Nippon Telegraph and Telephone Corporation, Nagoya University, and Hokkaido University successfully measured semiconductor soft error rates at continuously varying neutron energies from 1MeV to 800MeV. The findings reveal, for the first time, the complete picture of the energy dependence of semiconductor soft errors.
Data on soft error rate dependence on neutron energy are critical when studying the impact of cosmic rays on semiconductors and investigating countermeasures because the number of soft errors is heavily dependent on the incoming neutron energy. However, it has been impossible to measure data that have a wide and continuous energy range. Therefore, the soft error rates measured to date have been limited to several discrete neutron energy levels.
Researchers of Hokkaido University have developed an Ultra-high-speed error detection circuit that enables to precisely measure flight times of neutrons arriving at the semiconductor even if the velocities are close to the speed of light. From the flight time they could deduce the speed of the neutrons causing the soft errors. The circuit makes it possible to measure soft errors caused by neutrons across an extremely wide range of energies up to 800 MeV.
Soft error rates, which they measured successfully, are among the most basic and critical data to predict the number of soft errors caused by neutrons in various environments not only at ground level but also at high altitudes, in space, or even on another planet. The data will be useful in a variety of fields: evaluation of semiconductor reliability in space stations, study of soft error prevention measures to be taken in semiconductor materials, soft error tests using an accelerator, and simulation of the process in which soft errors occur.
The research results were published in IEEE Transactions on Nuclear Science on November 19, 2020. Click here to read the joint press release.
References: Hidenori Iwashita, Gentaro Funatsu, Hirotaka Sato, Takashi Kamiyama, Michihiro Furusaka, Stephen A. Wender, Eric Pitcher, and Yoshiaki Kiyanagi, “Energy-resolved Soft-Error Rate Measurements for 1-800 MeV Neutrons by the Time-of-flight Technique at LANSCE”, IEEE Transaction on Nuclear Science, 2020. https://ieeexplore.ieee.org/document/9201514 DOI: 10.1109/TNS.2020.3025727
A novel CAR T-cell therapy developed by researchers at UCL and designed to target cancerous tumours, has shown promising early results in children with neuroblastoma, a rare form of childhood cancer.
For this proof-of-principle study, researchers at the UCL Great Ormond Street Institute for Child Health (GOS ICH) and the UCL Cancer Institute modified the patient’s own T-cells (a type of immune cell), equipping them to recognise and kill neuroblastoma tumour cells.
Twelve children with relapsed or refractory (where the disease does not respond to treatment) neuroblastoma were treated as part of the Cancer Research UK-funded phase I clinical trial.
The research, published in Science Translational Medicine, is one of the first studies to demonstrate CAR T-cells achieving rapid regression against a solid cancer (non-blood cancer). Although the beneficial effects only lasted a short while, the study provides important evidence that this specific CAR T-cell treatment could be used as a future treatment for children with solid cancers.
Neuroblastoma is a rare type of cancer that mostly affects babies and young children and develops from specialised nerve cells (neuroblasts) left behind from a baby’s development in the womb.
Up to 100 children in the UK are diagnosed with neuroblastoma each year. Current treatment for children with an aggressive type of neuroblastoma includes surgical removal, chemotherapy with stem-cell transplant, radiotherapy and antibody therapy. Despite this intensive treatment long-term survival is between 50-60 per cent.
In CAR T-cell therapy, a type of immunotherapy, T-cells are engineered to contain a molecule called a chimeric antigen receptor (CAR) on their surface which can specifically recognise cancerous cells.
For this study the patients’ own T-cells were modified with a CAR to target the GD2 surface protein, which is highly abundant on almost all neuroblastoma cells, but found at very low levels in healthy cells.
Researchers found that when using a sufficient dose* of the modified CAR T-cells, this treatment induced rapid reduction in tumour size in some of the patients treated. These effects were transient. Importantly, in all patients the CAR T-cells did not cause any harmful side effects in healthy tissues that express the GD2 molecule.
Lead author, Dr Karin Straathof, research group leader at UCL GOS ICH and Consultant Paediatric Oncologist at Great Ormond Street Hospital NHS Trust said: “It’s encouraging to see the anti-tumour activity induced by these modified T-cells in some of the patients on this study.
