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138 Supporting Early-Career Faculty Grant Proposals through Narrative Development Training: A Proposal Narrative Development Program for Early-Career Faculty
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- Kharma Foucher, Kelly O’Shea, Rebecca Milczarek
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- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 41
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OBJECTIVES/GOALS: Faculty pursuing their first independent research grants often struggle to express their ideas in a concise, compelling way. Thus, we developed the “Research and Scholarship Storytelling Bootcamp” to equip these faculty with narrative development skills applicable across disciplines and mechanisms. METHODS/STUDY POPULATION: Early-career researchers who were preparing either their first NIH R-series application or an NSF CAREER award proposal were invited to participate. Enrollment was limited to 20 participants. Those accepted learned the “And-But-Therefore” narrative framework by reading a short book and attending 4 synchronous lectures. Between sessions, they applied the framework by drafting abstracts and Specific Aims/Project Summary documents and reviewing their fellow participants’ work. We assessed participants' comfort with storytelling, perceptions of preparedness, and confidence regarding funding chances, before and after the program using a visual analog scale (max 100 points) and calculated Cohen’s d to evaluate the effect size of any changes. RESULTS/ANTICIPATED RESULTS: Thirty people applied for 20 slots, indicating strong demand. Eleven NIH applicants and 9 NSF applicants enrolled. Before the program, participants rated their comfort with storytelling at 45 ± 25, their preparedness at 39 ± 24, and their funding confidence at 39 ± 26. Nine total participants completed all sessions, assignments, and surveys. Completion rates were comparable for NIH- and NSF-targeting participants. After the program, completing participants reported increases in their comfort with storytelling (68 ± 14 post vs 32 ± 20 pre, d = 1.46), perceived preparedness (64 ± 20 post vs 48 ± 26 pre, d=0.58), and confidence in funding chances (56 ± 19 post vs 40 ± 27 pre, d=0.75). DISCUSSION/SIGNIFICANCE: This program was the first of its kind for multidisciplinary early-career faculty at our institution. The program successfully achieved its objectives for those who completed all activities. Future analysis of survey comments and proposal success rates will reveal barriers to full program engagement and opportunities for further training.
Prediction of internalizing and externalizing symptoms in late childhood from attention-deficit/hyperactivity disorder symptoms in early childhood
- Agnieszka Mlodnicka, Maxwell Mansolf, Aruna Chandran, Izzuddin M. Aris, Catrina A. Calub, Shaikh Ahmad, Allison Shapiro, David Cochran, Bibiana Restrepo, Rebecca Schmidt, Irva Hertz-Picciotto, Deborah Bennett, Diane R. Gold, T. Michael O’Shea, Leslie Leve, Julie B. Schweitzer
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- Development and Psychopathology , First View
- Published online by Cambridge University Press:
- 27 March 2024, pp. 1-10
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Limited analyses based on national samples have assessed whether early attention-deficit/hyperactivity disorder (ADHD) symptoms predict later internalizing and externalizing symptoms in youth and the influence of sex and pubertal timing on subsequent psychiatric symptoms. This study analyzed data (n = 2818) from the Environmental influences on Child Health Outcomes Program national cohort. Analyses used data from early childhood (mean age = 5.3 years) utilizing parent-reported ADHD symptoms to predict rates of internalizing and externalizing symptoms from late childhood/adolescence (mean age = 11.9 years). Within a subsample age at peak height velocity (APHV) acted as a proxy to assess pubertal timing from early childhood (mean age = 5.4 years) to adolescence (mean age = 12.3 years). Early-childhood ADHD symptoms predicted later psychiatric symptoms, including anxiety, depression, aggressive behavior, conduct problems, oppositional defiant disorder, and rule-breaking behavior. Earlier APHV was associated with increased Conduct Disorder symptoms from late childhood to adolescence for females only. A stronger relation between ADHD symptoms and later aggression was observed in females with earlier APHV, whereas this same pattern with aggression, conduct problems and depression was observed in males with later APHV. Clinicians should consider that both young girls and boys with elevated ADHD symptoms, particularly with off-set pubertal timing, may be at risk for later psychiatric symptoms.
53 2-Back Performance Does Not Differ Between Cognitive Training Groups in Older Adults Without Dementia
- Nicole D Evangelista, Jessica N Kraft, Hanna K Hausman, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Cheshire Hardcastle, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven DeKosky, Georg A Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric Porges, Adam J Woods
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 360-361
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Objective:
Cognitive training is a non-pharmacological intervention aimed at improving cognitive function across a single or multiple domains. Although the underlying mechanisms of cognitive training and transfer effects are not well-characterized, cognitive training has been thought to facilitate neural plasticity to enhance cognitive performance. Indeed, the Scaffolding Theory of Aging and Cognition (STAC) proposes that cognitive training may enhance the ability to engage in compensatory scaffolding to meet task demands and maintain cognitive performance. We therefore evaluated the effects of cognitive training on working memory performance in older adults without dementia. This study will help begin to elucidate non-pharmacological intervention effects on compensatory scaffolding in older adults.
Participants and Methods:48 participants were recruited for a Phase III randomized clinical trial (Augmenting Cognitive Training in Older Adults [ACT]; NIH R01AG054077) conducted at the University of Florida and University of Arizona. Participants across sites were randomly assigned to complete cognitive training (n=25) or an education training control condition (n=23). Cognitive training and the education training control condition were each completed during 60 sessions over 12 weeks for 40 hours total. The education training control condition involved viewing educational videos produced by the National Geographic Channel. Cognitive training was completed using the Posit Science Brain HQ training program, which included 8 cognitive training paradigms targeting attention/processing speed and working memory. All participants also completed demographic questionnaires, cognitive testing, and an fMRI 2-back task at baseline and at 12-weeks following cognitive training.
