Acute exposure to mercury drives changes in gene expression in Drosophila melanogaster.

OBJECTIVE: We quantified the effect of acute exposure to a high dosage of inorganic mercury on gene expression in Drosophila melanogaster using RNA-sequencing of whole adult females. RESULTS: We found 119 genes with higher gene expression following treatment (including all 5 Drosophila metallothionine genes and a number of heat shock protein genes), and 31 with lower expression (several of which are involved in egg formation). Our results highlight biological processes and genetic pathways impacted by exposure to this toxic metal, and provide motivation for future studies to understand the genetic basis of response to mercury.

Social and leisure engagement moderates the association between care partner distress and cognitive status of care recipients with dementia.

OBJECTIVES: Despite the established impact of care recipient cognitive impairment on care partner (CP) distress, limited quantitative research has explored how social and leisure engagement may moderate this relationship, offering a potential avenue for enhancing well-being in both care partners and recipients. The current study therefore examined the between- and within-dyad associations between cognitive impairment of persons with dementia (PwD) and their family CP's distress, and whether social and leisure activity moderated this relationship. METHODS: Data were utilized from dyads (PwD, n = 33, and their CPs, n = 34) engaged in the Voices in Motion project, a social-cognitive choral intervention for PwD and their family CPs. Measures indexing PwD cognitive status, CP distress, and PwD and CP social and leisure engagement were assessed using an intensive repeated-measures burst design, with multilevel models of change employed to disaggregate between- and within-person effects. RESULTS: Diminished cognitive functioning in PwD was associated with increased CP distress (p < 0.01) between-dyads; however, this relationship was not significant within-dyads. The between-dyad association was significantly moderated by the extent of social and leisure engagement of both CPs (p < .001) and PwD (p = .04). Follow-up simple slopes demonstrated that, at mean- and high-levels (+1SD) of social and leisure engagement for PwD and/or CP, increased PwD cognitive function significantly predicted lower CP distress. CONCLUSION: The significant moderating influence of social and leisure engagement of dyads underscores the protective role of such engagement for reducing care-related distress. Activity engagement for CPs and PwD may help modulate the deleterious impact of PwD cognitive impairment and attenuate CP distress. These findings highlight the potential for dyadic interventions that promote social and leisure activities to mitigate caregiving challenges and enhance quality of life for both CPs and PwD.

Intraindividual Variability in Attention-Deficit/Hyperactivity Disorder: An Ex-Gaussian Approach.

Higher intraindividual variability (IIV) of response times is consistently noted in children with attention-deficit/hyperactivity disorder (ADHD). The current study investigated whether an ex-Gaussian estimate of IIV in children ages 6-13 years-old could differentiate between children with and without ADHD. Children completed a computerized go/no-go task to estimate trial-by-trial IIV and a continuous performance test (CPT) to estimate inattention and hyperactivity/impulsivity. Parents completed questionnaires assessing inattention and hyperactive/impulsive behaviors. IIV, commission errors, and attention problems as rated by parents were significantly greater in the ADHD group. Groups did not differ on errors of omission, but IIV was predictive of omission errors and parent ratings of inattention and hyperactivity/impulsivity. IIV predicted group membership (ADHD vs Control) whereas errors of omission did not. However, IIV did not improve diagnostic accuracy when parent ratings were used, such that parent ratings were superior at determining diagnosis. Current results support the use of IIV, based on the ex-Gaussian approach, as an objective measure of attention problems over omission errors on sustained attention CPT-type tasks. Additionally, while parent ratings of attention impairment remain the best predictor of ADHD diagnostic status, IIV may be helpful in determining when further assessment is required in the absence of those ratings.

Cognitive Speed in Neurodegenerative Disease: Comparing Mean Rate and Inconsistency Within and Across the Alzheimer's and Lewy Body Spectra in the COMPASS-ND Study.

