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15 Exploratory Factor Analysis of Cognitive and Positive Valence Measures for the RDoC
- Emily T Sturm, John R Duffy, Anastasia G Sares, Andrea Mendez-Colmenares, Lauren Sarabia, Eve Delao, Max Henneke, Raana Manavi, Donald C Rojas, Jason R Tregellas, Jared W Young, Michael L Thomas
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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. 698-699
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Objective:
As part of the Research Domain Criteria (RDoC) initiative, the NIMH seeks to improve experimental measures of cognitive and positive valence systems for use in intervention research. However, many RDoC tasks have not been psychometrically evaluated as a battery of measures. Our aim was to examine the factor structure of 7 such tasks chosen for their relevance to schizophrenia and other forms of serious mental illness. These include the n-back, Sternberg, and self-ordered pointing tasks (measures of the RDoC cognitive systems working memory construct); flanker and continuous performance tasks (measures of the RDoC cognitive systems cognitive control construct); and probabilistic learning and effort expenditure for reward tasks (measures of reward learning and reward valuation constructs).
Participants and Methods:The sample comprised 286 cognitively healthy participants who completed novel versions of all 7 tasks via an online recruitment platform, Prolific, in the summer of 2022. The mean age of participants was 38.6 years (SD = 14.5, range 18-74), 52% identified as female, and stratified recruitment ensured an ethnoracially diverse sample. Excluding time for instructions and practice, each task lasted approximately 6 minutes. Task order was randomized. We estimated optimal scores from each task including signal detection d-prime measures for the n-back, Sternberg, and continuous performance task, mean accuracy for the flanker task, win-stay to win-shift ratio for the probabilistic learning task, and trials completed for the effort expenditure for reward task. We used parallel analysis and a scree plot to determine the number of latent factors measured by the 7 task scores. Exploratory factor analysis with oblimin (oblique) rotation was used to examine the factor loading matrix.
Results:The scree plot and parallel analyses of the 7 task scores suggested three primary factors. The flanker and continuous performance task both strongly loaded onto the first factor, suggesting that these measures are strong indicators of cognitive control. The n-back, Sternberg, and self-ordered pointing tasks strongly loaded onto the second factor, suggesting that these measures are strong indicators of working memory. The probabilistic learning task solely loaded onto the third factor, suggesting that it is an independent indicator of reinforcement learning. Finally, the effort expenditure for reward task modestly loaded onto the second but not the first and third factors, suggesting that effort is most strongly related to working memory.
Conclusions:Our aim was to examine the factor structure of 7 RDoC tasks. Results support the RDoC suggestion of independent cognitive control, working memory, and reinforcement learning. However, effort is a factorially complex construct that is not uniquely or even most strongly related to positive valance. Thus, there is reason to believe that the use of at least 6 of these tasks are appropriate measures of constructs such as working memory, reinforcement learning and cognitive control.
27 Clinical Symptoms, Cognitive Functioning, and Brain Health in Agricultural Workers
- Jazmin M. Diaz, Stephen R. Kellam, Emily T. Sturm, Max Henneke, Emily Pehlke, John R. Duffy, Andrea Mendez-Colmenares, Agnieszka Z. Burzynska, Lorann Stallones, Michael L. Thomas
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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. 903
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Objective:
Agricultural workers are immersed in environments associated with increased risk for adverse psychiatric and neurological outcomes. Agricultural work-related risks to brain health include exposure to pesticides, heavy metals, and organic dust. Despite this, there is a gap in our understanding of the underlying brain systems impacted by these risks. This study explores clinical and cognitive domains, and functional brain activity in agricultural workers. We hypothesized that a history of agricultural work-related risks would be associated with poorer clinical and cognitive outcomes as well as changes in functional brain activity within cortico-striatal regions.
Participants and Methods:The sample comprised 17 agricultural workers and a comparison group of 45 non-agricultural workers recruited in the Northern Colorado area. All participants identified as White and non-Hispanic. The mean age of participants was 51.7 years (SD = 21.4, range 18-77), 60% identified as female, and 37% identified as male. Participants completed the National Institute of Health Toolbox (NIH Toolbox) and Montreal Cognitive Assessment (MoCA) on their first visit. During the second visit, they completed NIH Patient-Reported Outcomes Measurement Information System (PROMIS) measures and underwent functional magnetic resonance imaging (fMRI; N = 15 agriculture and N = 35 non-agriculture) while completing a working memory task (Sternberg). Blood oxygen-level dependent (BOLD) response was compared between participants. Given the small sample size, the whole brain voxel-wise group comparison threshold was set at alpha = .05, but not otherwise corrected for multiple comparisons. Cohen’s d effect sizes were estimated for all voxels.
