Day: October 13, 2023

Evidence Points to Consciousness Emerging Shortly after Birth or in Late Pregnancy

Figure I Neural measurement tools for studying the emergence of consciousness. Examples of techniques for recording brain activity and/or neuroimaging in infants and foetuses. (A) Infant electroencephalography (EEG) with a geodesic electrode net. (B) Foetal magnetoencephalography (MEG) recorded from a pregnant woman. (C) Infant functional near infrared spectroscopy (fNIRS) recording with multichannel optode cap. (D) An infant is prepared for functional magnetic resonance imaging (fMRI). Source: Bayne et al., 2023

There is evidence that some form of conscious experience is present by birth, and perhaps even in late pregnancy, an international team of researchers has found. The findings, published today in Trends in Cognitive Science, have important clinical, ethical and potentially legal implications, according to the authors. 

Converging evidence from studies of functional network connectivity, attention, multimodal integration, and cortical responses to global oddballs suggests that consciousness is likely to be in place in early infancy and may even occur before birth. Over the decades, theorists have argued that consciousness emerges from anywhere from 30 to 35 weeks of pregnancy (based on EEG of the foetus’s brain) to 12 to 15 months of age (based on higher-order representational theory).

In the study, the researchers argue that by birth the infant’s developing brain is capable of conscious experiences that can leave a lasting imprint on their developing sense of self and understanding of their environment.

The team comprised neuroscientists and philosophers from Monash University, in Australia, University of Tübingen, in Germany, University of Minnesota, in the USA, and Trinity College Dublin.

Although each of us was once a baby, infant consciousness remains mysterious, because infants cannot tell us what they think or feel, explains one of the two lead authors of the paper Dr Tim Bayne, Professor of Philosophy at Monash University. 

“Nearly everyone who has held a newborn infant has wondered what, if anything, it is like to be a baby. But of course we cannot remember our infancy, and consciousness researchers have disagreed on whether consciousness arises ‘early’ (at birth or shortly after) or ‘late’ ­– by one year of age, or even much later.”

To provide a new perspective on when consciousness first emerges, the team built upon recent advances in consciousness science. In adults, some markers from brain imaging have been found to reliably differentiate consciousness from its absence, and are increasingly applied in science and medicine. This is the first time that a review of these markers in infants has been used to assess their consciousness.

Co-author of the study, Lorina Naci, Associate Professor in the School of Psychology, who leads Trinity’s ‘Consciousness and Cognition Group, explained: “Our findings suggest that newborns can integrate sensory and developing cognitive responses into coherent conscious experiences to understand the actions of others and plan their own responses.”

The paper also sheds light into ‘what it is like’ to be a baby. We know that seeing is much more immature in babies than hearing, for example. Furthermore, this work suggests that, at any point in time, infants are aware of fewer items than adults, and can take longer to grasp what’s in front of them, but it is easier for them to process more diverse information, such as sounds from other languages.

Source: Trinity College Dublin

Mapping the ‘Light’ Seen by Closed Eyes could Help Prosthetic Eyes See Better

Photo by Arteum.ro on Unsplash

Researchers at Monash University have identified a new way of mapping ‘phosphenes’ – the visual perception of the bright flashes we see when no light is entering the eye – to improve the outcome of surgery for patients receiving a cortical visual prosthesis.

Cortical visual prostheses are devices implanted onto the brain with the aim of restoring sight by directly stimulating the area responsible for vision, the visual cortex, bypassing damage to the retina of the eye or the optic nerve. Phosphenes, apparent flashes and patterns of lights, were described by the ancient Greeks and can be elicited by pressure, injury, disease, certain medications or direct electrical stimulation.

A typical prosthesis consists of an array of fine electrodes, each of which is designed to trigger a phosphene. Given the limited number of electrodes, understanding how electrodes can best be placed to generate useful perceived images becomes critical.

Published in the Journal of Neural Engineering, the study presents a more realistic simulation for cortical prosthetic vision.

As part of this researchers from the Department of Electrical and Computer Systems Engineering at Monash University, led by Associate Professor Yan Tat Wong, are honing in on the ideal distribution of phosphenes.

“Phosphenes are likely to be distributed unevenly in an individual’s visual field, and differences in the surface of the brain also affect how surgeons place implants, which together result in a phosphene map unique to each patient,” Associate Professor Wong said.

The study used a retinotopy dataset based on magnetic resonance imaging (MRI) scans, consulting with a neurosurgeon about realistic electrode implantation sites in different individuals, and applying a clustering algorithm to determine the most suitable regions to present stimuli.