Background: Alzheimer's disease (AD) and Lewy body disease (LBD) are characterized by early and gradual worsening perturbations in speeded cognitive responses. Objective: Using simple and choice reaction time tasks, we compared two indicators of cognitive speed within and across the AD and LBD spectra: mean rate (average reaction time across trials) and inconsistency (within person variability). Methods: The AD spectrum cohorts included subjective cognitive impairment (SCI, n = 28), mild cognitive impairment (MCI, n = 121), and AD (n = 45) participants. The LBD spectrum included Parkinson's disease (PD, n = 32), mild cognitive impairment in PD (PD-MCI, n = 21), and LBD (n = 18) participants. A cognitively unimpaired (CU, n = 39) cohort served as common benchmark. We conducted multivariate analyses of variance and discrimination analyses. Results: Within the AD spectrum, the AD cohort was slower and more inconsistent than the CU, SCI, and MCI cohorts. The MCI cohort was slower than the CU cohort. Within the LBD spectrum, the LBD cohort was slower and more inconsistent than the CU, PD, and PD-MCI cohorts. The PD-MCI cohort was slower than the CU and PD cohorts. In cross-spectra (corresponding cohort) comparisons, the LBD cohort was slower and more inconsistent than the AD cohort. The PD-MCI cohort was slower than the MCI cohort. Discrimination analyses clarified the group difference patterns. Conclusions: For both speed tasks, mean rate and inconsistency demonstrated similar sensitivity to spectra-related comparisons. Both dementia cohorts were slower and more inconsistent than each of their respective non-dementia cohorts.

Gene expression variation underlying tissue-specific responses to copper stress in Drosophila melanogaster.

Copper is one of a handful of biologically necessary heavy metals that is also a common environmental pollutant. Under normal conditions, copper ions are required for many key physiological processes. However, in excess, copper results in cell and tissue damage ranging in severity from temporary injury to permanent neurological damage. Because of its biological relevance, and because many conserved copper-responsive genes respond to nonessential heavy metal pollutants, copper resistance in Drosophila melanogaster is a useful model system with which to investigate the genetic control of the heavy metal stress response. Because heavy metal toxicity has the potential to differently impact specific tissues, we genetically characterized the control of the gene expression response to copper stress in a tissue-specific manner in this study. We assessed the copper stress response in head and gut tissue of 96 inbred strains from the Drosophila Synthetic Population Resource using a combination of differential expression analysis and expression quantitative trait locus mapping. Differential expression analysis revealed clear patterns of tissue-specific expression. Tissue and treatment specific responses to copper stress were also detected using expression quantitative trait locus mapping. Expression quantitative trait locus associated with MtnA, Mdr49, Mdr50, and Sod3 exhibited both genotype-by-tissue and genotype-by-treatment effects on gene expression under copper stress, illuminating tissue- and treatment-specific patterns of gene expression control. Together, our data build a nuanced description of the roles and interactions between allelic and expression variation in copper-responsive genes, provide valuable insight into the genomic architecture of susceptibility to metal toxicity, and highlight candidate genes for future functional characterization.

Premorbid personality traits as predictors for incident predementia syndromes: a multistate model approach.

OBJECTIVE: Associations have been found between five-factor model (FFM) personality traits and risk of developing specific predementia syndromes such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). The aims of this study were to: 1) Compare baseline FFM traits between participants who transitioned from healthy cognition or SCD to amnestic MCI (aMCI) versus non-amnestic MCI (naMCI); and 2) Determine the relationship between FFM traits and risk of transition between predementia cognitive states. METHODS: Participants were 562 older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment. Baseline data collected included levels of FFM personality traits, anxiety and depressive symptoms, medical history, performance on a cognitive battery, and demographics. Follow-up cognitive diagnoses were also recorded. RESULTS: Mann-Whitney U tests revealed no differences in baseline levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. A four-state multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, higher levels of extraversion were protective against developing naMCI. CONCLUSIONS: FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. Information on these personality traits could enrich clinical trials by permitting trials to target individuals who are at greatest risk for developing specific forms of cognitive impairment. These results should be replicated in future studies with larger sample sizes and younger participants.