“While the anti-tumour activity seen was only transient, it provides an important proof-of-principle that CAR T-cells directed at the GD2 molecule could be used against solid cancers in children.
“New treatments are needed for high-risk neuroblastoma and with more research we hope to develop this further into a treatment that results in lasting responses and increases the number of patients that can be cured.”
Senior author, Dr Martin Pule (UCL Cancer Institute) said: “Targeting of solid cancers by CAR T-cells is dependent on their infiltration and expansion within the tumour microenvironment, and thus far fewer clinical responses have been reported.
“The rapid regression in neuroblastoma cells is promising, particularly as this activity was observed in the absence of neurotoxicity which occurs with antibody-based approaches that target GD2.”
Dr Pule added: “Targeting neuroblastoma with GD2 CAR T-cells appears to be a valid and safe strategy but requires further modification to promote CAR T-cell longevity.”
Dr Sue Brook, medical advisor at Cancer Research UK, said: “Children who have hard to treat cancers like neuroblastoma have limited treatment options open to them, especially when the cancer returns.
“The early results for the GD2 CAR-T treatment look promising, especially due to the initial safety data. However more work is needed on making the response last longer, and we are looking forward to seeing the next steps in its development.”
The research team are preparing for their next clinical study in collaboration with Autolus, a clinical-stage biopharmaceutical company developing next-generation, programmed T-cell therapies for the treatment of cancer. This study will evaluate AUTO6NG, which builds on this approach utilising the same GD2 CAR alongside additional programming modules designed to enhance efficacy and persistence.
* To establish the minimal effective dose, escalating doses of GD2-directed CAR T-cells were used. The first group of patients was given a low dose, the second group a higher dose, and a third group a higher dose still. Each patient received one dose only. Researchers found that a minimal cell dose of 108/m2** was needed for the CAR T-cells to divide and become activated once administered to the patient.
** The dose is expressed per square metre surface area as this is a paediatric study and that is how doses are calculated in children (or alternatively per kilogram of body weight). The cell dose is 108 per square metre body surface area or 100 million cells per square metre body surface area.
References: Karin Straathof, Barry Flutter, Rebecca Wallace, Neha Jain, Thalia Loka, Sarita Depani, Gary Wright, Simon Thomas, Gordon Weng-Kit Cheung, Talia Gileadi, Sian Stafford, Evangelia Kokalaki, Jack Barton, Clare Marriott, Dyanne Rampling, Olumide Ogunbiyi, Ayse U. Akarca, Teresa Marafioti, Sarah Inglott, Kimberly Gilmour, Muhammad Al-Hajj, William Day, Kieran McHugh, Lorenzo Biassoni, Natalie Sizer, Claire Barton, David Edwards, Ilaria Dragoni, Julie Silvester, Karen Dyer, Stephanie Traub, Lily Elson, Sue Brook, Nigel Westwood, Lesley Robson, Ami Bedi, Karen Howe, Ailish Barry, Catriona Duncan, Giuseppe Barone, Martin Pule, John Anderson, “Antitumor activity without on-target off-tumor toxicity of GD2–chimeric antigen receptor T cells in patients with neuroblastoma”, Science Translational Medicine 25 Nov 2020: Vol. 12, Issue 571, eabd6169 DOI: 10.1126/scitranslmed.abd6169https://stm.sciencemag.org/content/12/571/eabd6169
The 2018 eruption of Kīlauea Volcano was one of the largest volcanic events in Hawaiʻi in 200 years. This eruption was triggered by a relatively small and rapid change at the volcano after a decade-long build-up of pressure in the upper parts of the volcano, according to a recent study published in Nature Communications by earth scientists from the University of Hawai‘i (UH) at Mānoa and U.S. Geological Survey (USGS).
Using USGS Hawaiian Volcanoes Observatory (HVO) data from before and during the 2018 eruptions at the summit and flank, the research team reconstructed the geologic events.
“The data suggest that a backup in the magma plumbing system at the long-lived Puʻu ʻŌʻō eruption site caused widespread pressurization in the volcano, driving magma into the lower flank,” said Matthew Patrick, research geologist at the USGS HVO and lead author of the study.
The eruption evolved, and its impact expanded, as a sequence of cascading events allowed relatively minor changes at Puʻu ʻŌʻō to cause major destruction and historic changes across the volcano.
