Mount Sinai is first in New York to study a brain-computer interface designed to record and map the brain’s activity in unprecedented detail

THE MOUNT SINAI HOSPITAL / MOUNT SINAI SCHOOL OF MEDICINE

 

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THE MOUNT SINAI HOSPITAL CAMPUS

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CREDIT: MOUNT SINAI HEALTH SYSTEM

A multidisciplinary team of neurosurgeons and neuroscientists from the Icahn School of Medicine at Mount Sinai are the first in New York to study a new brain-computer interface that’s engineered to map a large area of the brain’s surface, in real time, at resolutions hundreds of times more detailed than typical arrays used in neurosurgical procedures.

A brain-computer interface (BCI) is a system that deciphers brain signals and translates them into commands for external technologies. The ultimate goal of a BCI is to restore function to patients with debilitating neurological conditions by enabling them to operate digital devices using only their thoughts.

The Layer 7 Cortical Interface, developed by Precision Neuroscience Corporation, contains 1,024 tiny electrodes spanning an area of 1.5 square centimeter, embedded in a flexible film that conforms to the brain’s surface. The film is one-fifth the thickness of a human hair and was designed to be implanted and removed by neurosurgeons without damaging brain tissue.

“Mount Sinai has established an international reputation for our ability to conduct the most advanced biomedical and scientific research, for our commitment to exceptional patient care, and for our entrepreneurial approach to generating new treatments and advancements in care,” said Joshua B. Bederson, MD, Chair of Neurosurgery at the Mount Sinai Health System and Co-Founder of Mount Sinai BioDesign. “This culture of excellence, innovation, and collaboration attracts some of the brightest and best clinicians and researchers in the world who are capable of rapidly translating research breakthroughs into new products and services that provide meaningful benefit to patients and our society. We are proud to be one of the leading sites participating in the trials for the new array and eager to see what we learn from the detailed information we will collect and analyze.”

As part of an open-label, single-arm feasibility study, Mount Sinai neurosurgeons are temporarily placing the investigational device on the surface of the study participants’ brains during intracranial procedures where surface mapping is routinely performed and correlated to evoked potentials (tests that measure the brain’s response to sensory stimulation) or standardized behavioral tasks that are routinely performed as part of these procedures. The device records high-resolution electrophysiological signals and the data collected is compared to that obtained using standard-of-care cortical surface arrays.

A team of Mount Sinai neuroscientists who have deep expertise in human electrophysiology will analyze and interpret the massive amount of data collected from the device. A secondary objective of the study is to assess the ability of the thin-film electrode to map electrophysiological correlates of awake behavioral tasks, including motor, speech, and cognitive tasks.

“Despite the vast complexity of activity across the human brain, standard monitoring tools can only capture a tiny fraction of the data we need—from a small handful of areas, or at very slow temporal resolution. This low-resolution data significantly limits our understanding of brain function and brain disorders,” says Ignacio Saez, PhD, Associate Professor of Neuroscience, and Neurosurgery, Director of the Human Neurophysiology Laboratory, and Principal Investigator of the trial at Icahn Mount Sinai. “The new device is exciting because it provides us with an extremely detailed depiction of electrical activity in the brain, capturing thousands of data points per second from a thousand brain sites in each participant. By monitoring neuronal activity at this unprecedented resolution, our interdisciplinary team at Mount Sinai hopes to gain important insights into how brain function supports behavior and is affected by disease states. Our ultimate goal is to obtain actionable knowledge that will open the door to new treatments for neurological and psychiatric disorders and improve quality of life for our patients.”

Precision Neuroscience was co-founded by Benjamin Rapoport, MD, PhD, Assistant Professor of Neurosurgery at Icahn Mount Sinai, a practicing neurosurgeon who has a PhD in electrical engineering and computer science. Dr. Rapoport also serves as the Scientific Director of Mount Sinai BioDesign, a medical technology prototyping center and incubator housed within the Mount Sinai Health System.