Electrophysiological variability during tests of executive functioning: A comparison of athletes with and without concussion and sedentary control participants.

OBJECTIVE: Sport participation may benefit executive functioning (EF), but EF can also be adversely affected by concussion, which can occur during sport participation. Neural variability is an emerging proxy of brain health that indexes the brain's range of possible responses to incoming stimuli (i.e., dynamic range) and interconnectedness, but has yet to be characterized following concussion among athletes. This study examined whether neural variability was enhanced by athletic participation and attenuated by concussion. METHOD: Seventy-seven participants (18-25 years-old) were classified as sedentary controls (n = 33), athletes with positive concussion history (n = 21), or athletes without concussion (n = 23). Participants completed tests of attention switching, response inhibition, and updating working memory while undergoing electroencephalography recordings to index neural variability. RESULTS: Compared to sedentary controls and athletes without concussion, athletes with concussion exhibited a restricted whole-brain dynamic range of neural variability when completing a test of inhibitory control. There were no group differences observed for either the switching or working memory tasks. CONCLUSIONS: A history of concussion was related to reduced dynamic range of neural activity during a task of response inhibition in young adult athletes. Neural variability may have value for evaluating brain health following concussion.

Gene expression variation underlying tissue-specific responses to copper stress in Drosophila melanogaster.

Copper is one of a handful of biologically necessary heavy metals that is also a common environmental pollutant. Under normal conditions, copper ions are required for many key physiological processes. However, in excess, copper quickly results in cell and tissue damage that can range in severity from temporary injury to permanent neurological damage. Because of its biological relevance, and because many conserved copper-responsive genes also respond to other non-essential heavy metal pollutants, copper resistance in Drosophila melanogaster is a useful model system with which to investigate the genetic control of the response to heavy metal stress. Because heavy metal toxicity has the potential to differently impact specific tissues, we genetically characterized the control of the gene expression response to copper stress in a tissue-specific manner in this study. We assessed the copper stress response in head and gut tissue of 96 inbred strains from the Drosophila Synthetic Population Resource (DSPR) using a combination of differential expression analysis and expression quantitative trait locus (eQTL) mapping. Differential expression analysis revealed clear patterns of tissue-specific expression, primarily driven by a more pronounced gene expression response in gut tissue. eQTL mapping of gene expression under control and copper conditions as well as for the change in gene expression following copper exposure (copper response eQTL) revealed hundreds of genes with tissue-specific local cis-eQTL and many distant trans-eQTL. eQTL associated with MtnA, Mdr49, Mdr50, and Sod3 exhibited genotype by environment effects on gene expression under copper stress, illuminating several tissue- and treatment-specific patterns of gene expression control. Together, our data build a nuanced description of the roles and interactions between allelic and expression variation in copper-responsive genes, provide valuable insight into the genomic architecture of susceptibility to metal toxicity, and highlight many candidate genes for future functional characterization.

Genetic variation in chromatin state across multiple tissues in Drosophila melanogaster.

We use ATAC-seq to examine chromatin accessibility for four different tissues in Drosophila melanogaster: adult female brain, ovaries, and both wing and eye-antennal imaginal discs from males. Each tissue is assayed in eight different inbred strain genetic backgrounds, seven associated with a reference quality genome assembly. We develop a method for the quantile normalization of ATAC-seq fragments and test for differences in coverage among genotypes, tissues, and their interaction at 44099 peaks throughout the euchromatic genome. For the strains with reference quality genome assemblies, we correct ATAC-seq profiles for read mis-mapping due to nearby polymorphic structural variants (SVs). Comparing coverage among genotypes without accounting for SVs results in a highly elevated rate (55%) of identifying false positive differences in chromatin state between genotypes. After SV correction, we identify 1050, 30383, and 4508 regions whose peak heights are polymorphic among genotypes, among tissues, or exhibit genotype-by-tissue interactions, respectively. Finally, we identify 3988 candidate causative variants that explain at least 80% of the variance in chromatin state at nearby ATAC-seq peaks.