Results:Repeated measures analysis of covariance (ANCOVA), adjusted for training adherence, transcranial direct current stimulation (tDCS) condition, age, sex, years of education, and Wechsler Test of Adult Reading (WTAR) raw score, revealed a significant 2-back by training group interaction (F[1,40]=6.201, p=.017, η2=.134). Examination of simple main effects revealed baseline differences in 2-back performance (F[1,40]=.568, p=.455, η2=.014). After controlling for baseline performance, training group differences in 2-back performance was no longer statistically significant (F[1,40]=1.382, p=.247, η2=.034).
Conclusions:After adjusting for baseline performance differences, there were no significant training group differences in 2-back performance, suggesting that the randomization was not sufficient to ensure adequate distribution of participants across groups. Results may indicate that cognitive training alone is not sufficient for significant improvement in working memory performance on a near transfer task. Additional improvement may occur with the next phase of this clinical trial, such that tDCS augments the effects of cognitive training and results in enhanced compensatory scaffolding even within this high performing cohort. Limitations of the study include a highly educated sample with higher literacy levels and the small sample size was not powered for transfer effects analysis. Future analyses will include evaluation of the combined intervention effects of a cognitive training and tDCS on nback performance in a larger sample of older adults without dementia.
2 Higher White Matter Hyperintensity Load Adversely Affects Pre-Post Proximal Cognitive Training Performance in Healthy Older Adults
- Emanuel M Boutzoukas, Andrew O’Shea, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Hanna K Hausman, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Samantha G Smith, Hyun Song, Eric C Porges, Alex Hishaw, Steven T DeKosky, Samuel S Wu, Michael Marsiske, Gene E Alexander, Ronald Cohen, Adam J Woods
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 671-672
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Objective:
Cognitive training has shown promise for improving cognition in older adults. Aging involves a variety of neuroanatomical changes that may affect response to cognitive training. White matter hyperintensities (WMH) are one common age-related brain change, as evidenced by T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) MRI. WMH are associated with older age, suggestive of cerebral small vessel disease, and reflect decreased white matter integrity. Higher WMH load associates with reduced threshold for clinical expression of cognitive impairment and dementia. The effects of WMH on response to cognitive training interventions are relatively unknown. The current study assessed (a) proximal cognitive training performance following a 3-month randomized control trial and (b) the contribution of baseline whole-brain WMH load, defined as total lesion volume (TLV), on pre-post proximal training change.
Participants and Methods:Sixty-two healthy older adults ages 65-84 completed either adaptive cognitive training (CT; n=31) or educational training control (ET; n=31) interventions. Participants assigned to CT completed 20 hours of attention/processing speed training and 20 hours of working memory training delivered through commercially-available Posit Science BrainHQ. ET participants completed 40 hours of educational videos. All participants also underwent sham or active transcranial direct current stimulation (tDCS) as an adjunctive intervention, although not a variable of interest in the current study. Multimodal MRI scans were acquired during the baseline visit. T1- and T2-weighted FLAIR images were processed using the Lesion Segmentation Tool (LST) for SPM12. The Lesion Prediction Algorithm of LST automatically segmented brain tissue and calculated lesion maps. A lesion threshold of 0.30 was applied to calculate TLV. A log transformation was applied to TLV to normalize the distribution of WMH. Repeated-measures analysis of covariance (RM-ANCOVA) assessed pre/post change in proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures in the CT group compared to their ET counterparts, controlling for age, sex, years of education and tDCS group. Linear regression assessed the effect of TLV on post-intervention proximal composite and sub-composite, controlling for baseline performance, intervention assignment, age, sex, years of education, multisite scanner differences, estimated total intracranial volume, and binarized cardiovascular disease risk.
Results:RM-ANCOVA revealed two-way group*time interactions such that those assigned cognitive training demonstrated greater improvement on proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures compared to their ET counterparts. Multiple linear regression showed higher baseline TLV associated with lower pre-post change on Processing Speed Training sub-composite (ß = -0.19, p = 0.04) but not other composite measures.
Conclusions:These findings demonstrate the utility of cognitive training for improving postintervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appear to be particularly sensitive to white matter hyperintensity load versus working memory training change. These data suggest that TLV may serve as an important factor for consideration when planning processing speed-based cognitive training interventions for remediation of cognitive decline in older adults.
1 Task-Based Functional Connectivity and Network Segregation of the Useful Field of View (UFOV) fMRI task
- Jessica N Kraft, Hanna K Hausman, Cheshire Hardcastle, Alejandro Albizu, Andrew O’Shea, Nicole D Evangelista, Emanuel M Boutzoukas, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven T DeKosky, Georg A Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Eric Porges, Adam J Woods
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 606-607
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Objective:
Interventions using a cognitive training paradigm called the Useful Field of View (UFOV) task have shown to be efficacious in slowing cognitive decline. However, no studies have looked at the engagement of functional networks during UFOV task completion. The current study aimed to (a) assess if regions activated during the UFOV fMRI task were functionally connected and related to task performance (henceforth called the UFOV network), (b) compare connectivity of the UFOV network to 7 resting-state functional connectivity networks in predicting proximal (UFOV) and near-transfer (Double Decision) performance, and (c) explore the impact of network segregation between higher-order networks and UFOV performance.