Dr. Rapoport is an equity owner in Precision Neuroscience and serves as their Chief Scientific Officer and a member of their board of directors. As a faculty member in the Department of Neurosurgery, he reports to Dr. Bederson. Neither Dr. Bederson nor Mount Sinai have a financial interest in Precision Neuroscience. All Precision Neuroscience research at Mount Sinai is conducted by independent investigators without financial ties to the company.

About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, more than 400 outpatient practices, more than 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it. Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,400 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2023-2024.

About Mount Sinai BioDesign
Mount Sinai BioDesign is the medical technology prototyping center and incubator housed within the Mount Sinai Health System. The team comprises a unique blend of entrepreneurs, engineers, clinicians, trialists, and project managers with a mission to improve clinical care through the invention, development, and commercialization of new medical technologies. Sinai BioDesign works with internal and external partners, assisting Mount Sinai faculty to develop and launch new technologies, and assisting external industry partners in the optimization and validation of existing technologies. The team has core competencies around rapid iterative prototype development, benchtop testing within bespoke anatomical models, preclinical testing, and the design and operation of early-stage clinical trials. Sinai BioDesign has numerous patent applications, has launched several funded startups, and has existing partnerships with major surgical technology corporations. Originating from the Department of Neurosurgery and led by Dr. Joshua Bederson, the team has a deep portfolio of neurotechnology innovations and partnerships.

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METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

 

Multiple unsafe sleep practices found in most sudden infant deaths

UNIVERSITY OF VIRGINIA HEALTH SYSTEM

 

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FERN HAUCK, MD, MS, IS A SAFE-SLEEP EXPERT AT UVA HEALTH AND THE UNIVERSITY OF VIRGINIA SCHOOL OF MEDICINE. 

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CREDIT: DAN ADDISON | UVA COMMUNICATIONS

There were multiple unsafe sleep practices at play in more than three-quarters of Sudden Unexpected Infant Deaths reported in 23 jurisdictions between 2011 and 2020, a new study reveals. The researchers say the findings underscore the need for more comprehensive safe-sleep education for new parents, including from healthcare providers.

Of 7,595 infant deaths reviewed, almost 60% of the infants were sharing a sleep surface, such as a bed, when they died. This practice is strongly discouraged by sleep experts, who warn that a parent or other bed partner could unintentionally roll over and suffocate the baby.

Infants who died while sharing a sleep surface were typically younger (less than 3 months old), non-Hispanic Black, publicly insured, and either in the care of a parent at the time of death or being supervised by someone impaired by drugs or alcohol. These infants were typically found in an adult bed, chair or couch instead of the crib or bassinet recommended by sleep experts.

“The large number of hazardous sleep practices for both infants who were sharing a sleep surface and sleeping alone at the time of death is alarming,” said researcher Fern Hauck, MD, MS, a safe-sleep expert at UVA Health and the University of Virginia School of Medicine. “These are known risk factors for SUID [Sudden Unexpected Infant Death], and tells us that we need to do a better job of working with families to increase acceptance of the recommendations to create safer sleep spaces for their infants.” 

Sudden Unexpected Infant Deaths

To better understand the factors contributing to SUID and improve safe-sleep messaging, Hauck and her collaborators analyzed data from the federal Centers for Disease Control and Prevention’s SUID Case Registry. That data reflects localities from Alaska to Wyoming, including the Tidewater area of Virginia. 

Examining the registry allowed the researchers to obtain important insights on the prevalence of practices such as prenatal smoking, a known risk factor for SUID, and breastfeeding, which is thought to have a protective benefit. More than 36% of mothers of infants who died had smoked while pregnant. This percentage was higher among moms who bed shared than those who didn’t, 41.4% to 30.5%. Both bed sharers and non-bed sharers had breastfed at similar rates. 

The researchers note that it was rare for bedsharing to be the only risk factor present during a child’s death. The findings highlight the need for better public education about safe-sleep practices, and for care providers to take a more active role in teaching new parents about the practices, the researchers say.

