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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.
17 Norming for the reverse-translated 5-choice continuous performance test (5C-CPT) of attention and cognitive control
- Michael Noback, Donald R Franklin, Anya Umlauf, Arpi Minassian, Robert Heaton, Jared W Young
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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. 808-809
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Objective:
Translatability of preclinical results remains a major obstacle in neuropsychiatric research. Even when cognitive tests in preclinical models show translational validity for human testing, with sensitivity to clinical deficits, there remains the issue of heterogeneity among human participants. Norming of performance on cognitive tasks enable corrections for any differences in performance that may arise from the influence of socioeconomic factors, and thus a more direct comparison with preclinical testing results. The 5-choice continuous performance task (5C-CPT) is a test sensitive to changes in sustained attention and cognitive control in rodent manipulations and clinical populations, including schizophrenia and bipolar disorder. Herein, we present normed results of 5C-CPT data from a cohort of human participants, enabling greater comparison to future clinical and rodent testing.
Participants and Methods:5C-CPT data were generated from a range of participants from the Translational Methamphetamine AIDS Research Center (n=82) and a study of bipolar disorder (n=45). Participant demographics were as follows: Age M=38.5, SD=16.7, Education: M=14.5, SD=1.9, 45% female, 10% Asian, 17% African American, 27% Hispanic, and 46% non-Hispanic White. We used the test2norm R-package to create norms for each of the major outcomes from the 5C-CPT. Non-normally distributed raw scores were transformed to generate more normally distributed data needed for the norming process. Raw scores were first converted into uniform scaled scores that range from 0-20 where a higher score indicated better performance. We then generated T-score formulas, which are standardized residuals and scaled to have a mean of 50 and standard deviation of 10. The residuals are obtained from regressions, modeled using multiple fractional polynomial method (MFP), which regresses scaled scores on demographic variables, which a user wishes to control for (gender, age, education, ethnicity, etc.). MFP models allow to fit non-linear effects for numeric demographic factors (e.g., age), if such effects exist.
Results:New, demographically corrected T-score formulas were calculated for each major outcome of the 5C-CPT: reaction time (MCL), reaction time variability (VarRT), dprime, hit rate (HR) and false-alarm rate (FAR). MFP models showed that age had a significant effect on MCL, VarRT, dprime, and HR (all p<0.01), while gender only showed a significant effect for MCL and VarRT (all p<0.05). Interestingly, education and ethnicity did not show a significant effect for any MFP model and none of the demographic factors (age, education, gender, ethnicity) were significant in the model for FAR. As defined in the test2norm package, all scaled scores had a mean of 10 and SD of 3 and all T-scores had a mean of 50 and SD of 10.
Conclusions:The 5C-CPT is a test of attention and cognitive control available for human testing, reverse-translated from rodent studies. The normative data generated here will enable future comparisons of data without the need for additional control studies. Furthermore, comparing these normative data to manipulations will enable further comparisons to rodent testing, with manipulations relative to baseline becoming more meaningful. Thus, the 5C-CPT is a viable tool for conducting cross-species translational research toward developing novel therapeutics that treat dysfunctional attentional and cognitive control.
63 Sex-Dependent Effects in Dopaminergic Modulation of Risky Decision-Making in Rats
- Samantha M. Ayoub, Avraham M. Libster, Stephanie Dulawa, Jared W. Young
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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. 848-849
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Objective:
Determining neurobiological mechanisms underlying risk-taking behavior is paramount toward developing targeted therapeutics for psychiatric conditions with such behavioral deficits. Therapies are urgently needed given risk-taking is strongly linked to suicidal behavior. Risk-taking is often assessed in tasks of varied rewards and losses, complicating the interpretation of chasing rewards vs. avoiding punishments. A novel task in rats was designed which utilizes varying rewards only, so as to determine mechanisms contributing to ‘chasing’ higher rewards. This task was used to determine that the high reward (risk) preference of male rats was increased by pramipexole treatment [a dopamine D2 receptor-(D2R) family agonist] and decreased by optogenetic inhibition of D2R expressing neurons. The impact of D2R antagonists and sex-dependent differences were not examined however and remains unclear. Here, we trained female and male rats in the task to determine sex-differences in risk preference at baseline and in response to pharmacological challenges of pramipexole, the D2R antagonist sulpiride, and the dopamine transporter inhibitor GBR-12909.
Participants and Methods:In operant boxes animals could choose from one of two nose-pokes, one that delivered a 50 μl strawberry milkshake reward (safe-option), and the other a 10 μl reward with 75% probability and 170 μl reward with 25% probability (risky-option). Once trained to a stable baseline of risk preference, rats were treated with pramipexole (0.15- or 0.3-mg/kg; Experiment 1) or sulpiride (30-mg/kg; Experiment 2) for 3 days, each separated by a saline washout. Animals were once again trained to a stable baseline, then injected with GBR-12909 (5- or 16-mg/kg; Experiment 3).