Sighted participants recruited for the study were asked to test and verify the phosphene maps based on visual acuity and object recognition.

“We’re proposing a new process that incorporates our simulation paradigm into surgical planning to help optimise the implantation of a cortical prosthesis,” Associate Professor Wong said.

The process would begin with an MRI scan to plot the recipient’s brain surface in the area of the visual cortex. Potential implant locations would then be identified, and the simulation developed in the Monash research would be used to plot phosphene maps.

“We can use the metrics we computed to find practical implant locations that are more likely to give us a usable phosphene map, and we can verify those options through psychophysics tests on sighted participants using a virtual reality headset,” Associate Professor Wong said.

“We believe this is the first approach that realistically simulates the visual experience of cortical prosthetic vision.”

Source: Monash University

Difficulty with Turning when Walking could be a Sign of Early Alzheimer’s

In a study published in Current Biology, people with early Alzheimer’s disease were found to have difficulty turning when walking. The new study used virtual reality and a computational model to further explore the intricacies of navigational errors previously observed in Alzheimer’s disease.

Researchers, led by Professor Neil Burgess and colleagues in the Space and Memory group at the UCL Institute of Cognitive Neuroscience, grouped participants into three categories: healthy younger participants (31 total), healthy elderly participants (36 total) and patients with mild cognitive impairment (43 total). They then asked them to complete a task while wearing virtual reality goggles, which allowed them to make real movements.

In the trial, participants walked an outbound route guided by numbered cones, consisting of two straight legs connected by a turn. They then had to return to their starting position unguided.

The task was performed under three different environmental conditions aimed at stressing the participant’s navigational skills: an unchanged virtual environment, the ground details being replaced by a plain texture, and the temporary removal of all landmarks from the virtual reality world.

The researchers found that people with early Alzheimer’s consistently overestimated the turns on the route and showed increased variability in their sense of direction. However, these specific impairments were not observed in the healthy older participants or people with mild cognitive impairment, who did not show underlying signs of Alzheimer’s.

This suggests that these navigational errors are specific to Alzheimer’s disease – rather than an extension of healthy ageing or general cognitive decline – and could help with diagnosis.

Joint first author, Dr Andrea Castegnaro (UCL Institute of Cognitive Neuroscience), said: “Our findings offer a new avenue for the early diagnosis of Alzheimer’s disease by focusing on specific navigational errors. However, we know that more work is needed to confirm these early findings.

Dr Castegnaro added, “Cognitive assessments are still needed to understand when the first cognitive impairments develop, and when it comes to existing spatial memory tests used in clinics, those often rely on verbal competence. Our tests aim to offer a more practical tool that doesn’t rely on language or cultural background.”

Source: University College of London

Neanderthal Gene Variants Associated with Greater Sensitivity to Some Types of Pain

Source: Pixabay CC0

People who carry three gene variants that have bene inherited from Neanderthals are more sensitive to some types of pain, according to a new study co-led by UCL researchers. The findings, published in Communications Biology, are the latest findings to show how past interbreeding with Neanderthals has influenced the genetics of modern humans.

The researchers found that people carrying three so-called Neanderthal variants in the gene SCN9A, which is implicated in sensory neurons, are more sensitive to pain from skin pricking after prior exposure to mustard oil.

Previous research has identified three variations in the SCN9A gene – known as M932L, V991L, and D1908G – in sequenced Neanderthal genomes and reports of greater pain sensitivity among humans carrying all three variants. However, prior to this study the specific sensory responses affected by these variants was unclear.

An international team measured the pain thresholds of 1963 people from Colombia in response to a range of stimuli.

The SCN9A gene encodes a sodium channel that is expressed at high levels in sensory neurons that detect signals from damaged tissue. The researchers found that the D1908G variant of the gene was present in around 20% of chromosomes within this population and around 30% of chromosomes carrying this variant also carried the M932L and V991L variants.

The authors found that the three variants were associated with a lower pain threshold in response to skin pricking after prior exposure to mustard oil, but not in response to heat or pressure. Additionally, carrying all three variants was associated with greater pain sensitivity than carrying only one.

When they analysed the genomic region including SCN9A using genetic data from 5971 people from Brazil, Chile, Colombia, Mexico and Peru, the authors found that the three Neanderthal variants were more common in populations with higher proportions of Native American ancestry, such as the Peruvian population, in which the average proportion of Native American ancestry was 66%.