Participants and Methods:336 healthy older adults (mean age=71.6) completed the UFOV fMRI task in a Siemens 3T scanner. UFOV fMRI accuracy was calculated as the number of correct responses divided by 56 total trials. Double Decision performance was calculated as the average presentation time of correct responses in log ms, with lower scores equating to better processing speed. Structural and functional MRI images were processed using the default pre-processing pipeline within the CONN toolbox. The Artifact Rejection Toolbox was set at a motion threshold of 0.9mm and participants were excluded if more than 50% of volumes were flagged as outliers. To assess connectivity of regions associated with the UFOV task, we created 10 spherical regions of interest (ROIs) a priori using the WFU PickAtlas in SPM12. These include the bilateral pars triangularis, supplementary motor area, and inferior temporal gyri, as well as the left pars opercularis, left middle occipital gyrus, right precentral gyrus and right superior parietal lobule. We used a weighted ROI-to-ROI connectivity analysis to model task-based within-network functional connectivity of the UFOV network, and its relationship to UFOV accuracy. We then used weighted ROI-to-ROI connectivity analysis to compare the efficacy of the UFOV network versus 7 resting-state networks in predicting UFOV fMRI task performance and Double Decision performance. Finally, we calculated network segregation among higher order resting state networks to assess its relationship with UFOV accuracy. All functional connectivity analyses were corrected at a false discovery threshold (FDR) at p<0.05.
Results:ROI-to-ROI analysis showed significant within-network functional connectivity among the 10 a priori ROIs (UFOV network) during task completion (all pFDR<.05). After controlling for covariates, greater within-network connectivity of the UFOV network associated with better UFOV fMRI performance (pFDR=.008). Regarding the 7 resting-state networks, greater within-network connectivity of the CON (pFDR<.001) and FPCN (pFDR=. 014) were associated with higher accuracy on the UFOV fMRI task. Furthermore, greater within-network connectivity of only the UFOV network associated with performance on the Double Decision task (pFDR=.034). Finally, we assessed the relationship between higher-order network segregation and UFOV accuracy. After controlling for covariates, no significant relationships between network segregation and UFOV performance remained (all p-uncorrected>0.05).
Conclusions:To date, this is the first study to assess task-based functional connectivity during completion of the UFOV task. We observed that coherence within 10 a priori ROIs significantly predicted UFOV performance. Additionally, enhanced within-network connectivity of the UFOV network predicted better performance on the Double Decision task, while conventional resting-state networks did not. These findings provide potential targets to optimize efficacy of UFOV interventions.
78 BVMT-R Learning Ratio Moderates Cognitive Training Gains in Useful Field of View Task in Healthy Older Adults
- Cheshire Hardcastle, Jessica N. Kraft, Hanna K. Hausman, Andrew O’Shea, Alejandro Albizu, Nicole D. Evangelista, Emanuel Boutzoukas, Emily J. Van Etten, Pradyumna K. Bharadwaj, Hyun Song, Samantha G. Smith, Eric Porges, Steven DeKosky, Georg A. Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Gene E. Alexander, Adam J. Woods
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 180-181
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Objective:
Cognitive training using a visual speed-of-processing task, called the Useful Field of View (UFOV) task, reduced dementia risk and reduced decline in activities of daily living at a 10-year follow-up in older adults. However, there is variability in the level of cognitive gains after cognitive training across studies. One potential explanation for this variability could be moderating factors. Prior studies suggest variables moderating cognitive training gains share features of the training task. Learning trials of the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) recruit similar cognitive abilities and have overlapping neural correlates with the UFOV task and speed-ofprocessing/working memory tasks and therefore could serve as potential moderators. Exploring moderating factors of cognitive training gains may boost the efficacy of interventions, improve rigor in the cognitive training literature, and eventually help provide tailored treatment recommendations. This study explored the association between the HVLT-R and BVMT-R learning and the UFOV task, and assessed the moderation of HVLT-R and BVMT-R learning on UFOV improvement after a 3-month speed-ofprocessing/attention and working memory cognitive training intervention in cognitively healthy older adults.
Participants and Methods:75 healthy older adults (M age = 71.11, SD = 4.61) were recruited as part of a larger clinical trial through the Universities of Florida and Arizona. Participants were randomized into a cognitive training (n=36) or education control (n=39) group and underwent a 40-hour, 12-week intervention. Cognitive training intervention consisted of practicing 4 attention/speed-of-processing (including the UFOV task) and 4 working memory tasks. Education control intervention consisted of watching 40-minute educational videos. The HVLT-R and BVMT-R were administered at the pre-intervention timepoint as part of a larger neurocognitive battery. The learning ratio was calculated as: trial 3 total - trial 1 total/12 - trial 1 total. UFOV performance was measured at pre- and post-intervention time points via the POSIT Brain HQ Double Decision Assessment. Multiple linear regressions predicted baseline Double Decision performance from HVLT-R and BVMT-R learning ratios controlling for study site, age, sex, and education. A repeated measures moderation analysis assessed the moderation of HVLT-R and BVMT-R learning ratio on Double Decision change from pre- to post-intervention for cognitive training and education control groups.
Results:Baseline Double Decision performance significantly associated with BVMT-R learning ratio (β=-.303, p=.008), but not HVLT-R learning ratio (β=-.142, p=.238). BVMT-R learning ratio moderated gains in Double Decision performance (p<.01); for each unit increase in BVMT-R learning ratio, there was a .6173 unit decrease in training gains. The HVLT-R learning ratio did not moderate gains in Double Decision performance (p>.05). There were no significant moderations in the education control group.
Conclusions:Better visuospatial learning was associated with faster Double Decision performance at baseline. Those with poorer visuospatial learning improved most on the Double Decision task after training, suggesting that healthy older adults who perform below expectations may show the greatest training gains. Future cognitive training research studying visual speed-of-processing interventions should account for differing levels of visuospatial learning at baseline, as this could impact the magnitude of training outcomes.
