Single gene alterations have been estimated to account for nearly half of neurodevelopmental conditions (NDCs), providing a crucial opportunity for animal models to understand the underlying mechanisms, causes and potential treatments. The use of systematic reviews (SRs) can, in principle, provide a powerful means to synthesise this evidence-base; however, the reporting quality of previous SRs in preclinical animal research has been found lacking (Hunniford et al., 2021). In the current study, Wilson et al. (2023) will undertake an umbrella review – a systematic review of systematic reviews – to assess the characteristics and reporting quality of SRs that, in turn, synthesise research in genetically-modified animals to model NDCs. In particular, the authors will extract key features of reviews (including, among others, the aim and primary research questions, relevant animal model, and number of studies in the SR), in addition to quality indicators such as risk of bias and completeness of reporting. In doing so, the authors aim to enhance guidance on the conduct and reporting of systematic reviews in this area.

 

The Stage 1 manuscript was evaluated over two rounds of in-depth review. Based on detailed responses to the reviewers' comments, the recommender judged that the manuscript met the Stage 1 criteria and therefore awarded in-principle acceptance (IPA).
 
URL to the preregistered Stage 1 protocol: https://osf.io/952qk

 

Level of bias control achieved: Level 4. At least some of the data/evidence that will be used to answer the research question already exists AND is accessible in principle to the authors BUT the authors certify that they have not yet accessed any part of that data/evidence.

 
List of eligible PCI RR-friendly journals:

 

 

1. Hunniford V. T., Montroy J., Fergusson D. A., Avey M. T., Wever K. E., McCann S. K., Foster M., Fox G., Lafreniere M., Ghaly M., Mannell S., Godwinska K., Gentles A., Selim S., MacNeil J., Sikora L., Sena E. S., Page M. J., Macleod M., Moher D., & Lalu M. M. (2021). Epidemiology and reporting characteristics of preclinical systematic reviews. PLOS Biology, 19:e3001177. https://doi.org/10.1371/journal.pbio.3001177

 

2. Wilson, E., Currie, G., Macleod, M., Kind, P. & Sena, E. S. (2023). Genetically-modified animals as models of neurodevelopmental conditions: an umbrella review, in principle acceptance of Version 3 by Peer Community in Registered Reports. https://osf.io/952qk

Paid loot boxes – items bought for real-world money that offer randomised rewards – are a prevalent feature of contemporary video games (Zendle et al., 2020). Because they employ random chance to provide rewards after spending real money, loot boxes have been considered a form of gambling, raising concerns about risk of harm to children and other vulnerable users. In response, some countries have taken legal steps to regulate and even ban the use of loot boxes, with only limited success so far (Xiao, 2022). At the same time, the Entertainment Software Rating Board (ESRB) and PEGI (Pan-European Game Information) now expect games that contain loot boxes to be marked with warning labels that, in theory, will enable users (including parents) to make more informed decisions. These requirements by ESRB/PEGI are not legally binding and may be considered a form of industry self-regulation.

 

In the current study, Xiao (2023) will investigate the effectiveness of self-regulation in the use of loot box labels. Study 1 examines the consistency of warning labels by the ESRB and PEGI, with the expectation that if self-regulation works as it should then these labels should always (or nearly always) co-occur. Study 2 establishes the compliance rate for labelling among popular games that are known to contain loot boxes, with a rate of ≥95% considered to be successful. The findings should prove useful in identifying the success or failure of self-regulation as a means of ensuring industry compliance with loot box labelling.

 

The Stage 1 manuscript was evaluated over two rounds of in-depth review. Based on detailed responses to the reviewers' comments, the recommender judged that the manuscript met the Stage 1 criteria and therefore awarded in-principle acceptance (IPA).
 
URL to the preregistered Stage 1 protocol: https://osf.io/e6qbm

 

Level of bias control achieved: Level 3. At least some data/evidence that will be used to the answer the research question has been previously accessed by the authors (e.g. downloaded or otherwise received), but the authors certify that they have not yet observed ANY part of the data/evidence.
 