A cascading series of events of this type was not considered the most likely outcome in the weeks prior to the onset of the eruption.
“This form of tunnel vision, which gives less attention to the least likely outcomes, is a bias that can be overcome by considering the broader, longer history of the volcano,” said Bruce Houghton, the Hawai‘i State Volcanologist, earth sciences professor at the UH Mānoa School of Ocean and Earth Science and Technology and study co-author. “For Kīlauea, this consists of widening the scope to consider the types of behavior seen in the first half of the 20th century and perhaps earlier.”
“Our study demonstrates that eruption forecasting can be inherently challenging in scenarios where volcanoes prime slowly and trigger due to a small event, as the processes that build to eruption may be hard to detect and are easy to overlook on the scale of the entire volcano,” said Patrick. “It is also a cautionary tale against over-reliance on recent activity as a guide for future eruptions.”
The State of Hawai‘i absorbed a significant amount of the economic and social cost of the 2018 eruption and likely will do so again as Kīlauea and Mauna Loa continue to erupt, suggested Houghton. Studies like this, which probe the more subtle influences of the behavior of these volcanoes, are targeted at reducing the costs, human and physical, of the next eruptions.
With future work the research team aims to adopt diverse approaches to understanding the subsurface structure and movement of magma on Kīlauea’s East Rift Zone.
References: Patrick, M.R., Houghton, B.F., Anderson, K.R. et al. The cascading origin of the 2018 Kīlauea eruption and implications for future forecasting. Nat Commun 11, 5646 (2020). https://doi.org/10.1038/s41467-020-19190-1
Data reported can guide new therapeutic avenues for pediatric patients.
A comprehensive “proteogenomic” analysis of the proteins, genes, and RNA transcription involved in pediatric brain tumors has yielded a more complete understanding of these tumors, which are the leading cause of cancer-related deaths in children. The results could help physicians more accurately identify different types of tumors and methods for treating them.
Researchers from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Children’s Brain Tumor Network (CBTN) collected and analyzed what’s known as genetic, genomic, and proteomic data from multiple types of brain tumors in children. The consortia consist of collaborators from the Icahn School of Medicine at Mount Sinai, National Cancer Institute, Fred Hutchinson Cancer Research Center, Children’s National Hospital, and Children’s Hospital of Philadelphia. The study, the first large-scale multicenter study focused on pediatric brain tumors, was available online in Cell on November 25.
“Pediatric cancers in general, and pediatric brain tumors in particular, have a relatively low mutational burden,” explains Pei Wang, PhD, lead corresponding author of the study and Professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. “Thus, comprehensive characterization of the functional molecular biology of these tumors, including the proteogenomic analysis done in this study, is essential to better understand and treat pediatric brain tumors.”
This study is the first comprehensive survey of genomics (which aims to characterize DNA sequence alterations in a sample), transcriptomics (which aims to quantify copies of RNAs), global proteomics (which aims to identify and quantify proteins), and phosphoproteomics (which quantifies active proteins) across a large cohort of 218 tumor samples representing seven distinct types of brain tumors.
By characterizing biological themes that are shared among these different types of tumors, the study revealed new insights suggesting that current treatments being used for specific tumor types could be applied to others that share the same proteomic features. Specifically, the analyses revealed two distinct subgroups of pediatric craniopharyngioma, a type of pediatric brain tumor. One subgroup showed proteomic/phosphoproteomic characteristics that were strikingly similar to those of another type of tumor, known as “low-grade glioma (LGG) with BRAFV600E mutation.” This observation suggests that MEK/MAPK inhibitors, a type of chemotherapy that has been used against LGG-with-BRAFV600E-mutation tumors, might also help with this subset of pediatric craniopharyngiomas, which currently has no robust chemotherapeutic options.
“The driver of this joint study has been a commitment to data-sharing and open science. Coming together has given both CPTAC and CBTN an opportunity to expand our available resources for answering critically important biological questions. Harnessing the collective expertise across these consortia enables us to better understand the mechanisms of pediatric tumors, improve the process of target protein identification, and potentially improve cancer treatments,” said Adam Resnick, PhD, contributing researcher, Scientific Co-Chair for CBTN, and Director of the Center for Data Driven Discovery in Biomedicine (D3b) at Children’s Hospital of Philadelphia.