6 Adjunctive Transcranial Direct Current Stimulation and Cognitive Training Alters Default Mode and Frontoparietal Control Network Connectivity in Older Adults
- Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Emanuel M Boutzoukas, Andrew O’Shea, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Eric S Porges, Georg A Hishaw, Samuel Wu, Steven DeKosky, Gene E Alexander, Michael Marsiske, Ronald A Cohen, Adam J Woods
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 675-676
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Aging is associated with disruptions in functional connectivity within the default mode (DMN), frontoparietal control (FPCN), and cingulo-opercular (CON) resting-state networks. Greater within-network connectivity predicts better cognitive performance in older adults. Therefore, strengthening network connectivity, through targeted intervention strategies, may help prevent age-related cognitive decline or progression to dementia. Small studies have demonstrated synergistic effects of combining transcranial direct current stimulation (tDCS) and cognitive training (CT) on strengthening network connectivity; however, this association has yet to be rigorously tested on a large scale. The current study leverages longitudinal data from the first-ever Phase III clinical trial for tDCS to examine the efficacy of an adjunctive tDCS and CT intervention on modulating network connectivity in older adults.
Participants and Methods:This sample included 209 older adults (mean age = 71.6) from the Augmenting Cognitive Training in Older Adults multisite trial. Participants completed 40 hours of CT over 12 weeks, which included 8 attention, processing speed, and working memory tasks. Participants were randomized into active or sham stimulation groups, and tDCS was administered during CT daily for two weeks then weekly for 10 weeks. For both stimulation groups, two electrodes in saline-soaked 5x7 cm2 sponges were placed at F3 (cathode) and F4 (anode) using the 10-20 measurement system. The active group received 2mA of current for 20 minutes. The sham group received 2mA for 30 seconds, then no current for the remaining 20 minutes.
Participants underwent resting-state fMRI at baseline and post-intervention. CONN toolbox was used to preprocess imaging data and conduct region of interest (ROI-ROI) connectivity analyses. The Artifact Detection Toolbox, using intermediate settings, identified outlier volumes. Two participants were excluded for having greater than 50% of volumes flagged as outliers. ROI-ROI analyses modeled the interaction between tDCS group (active versus sham) and occasion (baseline connectivity versus postintervention connectivity) for the DMN, FPCN, and CON controlling for age, sex, education, site, and adherence.
Results:Compared to sham, the active group demonstrated ROI-ROI increases in functional connectivity within the DMN following intervention (left temporal to right temporal [T(202) = 2.78, pFDR < 0.05] and left temporal to right dorsal medial prefrontal cortex [T(202) = 2.74, pFDR < 0.05]. In contrast, compared to sham, the active group demonstrated ROI-ROI decreases in functional connectivity within the FPCN following intervention (left dorsal prefrontal cortex to left temporal [T(202) = -2.96, pFDR < 0.05] and left dorsal prefrontal cortex to left lateral prefrontal cortex [T(202) = -2.77, pFDR < 0.05]). There were no significant interactions detected for CON regions.
Conclusions:These findings (a) demonstrate the feasibility of modulating network connectivity using tDCS and CT and (b) provide important information regarding the pattern of connectivity changes occurring at these intervention parameters in older adults. Importantly, the active stimulation group showed increases in connectivity within the DMN (a network particularly vulnerable to aging and implicated in Alzheimer’s disease) but decreases in connectivity between left frontal and temporal FPCN regions. Future analyses from this trial will evaluate the association between these changes in connectivity and cognitive performance post-intervention and at a one-year timepoint.
28 Factor Structure of Conventional Neuropsychological Tests and NIH-Toolbox in Healthy Older Adults
- Kailey Langer, Cheshire Hardcastle, Hanna Hausman, Jessica Kraft, Alejandro Albizu, Nicole Evangelista, Emanuel Boutzoukas, Andrew O’Shea, Emily Van Etten, Samantha Smith, Hyun Song, Pradyumna Bharadwaj, Georg Hishaw, Samuel Wu, Steven DeKosky, Gene Alexander, Eric Porges, Michael Marsiske, Ronald Cohen, Adam Woods
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 710
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Objective:
The National Institutes of Health-Toolbox cognition battery (NIH-TCB) is widely used in cognitive aging studies and includes measures in cognitive domains evaluated for dimensional structure and psychometric properties in prior research. The present study addresses a current literature gap by demonstrating how NIH-TCB integrates into a battery of traditional clinical neuropsychological measures. The dimensional structure of NIH-TCB measures along with conventional neuropsychological tests is assessed in healthy older adults.
Participants and Methods:Baseline cognitive data were obtained from 327 older adults. The following measures were collected: NIH-Toolbox cognitive battery, Controlled Oral Word Association (COWA) letter and animals tests, Wechsler Test of Adult Reading (WTAR), Stroop Color-Word Interference Test, Paced Auditory Serial Addition Test (PASAT), Brief Visuospatial Memory Test (BVMT), Letter-Number Sequencing (LNS), Hopkins Verbal Learning Test (HVLT), Trail Making Test A&B, Digit Span. Hmisc, psych, and GPARotation packages for R were used to conduct exploratory factor analyses (EFA). A 5-factor solution was conducted followed by a 6-factor solution. Promax rotation was used for both EFA models.