List of eligible PCI RR-friendly journals:

 

 

 

1. Zendle, D., Meyer, R., Cairns, P., Waters, S., & Ballou, N. (2020). The prevalence of loot boxes in mobile and desktop games. Addiction, 115(9), 1768-1772. https://doi.org/10.1111/add.14973

2. Xiao, L. Y. (2022). Breaking Ban: Belgium’s ineffective gambling law regulation of video game loot boxes. Stage 2 Registered Report, acceptance of Version 2 by Peer Community in Registered Reports. https://doi.org/10.31219/osf.io/hnd7w 

 

3. Xiao, L. Y. (2023). Beneath the label: Assessing video games’ compliance with ESRB and PEGI loot box warning label industry self-regulation, in principle acceptance of Version 3 by Peer Community in Registered Reports. https://osf.io/e6qbm

Rapid learning in response to pain is a crucial survival mechanism, relying on forming associations between cues in the environment and subsequent pain or injury. Existing evidence suggests that associations between conditioned stimuli (cues) and unconditioned aversive stimuli (such as pain) are learned faster than for appetitive stimuli that signal pain relief. In addition, when the link between a conditioned and unconditioned stimulus is broken (by unpairing them), the extinction of this learning effect is slower for aversive that appetitive stimuli, resulting in a flatter extinction slope. Understanding why extinction slopes are reduced for aversive stimuli is important for advancing theoretical models of learning, and for devising ways of increasing the slope (and thus facilitating extinction learning) could help develop more effective methods of pain relief, particularly in the treatment of chronic pain.

 

In the current programmatic submission, Busch et al. (2023) will undertake two Registered Reports to test whether a verbal instruction intervention that explicitly informs participants about contingency changes between conditioned and unconditioned stimuli facilitates extinction learning, especially for aversive (painful) stimuli, and how changes in extinction learning relate to neural biomarkers of functional connectivity. In the first Registered Report, they will initially seek to replicate previous findings including faster acquisition of aversive than appetitive conditioned stimuli as well as incomplete extinction of aversive conditioned stimuli without verbal instruction. They will then test how the instruction intervention alters extinction slopes and the completeness of extinction for appetitive and aversive stimuli, using a range of behavioral measures (expectancy and valence ratings) and physiological measures (pupillometry, skin conductance responses). To shed light on the neural correlates of these processes, in the second Registered Report the authors will use functional magnetic resonance imaging (fMRI) to ask firstly how acquisition and extinction of aversive and appetitive conditioned responses are related to resting state brain connectivity within a network that includes ventromedial prefrontal cortex, amygdala, and striatum, and secondly, whether the effectiveness of instruction on extinction learning is associated with differences in resting state connectivity across this network.

 

The Stage 1 manuscript was evaluated over two rounds of in-depth review. Based on detailed responses to the reviewers' comments, the recommender judged that the manuscript met the Stage 1 criteria and therefore awarded in-principle acceptance (IPA).

 

URL to the preregistered Stage 1 protocol: https://osf.io/cj75p (under temporary private embargo)
 
Level of bias control achieved: Level 6. No part of the data or evidence that will be used to answer the research question yet exists and no part will be generated until after IPA.
 
List of eligible PCI RR-friendly journals:
 

 

1. Busch, L., Wiech, K., Gamer, M., Knicses, B., Spisak, T., Schmidt, K., & Bingel, U. (2023). Modulatory effects of instructions on extinction efficacy in appetitive and aversive learning: A registered report. In principle acceptance of Version 3 by Peer Community in Registered Reports. https://osf.io/cj75p

Language production is associated with a distinct lateralised pattern of brain activation biased toward the left cerebral hemisphere. This also applies to writing. It has also been shown to be modulated by handedness, with less pronounced lateralisation in left-handers. However, in recent decades the use of handwriting has declined significantly while the use of smartphones has exploded. To date, no study has explored whether the same neural correlates of written language production found for handwriting also hold for typing on a smartphone.