By leveraging the rich clinical outcome data of this cohort, the research team also identified new prognostic biomarkers for a type of tumor known as high-grade glioma (HGG). When HGG tumors have a genetic mutation known as a H3K27M mutation, they tend to be very aggressive and the patients have relatively short survival time. However, in those without the mutation, this study suggests that the abundance of proteins named IDH1 and IDH2 in the tumor tissues could help to identify which tumors with the non-mutated H3K27M gene may be less aggressive.
“Integration of the clinical, proteomic, and genetic data generated in this study allows us to construct a more comprehensive model of brain tumor biology, which will lead to more targeted treatments,” said Brian Rood, MD, contributing researcher, Executive Co-Chair for CBTN, and Medical Director of the Brain Tumor Institute at Children’s National Hospital.
The data analysis also showed key biological differences in samples from primary and recurrent tumors from the same patients, indicating the need for independent assessment and therapeutic decisions for these tumors.
“The current study is the first to reveal in pediatric brain tumors the power of proteins to better determine which patient might benefit from a given therapy, and our validation studies using targeted proteomics provide a platform for clinical implementation of the findings” said co-author Amanda Paulovich, MD, PhD, Aven Foundation Endowed Chair and professor in the Clinical Research Division at Fred Hutchinson Cancer Research Center. “As this work moves further along toward clinical validation, I hope it brings comfort to patients and their families who have suffered from this terrible disease.”
Scientists at Osaka University create seaweed-shaped sodium titanate mats made of nanofibers that can remove cobalt ions from water, which may help provide a source of safe, recycled drinking water by removal of heavy metals and radionuclides.
A team of researchers at Osaka University has developed a nanopowder shaped like seaweed for a water filter to help remove toxic metal ions (Fig. 1). Made of layered sodium titanate, the randomly oriented nanofibers increase the efficacy of cobalt-II (Co2+) ion capture. This work might lead to cheaper and more effective solutions for filtering water that is currently unusable due to hazardous heavy metals or radioactive fallout.
As the global population continues to increase, so will the need for drinkable water. Sadly, many water sources have become contaminated with heavy metals, such as cobalt, from industrial waste or radioactive runoff. Sodium titanate has been widely used to filter out these toxic substances, but its efficiency is not enough. Sodium titanate is generally a two-dimensional layered material, but its crystal structure can vary based on the chemical composition and preparation method. To effectively capture radioactive and/or heavy metal ions, the morphological control of the sodium titanate is very important.
Now, researchers from the Institute of Scientific and Industrial Research at Osaka University have developed a new method to create highly efficient sodium titanate filters. “We used a template-free alkaline hydrothermal process to produce the mats,” first author Yoshifumi Kondo says. The researchers found that increasing the hydrothermal synthesis time caused the initially round crystals to become elongated and fibrous, and to form the seaweed-shaped mats consisting of the randomly oriented nanofibers (Fig. 2). This seaweed-like nanoscale morphology increased the surface area of the mats, which improved the removal efficiency of Co2+ during sorption tests.
“Due to the progress of global warming and serious environmental pollution, the need for safe ways to remove radioactive materials and heavy metals from water resources has become even more critical,” senior author Tomoyo Goto says. Compared with a commercially available material, the nanostructured sodium titanate mats showed improved performance for capturing Co2+ ions. The method is expected to be applied for other purification systems that remove heavy metals and radionuclides from wastewater (Fig. 3).
New data from the NASA/ESA Hubble Space Telescope provides further evidence for tidal disruption in the galaxy NGC 1052-DF4. This result explains a previous finding that this galaxy is missing most of its dark matter. By studying the galaxy’s light and globular cluster distribution, astronomers have concluded that the gravity forces of the neighbouring galaxy NGC 1035 stripped the dark matter from NGC 1052-DF4 and are now tearing the galaxy apart.
In 2018 an international team of researchers using the NASA/ESA Hubble Space Telescope and several other observatories uncovered, for the first time, a galaxy in our cosmic neighbourhood that is missing most of its dark matter. This discovery of the galaxy NGC 1052-DF2 was a surprise to astronomers, as it was understood that Dark matter (DM) is a key constituent in current models of galaxy formation and evolution. In fact, without the presence of DM, the primordial gas would lack enough gravity pull to start collapsing and forming new galaxies. A year later, another galaxy that misses dark matter was discovered, NGC 1052-DF4, which further triggered intense debates among astronomers about the nature of these objects.