Results:Analyses of cognitive scores showed significant deficits in episodic memory for the agricultural work group. Additionally, the agricultural work group scored higher on measures of self-reported anger, cognitive concerns, and social participation. Analyses of fMRI data showed increased BOLD activity around the orbitofrontal cortex (medium to large effects) and bilaterally in the entorhinal cortex (large effects) for the agricultural work group. The agricultural work group also showed decreased BOLD activity in the cerebellum and basal ganglia (medium to large effects).
Conclusions:To our knowledge, this study provides the first-ever evidence showing differences in brain activity associated with a history of working in agriculture. These findings of poorer memory, concerns about cognitive functioning, and increased anger suggest clinical relevance. Social participation associated with agricultural work should be explored as a potential protective factor for cognition and brain health. Brain imaging data analyses showed increased activation in areas associated with motor functioning, cognitive control, and emotion. These findings are limited by small sample size, lack of diversity in our sample, and coarsely defined risk. Despite these limitations, the results are consistent with an overall concern that risks associated with agricultural work can lead to cognitive and psychiatric harm via changes in brain health. Replications and future studies with larger sample sizes, more diverse participants, and more accurately defined risks (e.g., pesticide exposure) are needed.
70 Comparison of MCCB Autocorrelations Between Schizophrenia and Healthy Comparison Populations
- Max Henneke, Emily T. Sturm, John R. Duffy, Anastasia Sares, Andrea Mendez-Colmenares, Lauren Sarabia, Eve Delao, Tessa Mitchell, Raana Manavi, Michael L. Thomas
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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. 854-855
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Objective:
Deficits in cognitive ability are common among patients with schizophrenia. The MATRICS Consensus Cognitive Battery (MCCB) was designed to assess cognitive ability in studies of patients diagnosed with schizophrenia and has demonstrated high test-retest reliability with minimal practice effects, even in multi-site trials. However, given the motivational challenges associated with schizophrenia, it is unknown whether performance on MCCB tasks affects performance at later stages of testing. The goal of this study was to determine whether there are differences between people with and without schizophrenia in how their performance on individual MCCB tasks influences their performance throughout the battery.
Participants and Methods:The sample comprised 92 total participants including 49 cognitively healthy comparison participants and 43 outpatients diagnosed with schizophrenia. The mean age of participants was 44.2 years (SD = 12.0, range 21–69) and 61% identified as male. The Trail Making Test, Brief Assessment of Cognition in Schizophrenia, Hopkins Verbal Learning Test – Revised, Letter-Number Span, and Category Fluency from the MCCB were administered in the same order at 2 different sites and studies from 2016–2022. The autocorrelation between t-scores for task scores within each participant was computed and then compared between control and outpatient participants to determine if there are differences between groups. Group mean t-scores for each task were also compared between groups.
Results:We found no significant difference in autocorrelations across MCCB tasks between healthy comparison participants and outpatients. However, mean performance in all tasks was lower for the outpatient group than for the healthy comparison group. None of the tasks used stood out as having significantly lower mean scores than other tasks for either group.
Conclusions:Our findings suggest that performance on individual MCCB tasks do not affect performance throughout the battery differently between the healthy comparison group and outpatients. This suggests that participants with schizophrenia are not particularly reactive to past performance on MCCB tasks. Additionally, this finding further supports use of the MCCB in this population. Further research is needed to determine whether subgroups of patients and/or different batteries of measures show different patterns of reactivity.