 “Our findings support comprehensive safe sleep counseling for every family at every encounter beyond just asking where an infant is sleeping,” the researchers write in a new paper in the journal Pediatrics.

In addition to helping parents understand safe-sleep practices, care providers should take steps to ensure parents can follow those practices once they leave the hospital. For example, some families may not have the means to purchase a crib or bassinet; a hospital might direct them to resources to help with that.

“SUID deaths in the U.S. are still higher than in most other countries, and this is unacceptable,” Hauck said. “Clinicians and others caring for infants need to have thoughtful conversations with families at risk to understand the barriers to following safe-sleep guidelines and find ways to work together to overcome them.”

About the SUID Research Team

The SUID research team consisted of Alexa B. Erck Lambert, Carrie K. Shapiro-Mendoza, Sharyn E. Parks, Carri Cottengim, Meghan Faulkner and Hauck. The researchers have no financial interest in the work.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog

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JOURNAL

PEDIATRICS

DOI

10.1542/peds.2023-061984 

An avocado a day may improve overall diet quality, researchers report

NO MENTION OF TOAST

PENN STATE

UNIVERSITY PARK, Pa. — Eating one avocado per day may improve overall diet quality, according to a team led by researchers in Penn State’s Department of Nutritional Sciences. Poor diet quality is a risk factor for many diseases, including heart disease, and many American adults have poor diet quality and do not meet key dietary recommendations provided by the Dietary Guidelines for Americans.

This study was led by Kristina Petersen, associate professor of nutritional sciences, and Penny Kris-Etherton, retired Evan Pugh University Professor of Nutritional Sciences, and recently published in the journal Current Developments in Nutrition.  The researchers examined how a food-based intervention — one avocado per day — impacts overall diet quality.

“Avocados are a nutrient-dense food, containing a lot of fiber and other important nutrients. We wanted to see if regular intake of this food would lead to an increase in diet quality,” Petersen said. “Previous observational research suggests avocado consumers have higher diet quality than non-consumers. So, we developed this study to determine if there is a causational link between avocado consumption and overall diet quality.” 

Petersen stated that because only 2% of American adults are regular avocado consumers, the researchers wanted to determine if including avocados in an individual’s daily diet could significantly increase their diet quality.

Researchers conducted phone interviews with participants before the study began and at a few points throughout to determine what their dietary intake was like in the previous 24 hours and evaluated their diets using the Healthy Eating Index to determine how well they adhered to the Dietary Guidelines for Americans. Adherence to the guidelines was used as a measure of overall diet quality.

The study consisted of 1,008 participants who were split into two groups. One group continued their usual diet and limited their avocado intake during the 26-week study, while the other group incorporated one avocado per day into their diet.

“We found that the participants who had an avocado per day significantly increased their adherence to dietary guidelines,” Petersen said. “This suggests that strategies, like eating one avocado per day, can help people follow dietary guidelines and improve the quality of their diets.”

Although researchers said they were not surprised to see that eating avocados daily improved diet quality, they had not predicted how participants were able to achieve it.

“We determined that participants were using avocados as a substitute for some foods higher in refined grains and sodium,” Petersen said. “In our study, we classified avocados as a vegetable and did see an increase in vegetable consumption attributed to the avocado intake, but also participants used the avocados to replace some unhealthier options.”

According to Petersen, having poor diet quality substantially increases the risk for conditions like heart disease, type 2 diabetes, kidney disease and many other preventable diseases.

“By improving people’s adherence to dietary guidelines, we can help to reduce their risk of developing these chronic conditions and prolong healthy life expectancy,” Petersen said.

Petersen has also conducted similar studies investigating the impact of food-based interventions, including the relationship between pistachios and diet quality, but said that more research is needed to determine what other food-based strategies can be used to improve people’s adherence to dietary guidelines. 

“In studies like this one, we are able to determine food-based ways to improve diet quality, but behavioral strategies are also needed to help people adhere to dietary guidelines and reduce their risk of chronic disease,” Petersen said.

