Navigating the garden of forking paths for data exclusions in fear conditioning research

  1. Tina B Lonsdorf  Is a corresponding author
  2. Maren Klingelhöfer-Jens
  3. Marta Andreatta
  4. Tom Beckers
  5. Anastasia Chalkia
  6. Anna Gerlicher
  7. Valerie L Jentsch
  8. Shira Meir Drexler
  9. Gaetan Mertens
  10. Jan Richter
  11. Rachel Sjouwerman
  12. Julia Wendt
  13. Christian Josef Merz
  1. University Medical Center Hamburg-Eppendorf, Germany
  2. University of Würzburg, Germany
  3. KU Leuven, Belgium
  4. University of Amsterdam, Netherlands
  5. Ruhr University Bochum, Germany
  6. Utrecht University, Netherlands
  7. University of Greifswald, Germany

Abstract

In this report, we illustrate the considerable impact of researcher degrees of freedom with respect to exclusion of participants in paradimgs with a learning element. We illustrate this empirically through case examples from human fear conditioning research where the exclusion of 'non-learners' and 'non-responders' is common - despite a lack of consensus on how to define these groups. We illustrate the substantial heterogeneity in exclusion criteria based on a systematic literature search and highlight potential problems and pitfalls of different definitions through case examples based on re-analyses of existing data sets. Based on this, we propose a consensus on evidence-based rather than idiosyncratic criteria including clear guidelines on reporting details. Taken together, we illustrate how flexibility in data collection and analysis can be avoided, which will benefit the robustness and replicability of research findings and can be expected to be applicable to other fields of research that involve a learning element.

Data availability

The minimal data sets (data set 1 and data set 2, both represent re-analysis of existing data), which were analysed during the current study, as well as code for figure production are are available at OSF under https://osf.io/mkxqe/ and DOI 10.17605/OSF.IO/MKXQE.

The following data sets were generated
    1. Lonsdorf et al
    (2019) Data_and_code_dataset1
    Open Science Framework, w9y8z.
    1. Lonsdorf et al
    (2019) Data_and_code_dataset1
    Open Science Framework, 7c5ag.

Article and author information

Author details

  1. Tina B Lonsdorf

    Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    For correspondence
    t.lonsdorf@uke.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1501-4846
  2. Maren Klingelhöfer-Jens

    Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Marta Andreatta

    Department of Psychology, Biological Psychology,Clinical Psychology and Psychotherapy, University of Würzburg, Würzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1217-8266
  4. Tom Beckers

    Centre for the Psychology of Learning and Experimental Psychopathology and Leuven Brain Institute, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9581-1505
  5. Anastasia Chalkia

    Centre for the Psychology of Learning and Experimental Psychopathology and Leuven Brain Institute, KU Leuven, Leuven, Belgium
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1613-2281
  6. Anna Gerlicher

    Faculty of Social and Behavioural Sciences, Programme group Clinical Psychology, University of Amsterdam, the Netherlands, University of Amsterdam, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Valerie L Jentsch

    Institute of Cognitive Neuroscience, Department of Cognitive Psychology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9318-9540
  8. Shira Meir Drexler

    Institute of Cognitive Neuroscience, Department of Cognitive Psychology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8797-6900
  9. Gaetan Mertens

    Department of Psychology, Utrecht University, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  10. Jan Richter

    Department of Physiological and Clinical Psychology/Psychotherapy, University of Greifswald, Greifswald, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7127-6990
  11. Rachel Sjouwerman

    Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Julia Wendt

    Department of Physiological and Clinical Psychology/Psychotherapy, University of Greifswald, Greifwald, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2299-5881
  13. Christian Josef Merz

    Institute of Cognitive Neuroscience, Department of Cognitive Psychology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5679-6595

Funding

Deutsche Forschungsgemeinschaft (LO 1980/2-1)

  • Tina B Lonsdorf

Deutsche Forschungsgemeinschaft (LO 1980/1-1)

  • Tina B Lonsdorf
  • Rachel Sjouwerman

Deutsche Forschungsgemeinschaft (44541416)

  • Tina B Lonsdorf

Deutsche Forschungsgemeinschaft (316803389)

  • Christian Josef Merz

Deutsche Forschungsgemeinschaft (WE 5873/1-1)

  • Julia Wendt

Deutsche Forschungsgemeinschaft (WE 5873/5-1)

  • Julia Wendt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Study 1: All participants gave written informed consent to the protocol which was approved by the local ethics committee (PV 5157, Ethics Committee of the General Medical Council Hamburg).Study 2: All participants gave written informed consent to the protocol which was approved by the Ethical Review Board of the German Psychological Association (TL072015).