Results:The 6-factor EFA solution is reported here. Results indicated the following 6 factors: working memory (Digit Span forward, backward, and sequencing, PASAT trials 1 and 2, NIH-Toolbox List Sorting, LNS), speed/executive function (Stroop color naming, word reading, and color-word interference, NIH-Toolbox Flanker, Dimensional Change, and Pattern Comparison, Trail Making Test A&B), verbal fluency (COWA letters F-A-S), crystallized intelligence (WTAR, NIH-Toolbox Oral Recognition and Picture Vocabulary), visual memory (BVMT immediate and delayed), and verbal memory (HVLT immediate and delayed. COWA animals and NIH-Toolbox Picture Sequencing did not adequately load onto any EFA factor and were excluded from the subsequent CFA.
Conclusions:Findings indicate that in a sample of healthy older adults, these collected measures and those obtained through the NIH-Toolbox battery represent 6 domains of cognitive function. Results suggest that in this sample, picture sequencing and COWA animals did not load adequately onto the factors created from the rest of the measures collected. These findings should assist in interpreting future research using combined NIH-TCB and neuropsychological batteries to assess cognition in healthy older adults.
9 Connecting memory and functional brain networks in older adults: a resting state fMRI study
- Jori L Waner, Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven T DeKosky, Georg A Hishaw, Samuel S Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric C Porges, Adam J Woods
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 527-528
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Objective:
Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.
Participants and Methods:330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.
Results:Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.
Conclusions:Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.
10 Female APOE ε4 Carriers with Slow Rates of Biological Aging Have Better Verbal Memory Performance Compared to Female Carriers with Faster Rates of Aging, Independent of Chronological Age, Education, and Depressive Symptoms.
- Burcu Kaplan, Deirdre M. O’Shea
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 324-325
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Objective:
The presence of an e4 allele of the apolipoprotein E gene (APOE ε4) is considered the strongest genetic risk factor for Alzheimer’s disease (AD) in the US. Evidence suggests that APOE ε4 carriers have worse memory performances compared to APOE ε4 non-carriers in cognitively normal older adults and that female APOE ε4 carriers are at greater risk of AD compared to male carriers. Recent advancements in estimating biological age using DNA methylation markers may enhance understanding of the associations between sex and APOE ε4 on cognitive aging. Thus, the current study aimed to investigate whether associations between APOE ε4 status and memory vary according to rates of biological aging, using a DNA methylation age biomarker, in older men and women without dementia.
Participants and Methods:Cross-sectional data were obtained from 1771 older adults enrolled in the 2016 wave of the Health and Retirement Study (Mean age = 75, SD = 7; 57% female; 76% non-Hispanic white). The standardized residual from regressing chronological age on the epigenetic clock “DNAGrimAge” was used as a measure of the aging rate. A series of ANCOVAs with Bonferroni corrected post hoc pairwise tests, adjusting for education, white blood cell count, chronological age, and depressive symptoms were used to test the main and interaction effects of APOE ε4 status (non-carriers = 0; carriers = 1) and aging rates, defined as 1 standard deviation below (i.e., slow rate), or above (i.e., fast rate) sex-specific mean rate (i.e., average) of aging, on a standardized composite measure of verbal memory. Alpha was set at .05 and all raw scores were converted to z-score metric prior to analyses.
Results:APOE ε4 female carriers with slow rates of aging (n = 34) had significantly better memory performances compared to APOE ε4 female carriers with fast rates of aging (n = 41), mean difference = .61, p = .006, and average rates of aging (n = 170), mean difference = .44, p = .017. There was no effect of aging rate on memory in the female non-carriers and there were no significant differences in memory performances based on rates of aging in either male APOE ε4 carriers or non-carriers.
Conclusions:Although the presence of the APOE ε4 has previously been shown to represent a stronger risk of AD for women compared to men, results from the current study suggest that slower rates of aging in this high-risk group may confer protection against clinical symptoms (i.e., memory impairment). Conversely, faster than average aging in female APOE ε4 carriers may represent a group at greater risk of memory impairment due to AD. However, longitudinal studies with larger sample sizes are needed to evaluate the risk of dementia/memory impairment based on rates of aging in female APOE ε4 carriers.
18 Regional patterns of mitochondrial function using phosphorus magnetic resonance spectroscopy in older adults at-risk for Alzheimer’s disease.
- Francesca V Lopez, Andrew O’Shea, Stacey Alvarez-Alvarado, Adrianna Ratajska, Lauren Kenney, Rachel Schade, Katie Rodriguez, Alyssa Ray, Rebecca O’Connell, Lauren Santos, Emily Van Etten, Hyun Song, Emma Armstrong, Tiffany Gin, Zhiguang Huo, Gene Alexander, Adam J Woods, Dawn Bowers
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 331-332
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Objective:
The brain is reliant on mitochondria to carry out a host of vital cellular functions (e.g., energy metabolism, respiration, apoptosis) to maintain neuronal integrity. Clinically relevant, dysfunctional mitochondria have been implicated as central to the pathogenesis of Alzheimer’s disease (AD). Phosphorous magnetic resonance spectroscopy (31p MRS) is a non-invasive and powerful method for examining in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. At least one prior 31p MRS study found temporal-frontal differences for high energy phosphates in persons with mild AD. The goal of the current study was to examine regional (i.e., frontal, temporal) 31p MRS ratios of mitochondrial function in a sample of older adults at-risk for AD. Given the high energy consumption in temporal lobes (i.e., hippocampus) and preferential age-related changes in frontal structure-function, we predicted 31p MRS ratios of mitochondrial function would be greater in temporal as compared to frontal regions.