45698 Molecular Signatures of Cocaine Neurotoxicity in Human Brain Models
- Emily Mendez, Laura Stertz, Gabriel Fries, Ruifeng Hu, Thomas Meyer, Zhongming Zhao, Consuelo Walss-Bass
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- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue s1 / March 2021
- Published online by Cambridge University Press:
- 30 March 2021, p. 115
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ABSTRACT IMPACT: This project will use human neuron models and bioinformatics techniques to elucidate mechanisms of cocaine neurotoxicity, which will allow treatments to be developed for minimizing or preventing neurological damage caused by cocaine abuse and overdose. OBJECTIVES/GOALS: The goals of this project are to identify genes and gene networks altered by cocaine exposure in neurons (short term), and to use these pathways to understand mechanisms of cocaine neurotoxicity for the establishment of therapeutic targets (long term). METHODS/STUDY POPULATION: To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine overdose subjects and 17 controls. Future directions for this project include RNAseq analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF FINDINGS: Transcriptomic signatures found with this analysis can help us understand mechanisms of cocaine neurotoxicity in human neurons. With this work and future proposed studies, we can discover targetable molecular pathways to develop drugs that can reduce or reverse cocaine-related impairment.
4141 Molecular Signatures of Cocaine Toxicity in Postmortem Human Brain and Neurons
- Emily Frances Mendez, Laura Stertz, Gabriel Fries, Ruifeng Hu, Thomas Meyer, Zhongming Zhao, Consuelo Walss-Bass
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, p. 140
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OBJECTIVES/GOALS: The goal of this project is to identify new therapeutic targets and biomarkers to treat or prevent cocaine toxicity by investigating proteomic, transcriptomic and epigenetic signatures of cocaine exposure in human subjects. METHODS/STUDY POPULATION: Cocaine is a highly addictive neurotoxic substance, and it is estimated that 1.9 million Americans are current users of cocaine. To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem dorsolateral prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine-exposed subjects and 17 controls. Future directions for this project include RNAseq and DNA methylation analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF IMPACT: Neuronal signatures found with this analysis can help us understand mechanisms of cognitive decline in long-term cocaine users as well as the acute effects on the brain of cocaine taken in overdose. With this work and future proposed studies, we can discover novel clinical biomarkers for cocaine neurotoxicity in patients with cocaine use disorder and determine readouts for future therapeutic development on cocaine addiction and overdose.
Vitamin D status among indigenous Mayan (Kekchi) and Afro-Caribe (Garifuna) adolescents from Guatemala: a comparative description between two ethnic groups residing on the Rio Dulce at the Caribbean coast in Izabal Province, Guatemala
- Ali Naqvi, Noel W Solomons, Raquel Campos, María José Soto-Méndez, Emily Caplan, Laura Armas, Odilia I Bermudez
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- Journal:
- Public Health Nutrition / Volume 20 / Issue 10 / July 2017
- Published online by Cambridge University Press:
- 31 March 2016, pp. 1729-1737
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Objective
To assess vitamin D status and the influence of risk factors such as skin pigmentation and time spent outdoors on hypovitaminosis D among Guatemalan Kekchi and Garifuna adolescents.
DesignCross-sectional study, with convenient sampling design. Blood samples, anthropometric and behavioural data were all collected during the dry season. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by RIA.
SettingCommunities of Rio Dulce and Livingston, Izabal Province, Caribbean coast of Guatemala, with latitude and longitude of 15°49′N and 88°45′W for Livingston and 15°46′N and 88°49′W for Rio Dulce, respectively.
SubjectsEighty-six adolescents, divided evenly by sex and ethnicity, with mean age of 14 years.
ResultsMean (sd) 25(OH)D value was 27·8 (7·2) ng/ml for the total group, with 25·8 (5·9) and 29·8 (7·9) ng/ml, respectively, in Kekchis and Garifunas (P=0·01). Use of vitamin D supplementation, clothing practices and sun protection were not statistically different between groups. Skin area exposed on the day of data collection ranged from 20·0 % minimum to 49·4 % maximum, with mean (sd) exposure of 32·0 (8.5) %. With univariate regression analysis, age (P=0·034), sex (P=0·044), ethnicity (P=0·010), time spent outdoors (P=0·006) and percentage skin area exposed (P=0·001) were predictive. However, multivariate analysis indicated that only sex (P=0·034) and percentage skin area exposed (P=0·044) remained as predictors of 25(OH)D.
ConclusionsDespite residing in an optimal geographic location for sunlight exposure, nearly 65 % of study adolescents were either insufficient or deficient in vitamin D. Correction and long-term prevention of this nutritional problem may be instrumental in avoiding adverse effects in adulthood attributed to low 25(OH)D during adolescence.