, p>.10), but haplogroup J had slower rates of improvement (B=-.097, p < .01). There were no differences in attention across groups in performance (B=.135, p>.10) or change (B=-.01, p>.10). Our results reinforce the important role of mtDNA in changes to cognitive function with aging and imply that the effects of haplogroup J may vary across cognitive domains. Future research should investigate the mechanisms by which mtDNA might affect performance on specific cognitive domains across haplogroups.

Methodological considerations of assessing meaningful/reliable change in computerized neurocognitive testing following sport-related concussion

Objective Traditional reliable change index (RCI) methods may be psychometrically limited due to their inability to account for particularly high or low baseline performance and regression to the mean following serial testing. The current study sought to examine differences between RCI and standardized regression-based (RBz) methods in a cohort of adolescent athletes engaged in sport-related concussion recovery. Methods Consultation records and results of computerized testing data via the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery were retrospectively reviewed among 240 adolescent athletes involved in return-to-play protocols following a sport-related concussion. Results High concordance rates were found between RCI and RBz metrics across ImPACT composites, consistent with previous literature. However, especially for those with lower baseline performance, RBz scores tended to suggest cognitive performance not meeting or exceeding baseline scores despite RCI metrics being appropriate across speed-based ImPACT composites. In contrast, results revealed high rates of RCI scores suggesting continued cognitive difficulties despite RBz metrics being within normal limits, especially for adolescents with higher baseline performance. Conclusions Results suggest value in interpreting RBz values in addition to RCI values as these allow for clinical interpretation more sensitive to statistical confounds, including baseline performance and regression to the mean.

Gamma oscillations modulate working memory recall precision

Working memory (WM)—the ability to keep information in mind for short periods of time—is linked to attention and inhibitory abilities, i.e., the capacity to ignore task-irrelevant information. These abilities have been associated with brain oscillations, especially parietal gamma and alpha bands, but it is yet unknown whether these oscillations also modulate attention and inhibitory abilities. To test this, we compared parietal gamma-transcranial alternating current stimulation (tACS) to alpha-tACS and to a non-stimulation condition (Sham) in 51 young participants. Stimulation was coupled with a WM task probing memory-based attention and inhibitory abilities by means of probabilistic retrospective cues, including informative (valid), uninformative (invalid) and neutral. Our results show that relative to alpha and sham stimulation, parietal gamma-tACS significantly increased working memory recall precision. Additional post hoc analyses also revealed strong individual variability before and following stimulation; low-baseline performers showed no significant changes in performance following both gamma and alpha-tACS relative to sham. In contrast, in high-baseline performers gamma- (but not alpha) tACS selectively and significantly improved misbinding-feature errors as well as memory precision, particularly in uninformative (invalid) cues which rely more strongly on attentional abilities. We concluded that parietal gamma oscillations, therefore, modulate working memory recall processes, although baseline performance may further influence the effect of stimulation.

Task-dependent effects of nicotine treatment on auditory performance in young-adult and elderly human nonsmokers

Electrophysiological studies show that nicotine enhances neural responses to characteristic frequency stimuli. Previous behavioral studies partially corroborate these findings in young adults, showing that nicotine selectively enhances auditory processing in difficult listening conditions. The present work extended previous work to include both young and older adults and assessed the nicotine effect on sound frequency and intensity discrimination. Hypotheses were that nicotine improves auditory performance and that the degree of improvement is inversely proportional to baseline performance. Young (19–23 years old) normal-hearing nonsmokers and elderly (61–80) nonsmokers with normal hearing between 500 and 2000 Hz received nicotine gum (6 mg) or placebo gum in a single-blind, randomized crossover design. Participants performed three experiments (frequency discrimination, frequency modulation identification, and intensity discrimination) before and after treatment. The perceptual differences were analyzed between pre- and post-treatment, as well as between post-treatment nicotine and placebo conditions as a function of pre-treatment baseline performance. Compared to pre-treatment performance, nicotine significantly improved frequency discrimination. Compared to placebo, nicotine significantly improved performance for intensity discrimination, and the improvement was more pronounced in the elderly with lower baseline performance. Nicotine had no effect on frequency modulation identification. Nicotine effects are task-dependent, reflecting possible interplays of subjects, tasks and neural mechanisms.