The genetic basis of adaptation to copper pollution in Drosophila melanogaster.

Introduction: Heavy metal pollutants can have long lasting negative impacts on ecosystem health and can shape the evolution of species. The persistent and ubiquitous nature of heavy metal pollution provides an opportunity to characterize the genetic mechanisms that contribute to metal resistance in natural populations. Methods: We examined variation in resistance to copper, a common heavy metal contaminant, using wild collections of the model organism Drosophila melanogaster. Flies were collected from multiple sites that varied in copper contamination risk. We characterized phenotypic variation in copper resistance within and among populations using bulked segregant analysis to identify regions of the genome that contribute to copper resistance. Results and Discussion: Copper resistance varied among wild populations with a clear correspondence between resistance level and historical exposure to copper. We identified 288 SNPs distributed across the genome associated with copper resistance. Many SNPs had population-specific effects, but some had consistent effects on copper resistance in all populations. Significant SNPs map to several novel candidate genes involved in refolding disrupted proteins, energy production, and mitochondrial function. We also identified one SNP with consistent effects on copper resistance in all populations near CG11825, a gene involved in copper homeostasis and copper resistance. We compared the genetic signatures of copper resistance in the wild-derived populations to genetic control of copper resistance in the Drosophila Synthetic Population Resource (DSPR) and the Drosophila Genetic Reference Panel (DGRP), two copper-naïve laboratory populations. In addition to CG11825, which was identified as a candidate gene in the wild-derived populations and previously in the DSPR, there was modest overlap of copper-associated SNPs between the wild-derived populations and laboratory populations. Thirty-one SNPs associated with copper resistance in wild-derived populations fell within regions of the genome that were associated with copper resistance in the DSPR in a prior study. Collectively, our results demonstrate that the genetic control of copper resistance is highly polygenic, and that several loci can be clearly linked to genes involved in heavy metal toxicity response. The mixture of parallel and population-specific SNPs points to a complex interplay between genetic background and the selection regime that modifies the effects of genetic variation on copper resistance.

Intraindividual variability measured with dispersion across diagnostic groups in a memory clinic sample.

Increased intraindividual variability (IIV) has been linked to outcomes such as cognitive decline and dementia, suggesting IIV might add valuable diagnostic information beyond traditional neuropsychological interpretation. We explored whether a subtype of IIV, dispersion, can provide additional information for dementia diagnosis. In a sample of memory clinic patients, three cognitive status groups were identified: subjective cognitive impairment (SCI; n = 85), amnestic mild cognitive impairment (a-MCI; n = 16), and dementia due to Alzheimer's disease (AD; n = 48). Dispersion was computed as intraindividual standard deviations across multiple neuropsychological measures within three cognitive domains (executive functioning; immediate and delayed memory) and was compared for each diagnostic group using profile analysis. Patients with AD and a-MCI demonstrated less dispersion than patients with SCI in delayed memory. Results support existing theoretic perspectives on cognitive variability and age-related cognitive decline but suggest floor effects underlie suppression of dispersion in amnestic cognitive presentations. Questions remain about the contribution of IIV beyond impressions of impairment versus no impairment in these constrained representations of cognitive domains. Future investigations should investigate variability in SCI groups against controls to examine whether observed dispersion similarities between SCI and a-MCI or AD in immediate memory and executive functioning are meaningful.

Exploring the impact of community-based choral participation on cognitive function and well-being for persons with dementia: evidence from the Voices in Motion project.