Participants and Methods:The current study leveraged baseline neuroimaging data from an ongoing multisite study at the University of Florida and University of Arizona. Participants were older adults with memory complaints and a first-degree family history of AD [N = 70; mean [M] age [years] = 70.9, standard deviation [SD] =5.1; M education [years] = 16.2, SD = 2.2; M MoCA = 26.5, SD = 2.4; 61.4% female; 91.5% non-latinx white]. To achieve optimal sensitivity, we used a single voxel method to examine 31p MRS ratios (bilateral prefrontal and left temporal). Mitochondrial function was estimated by computing 5 ratios for each voxel: summed adenosine triphosphate to total pooled phosphorous (ATP/TP; momentary energy), ATP to inorganic phosphate (ATP/Pi; energy consumption), phosphocreatine to ATP (PCr/ATP; energy reserve), phosphocreatine to inorganic phosphate (PCr/Pi; oxidative phosphorylation), and phosphomonoesters to phosphodiesters (PME/PDE; cellular membrane turnover rate). All ratios were corrected for voxel size and cerebrospinal fluid fraction. Separate repeated measures analyses of variance controlling for scanner site differences (RM ANCOVAs) were performed.
Results:31p MRS ratios were unrelated to demographic characteristics and were not included as additional covariates in analyses. Results of separate RM ANCOVAs revealed all 31p MRS ratios of mitochondrial function were greater in left temporal relative to bilateral prefrontal voxel: ATP/TP (p < .001), ATP/Pi (p = .001), PCr/ATP (p = .004), PCr/Pi (p = .004), and PME/PDE (p = .017). Effect sizes (partial eta squared) ranged from 0.6-.20.
Conclusions:Consistent and extending one prior study, all 31p MRS ratios of mitochondrial function were greater in temporal as compared to frontal regions in older adults at-risk for AD. This may in part be related to the intrinsically high metabolic rate of the temporal region and preferential age-related changes in frontal structure-function. Alternatively, findings may reflect the influence of unaccounted factors (e.g., hemodynamics, auditory stimulation). Longitudinal study designs may inform whether patterns of mitochondrial function across different brain regions are present early in development, occur across the lifespan, or some combination. In turn, this may inform future studies examining differences in mitochondrial function (as measured using 31p MRS) in AD.
39 Co-Occurring Depression and Anxiety is Associated with Greater Cognitive Variability in Persons with Multiple Sclerosis
- Garrett A. Thomas, Kaitlin E. Riegler, Megan L. Bradson, Dede U. O'Shea, Peter A. Arnett
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 553
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Objective:
Research examining co-occurring anxiety and depression in persons with multiple sclerosis (PwMS) is scarce, though an estimated 20% of PwMS experience clinically significant anxiety and depression (Gascoyne et al., 2019). Recent work by Hanna & Strober (2020) found that PwMS with comorbid anxiety and depression reported worse outcomes in all constructs of symptomatology, disease management, psychological well-being, and quality of life. However, it is unclear how co-occurring anxiety and depression symptoms may influence or exacerbate cognitive difficulties in PwMS. Further, considering there are high levels of comorbidity between depression, anxiety, and fatigue in PwMS, this study aims to examine the unique variances of depression, anxiety, co-occurring depression and anxiety, and fatigue on cognitive functioning.
Participants and Methods:86 PwMS (F=65,M=21) completed a comprehensive neuropsychological battery that included self-report measures of anxiety, depression, and fatigue. An intraindividual variability (IIV) composite score was calculated by combining standardized intraindividual standard deviation and maximum discrepancy scores on measures of attention/processing speed and memory for each participant. Lower scores indicate worse performance (i.e., greater variability). A hierarchical regression was conducted with IIV as the outcome variable and with depression, anxiety, cognitive fatigue, physical fatigue, and the interaction between depression and anxiety as predictors. Expanded Disability Status Scale (EDSS) scores were included as a covariate.
Results:The only model that included a statistically significant predictor of IIV was the final model, which included EDSS, depression, anxiety, cognitive fatigue, physical fatigue, and the interaction between depression and anxiety, F(6,77)=2.97, p=.01, AR2=.08. While the main effects of depression and anxiety were not significant, the interaction between depression and anxiety was significant, F(6,77)=7.20, p=.01, n2=.09. Simple effects tests revealed that the relationship between IIV and anxiety was marginally significant for those at the cutoff for clinical depression (square root BDI-FS=2; BDI-FS=4), F(6,77)=3.52, p=.07, n2=.04. However, the effect of anxiety on IIV increased as depression increased. For example, in those with high levels of depression (1.5 SD above the mean), there was a significant relationship between anxiety and IIV, F(6,77)=4.16, p=.04, n2=.05, though this was not the case for those with low levels of depression (1.5 SD below the mean), F(6,77)=0.01, p=.92, n2=.00.
Conclusions:The interaction between depression and anxiety predicted variability in performance such that those with high levels of depression and anxiety demonstrated significantly greater IIV. Since dispersion is considered a marker for neurocognitive integrity, this may suggest that co-occurring psychological disturbances are associated with poorer cognitive integrity, an important consideration for interventions and outcomes. While interventions aimed at treating co-occurring depression and anxiety have been largely overlooked within the MS literature (Butler et al., 2016), transdiagnostic interventions have been beneficial for general adult populations with co-occurring anxiety and depression (McEvoy et al., 2009). Future work should examine the efficacy of interventions aimed at addressing co-occurring depression and anxiety in PwMS, as this may help to improve cognitive functioning, as well as perception of functioning, which will likely further improve quality of life and overall well-being.