Copyright

© 2019, Lonsdorf et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,587
    views
  • 431
    downloads
  • 102
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Tina B Lonsdorf
  2. Maren Klingelhöfer-Jens
  3. Marta Andreatta
  4. Tom Beckers
  5. Anastasia Chalkia
  6. Anna Gerlicher
  7. Valerie L Jentsch
  8. Shira Meir Drexler
  9. Gaetan Mertens
  10. Jan Richter
  11. Rachel Sjouwerman
  12. Julia Wendt
  13. Christian Josef Merz
(2019)
Navigating the garden of forking paths for data exclusions in fear conditioning research
eLife 8:e52465.
https://doi.org/10.7554/eLife.52465

Share this article

https://doi.org/10.7554/eLife.52465

Further reading

    1. Developmental Biology
    2. Neuroscience
    Xingsen Zhao, Qihang Sun ... Xuekun Li
    Research Article

    Williams syndrome (WS; OMIM#194050) is a rare disorder, which is caused by the microdeletion of one copy of 25–27 genes, and WS patients display diverse neuronal deficits. Although remarkable progresses have been achieved, the mechanisms for these distinct deficits are still largely unknown. Here, we have shown that neural progenitor cells (NPCs) in WS forebrain organoids display abnormal proliferation and differentiation capabilities, and synapse formation. Genes with altered expression are related to neuronal development and neurogenesis. Single cell RNA-seq (scRNA-seq) data analysis revealed 13 clusters in healthy control and WS organoids. WS organoids show an aberrant generation of excitatory neurons. Mechanistically, the expression of transthyretin (TTR) are remarkably decreased in WS forebrain organoids. We have found that GTF2IRD1 encoded by one WS associated gene GTF2IRD1 binds to TTR promoter regions and regulates the expression of TTR. In addition, exogenous TTR can activate ERK signaling and rescue neurogenic deficits of WS forebrain organoids. Gtf2ird1-deficient mice display similar neurodevelopmental deficits as observed in WS organoids. Collectively, our study reveals critical function of GTF2IRD1 in regulating neurodevelopment of WS forebrain organoids and mice through regulating TTR-ERK pathway.

    1. Computational and Systems Biology
    2. Neuroscience
    Jian Qiu, Margaritis Voliotis ... Martin J Kelly
    Research Article

    Hypothalamic kisspeptin (Kiss1) neurons are vital for pubertal development and reproduction. Arcuate nucleus Kiss1 (Kiss1ARH) neurons are responsible for the pulsatile release of gonadotropin-releasing hormone (GnRH). In females, the behavior of Kiss1ARH neurons, expressing Kiss1, neurokinin B (NKB), and dynorphin (Dyn), varies throughout the ovarian cycle. Studies indicate that 17β-estradiol (E2) reduces peptide expression but increases Slc17a6 (Vglut2) mRNA and glutamate neurotransmission in these neurons, suggesting a shift from peptidergic to glutamatergic signaling. To investigate this shift, we combined transcriptomics, electrophysiology, and mathematical modeling. Our results demonstrate that E2 treatment upregulates the mRNA expression of voltage-activated calcium channels, elevating the whole-cell calcium current that contributes to high-frequency burst firing. Additionally, E2 treatment decreased the mRNA levels of canonical transient receptor potential (TPRC) 5 and G protein-coupled K+ (GIRK) channels. When Trpc5 channels in Kiss1ARH neurons were deleted using CRISPR/SaCas9, the slow excitatory postsynaptic potential was eliminated. Our data enabled us to formulate a biophysically realistic mathematical model of Kiss1ARH neurons, suggesting that E2 modifies ionic conductances in these neurons, enabling the transition from high-frequency synchronous firing through NKB-driven activation of TRPC5 channels to a short bursting mode facilitating glutamate release. In a low E2 milieu, synchronous firing of Kiss1ARH neurons drives pulsatile release of GnRH, while the transition to burst firing with high, preovulatory levels of E2 would facilitate the GnRH surge through its glutamatergic synaptic connection to preoptic Kiss1 neurons.