OBJECTIVES: Music-based interventions are postulated to mitigate cognitive decline in individuals with dementia. However, the mechanisms underlying why music-based interventions facilitate cognitive benefits remain unknown. The present study examines whether a choral intervention can modulate patterns of cognitive change in persons with dementia and whether within-person variation in affect is associated with this change. METHODS: Thirty-three older adults with dementia engaged weekly in the Voices in Motion (ViM) study consisting of 3 choral seasons spanning 18-months. Performance on the Mini-Mental State Examination (MMSE) and the Positive and Negative Affect Schedule was assessed monthly within each choral season using a longitudinal intensive repeated-measures design. Three-level multilevel models were employed to disaggregate between- and within-person effects across short- (month-to-month) and long-term (season-to-season) intervals. RESULTS: ViM participants exhibited an annual MMSE decline of 1.8 units, notably less than the clinically meaningful 3.3 units indicated by non-intervention literature. Further, variability in negative affect shared a within-person time-varying association with MMSE performance; decreases in negative affect, relative to one's personal average, were linked to corresponding improvements in cognitive function. CONCLUSION: Engagement in the ViM choral intervention may attenuate cognitive decline for persons with dementia via a reduction of psychological comorbidities such as elevated negative affect.

Genetic variation in P-element dysgenic sterility is associated with double-strand break repair and alternative splicing of TE transcripts.

The germline mobilization of transposable elements (TEs) by small RNA mediated silencing pathways is conserved across eukaryotes and critical for ensuring the integrity of gamete genomes. However, genomes are recurrently invaded by novel TEs through horizontal transfer. These invading TEs are not targeted by host small RNAs, and their unregulated activity can cause DNA damage in germline cells and ultimately lead to sterility. Here we use hybrid dysgenesis-a sterility syndrome of Drosophila caused by transposition of invading P-element DNA transposons-to uncover host genetic variants that modulate dysgenic sterility. Using a panel of highly recombinant inbred lines of Drosophila melanogaster, we identified two linked quantitative trait loci (QTL) that determine the severity of dysgenic sterility in young and old females, respectively. We show that ovaries of fertile genotypes exhibit increased expression of splicing factors that suppress the production of transposase encoding transcripts, which likely reduces the transposition rate and associated DNA damage. We also show that fertile alleles are associated with decreased sensitivity to double-stranded breaks and enhanced DNA repair, explaining their ability to withstand high germline transposition rates. Together, our work reveals a diversity of mechanisms whereby host genotype modulates the cost of an invading TE, and points to genetic variants that were likely beneficial during the P-element invasion.

Choral singing and dementia: Exploring musicality as embodied and relational accomplishment.

This study explored the impact of participation in Voices in Motion (ViM), an intergenerational community choir program that involved persons with dementia, care partners, and high school students in Victoria, British Columbia, Canada. Data came from interviews with 23 duets, each consisting of a person with dementia and their care partner; additionally, five focus groups with 29 students across two ViM choirs were conducted. Choir rehearsals and concerts were also observed. The analysis revealed that those with dementia have an embodied ability to fully participate in the choir and perform songs despite cognitive decline and memory loss. Involvement in the choirs also facilitated the emergence of strong social relationships among participants while students reported gaining a deeper understanding of the everyday experiences of living with dementia. Through well-attended concerts and performances at public events, ViM also helped re-humanize persons living with dementia by challenging the narrative of decline and its associated stigma.

Discovery of malathion resistance QTL in Drosophila melanogaster using a bulked phenotyping approach.

Drosophila melanogaster has proved an effective system with which to understand the evolutionary genetics and molecular mechanisms of insecticide resistance. Insecticide use has left signatures of selection in the fly genome, and both functional and quantitative genetic studies in the system have identified genes and variants associated with resistance. Here, we use D. melanogaster and leverage a bulk phenotyping and pooled sequencing "extreme quantitative trait loci" approach to genetically dissect variation in resistance to malathion, an organophosphate insecticide. We resolve 2 quantitative trait loci, one of which implicates allelic variation at the cytochrome P450 gene Cyp6g1, a strong candidate based on previous work. The second shows no overlap with hits from a previous genome-wide association study for malathion resistance, recapitulating other studies showing that different strategies for complex trait dissection in flies can yield apparently different architectures. Notably, we see no genetic signal at the Ace gene. Ace encodes the target of organophosphate insecticide inhibition, and genome-wide association studies have identified strong Ace-linked associations with resistance in flies. The absence of quantitative trait locus implicating Ace here is most likely because our mapping population does not segregate for several of the known functional polymorphisms impacting resistance at Ace, perhaps because our population is derived from flies collected prior to the widespread use of organophosphate insecticides. Our fundamental approach can be an efficient, powerful strategy to dissect genetic variation in resistance traits. Nonetheless, studies seeking to interrogate contemporary insecticide resistance variation may benefit from deriving mapping populations from more recently collected strains.