Other contributors to the study include Sydney Smith and David M. Reboussin, Wake Forest University School of Medicine; Alice H. Lichtenstein and Nirupa R. Matthan, Tufts University; Zhaoping Li, David Geffen School of Medicine at the University of California, Los Angeles; and Joan Sabate, Sujatha Rajaram and Gina Segovia-Siapco, Loma Linda University. 

The Avocado Nutrition Center supported this study. The funder did not influence the data analysis, data interpretation or writing of the published study.

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JOURNAL

Current Developments in Nutrition

DOI

10.1016/j.cdnut.2024.102079 

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

One Avocado per Day as Part of Usual Intake Improves Diet Quality: Exploratory Results from a Randomized Controlled Trial

 

Accumulation of 'junk proteins' identified as one cause of aging and possible source of ALS

CENTRO NACIONAL DE INVESTIGACIONES ONCOLÓGICAS (CNIO)

 

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ACCUMULATION OF "JUNK PROTEINS": NORMAL CELLS (LEFT) AND CELLS SUBJECTED TO THE EFFECT OF THE TOXIC ARGININE-RICH PROTEIN (RIGHT). IN THE LATTER, RIBOSOMAL PROTEINS (GREEN FLUORESCENT) AND THE SIZE OF NUCLEOLI (RED) ARE INCREASED.

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CREDIT: CN

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• CNIO researchers provide a new hypothesis to understand the origin of amyotrophic lateral sclerosis, or ALS. It would be triggered by a similar problem to that occurring in a group of rare diseases called ribosomopathies.
• In ALS patients, motor neurons would accumulate an excess of non-functional ribosomal proteins that eventually collapse the cell's clearance systems and cause toxicity.
• The study also opens a new front in aging research. The authors provide experimental evidence that formally proves a kind of stress called ‘nucleolar stress’ cause aging in mammals.

Amyotrophic lateral sclerosis (ALS) is a degenerative disease. The neurons responsible for movement begin to die and muscle control is progressively lost, leading to a fatal outcome. The causes of ALS are currently unknown, and there is no effective treatment.

In a paper published in Molecular Cell, a team led by Óscar Fernández-Capetillo, head of the Genomic Instability Group at the Spanish National Cancer Research Center (CNIO), provides the first evidence that a possible cause of the hereditary type of ALS –familial ALS– is the accumulation in motor neurons of 'junk proteins', proteins with no function that wrongly accumulate and prevent the cell from functioning properly.

Specifically, these non-functional proteins that accumulate are ribosomal proteins, which normally form ribosomes, molecular factories in charge of protein production.

Thus, this study provides a new hypothesis for understanding the origin of ALS, by suggesting that it has a similar origin to another group of rare diseases known as ribosomopathies, also associated with an excess of non-functional ribosomal proteins (in the case of ALS, this problem is restricted to motor neurons).

The new study also opens a new front in a different area, aging research. The authors propose a new causal factor in the aging process, which until now would have been overlooked: nucleolar stress, a mechanism by which organelles called nucleoli react to various damages in the cell.

"In our work we report a new model that explains how nucleolar stress induces toxicity in animal cells, and we provide direct evidence that it accelerates aging in mammals," Vanesa Lafarga, corresponding co-author of the study says.

A 'tar' that blocks RNA

Most patients with hereditary ALS share mutations in a gene called C9ORF72. This mutation results in the production of toxic proteins –or peptides– rich in the amino acid arginine. In a previous work, Fernandez Capetillo's group took the first steps to understand why these peptides are toxic. The reason is that these toxins stick to DNA and RNA "as if they were tar," affecting virtually all reactions in the cell that use these nucleic acids.

The study now published in Molecular Cell, with Oleksandra Sirozh as first author, shows that the toxin has a particularly acute effect on the manufacture of new ribosomes, production factories inside the cell, which are made up of RNA and proteins.

