Evidence map›Paper›PMID 33488363›Full record

ArticleFrontiers in neural circuits2020

Calcium Imaging and the Curse of Negativity.

Gilles Vanwalleghem, Lena Constantin, Ethan K Scott

Abstract read
In one paragraph

Article in Frontiers in neural circuits, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed.

  1. Article
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  4. Deriving functional network topology frombioRxiv : the preprint server for biology · 2026
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  9. Brain-Wide Impacts of Sedation on Spontaneous Activity and Auditory Processing in Larval Zebrafish.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
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  16. Mixed Representations of Sound and Action in the Auditory Midbrain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Gilles VanwalleghemNeural Circuits and Behavior Laboratory, Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia.
Lena ConstantinNeural Circuits and Behavior Laboratory, Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia.
Ethan K ScottNeural Circuits and Behavior Laboratory, Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia.

Funding

An integrated platform for studying sensory networks in the vertebrate brainRF1NS118406 · NINDS · UNIVERSITY OF QUEENSLAND · PI SCOTT, ETHAN KIME · 2020 to 2020
$1.2M
An integrated platform for studying sensory networks in the vertebrate brainR01NS118406 · NINDS · UNIVERSITY OF MELBOURNE · PI SCOTT, ETHAN KIME · 2023 to 2024
$747k
NINDS NIH HHS R01 NS118406NINDS NIH HHS RF1 NS118406
6 · The paper itself

Abstract

The imaging of neuronal activity using calcium indicators has become a staple of modern neuroscience. However, without ground truths, there is a real risk of missing a significant portion of the real responses. Here, we show that a common assumption, the non-negativity of the neuronal responses as detected by calcium indicators, biases all levels of the frequently used analytical methods for these data. From the extraction of meaningful fluorescence changes to spike inference and the analysis of inferred spikes, each step risks missing real responses because of the assumption of non-negativity. We first show that negative deviations from baseline can exist in calcium imaging of neuronal activity. Then, we use simulated data to test three popular algorithms for image analysis, CaImAn, suite2p, and CellSort, finding that suite2p may be the best suited to large datasets. We also tested the spike inference algorithms included in CaImAn, suite2p, and Cellsort, as well as the dedicated inference algorithms MLspike and CASCADE, and found each to have limitations in dealing with inhibited neurons. Among these spike inference algorithms, FOOPSI, from CaImAn, performed the best on inhibited neurons, but even this algorithm inferred spurious spikes upon the return of the fluorescence signal to baseline. As such, new approaches will be needed before spikes can be sensitively and accurately inferred from calcium data in inhibited neurons. We further suggest avoiding data analysis approaches that, by assuming non-negativity, ignore inhibited responses. Instead, we suggest a first exploratory step, using k-means or PCA for example, to detect whether meaningful negative deviations are present. Taking these steps will ensure that inhibition, as well as excitation, is detected in calcium imaging datasets.

Indexed as

Action PotentialsAlgorithmsAnimalsCalciumCalcium SignalingImage Processing, Computer-AssistedModels, NeurologicalNeuronsZebrafishCalciumbaseline fluorescencecalcium imagingcerebellar circuitrydata analysisGCaMPsegmentationspike inferencezebrafish

Identifiers

PMID33488363
PMCPMC7815594

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.