Now, new Hubble data have been used to explain the reason behind the missing dark matter in NGC 1052-DF4, which resides 45 million light-years away. Mireia Montes of the University of New South Wales in Australia led an international team of astronomers to study the galaxy using deep optical imaging. They discovered that the missing dark matter can be explained by the effects of tidal disruption. The gravity forces of the neighbouring massive galaxy NGC 1035 are tearing NGC 1052-DF4 apart. During this process, the dark matter is removed, while the stars feel the effects of the interaction with another galaxy at a later stage.
Until now, the removal of dark matter in this way has remained hidden from astronomers as it can only be observed using extremely deep images that can reveal extremely faint features. “We used Hubble in two ways to discover that NGC 1052-DF4 is experiencing an interaction,” explained Montes. “This includes studying the galaxy’s light and the galaxy’s distribution of globular clusters.”
Thanks to Hubble’s high resolution, the astronomers could identify the galaxy’s globular clusters population. The 10.4-metre Gran Telescopio Canarias (GTC) telescope and the IAC80 telescope in the Canaries, Spain, were also used to complement Hubble’s observations by further studying the data.
“It is not enough just to spend a lot of time observing the object, but a careful treatment of the data is vital,” explained team member Raúl Infante-Sainz of the Instituto de Astrofísica de Canarias in Spain. “It was therefore important that we use not just one telescope/instrument, but several (both ground- and space-based) to conduct this research. With the high resolution of Hubble, we can identify the globular clusters, and then with GTC photometry we obtain the physical properties.”
Globular clusters are thought to form in the episodes of intense star formation that shaped galaxies. Their compact sizes and luminosity make them easily observable and they are therefore good tracers of the properties of their host galaxy. In this way, by studying and characterising the spatial distribution of the clusters in NGC 1052-DF4, astronomers can develop insight into the present state of the galaxy itself. The alignment of these clusters suggests they are being “stripped” from their host galaxy, and this supports the conclusion that tidal disruption is occurring.
By studying the galaxy’s light, the astronomers also found evidence of tidal tails, which are formed of material moving away from NGC1052-DF4—this further supports the conclusion that this is a disruption event. Additional analysis concluded that the central parts of the galaxy remain untouched and only ∼ 7% of the stellar mass of the galaxy is hosted in these tidal tails. This means that dark matter, which is less concentrated than stars, was previously and preferentially stripped from the galaxy, and now the outer stellar component is starting to be stripped as well.
“This result is a good indicator that, while the dark matter of the galaxy was evaporated from the system, the stars are only now starting to suffer the disruption mechanism,” explained team member Ignacio Trujillo of the Instituto de Astrofísica de Canarias in Spain. “In time, NGC1052-DF4 will be cannibalised by the large system around NGC1035, with at least some of their stars floating free in deep space.”
The discovery of evidence to support the mechanism of tidal disruption as the explanation for the galaxy’s missing dark matter has not only solved an astronomical conundrum, but has also brought a sigh of relief to astronomers. Without it, scientists would be faced with having to revise our understanding of the laws of gravity.
“This discovery reconciles existing knowledge of how galaxies form and evolve with the most favorable cosmological model,” added Montes.
These results have been published in the Astrophysical Journal.
References: Mireia Montes, Raúl Infante-Sainz, Alberto Madrigal-Aguado, Javier Román, Matteo Monelli, Alejandro S. Borlaff, Ignacio Trujillo, “The galaxy “missing dark matter” NGC1052-DF4 is undergoing tidal disruption”, ArXiv, 2020. arXiv:2010.09719 [astro-ph.GA] arxiv.org/abs/2010.09719https://arxiv.org/abs/2010.09719v1
Simulations by University of Warwick astrophysicists show that interactions with giant planets could result in protoplanetary discs that look older than they should
Massive young discs are expected to show spiral structures, but these are rarely observed with telescopes
Could be explained by the presence of giant planets early in the disc’s lifecycle
Images and video simulations available in Notes to Editors
Giant planets that developed early in a star system’s life could solve a mystery of why spiral structures are not observed in young protoplanetary discs, according to a new study by University of Warwick astronomers.