Results:Baseline: females were less risk-adverse/more risk-prone than males. Experiment 1: there was a main effect of drug on percent risk choice (%RC) change from baseline [F(1,18)=10.5, p<0.01], with pramipexole increasing %RC. When analyzed across each testing day, a main effect of session [F(6,108)=3.6, p<0.005] was observed, as was a session*sex*drug interaction [F(6,108)=2.2, p<0.05]. Post hoc analyses revealed females differed from males in the timing of their response to pramipexole based on dose. Experiment 2: there was a main effect of drug on %RC change from baseline [F(1,6)=20, p<0.01], with sulpiride decreasing %RC. There was also evidence for a drug*sex interaction [F(1,6)=3.6, p=0.11], with more pronounced attenuation by sulpiride in females. A similar pattern was observed when analyzed across testing days. Experiment 3: there was a main effect of drug on %RC change from baseline [F(2,26)=4.0, p<0.05], with the high dose of GBR-12909 (16-mg/kg) increasing %RC compared to VEH (p<0.05) and low dose (5-mg/kg).
Conclusions:Together these data indicate a sex-specific modulation of baseline risk preferences as measured explicitly via reward seeking behaviors. Additionally, female rats may be more sensitive to D2R manipulations on such risky decision-making behavior, highlighting the necessity of tracking sex-based differences in such tasks. Ongoing studies will determine whether D2R activity reveal a similar sex-specific change during such reward-seeking risk-preference. Furthermore, ongoing studies will determine the link of such behavior to effortful decision making and more traditional measures of risk-taking behavior, such as the Iowa Gambling Task used both in rodents and humans.
Amphetamine Modestly Improves Conners’ Continuous Performance Test Performance in Healthy Adults
- David A. MacQueen, Arpi Minassian, Brook L. Henry, Mark A. Geyer, Jared W. Young, William Perry
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- Journal:
- Journal of the International Neuropsychological Society / Volume 24 / Issue 3 / March 2018
- Published online by Cambridge University Press:
- 16 October 2017, pp. 283-293
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Objectives: Amphetamine improves vigilance as assessed by continuous performance tests (CPT) in children and adults with attention deficit hyperactivity disorder (ADHD). Less is known, however, regarding amphetamine effects on vigilance in healthy adults. Thus, it remains unclear whether amphetamine produces general enhancement of vigilance or if these effects are constrained to the remediation of deficits in patients with ADHD. Methods: We tested 69 healthy adults (35 female) on a standardized CPT (Conner’s CPT-2) after receiving 10- or 20-mg d-amphetamine or placebo. To evaluate potential effects on learning, impulsivity, and perseveration, participants were additionally tested on the Iowa Gambling Task (IGT) and Wisconsin Card Sorting Task (WCST). Results: Participants receiving placebo exhibited the classic vigilance decrement, demonstrated by a significant reduction in attention (D’) across the task. This vigilance decrement was not observed, however, after either dose of amphetamine. Consistent with enhanced vigilance, the 20-mg dose also reduced reaction time variability across the task and the ADHD confidence index. The effects of amphetamine appeared to be selective to vigilance since no effects were observed on the IGT, WCST, or response inhibition/perseveration measures from the CPT. Conclusions: The present data support the premise that amphetamine improves vigilance irrespective of disease state. Given that amphetamine is a norepinephrine/dopamine transporter inhibitor and releaser, these effects are informative regarding the neurobiological substrates of attentional control. (JINS, 2018, 24, 283–293)