7 - Organs
- David Michael O’Shea
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- Book:
- The Choral Foundation of the Chapel Royal, Dublin Castle
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- Boydell & Brewer
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- 10 January 2024
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- 23 May 2023, pp 134-163
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Summary
The role of the organ
The 1801 brief for the construction of the new Chapel mentioned ‘an Organ for Cathedral Service’. This refers to the principal function of the Chapel organ, which was to accompany the choir's singing of the musical parts of the choral service. The primacy of this function of the organ in English choral foundations is emphasized by John Jebb:
The English Cathedral organ, it should be remembered, is intended to be an accompaniment of a Choir, not a vehicle for Voluntaries or Concertos, as abroad, where its Choral use is generally subordinate.
In an era in which choirs were not conducted during church services, the choir was not merely accompanied by the organ, but led and directed by its sound, according to the interpretation of the organist. The organist was thus the superintendent of the entire musical service, for his playing shaped the singing. The distinctive sound of the organ, and the way in which the organist chose sonorities for accompaniment, would have affected the quality of the choir's singing. Thus, the combination of choir and organ resonating in the Chapel's peculiar dry acoustic would have created a distinctive sound-world for the worshippers who attended services at the Chapel.
Besides its principal use in accompanying the choir, the organ may have been used to provide ‘voluntaries’ – a term given to solo organ music, either composed or improvised, that accompanied liturgical action. Nowadays, the term ‘voluntary’ usually refers to a piece of organ music played at the conclusion of a service, but in past times there existed the tradition of the ‘middle voluntary’, which was played after the chanting of the psalm and before the reading of the first lesson in Morning and Evening Prayer:
A custom, formerly very general, still obtains in some Cathedrals, of playing a piece of music on the Organ after the Psalms. This is called a Voluntary, as the choice of the music is left to the discretion of the organist.
Jebb noted that this practice had ceased shortly before the time of writing (1843) in the Dublin cathedrals, but did not mention whether or not this middle voluntary was used in the Chapel Royal. According to Jebb, this voluntary ‘should be a short, slow movement, chiefly upon the diapasons and unisons’, and that ‘all shewy gavots, and noisy trumpet pieces’ should be avoided.
Appendix F - Organists of the Chapel Royal
- David Michael O’Shea
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- Book:
- The Choral Foundation of the Chapel Royal, Dublin Castle
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- Boydell & Brewer
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- 10 January 2024
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- 23 May 2023, pp 257-257
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5 - The Chapel Royal Music Collection
- David Michael O’Shea
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- The Choral Foundation of the Chapel Royal, Dublin Castle
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- Boydell & Brewer
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- 10 January 2024
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- 23 May 2023, pp 93-112
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Summary
An overview of the surviving collection
Scores of service settings, anthems, chants and miscellaneous litur-gical items sung by the choir of the Chapel Royal survive in two significant sets of music, held at the Representative Church Body Library, Dublin: thirty-two volumes (the ‘loft books’ and ‘score books’), mostly manuscript, which were transferred from St Patrick's Cathedral in 2014; and a further thirty-two volumes (‘Services’, ‘Anthems’, and ‘Services and Anthems’), all bound printed editions, transferred from Trinity College chapel in 2021.
These volumes together account for around two thirds of the music removed from the Chapel following the cessation of services there at the end of 1922. This music was listed in an inventory prepared in early 1923 by the last Chapel organist, William Edmond Hopkins. All of this collection was transferred in May 1926 to St Patrick's Cathedral on the request of Hugh Jackson Lawlor, Dean of St Patrick's and former Sub-Dean of the Chapel Royal. The exact circumstances of this transfer will be discussed below.
The inventory of the Chapel music collection prepared by Hopkins in 1923, later amended and typed up by the government officials who handed this material over to Lawlor in 1926, is reproduced in Table 1.3 Of these volumes, items 1, 4, 5 and 6 of the choir volumes are extant in the RCB Library, as are all of the organ volumes, and a single copy of T. H. Weaving's Communion Service. All the remaining material is lost.
What the cases of parts for ‘Cathedral Anthems’ might have contained is difficult to determine, since it is uncertain if ‘Cathedral Anthems’ was the name of a publication or merely a generic term for individual printed copies of music. It is possible that it may have been Vincent Novello's 1849 edition of William Boyce's Cathedral Music, which is a late example of a collection published with separate scores for individual vocal parts. The term ‘Cathedral Anthems’ may have been used by Hopkins in his inventory as an unconscious reference to the anthem word-book of the same name, which was also used in the Chapel.
Since none of the ‘Old Anthem’ books survive, it is difficult to determine what these volumes may have contained. There is, however, a clue in an annotation made by Hopkins to his inventory regarding these books:
Many in need of repair.
1 - Precedents, Polity and Politics
- David Michael O’Shea
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- Book:
- The Choral Foundation of the Chapel Royal, Dublin Castle
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- Boydell & Brewer
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- 10 January 2024
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- 23 May 2023, pp 14-37
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Summary
Chapels royal
Though the history of Anglican choral composition and practice is often described as the ‘English cathedral tradition’, the cradle of the choral service of the reformed English church was not the cathedrals but the household chapel of Henry VIII and his children, Edward VI and Elizabeth I. The English Chapel Royal originated in the thirteenth and fourteenth centuries, when monarchs began to appoint singing clerks to travel as part of their entourage to perform private liturgies. This ‘Chapel’ was a peripatetic corporation of clergy and musicians rather than a church building, although the chapels of royal palaces – the physical spaces in which the liturgies were performed by the Chapel Royal – were frequently called ‘chapels royal’. As we shall see, this distinction between the corporation and the place became blurred in later centuries.