Pre-adult exposure to three heavy metals leads to changes in the head transcriptome of adult flies.

We examined the effect of developmental exposure to three heavy metals - cadmium, copper, and lead - on gene expression in adult head tissue in the model organism Drosophila melanogaster . All metals affected development time and/or gene expression level. While variation in the response to each metal was apparent, two differentially-expressed genes were upregulated in response to all three metal treatments, and 11 genes were downregulated in two of the three treatments. Our work reveals that developmental metal exposure has the potential to have long-lasting, metal-specific effects on gene expression in adults, even after the metal stress has been removed.

Parameterizing Practice in a Longitudinal Measurement Burst Design to Dissociate Retest Effects From Developmental Change: Implications for Aging Neuroscience.

Background: In longitudinal designs, the extraneous influence of retest effects can confound and obscure estimates of developmental change. The current study provides a novel approach to independently parameterize short-term retest effects and long-term developmental change estimates by leveraging a measurement burst design and three-level multilevel modeling. We further employ these short- and long-term slopes as predictors of cognitive status at long-term follow-up assessments. Methods: Participants included 304 older adults from Project MIND: a longitudinal measurement burst study assessing cognitive performance across both biweekly sessions and annual retests. Participants were classified as either Healthy controls (HC) or Cognitively Impaired, not Demented (CIND) at baseline, the final burst assessment (Year 4), and at an additional four-year follow-up (Year 8). Response time inconsistencies (RTI) were computed at each burst occasion for a simple choice response time (CRT) task and a one-back response time (BRT) task. Three-level multilevel models were employed to simultaneously examine change in RTI for both CRT and BRT across weeks within years, as well as across years, in order to dissociate within-individual retest effects (short-term) from developmental (long-term) change slopes. Individual slopes were then extracted and utilized in a series of multinomial logistic regression equations to contrast short- vs. long-term RTI change as predictors of cognitive status. Results: Separately parameterizing short- and long-term change estimates yielded distinct patterns of variation. CRT RTI remained stable across short-term weekly assessments, while significantly increasing across years. In contrast, BRT RTI decreased significantly across short-term assessments but showed no change across long-term assessments. After dissociating change estimates, short-term BRT as well as long-term CRT and BRT estimates predicted cognitive status at long-term follow-ups; increases in RTI, suggesting either an inability to benefit from retest or process-based developmental decline, were associated with an increased likelihood of being classified as CIND. Conclusions: We showcase an innovative approach to dissociate retest effects from developmental change across and within individuals. Accurately parameterizing these distinct change estimates can both reduce systematic bias in longitudinal trend estimates as well as provide a clinically useful tool by utilizing retest effects to predict cognitive health and impairment.

CVLT-II short form forced choice recognition in a clinical dementia sample: Cautions for performance validity assessment.