The research, published today (26 November) in the Astrophysical Journal Letters andpart supported by the Royal Society, provides an explanation for the lack of spiral structure that astronomers expect to see in protoplanetary discs around young stars that also suggests that scientists may have to reassess how quickly planets form in a disc’s lifecycle.
Protoplanetary discs are the birthplaces of planets, harbouring the material that will eventually coalesce into the array of planets that we see in the Universe. When these discs are young they form spiral structures, with all their dust and material dragged into dense arms by the massive gravitational effect of the disc spinning. A similar effect occurs at the galactic level, hence why we see spiral galaxies such as our own, the Milky Way.
Over the course of three to ten million years material from the disc comes together to form planets, falls onto the star it is orbiting or just disperses into space through winds coming off the disc. When a disc is young it is self-gravitating, and the material within it forms a spiral structure which it loses when it becomes gravitationally stable. Young planets that develop then carve out gaps in the disc as they consume and disperse material in their way, resulting in the ‘ring and gap’ features that astronomers most commonly see in protoplanetary discs.
But astronomers have struggled to account for observations of young protoplanetary discs that show no signs of spirals, but instead look like a disc much older with a ring and gap structure. To provide an explanation, Sahl Rowther and Dr Farzana Meru from the University of Warwick Department of Physics conducted computer simulations of massive planets in young discs to determine what would happen when they interacted.
They found that a giant planet, around three times the mass of Jupiter, migrating from the outer regions of the disc towards its star would cause enough disruption to wipe out the disc’s spiral structure with results much like the discs observed by astronomers. However, to be present in the spiral stage of the disc those planets would have to form rapidly and early in the disc’s lifecycle.
Lead author Sahl Rowther, PhD student in the Department of Physics, said: “When discs are young, we expect them to be massive with spiral structures. But we don’t see that in observations.
“Our simulations suggest that a massive planet in one of these young discs can actually shorten the time spent in the self-gravitating spiral phase to one that looks more like some of the observations that astronomers are seeing.
Co-author Dr Farzana Meru from the Department of Physics adds: “If some of these discs that astronomers are observing were recently self-gravitating then that suggests they formed a planet while the disc was still young. The self-gravitating phase for a protoplanetary disc is much less than about half a million years, which means the planet would have to have formed incredibly quickly.
“Irrespective of what mechanism explains how these planets form, this probably means that we have to consider that planets form much faster than originally thought.”
Their simulations modelled a giant planet in the outer regions of a protoplanetary disc as it migrates inwards, a process that astronomers expect to see as the torque pushes the planet inwards as it exchanges angular momentum with the gas in the disc. This also means that the planet would interact with and disrupt a large proportion of the disc and be massive enough to open a gap in the gas, resulting in the ring and gap structure.
Sahl Rowther adds: “This is exciting given the unknowns associated with the masses of observed discs. If massive discs with ring and gap structures are common, it could provide more pathways in explaining disc architectures.
“Our results suggest that it may even be possible to see signs of these giant planets, given the right conditions and technology. The next stage of our research will be to determine what those conditions are, to help astronomers in trying to determine the presence of these planets.”
Dr Meru adds: “It’s quite possible for that spiral structure to be wiped out, don’t be fooled when you look at a disc. It could still be reasonably massive, it’s just that a giant planet has caused it to lose its spirals.
“We have these amazing images of protoplanetary discs and what’s really exciting about them is their structure. In the past few years telescopes have become very powerful and we’re able to see features like gaps and rings. With computer simulations like ours, we can now try to understand if some of the processes that we expect to happen, like planets migrating in young discs, can lead to the kind of images that observers are seeing. This is possible with the combination of powerful telescopes and supercomputers.”
A team led by researchers at Baylor College of Medicine and Rice University has developed artificial intelligence models that help them better understand the brain computations that underlie thoughts. This is new, because until now there has been no method to measure thoughts.
The researchers first developed a new model that can estimate thoughts by evaluating behavior, and then tested their model on a trained artificial brain where they found neural activity associated with those estimates of thoughts. The theoretical study appears in the Proceedings of the National Academy of Sciences.