ALS as a ribosomopathy

Thus, as they are unable to complete their assembly, "the cell accumulates an excess of orphan ribosomal proteins, incapable of forming ribosomes," explains Fernández Capetillo. "These proteins end up collapsing the cellular clearance systems, which finally leads to the death of the motor neurons".

For the authors, this work suggests for the first time a similarity between the cause of ALS and another type of diseases known as ribosomopathies, also associated with the accumulation of dysfunctional ribosomal proteins in a generalized manner in all cells of the human body.

Potential treatment pathway

Based on this finding, the CNIO group has explored a solution. "As the problem is the excess of ribosomal junk, we explored strategies to make cells produce fewer ribosomes," explains Fernández-Capetillo. To achieve this, they used genetic and pharmacological manipulation to switch off two of the mechanisms that generate ribosomes in tissues in vitro, and found that, by producing less "garbage", toxicity is actually reduced.

However, Fernández-Capetillo says that these results should be interpreted with caution: "We are in the first steps to see if we can give a therapeutic angle to these findings”. For the moment, these experiments simply indicate "the possible existence of avenues that had not been explored in the search for treatments" against ALS. "We must find ways to reduce the production of ribosomes so that waste decreases, while still keeping a sufficient number to guarantee the correct functioning of the cells."

A new cause of aging: nucleolar stress

The nucleolus is the cellular component where ribosomes are synthesized. In recent decades it has been observed that one of its functions is also to detect stress situations in the cell, such as DNA damage or lack of nutrients. Nucleolar stress can eventually alter protein production, and its triggers are the object of a very active area of research.

In the work now published in Molecular Cell, the authors generated animals expressing throughout the body the toxin found in ALS patients, which induced severe nucleolar stress. But the researchers also observed, unexpectedly, that these animals aged very rapidly.

Junk proteins accelerate aging

Based on their previous studies, they found that this aging was also due to the accumulation of non-functional ribosomal proteins: when animals were given a drug that reduces the rate of ribosome production, their life expectancy doubled.

There had been speculation about the relationship between nucleolar stress and aging, but it had not been possible to demonstrate a causal relationship. This work "is the first experimental evidence that generating nucleolar stress accelerates aging," says Fernández Capetillo.

The work has been co-financed by the Ministry of Science, Innovation and Universities, FEDER funds from the European Union, the Spanish Association Against Cancer and the "la Caixa" Foundation in alliance with the Francisco Luzón Foundation.

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JOURNAL

Molecular Cell

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates aging in mice

ARTICLE PUBLICATION DATE

22-Mar-2024

 

Your dog understands that some words “stand for” objects

CELL PRESS

 

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THIS PHOTOGRAPH SHOWS A DOG EEG EXPERIMENTAL SETUP.

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CREDIT: GRZEGORZ ELIASIEWICZ

It’s no surprise that your dog can learn to sit when you say “sit” and come when called. But a study appearing March 22 in the journal Current Biology has made the unexpected discovery that dogs generally also know that certain words “stand for” certain objects. When dogs hear those words, brain activity recordings suggest they activate a matching mental representation in their minds.

“Dogs do not only react with a learned behavior to certain words,” says Marianna Boros (@FamDogProject) of the Department of Ethology at the Eötvös Loránd University, Budapest, Hungary, one of the paper’s co-first authors. “They also don’t just associate that word with an object based on temporal contiguity without really understanding the meaning of those words, but they activate a memory of an object when they hear its name.”

Word understanding tests with individuals who do not speak, such as infants and animals, usually require active choice, the researchers say. They’re asked to show or get an object after hearing its name. Very few dogs do well on such tests in the lab, often fetching objects correctly at a rate expected by chance.

The researchers wanted to look closer at dogs’ implicit understanding of object words by measuring brain activity using non-invasive EEG without asking them to act. The idea was that this might offer a more sensitive measure of their understanding of language.

In their studies, they had 18 dog owners say words for toys their dogs knew and then present the objects to them. Sometimes they presented the matching toy, while other times they would present an object that didn’t match. For example, an owner would say, “Zara, look, the ball,” and present the object while the dog’s brain activity was captured on EEG.