Performance validity tests are susceptible to false positives from genuine cognitive impairment (e.g., dementia); this has not been explored with the short form of the California Verbal Learning Test II (CVLT-II-SF). In a memory clinic sample, we examined whether CVLT-II-SF Forced Choice Recognition (FCR) scores differed across diagnostic groups, and how the severity of impairment [Clinical Dementia Rating Sum of Boxes (CDR-SOB) or Mini-Mental State Examination (MMSE)] modulated test performance. Three diagnostic groups were identified: subjective cognitive impairment (SCI; n = 85), amnestic mild cognitive impairment (a-MCI; n = 17), and dementia due to Alzheimer's Disease (AD; n = 50). Significant group differences in FCR were observed using one-way ANOVA; post-hoc analysis indicated the AD group performed significantly worse than the other groups. Using multiple regression, FCR performance was modeled as a function of the diagnostic group, severity (MMSE or CDR-SOB), and their interaction. Results yielded significant main effects for MMSE and diagnostic group, with a significant interaction. CDR-SOB analyses were non-significant. Increases in impairment disproportionately impacted FCR performance for persons with AD, adding caution to research-based cutoffs for performance validity in dementia. Caution is warranted when assessing performance validity in dementia populations. Future research should examine whether CVLT-II-SF-FCR is appropriately specific for best-practice testing batteries for dementia.

Powerful, efficient QTL mapping in Drosophila melanogaster using bulked phenotyping and pooled sequencing.

Despite the value of recombinant inbred lines for the dissection of complex traits, large panels can be difficult to maintain, distribute, and phenotype. An attractive alternative to recombinant inbred lines for many traits leverages selecting phenotypically extreme individuals from a segregating population, and subjecting pools of selected and control individuals to sequencing. Under a bulked or extreme segregant analysis paradigm, genomic regions contributing to trait variation are revealed as frequency differences between pools. Here, we describe such an extreme quantitative trait locus, or extreme quantitative trait loci, mapping strategy that builds on an existing multiparental population, the Drosophila Synthetic Population Resource, and involves phenotyping and genotyping a population derived by mixing hundreds of Drosophila Synthetic Population Resource recombinant inbred lines. Simulations demonstrate that challenging, yet experimentally tractable extreme quantitative trait loci designs (≥4 replicates, ≥5,000 individuals/replicate, and selecting the 5-10% most extreme animals) yield at least the same power as traditional recombinant inbred line-based quantitative trait loci mapping and can localize variants with sub-centimorgan resolution. We empirically demonstrate the effectiveness of the approach using a 4-fold replicated extreme quantitative trait loci experiment that identifies 7 quantitative trait loci for caffeine resistance. Two mapped extreme quantitative trait loci factors replicate loci previously identified in recombinant inbred lines, 6/7 are associated with excellent candidate genes, and RNAi knock-downs support the involvement of 4 genes in the genetic control of trait variation. For many traits of interest to drosophilists, a bulked phenotyping/genotyping extreme quantitative trait loci design has considerable advantages.

Functional near infrared spectroscopy activation during an executive function task differs between healthy older and younger adults.

Background: Healthy aging can include declines in processing speed and executive function. Further research is needed to characterize the neurobiological underpinnings of these cognitive changes in older adulthood. The current study used functional near infrared spectroscopy (fNIRS), an optical neuroimaging technique, to examine differences in cerebral oxygenation between healthy older adults (OA) and younger adults (YA) during a measure of cognitive interference. Methods: Thirty-four participants were sampled from two age groups: YA (mean age = 28.1 years, SD = 2.8, F = 9) and OA (mean age = 70.9 years, SD = 5.4, F = 9). Participants completed the Multi-Source Interference Task (MSIT), a measure of executive function with high and low-demand conditions, while undergoing fNIRS recordings using a TechEn CW6 system with 34-source-detector channels, situated over the prefrontal cortex. Functional activation patterns, accuracy, and reaction time were compared between and within groups for each condition. Results: Behaviourally, during the control condition, OA and YA had comparable accuracy, although OA had significantly slower reaction times than YA. During the interference condition, OA had significantly lower accuracy and slower reaction times than YA. Results demonstrated a significant difference between groups with an age-related increase in HbO for OA in both conditions (p < 0.05). Within groups, OA showed greater activation during the control condition, while YA demonstrated greater activation during the interference condition. Conclusions: The findings suggest that OA recruit additional neural resources to achieve similar behavioural performance during low-level cognitive interference, but that compensation in OA may be insufficient to support behavioural performance at higher levels of interference.