“For centuries, neuroscientists have studied how the brain works by relating brain activity to inputs and outputs,” said corresponding author Xaq Pitkow, assistant professor of neuroscience at Baylor and of electrical and computer engineering at Rice. “For instance, when studying the neuroscience of movement, scientists measure muscle movements as well as neuronal activity and then relate those two measurements. To study cognition in the brain, however, we don’t have anything to compare the measured neural activity to.”
To understand how the brain gives rise to thought, researchers first need to measure a thought. They developed a method called “Inverse Rational Control” that looks at a behavior and infers the beliefs or thoughts that best explain that behavior.
Traditionally, researchers in this field have worked with the idea that animals solve tasks optimally, behaving in a way that maximizes their net benefits. But when scientists study animal behavior, they find that this is not always the case.
“Sometimes animals have ‘wrong’ beliefs or assumptions about what’s going on in their environment, but still they try to find the best long-term outcomes for their task, given what they believe is going on around them,” said Pitkow, who also is a McNair Scholar at Baylor, co-director of Baylor’s Center for Neuroscience and Artificial Intelligence and member of the Rice Neuroengineering Initiative. “This could account for why animals seem to behave suboptimally.”
For example, consider an animal that is hunting and hears many noises it associates with prey. If one potential prey is making all the noises, the optimal behavior for the hunter is to consistently target its movements to a single noise. If the hunter mistakenly believes the noises are coming from many different animals, it may choose a suboptimal behavior, like constantly scanning its surroundings to try and pinpoint one of them. By acting according to its belief or assumption that there are many potential prey nearby, the hunter is behaving in a way that is simultaneously rational and suboptimal.
In the second part of the work, Pitkow and his colleagues developed a model to relate thoughts that were identified using the Inverse Rational Control method to brain activity.
“We can look at the dynamics of the modeled thoughts and at the dynamics of the brain’s representations of those thoughts,” Pitkow said. “If those dynamics run parallel to each other, then we have confidence that we are capturing the aspects of the brain computations involved in those thoughts. By providing methods to estimate thoughts and interpret neural activity associated with them, this study can help scientists understand how the brain produces complex behavior and provide new perspectives on neurological conditions.”
Other contributors to this work include Zhengwei Wu of both Baylor College of Medicine and Rice; Minhae Kwon of Soongsil University in South Korea and formerly of Rice and Baylor College of Medicine; Rice alumnus Saurabh Daptardar ’18 of Google Maps; and Paul Schrater of the University of Minnesota.
This work was supported in part by in part by a BRAIN Initiative grant from the National Institutes of Health (NS094368), the McNair Foundation, the Simons Collaboration on the Global Brain (324143) and the National Science Foundation (1450923, 1552868).
References: Zhengwei Wu, Minhae Kwon, Saurabh Daptardar, Paul Schrater, Xaq Pitkow, “Rational thoughts in neural codes”, Proceedings of the National Academy of Sciences Nov 2020, 117 (47) 29311-29320; DOI: 10.1073/pnas.1912336117
Neuroscientists find that isolation provokes brain activity similar to that seen during hunger cravings.
Since the coronavirus pandemic began in the spring, many people have only seen their close friends and loved ones during video calls, if at all. A new study from MIT finds that the longings we feel during this kind of social isolation share a neural basis with the food cravings we feel when hungry.
The researchers found that after one day of total isolation, the sight of people having fun together activates the same brain region that lights up when someone who hasn’t eaten all day sees a picture of a plate of cheesy pasta.
“People who are forced to be isolated crave social interactions similarly to the way a hungry person craves food. Our finding fits the intuitive idea that positive social interactions are a basic human need, and acute loneliness is an aversive state that motivates people to repair what is lacking, similar to hunger,” says Rebecca Saxe, the John W. Jarve Professor of Brain and Cognitive Sciences at MIT, a member of MIT’s McGovern Institute for Brain Research, and the senior author of the study.
The research team collected the data for this study in 2018 and 2019, long before the coronavirus pandemic and resulting lockdowns. Their new findings, described today in Nature Neuroscience, are part of a larger research program focusing on how social stress affects people’s behavior and motivation.