 

In the current study, Samsouris et al. (2023) will use functional transcranial Doppler ultrasound (fTCD) to measure blood flow velocity within cerebral hemispheres to investigate this question. This technique is particularly suited for this purpose because it provides better control for the movement confounds associated with a writing task and the technical challenges of using a smart device than other neuroimaging techniques like fMRI or M/EEG. The authors hypothesise that there will be no difference in left cerebral lateralisation for handwriting and typing on a smartphone. They also expect to replicate previous findings of weaker lateralisation in left-handers in written language production when typing on a smartphone. To isolate the effect of written language production, both these conditions will be corrected for their corresponding motor component using control conditions without a linguistic component.

 

The Stage 1 manuscript was evaluated over 6 rounds of in-depth review by the recommender and two expert reviewers, before issuing in-principle acceptance.

 

URL to the preregistered Stage 1 protocol: https://osf.io/j7egz
 
Level of bias control achieved: Level 6. No part of the data or evidence that will be used to answer the research question yet exists and no part will be generated until after IPA.
 
List of eligible PCI RR-friendly journals:
 

 

1. Samsouris, C., Badcock, N. A., Vlachos, F., & Papadatou-Pastou, M. (2023). Cerebral laterality as assessed by functional transcranial Doppler ultrasound in left-and right-handers: A comparison between handwriting and writing using a smartphone. In principle acceptance of Version 7 by Peer Community in Registered Reports. https://osf.io/j7egz

A recent study has reported that the extent of cerebral small vessel disease (cSVD) shows associations with dynamic functional connectivity measures obtained from resting state functional MRI scans (Schlemm et al, 2022). Specifically, when the functional scan was parsed into time spent in discrete brain states, the proportion of time spent in the two most-occupied states was negatively related to a structural indicator of cSVD (volume of white matter hyperintensities of presumed vascular origin). This measure of 'fractional occupancy' was also associated with cognitive impairment as indicated by longer time to complete part B of the Trail Making Test. These findings were based on the analysis of data from 988 participants in the Hamburg City Health Study (HCHS).

 

In the present Registered Report, Schlemm (2023) will test whether these associations can be replicated in an independent sample of participants from the HCHS, not included in the earlier analysis (projected N for new analysis ~1500). In addition to the two main hypothesis tests, an exploratory multiverse analysis will be reported, systematically varying some key parameters of the MRI processing pipeline to provide further information about the robustness of the outcome of the primary hypothesis test. 

 

The Stage 1 plan was refined over two rounds of review by two relevant experts, with additional input from the recommender on the specification of the registered plan. Both reviewers are satisfied that the plan constitutes an appropriate approach to this question, and on the basis of their comments and his own evaluation, the recommender judged that the Stage 1 report meets the criteria for in-principle acceptance.

 

URL to the preregistered Stage 1 protocol: https://osf.io/9yhzc
 
Level of bias control achieved: Level 2. At least some data/evidence that will be used to answer the research question has been accessed and partially observed by the authors, but the authors certify that they have not yet observed the key variables within the data that will be used to answer the research question AND they have taken additional steps to maximise bias control and rigour.
 
List of eligible PCI RR-friendly journals:

 

 

 

1. Schlemm, E., Frey, B. M., Mayer, C., Petersen, M., Fiehler, J., Hanning, U., Kühn, S., Twerenbold, R., Gallinat, J., Gerloff, C., Thomalla, G. & Cheng, B. (2022). Equalization of brain state occupancy accompanies cognitive impairment in cerebral small vessel disease. Biological Psychiatry, 92, 592-602. https://doi.org/10.1016/j.biopsych.2022.03.019

 

2. Schlemm, E. (2023). Functional MRI brain state occupancy in the presence of cerebral small vessel disease – pre-registration for a replication analysis of the Hamburg City Health Study. In principle acceptance of Version 1.5 by Peer Community in Registered Reports. https://osf.io/9yhzc