The brain recording results showed a different pattern in the brain when the dogs were shown a matching object versus a mismatched one. That’s similar to what researchers have seen in humans and is widely accepted as evidence that they understand the words. The researchers also found a greater difference in those patterns for words that dogs knew better, offering further support for their understanding of object words. Interestingly, while the researchers thought this ability might depend on having a large vocabulary of object words, their findings showed that it doesn’t.

“Because typical dogs learn instruction words rather than object names, and there are only a handful of dogs with a large vocabulary of object words, we expected that dogs’ capacity for referential understanding of object words will be linked to the number of object words they know; but it wasn’t,” says Lilla Magyari, also of Eötvös Loránd University and University of Stavanger and the other co-first author.

“It doesn’t matter how many object words a dog understands—known words activate mental representations anyway, suggesting that this ability is generally present in dogs and not just in some exceptional individuals who know the names of many objects,” Boros added.

The discovery that dogs as a species may generally have a capacity to understand words in a referential way, just as humans do, might reshape the way scientists think about the uniqueness of how humans use and understand language, the researchers say. That has important implications for theories and models of language evolution. For dog owners, it’s also an important realization.

“Your dog understands more than he or she shows signs of,” Magyari says. “Dogs are not merely learning a specific behavior to certain words, but they might actually understand the meaning of some individual words as humans do.”

The researchers are now curious to know if this ability to understand referential language is specific to dogs or might be present in other mammals as well. Either way, they want to learn more about how this ability emerged and whether it depends on dogs’ unique experience of living with people. They also want to know why, if dogs understand object words, more of them don’t show it.

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Funding information can be found in the paper under acknowledgements. The authors declare no competing interests.

Current Biology, Boros and Magyari et al.: “Neural evidence for referential understanding of object words in dogs,” https://www.cell.com/current-biology/fulltext/S0960-9822(24)00171-4 

Current Biology (@CurrentBiology), published by Cell Press, is a bimonthly journal that features papers across all areas of biology. Current Biology strives to foster communication across fields of biology, both by publishing important findings of general interest and through highly accessible front matter for non-specialists. Visit http://www.cell.com/current-biology. To receive Cell Press media alerts, contact press@cell.com.

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JOURNAL

Current Biology

DOI

10.1016/j.cub.2024.02.029 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Neural evidence for referential understanding of object words in dogs

ARTICLE PUBLICATION DATE

22-Mar-2024

Your dog understands that some words ‘stand for’ objects, new study shows

It’s no surprise that dogs can learn to understand and respond to human words.

EÖTVÖS LORÁND UNIVERSITY

 

IMAGE: 

IT’S NO SURPRISE THAT DOGS CAN LEARN TO UNDERSTAND AND RESPOND TO HUMAN WORDS. YOUR DOG CAN LEARN TO SIT WHEN YOU SAY “SIT” AND COME WHEN CALLED. BUT A NEW STUDY HAS MADE THE SURPRISING DISCOVERY BY RECORDING BRAIN ACTIVITY THAT DOGS GENERALLY ALSO KNOW THAT CERTAIN WORDS “STAND FOR” CERTAIN OBJECTS. WHEN THEY HEAR THOSE WORDS, THEY ACTIVATE A MATCHING MENTAL REPRESENTATION IN THEIR MINDS. THE FINDINGS ARE REPORTED IN CURRENT BIOLOGY ON MARCH 22, 2024.

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CREDIT: PHOTO: GRZEGORZELIASIEWICZ

It’s no surprise that dogs can learn to understand and respond to human words. Your dog can learn to sit when you say “sit” and come when called. But a new study has made the surprising discovery by recording brain activity that dogs generally also know that certain words “stand for” certain objects. When they hear those words, they activate a matching mental representation in their minds. 

“Dogs do not only react with a learned behavior to certain words,” says Marianna Boros of the Department of Ethology at the Eötvös Loránd University, Budapest, Hungary. “They also don’t just associate that word with an object based on temporal contiguity without really understanding the meaning of those words, but they activate a memory of an object when they hear its name.”

