By Isabelle Wilson-–
The integrity of research papers conducted by an eminent Harvard scientist and his fellow researchers studying autism through assessments on mice has been attacked after duplication error were spotted.
The credibility of the broad research by multiple award winner, Professor Jui Lui from Harvard University has come under scrutiny after being flagged up by an anonymous observer.
It relates to a paper published by Nature Neuroscience over which the reputable professor presided entitled “Tracking neural activity from the same cells during the entire adult life of mice.”
The tracking of neural activity using new high-resolution imaging device tracks widespread brain activity in living mice, enabling researchers to map neural circuits across the entire brain. The tool could help scientists understand how these circuits are altered in autism.
Some of the flaws published by the research has in the meantime detracted from the reliability of the findings, putting pressure on Both the globally respected Harvard University and the acclaimed scientist to review the published work after correcting the error.
Researchers usually track activity throughout the brain by using functional magnetic resonance imaging (fMRI), which measures blood flow as a proxy for neuronal activity.
The technology’s resolution is usually limited to about 1 or 2 millimeters — too low for mapping neural circuits. It also requires animals to remain still, making it difficult to use in mice that are awake.
Rodents, most especially mice, are excellent animal models of autism because they have similar social relationships and neuroscience.
In assessing whether mice show autistic-like social interaction deficits, automated video tracking systems are often used to score the number and duration of interactions.
Neurons in the amygdala of children with autism are said by researchers to have an excess of the mushroom-like protrusions that link up with other neurons. The density of these ‘dendritic spines’ also drops over time in individuals with autism
Elisabeth Bik posted comments about the paper on PubPeer, a website that allows for anonymous review and commentary on peer-reviewed articles.
Bik is known for for spotting questionable images in academic publishing, and she pointed out that in two figures, some of the plots look identical, adding that the source data for other figures have repeating values.
Bik had been tipped off about the by an anonymous source, a person claiming to be a research associate who discovered the anomalies while reading the paper in a journal club. A few weeks later, the same source alerted Bik to a problem in another paper from the same group, this one published in Science Advances in late 2022.
Critics keeping an eye on the research believe the spooted error raises doubt about the credibility of the work led by Jia Liu, assistant professor of engineering and applied sciences at Harvard University, who is also the scientific adviser at Axoft, a company developing brain implants for neurological conditions. The company, which Liu co-founded with one of his former doctoral students, announced last year that it had raised $8 million in seed funding.
In the Nature Neuroscience paper, the group tracked neural activity in a mouse for a year using an open mesh probe brain implant — a notable task, as it is typically difficult to record activity for that long a period because of immune response and probe drift, according to the study.
Children with autism show an average of 11 percent more neurons than typically developing individuals during early childhood. But the number of neurons declines over time, so that by adulthood, the brains of people with autism have [roughly 20 percent] fewer neurons in the amygdala than do those of controls.
The amygdala- a brain region that governs emotions- may contain an unusually high number of neurons in young children with autism, each of which may also have an excess of connections to other cells. As these children grow up, however, some amygdala neurons, and many of their connections, seem to disappear.
Neurons in the amygdala of children with autism also have an excess of the mushroom-like protrusions that link up with other neurons. The density of these ‘dendritic spines’ also drops over time in individuals with autism
Bik pointed to extended figure 6a, which consists of plots of interspike interval (ISI) distributions from 18 neurons over seven months. Each of the subplots for a neuron is supposed to represent one of the seven months, but the anonymous observer spotted that the subplots for each neuron are identical.
Bik also pointed to another two ISI plots that appear to be duplicated, and an apparent duplication of data points in the source data spreadsheet for figure 2f, where the numbers shown are the “normalized fluorescence intensity.”
Mean and standard error of the mean values were duplicated in the datasheet between the astrocyte (GFAP) and microglia (Iba1). In additional mean and standard error values, strings of numbers that follow the decimal point were repeated between the same two neurons.
Liu explained the discrepancy, stating that a mistake in the Python code “caused the data from the last month of each neuron to be plotted seven times instead of plotting the data for each month correctly,” and that the raw data behind the two ISI plots are so similar that the differences between the two neurons are imperceptible in the image.
He also said the exact repeated means and standard errors in the dataset were “mixed up” during the data analysis process between Excel and OriginPro, but the repeating digits that appear in the dataset are explained by the data being divided by the same sample size.
Liu noted that none of these issues affect the conclusions of the paper itself, and his team hopes to “correct them as soon as possible to avoid confusing the community.” That includes filing a correction with Nature Neuroscience and providing a new version of the image in figure 10c to make it clear there are differences between the ISI histograms of the two neurons.
The issues in the second paper from Liu’s lab again center around an image. On behalf of the tipster, Bik pointed out on PubPeer that in figure 8b (found in the paper’s supplement), two panels in a graphic of neuron images representing nine different treatment groups are duplicated.
“When concerns are raised about any paper published in the journal, we look into them carefully following an established process.” Nature Neuroscience
Liu said his lab group noticed the error themselves and had already posted an updated version on their website, but the updated version has repurposed image panels, which “suggests that the authors may have had several negative control images, which they seemingly assigned to these negative control groups in an arbitrary manner.”
Harvard University was contacted for comment on the issue.