Contributor affiliations
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- By Frank Andrasik, Melissa R. Andrews, Ana Inés Ansaldo, Evangelos G. Antzoulatos, Lianhua Bai, Ellen Barrett, Linamara Battistella, Nicolas Bayle, Michael S. Beattie, Peter J. Beek, Serafin Beer, Heinrich Binder, Claire Bindschaedler, Sarah Blanton, Tasia Bobish, Michael L. Boninger, Joseph F. Bonner, Chadwick B. Boulay, Vanessa S. Boyce, Anna-Katharine Brem, Jacqueline C. Bresnahan, Floor E. Buma, Mary Bartlett Bunge, John H. Byrne, Jeffrey R. Capadona, Stefano F. Cappa, Diana D. Cardenas, Leeanne M. Carey, S. Thomas Carmichael, Glauco A. P. Caurin, Pablo Celnik, Kimberly M. Christian, Stephanie Clarke, Leonardo G. Cohen, Adriana B. Conforto, Rory A. Cooper, Rosemarie Cooper, Steven C. Cramer, Armin Curt, Mark D’Esposito, Matthew B. Dalva, Gavriel David, Brandon Delia, Wenbin Deng, Volker Dietz, Bruce H. Dobkin, Marco Domeniconi, Edith Durand, Tracey Vause Earland, Georg Ebersbach, Jonathan J. Evans, James W. Fawcett, Uri Feintuch, Toby A. Ferguson, Marie T. Filbin, Diasinou Fioravante, Itzhak Fischer, Agnes Floel, Herta Flor, Karim Fouad, Richard S. J. Frackowiak, Peter H. Gorman, Thomas W. Gould, Jean-Michel Gracies, Amparo Gutierrez, Kurt Haas, C.D. Hall, Hans-Peter Hartung, Zhigang He, Jordan Hecker, Susan J. Herdman, Seth Herman, Leigh R. Hochberg, Ahmet Höke, Fay B. Horak, Jared C. Horvath, Richard L. Huganir, Friedhelm C. Hummel, Beata Jarosiewicz, Frances E. Jensen, Michael Jöbges, Larry M. Jordan, Jon H. Kaas, Andres M. Kanner, Noomi Katz, Matthew S. Kayser, Annmarie Kelleher, Gerd Kempermann, Timothy E. Kennedy, Jürg Kesselring, Fary Khan, Rachel Kizony, Jeffery D. Kocsis, Boudewijn J. Kollen, Hubertus Köller, John W. Krakauer, Hermano I. Krebs, Gert Kwakkel, Bradley Lang, Catherine E. Lang, Helmar C. Lehmann, Angelo C. Lepore, Glenn S. Le Prell, Mindy F. Levin, Joel M. Levine, David A. Low, Marilyn MacKay-Lyons, Jeffrey D. Macklis, Margaret Mak, Francine Malouin, William C. Mann, Paul D. Marasco, Christopher J. Mathias, Laura McClure, Jan Mehrholz, Lorne M. Mendell, Robert H. Miller, Carol Milligan, Beth Mineo, Simon W. Moore, Jennifer Morgan, Charbel E-H. Moussa, Martin Munz, Randolph J. Nudo, Joseph J. Pancrazio, Theresa Pape, Alvaro Pascual-Leone, Kristin M. Pearson-Fuhrhop, P. Hunter Peckham, Tamara L. Pelleshi, Catherine Verrier Piersol, Thomas Platz, Marcus Pohl, Dejan B. Popović, Andrew M. Poulos, Maulik Purohit, Hui-Xin Qi, Debbie Rand, Mahendra S. Rao, Josef P. Rauschecker, Aimee Reiss, Carol L. Richards, Keith M. Robinson, Melvyn Roerdink, John C. Rosenbek, Serge Rossignol, Edward S. Ruthazer, Arash Sahraie, Krishnankutty Sathian, Marc H. Schieber, Brian J. Schmidt, Michael E. Selzer, Mijail D. Serruya, Himanshu Sharma, Michael Shifman, Jerry Silver, Thomas Sinkjær, George M. Smith, Young-Jin Son, Tim Spencer, John D. Steeves, Oswald Steward, Sheela Stuart, Austin J. Sumner, Chin Lik Tan, Robert W. Teasell, Gareth Thomas, Aiko K. Thompson, Richard F. Thompson, Wesley J. Thompson, Erika Timar, Ceri T. Trevethan, Christopher Trimby, Gary R. Turner, Mark H. Tuszynski, Erna A. van Niekerk, Ricardo Viana, Difei Wang, Anthony B. Ward, Nick S. Ward, Stephen G. Waxman, Patrice L. Weiss, Jörg Wissel, Steven L. Wolf, Jonathan R. Wolpaw, Sharon Wood-Dauphinee, Ross D. Zafonte, Binhai Zheng, Richard D. Zorowitz
- Edited by Michael Selzer, Stephanie Clarke, Leonardo Cohen, Gert Kwakkel, Robert Miller, Case Western Reserve University, Ohio
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- Book:
- Textbook of Neural Repair and Rehabilitation
- Published online:
- 05 May 2014
- Print publication:
- 24 April 2014, pp ix-xvi
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Contributor affiliations
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- By Frank Andrasik, Melissa R. Andrews, Ana Inés Ansaldo, Evangelos G. Antzoulatos, Lianhua Bai, Ellen Barrett, Linamara Battistella, Nicolas Bayle, Michael S. Beattie, Peter J. Beek, Serafin Beer, Heinrich Binder, Claire Bindschaedler, Sarah Blanton, Tasia Bobish, Michael L. Boninger, Joseph F. Bonner, Chadwick B. Boulay, Vanessa S. Boyce, Anna-Katharine Brem, Jacqueline C. Bresnahan, Floor E. Buma, Mary Bartlett Bunge, John H. Byrne, Jeffrey R. Capadona, Stefano F. Cappa, Diana D. Cardenas, Leeanne M. Carey, S. Thomas Carmichael, Glauco A. P. Caurin, Pablo Celnik, Kimberly M. Christian, Stephanie Clarke, Leonardo G. Cohen, Adriana B. Conforto, Rory A. Cooper, Rosemarie Cooper, Steven C. Cramer, Armin Curt, Mark D’Esposito, Matthew B. Dalva, Gavriel David, Brandon Delia, Wenbin Deng, Volker Dietz, Bruce H. Dobkin, Marco Domeniconi, Edith Durand, Tracey Vause Earland, Georg Ebersbach, Jonathan J. Evans, James W. Fawcett, Uri Feintuch, Toby A. Ferguson, Marie T. Filbin, Diasinou Fioravante, Itzhak Fischer, Agnes Floel, Herta Flor, Karim Fouad, Richard S. J. Frackowiak, Peter H. Gorman, Thomas W. Gould, Jean-Michel Gracies, Amparo Gutierrez, Kurt Haas, C.D. Hall, Hans-Peter Hartung, Zhigang He, Jordan Hecker, Susan J. Herdman, Seth Herman, Leigh R. Hochberg, Ahmet Höke, Fay B. Horak, Jared C. Horvath, Richard L. Huganir, Friedhelm C. Hummel, Beata Jarosiewicz, Frances E. Jensen, Michael Jöbges, Larry M. Jordan, Jon H. Kaas, Andres M. Kanner, Noomi Katz, Matthew S. Kayser, Annmarie Kelleher, Gerd Kempermann, Timothy E. Kennedy, Jürg Kesselring, Fary Khan, Rachel Kizony, Jeffery D. Kocsis, Boudewijn J. Kollen, Hubertus Köller, John W. Krakauer, Hermano I. Krebs, Gert Kwakkel, Bradley Lang, Catherine E. Lang, Helmar C. Lehmann, Angelo C. Lepore, Glenn S. Le Prell, Mindy F. Levin, Joel M. Levine, David A. Low, Marilyn MacKay-Lyons, Jeffrey D. Macklis, Margaret Mak, Francine Malouin, William C. Mann, Paul D. Marasco, Christopher J. Mathias, Laura McClure, Jan Mehrholz, Lorne M. Mendell, Robert H. Miller, Carol Milligan, Beth Mineo, Simon W. Moore, Jennifer Morgan, Charbel E-H. Moussa, Martin Munz, Randolph J. Nudo, Joseph J. Pancrazio, Theresa Pape, Alvaro Pascual-Leone, Kristin M. Pearson-Fuhrhop, P. Hunter Peckham, Tamara L. Pelleshi, Catherine Verrier Piersol, Thomas Platz, Marcus Pohl, Dejan B. Popović, Andrew M. Poulos, Maulik Purohit, Hui-Xin Qi, Debbie Rand, Mahendra S. Rao, Josef P. Rauschecker, Aimee Reiss, Carol L. Richards, Keith M. Robinson, Melvyn Roerdink, John C. Rosenbek, Serge Rossignol, Edward S. Ruthazer, Arash Sahraie, Krishnankutty Sathian, Marc H. Schieber, Brian J. Schmidt, Michael E. Selzer, Mijail D. Serruya, Himanshu Sharma, Michael Shifman, Jerry Silver, Thomas Sinkjær, George M. Smith, Young-Jin Son, Tim Spencer, John D. Steeves, Oswald Steward, Sheela Stuart, Austin J. Sumner, Chin Lik Tan, Robert W. Teasell, Gareth Thomas, Aiko K. Thompson, Richard F. Thompson, Wesley J. Thompson, Erika Timar, Ceri T. Trevethan, Christopher Trimby, Gary R. Turner, Mark H. Tuszynski, Erna A. van Niekerk, Ricardo Viana, Difei Wang, Anthony B. Ward, Nick S. Ward, Stephen G. Waxman, Patrice L. Weiss, Jörg Wissel, Steven L. Wolf, Jonathan R. Wolpaw, Sharon Wood-Dauphinee, Ross D. Zafonte, Binhai Zheng, Richard D. Zorowitz
- Edited by Michael E. Selzer, Stephanie Clarke, Leonardo G. Cohen, Gert Kwakkel, Robert H. Miller, Case Western Reserve University, Ohio
-
- Book:
- Textbook of Neural Repair and Rehabilitation
- Published online:
- 05 June 2014
- Print publication:
- 24 April 2014, pp ix-xvi
-
- Chapter
- Export citation