Word understanding tests with individuals who do not speak, such as infants and animals, usually require active choice, the researchers explained. They’re asked to show or get an object after hearing its name. Very few dogs do well on such tests in the lab, often fetching objects correctly at a rate expected by chance.

In the new study, the researchers wanted to look closer at dogs’ implicit understanding of object words by measuring brain activity using non-invasive EEG. The idea was that this might offer a more sensitive measure of their understanding of language.

They had 18 dog owners say words for toys their dogs knew and then present the objects to them. Sometimes they presented the matching toy while other times they would present an object that didn’t match. For example, an owner would say, “Zara, look, the ball,” and presented the object while the dog’s brain activity was captured on EEG.

The brain recording results showed a different pattern in the brain when the dogs were shown a matching object versus a mismatched one, similarly to what we see in humans, and what is widely accepted as evidence that they understand the words. The researchers also found a greater difference in those patterns for words that dogs knew better, offering further support for their understanding of object words. While the researchers thought this ability might depend on having a large vocabulary of object words, their findings showed that it doesn’t.

“Because typical dogs learn instruction words rather than object names, and there are only a handful of dogs with a large vocabulary of object words, we expected that dogs’ capacity for referential understanding of object words will be linked to the number of object words they know; but it wasn’t,” said Lilla Magyari, also of Eötvös Loránd University and University of Stavanger.

“It doesn’t matter how many object words a dog understands, known words activate mental representations anyway, suggesting that this ability is generally present in dogs and not just in some exceptional individuals who know the names of many objects,” Boros added.

The discovery that dogs as a species generally may have a capacity to understand words in a referential way, just as humans do, might reshape the way scientists think about the uniqueness of how humans use and understand language, the researchers say. That has important implications for theories and models of language evolution. For dog owners, it’s an important realization also.

“Your dog understands more than he or she shows signs of,” Magyari says. “Dogs are not merely learning a specific behavior to certain words, but they might actually understand the meaning of some individual words as humans do.”

The researchers are now curious to know if this ability to understand referential language is specific to dogs or might be present in other mammals as well. Either way, they’re curious how this ability emerged and whether it depends on dogs’ unique experience of living with people. They also want to know why, if dogs understand object words, more of them don’t show it.

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JOURNAL

Current Biology

DOI

10.1016/j.cub.2024.02.029. 

ARTICLE TITLE

Neural evidence for referential understanding of object words in dogs

ARTICLE PUBLICATION DATE

22-Mar-2024

Experimental setup 

EÖTVÖS LORÁND UNIVERSITY

CREDIT    Photo: Oszkár Dániel Gáti

Dog during EEG experiment 

EÖTVÖS LORÁND UNIVERSITY

This photograph shows a dog EEG experimental setup. 

CREDIT

Grzegorz Eliasiewicz

This photograph shows study participants Zara and Zsóka.

CREDIT

Marianna Boros

 

Stem cell model offers first glimpse of early human development

ROCKEFELLER UNIVERSITY

 

IMAGE: 

A BLASTOID, A STEM CELL MODEL SYSTEM THAT ALLOWS SCIENTISTS TO STUDY THE NUANCES OF HUMAN GASTRULATION.

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CREDIT: LABORATORY OF STEM CELL BIOLOGY AND MOLECULAR EMBRYOLOGY AT THE ROCKEFELLER UNIVERSITY

It’s one of life’s most defining moments—that crucial step in embryonic development, when an indistinct ball of cells rearranges itself into the orderly three-layered structure that sets the stage for all to come. Known as gastrulation, this crucial process unfolds in the third week of human development. “Gastrulation is the origin of our own individualization, the emergence of our axis,” says Rockefeller’s Ali Brivanlou. “It is the first moment that separates our heads from our behinds.”