Former MIT postdoc Livia Tomova, who is now a research associate at Cambridge University, is the lead author of the paper. Other authors include Kimberly Wang, a McGovern Institute research associate; Todd Thompson, a McGovern Institute scientist; Atsushi Takahashi, assistant director of the Martinos Imaging Center; Gillian Matthews, a research scientist at the Salk Institute for Biological Studies; and Kay Tye, a professor at the Salk Institute.
The new study was partly inspired by a recent paper from Tye, a former member of MIT’s Picower Institute for Learning and Memory. In that 2016 study, she and Matthews, then an MIT postdoc, identified a cluster of neurons in the brains of mice that represent feelings of loneliness and generate a drive for social interaction following isolation. Studies in humans have shown that being deprived of social contact can lead to emotional distress, but the neurological basis of these feelings is not well-known.
“We wanted to see if we could experimentally induce a certain kind of social stress, where we would have control over what the social stress was,” Saxe says. “It’s a stronger intervention of social isolation than anyone had tried before.”
To create that isolation environment, the researchers enlisted healthy volunteers, who were mainly college students, and confined them to a windowless room on MIT’s campus for 10 hours. They were not allowed to use their phones, but the room did have a computer that they could use to contact the researchers if necessary.
“There were a whole bunch of interventions we used to make sure that it would really feel strange and different and isolated,” Saxe says. “They had to let us know when they were going to the bathroom so we could make sure it was empty. We delivered food to the door and then texted them when it was there so they could go get it. They really were not allowed to see people.”
After the 10-hour isolation ended, each participant was scanned in an MRI machine. This posed additional challenges, as the researchers wanted to avoid any social contact during the scanning. Before the isolation period began, each subject was trained on how to get into the machine, so that they could do it by themselves, without any help from the researcher.
“Normally, getting somebody into an MRI machine is actually a really social process. We engage in all kinds of social interactions to make sure people understand what we’re asking them, that they feel safe, that they know we’re there,” Saxe says. “In this case, the subjects had to do it all by themselves, while the researcher, who was gowned and masked, just stood silently by and watched.”
Each of the 40 participants also underwent 10 hours of fasting, on a different day. After the 10-hour period of isolation or fasting, the participants were scanned while looking at images of food, images of people interacting, and neutral images such as flowers. The researchers focused on a part of the brain called the substantia nigra, a tiny structure located in the midbrain, which has previously been linked with hunger cravings and drug cravings. The substantia nigra is also believed to share evolutionary origins with a brain region in mice called the dorsal raphe nucleus, which is the area that Tye’s lab showed was active following social isolation in their 2016 study.
The researchers hypothesized that when socially isolated subjects saw photos of people enjoying social interactions, the “craving signal” in their substantia nigra would be similar to the signal produced when they saw pictures of food after fasting. This was indeed the case. Furthermore, the amount of activation in the substantia nigra was correlated with how strongly the patients rated their feelings of craving either food or social interaction.
Degrees of loneliness
The researchers also found that people’s responses to isolation varied depending on their normal levels of loneliness. People who reported feeling chronically isolated months before the study was done showed weaker cravings for social interaction after the 10-hour isolation period than people who reported a richer social life.
“For people who reported that their lives were really full of satisfying social interactions, this intervention had a bigger effect on their brains and on their self-reports,” Saxe says.
The researchers also looked at activation patterns in other parts of the brain, including the striatum and the cortex, and found that hunger and isolation each activated distinct areas of those regions. That suggests that those areas are more specialized to respond to different types of longings, while the substantia nigra produces a more general signal representing a variety of cravings.
Now that the researchers have established that they can observe the effects of social isolation on brain activity, Saxe says they can now try to answer many additional questions. Those questions include how social isolation affect people’s behavior, whether virtual social contacts such as video calls help to alleviate cravings for social interaction, and how isolation affects different age groups.
The researchers also hope to study whether the brain responses that they saw in this study could be used to predict how the same participants responded to being isolated during the lockdowns imposed during the early stages of the coronavirus pandemic.
The research was funded by a SFARI Explorer Grant from the Simons Foundation, a MINT grant from the McGovern Institute, the National Institutes of Health, including an NIH Pioneer Award, a Max Kade Foundation Fellowship, and an Erwin Schroedinger Fellowship from the Austrian Science Fund.