CNTRICS Imaging Biomarkers Selection: Working Memory

Moore, Holly; Nee, Derek Evan; Manoach, Dara S.; Sj, Luck

doi:10.1093/schbul/sbr160

Cited by 73 publications

(50 citation statements)

References 47 publications

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“…Positive controls built into the experiment confirm that the absence of significant drug effects in the BOLD analysis cannot be comfortably attributed to inadequate image quality or limited data: these same scans were quite adequate to detect significant cognitive (2-back task) effects in a pattern consistent with previous functional imaging studies on working memory (Barch et al, 2012;Bledowski et al, 2010). BOLD is generally more sensitive than ASL for comparisons like this one that can be made over very brief time intervals (a minute or so) (Wang et al, 2003a).…”

Section: Discussionsupporting

confidence: 70%

Arterial spin labeling versus BOLD in pharmacological fMRI

Stewart

Koller

Campbell

et al. 2014

Preprint

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A carefully controlled study allowed us to compare the sensitivity of ASL (arterial spin labeling) and BOLD (blood oxygen level dependent) fMRI for detecting the effects of the adenosine A2a antagonist tozadenant in Parkinson disease . Only ASL detected the direct effect of tozadenant. BOLD was more sensitive to a cognitive task, which (unlike most drugs) allows on-off comparisons over short periods of time. Neither ASL nor BOLD could detect a cognitive-pharmacological interaction. These results are consistent with the known relative advantages of each fMRI method, and suggest that for drug development, directly imaging pharmacodynamic effects with ASL may have advantages over cognitive-pharmacological interaction BOLD, which has hitherto been the more common approach to pharmacological was more sensitive to a cognitive task, which (unlike most drugs) allows onoff comparisons over short periods of time. Neither ASL nor BOLD could detect a cognitive-pharmacological interaction. These results are consistent with the known relative advantages of each fMRI method, and suggest that for drug development, directly imaging pharmacodynamic effects with ASL may have advantages over cognitive-pharmacological interaction BOLD, which has hitherto been the more common approach to pharmacological fMRI.

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Section: Discussionsupporting

confidence: 70%

Arterial spin labeling versus BOLD in pharmacological fMRI

Stewart

Koller

Campbell

et al. 2014

Preprint

View full text Add to dashboard Cite

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“…Cross-species tasks have been devised with increasing recognition for the need of biomarkers that relate to specific cognitive domains. [98][99][100] Each task described above can be conducted in both humans and rodents because the tasks developed for humans do not involve verbal responses or rating scales. Instead, human subjects are required to emit responses upon presentation of discrete stimuli, providing performance-based quantified data.…”

Section: Resultsmentioning

confidence: 99%

Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia

Young

Markou

2015

SCHBUL

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Amotivation and reward-processing deficits have long been described in patients with schizophrenia and considered large contributors to patients' inability to integrate well in society. No effective treatments exist for these symptoms, partly because the neuromechanisms mediating such symptoms are poorly understood. Here, we propose a translational neuroscientific approach that can be used to assess reward/motivational deficits related to the negative symptoms of schizophrenia using behavioral paradigms that can also be conducted in experimental animals. By designing and using objective laboratory behavioral tools that are parallel in their parameters in rodents and humans, the neuromechanisms underlying behaviors with relevance to these symptoms of schizophrenia can be investigated. We describe tasks that measure the motivation of rodents to expend physical and cognitive effort to gain rewards, as well as probabilistic learning tasks that assess both reward learning and feedback-based decision making. The latter tasks are relevant because of demonstrated links of performance deficits correlating with negative symptoms in patients with schizophrenia. These tasks utilize operant techniques in order to investigate neural circuits targeting a specific domain across species. These tasks therefore enable the development of insights into altered mechanisms leading to negative symptom-relevant behaviors in patients with schizophrenia. Such findings will then enable the development of targeted treatments for these altered neuromechanisms and behaviors seen in schizophrenia.

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“…Future research could be made more powerful, reproducible and resource-efficient by the use of larger datasets and standardized paradigms and methods across centers. Recommendations of research practices and clinically relevant paradigms have been made by expert groups (122)(123)(124), and the last few years have seen a number of high-powered imaging genetics studies with hundreds or even thousands of subjects (30, 38, 62, 73,80,119,120,125,126). Much of the problem of small sample sizes can be attributed to the expense of acquiring imaging data, which limits the number of subjects that individual groups can afford to use.…”

Section: Discussionmentioning

confidence: 99%