Observing the molecular underpinnings of this pivotal event would go a long way toward helping scientists prevent miscarriages and developmental disorders. But studying human gastrulation has proven both technologically difficult and ethically complicated, and thus current approaches have had limited success in expanding our understanding of early human development. Now Brivanlou and colleagues have demonstrated how a stem cell model system known as a blastoid can allow the study of the nuances of human gastrulation in the presence of pre-implantation extra-embryonic cell types. Their study, published in Stem Cell Reports, describes the scientific and clinical potential of this new platform.

“Gastrulation was a tremendous black box. We had never seen ourselves at that stage,” Brivanlou says. “This moves us closer to understanding how we begin.”

A better blastocyst

Prior to implantation, an embryo is a ball of about 250 cells organized as a blastocyst. This elusive ball of cells was difficult to study directly, so scientists developed blastoids—stem-cell-based blastocyst models. Blastoids can be cloned, experimentally manipulated, and programmed, allowing scientists to study identical blastoids over and over again.

The question was whether blastoids could gastrulate in vitro. Unlike a blastocyst in vivo, which rolls around in the uterus until it attaches to maternal tissue, blastoids were good at modeling the ball of cells from which life emerges, but it remained unclear whether this in vitro model could model later stages of human development. That is, until Brivanlou developed a platform to allow blastoids to attach in vitro, and thereby progress toward gastrulation.

“We were then able to see epiblast symmetry breaking, marked by BRA expression, for the first time with the high molecular resolution,” says Riccardo De Santis, a research associate in the Brivanlou lab and lead author on the study. “This allowed us to start asking more detailed questions about the earliest moments of life.”

With this unprecedented clarity, the team directly observed two key moments in gastrulation: the first epiblast symmetry-breaking event and the emergence of the molecular markers of the primitive streak and mesoderm upon in vitro attachment.

The primitive streak is a structure that marks the beginning of gastrulation and lays the foundation for the three primary layers of the embryo. One of those layers, the mesoderm, forms during gastrulation and gives rise to muscles, bones, and the circulatory system. The team discovered that, as early as seven days after attachment, they were already able to use molecular markers to detect the earliest signature of a nascent primitive streak and mesodermal cells.

To confirm their findings, the team also compared the blastoid results with data from in vitro attached human embryos and demonstrated that blastoids express the same genes in vitro that a regular embryo would at that stage in vivo, a strong demonstration of the power of blastoids as models for human embryonic development. Further highlighting the power of the lab’s in vitro attached blastoid system, the team then used it to demonstrate that pathways that regulate the rise of the primitive streak and mesoderm in vivo also regulate blastoids symmetry breaking in vitro—all with nothing but stem-cell-derived blastoid models.

Along the way, the team also demonstrated that gastrulation in vitro can begin at day 12, earlier than once thought. “This will change textbooks,” Brivanlou says. “We’ve contributed to redefining the molecular signature and timing of the onset of gastrulation upon in vitro attachment”.

Therapeutic possibilities

The results demonstrate that blastoids, when combined with the Brivanlou lab’s unique attachment platform, are now capable of conveying insights into early human development that have long been inaccessible. De Santis envisions a future in which blastoid-based research leads to advancements in diagnosing and treating developmental disorders, or offers insights into potential causes of early miscarriages during gastrulation.

“Many couples can’t have babies because the embryo doesn’t attach properly, and many miscarriages occur in the first few weeks of pregnancy,” De Santis explains. “We now have a model system that can help us understand the molecular mechanism that defines whether a pregnancy will be successful or not.” In the near future, De Santis hopes to combine this method with machine learning to help predict pregnancy outcomes and the trajectories of developmental disorders by observing how model blastoids built with particular genetic makeups fare in vitro.

“A better understanding of gastrulation—and the ability to study it with a reliable model system—impacts everything from survival of the fetus to autism to neurodegeneration.”

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JOURNAL

Stem Cell Reports

DOI

10.1016/j.stemcr.2023.11.005 

ARTICLE TITLE

The emergence of human gastrulation upon in vitro attachment