The earliest example of a formal Chapel Royal of singing men superintended by an officer called Dean can be traced to the reign of Edward II, around the year 1312. Following the Black Death, the abbey churches which had hitherto been the centres of polyphonic composition were severely weakened, and so the Chapel Royal under Henry IV and his successors became the leading force in the development of new styles of liturgical music. The English Reformation of the mid-sixteenth century placed the Chapel Royal at the centre of liturgical and musical innovation: following the Act of Supremacy of 1534, which declared Henry VIII to be ‘Supreme Head of the Church of England’, Henry's Chapel Royal became a paragon of liturgical practice and ‘the exemplar of divine service to the whole kingdom’.
In spite of growing agitation for reform and vernacularization of the liturgy, Henry VIII maintained the Latin liturgies of the ancient English church in his Chapel Royal, with the sole and noteworthy exception of the English Litany introduced in 1544. After Henry's death, the influence of liturgical reform that had been stifled during his reign took hold quickly, and a service of compline was sung entirely in English by the Chapel Royal shortly after the coronation of Edward VI in February 1547.
10 - Organists and Composers
- David Michael O’Shea
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- Book:
- The Choral Foundation of the Chapel Royal, Dublin Castle
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- Boydell & Brewer
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- 10 January 2024
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- 23 May 2023, pp 193-212
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Summary
The ‘Organist and Master’
As we have seen, the annual estimates of the household of the Lord Lieutenant made provision for a salary for an ‘Organist and Master’, two roles which were usually undertaken by one person, but in at least one period were held by two different people. Between 1814 and 1922, nine different men held the position of organist of the Chapel. Some of these organists made notable contributions to the raising of musical standards in the Chapel through their stewardship of the choir and composition of new repertoire.
The ‘Propos’d Establishment’ of 1814 included the names of two organists: Sir John Stevenson, ‘Organist & Composer’, and James Duncan, ‘Organist’. This was an imitation of the ‘two Organists, and two Composers’ of the Chapel Royal, St James's Palace, as described by its Sub-Dean, William Holmes. Whilst, as we shall see, it appears that Stevenson undertook some duties as composer, there is no evidence that he ever played the organ in the Chapel or had any involvement in the running of the choir there. Several sources (including his memorial at Christ Church Cathedral) claim that he was the first organist of the Chapel, although it would seem that this distinction correctly belongs to Duncan, who was actually responsible for training the choir and playing the organ.
Duncan is first mentioned as organist in a Board of Works letter of April 1814, which shows that he was appointed prior to the opening of the Chapel. After the completion of the Chapel organ, Duncan played it in public for the first time on Sunday 6th August 1815. Though Duncan's son wrote to the Lord Lieutenant in February 1825 suggesting that his father would retire imminently, in 1827 Duncan placed an advertisement in the press denying a ‘frequently reported’ rumour that he had retired. He was still organist of the Chapel in September 1831, which suggests that he held the post right up until his death on 14th October 1831. His death notice stated that he had been ‘for 16 years Organist to the Castle Chapel’: this figure seems to have counted only from the time the organ was installed in 1815 (even though he had been appointed in 1814).
Acknowledgements
- David Michael O’Shea
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- Book:
- The Choral Foundation of the Chapel Royal, Dublin Castle
- Published by:
- Boydell & Brewer
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- 10 January 2024
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- 23 May 2023, pp xiii-xiii
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8 - Boy Choristers
- David Michael O’Shea
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- The Choral Foundation of the Chapel Royal, Dublin Castle
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- Boydell & Brewer
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- 10 January 2024
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- 23 May 2023, pp 164-174
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Summary
Numbers and hierarchies among boy choristers
As we have seen, the 1814 ‘Propos’d Establishment of the Castle Chapel’ recommended that the new choir have six boy choristers. The only information available on the boys in this period is contained in a letter of September 1817 from organist James Duncan in response to a query from the Under-Secretary as to why he ‘discontinued’ one of the boys, David Hastings, in the choir:
I was obliged to discontinue David Hastings from the Choir of the Castle Chapel, in consequence of the natural failure of his voice, and that from the same necessity which must exist in every boy who has passed the age of 15 years, Richard Gaudry, and John, and Charles Egan, were also discontinued.
No other substantial evidence concerning the boy choristers appears to survive until the 1830s. An ‘Allowance […] for six Singing Boys’ for the Castle Chapel appears in the parliamentary estimates for 1831, and it is possible that this allowance was in place as early as 1816. An account of annual expenses at the Chapel from May 1822 includes figures for the washing of three men's and six boys’ surplices, and since there were only three men in the choir in this period, the Sub-Dean's request in January 1823 for nine new choir surplices would seem to confirm there were six boys. Given, however, that not all the old surplices may have been replaced at this time, and that at least one of the new ones may have been a spare, these figures must be treated with caution.
No names of boys survive between Duncan's letter and a list of four ‘Boys of the Chapel Royal, 1837’ in one of the choir loft books. Only three of these names are legible: Henry A. Walker, Thomas Jackson and a second Jackson (perhaps with the first initial ‘P.’). The Musical World account that appeared the following year stated there were six boys in the choir, and the account of 1845 in the same publication claimed there were ‘four boy singers, who are paid’ and ‘a few supernumerary boys (who wait for the first vacancy amongst the paid boys)’. Presumably, therefore, the four names in the 1837 list were those of the four paid boys at that time, and excluded the two or more unpaid supernumeraries. A further such list that appears to date from 1850 also included four boys.
Abbreviations
- David Michael O’Shea
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- Book:
- The Choral Foundation of the Chapel Royal, Dublin Castle
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- Boydell & Brewer
- Published online:
- 10 January 2024
- Print publication:
- 23 May 2023, pp xvii-xviii
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