The authors propose that the Neanderthal variants may sensitise sensory neurons by altering the threshold at which a nerve impulse is generated. They speculate that the variants may be more common in populations with higher proportions of Native American ancestry as a result of random chance and population bottlenecks that occurred during the initial occupation of the Americas. Although acute pain can moderate behaviour and prevent further injury, the scientists that say additional research is needed to determine whether carrying these variants and having greater pain sensitivity may have been advantageous during human evolution.

Diagram comparing the nose shape of a Neanderthal with that of a modern human by Dr Macarena Fuentes-Guajardo.

Previous research by co-corresponding author Dr Kaustubh Adhikari (UCL Genetics, Evolution & Environment and The Open University) has shown that humans also inherited some genetic material from Neanderthals affecting the shape of our noses.

Dr Adhikari commented: “In the last 15 years, since the Neanderthal genome was first sequenced, we have been learning more and more about what we have inherited from them as a result of interbreeding tens of thousands of years ago.

“Pain sensitivity is an important survival trait that enables us to avoid painful things that could cause us serious harm. Our findings suggest that Neanderthals may have been more sensitive to certain types of pain, but further research is needed for us to understand why that is the case, and whether these specific genetic variants were evolutionarily advantageous.”

First author Dr Pierre Faux (Aix-Marseille University and University of Toulouse) said: “We have shown how variation in our genetic code can alter how we perceive pain, including genes that modern humans acquired from the Neanderthals. But genes are just one of many factors, including environment, past experience, and psychological factors, which influence pain.”

Source: University College London

New Clinical Guidelines for the Determination of Brain Death

Photo by Rodnae Productions on Pexels

New guidance has been issued for clinicians on the determination of brain death, also known as death by neurologic criteria. A new consensus practice guideline, developed through a collaboration between the American Academy of Neurology (AAN), the American Academy of Pediatrics (AAP), the Child Neurology Society (CNS), and the Society of Critical Care Medicine (SCCM) is published in Neurology, the medical journal of the American Academy of Neurology.

This guideline updates the 2010 AAN adult practice guidelines and the 2011 AAP/CNS/SCCM paediatric practice guidelines on the determination of brain death. Because of a lack of high-quality evidence on the subject, the experts used an evidence-informed consensus process to develop the guideline.

“Until now, there have been two separate guidelines for determining brain death, one for adults and one for children,” said author Matthew P. Kirschen, MD, PhD, FAAN, of the Children’s Hospital of Philadelphia, and a member of the Child Neurology Society and the Society of Critical Care Medicine. “This update integrates guidance for adults and children into a single guideline, providing clinicians with a comprehensive and practical way to evaluate someone who has sustained a catastrophic brain injury to determine if they meet the criteria for brain death.”

Brain death is a state in which there is complete and permanent cessation of function of the brain in a person who has suffered catastrophic brain injury.

“Brain death means that clinicians cannot observe or elicit any clinical signs of brain function,” said author David M. Greer, MD, FAAN, FCCM, of Boston University in Massachusetts. “Brain death is different from comatose and vegetative states. People do not recover from brain death. Brain death is legal death.”

The consensus practice guideline outlines the standardised procedure for trained clinicians to evaluate people for brain death. As part of this procedure, clinicians perform an evaluation to determine whether there is any clinical functioning of the brain and brainstem, including whether the person breathes on their own. Brain death is declared if a person has a catastrophic brain injury, has no possibility of recovering any brain function, is completely unresponsive, does not demonstrate any brain or brainstem function, and does not breathe on their own.

This guideline includes updates on the prerequisites for brain death determination, the examination and the examiners, apnoea testing and ancillary testing.

Source: American Academy of Neurology

Scientists may Have Found a Sixth Taste

Photo by Olga Vilkha 🇺🇦 on Unsplash

In the early 1900s, Japanese scientist Kikunae Ikeda first proposed umami as a basic taste in addition to sweet, sour, salty and bitter. About eight decades later, the scientific community officially agreed with him. Now, scientists led by researchers at the USC Dornsife College of Letters, Arts and Sciences have evidence of a sixth basic taste, which fans of salt licorice will recognise.

In research published in Nature Communications, USC Dornsife neuroscientist Emily Liman and her team found that the tongue responds to ammonium chloride through the same protein receptor that signals sour taste.

Salt licorice has been a popular sweet in northern European countries since at least since the early 20th century, and also appears on South African shelves. The treat counts among its ingredients salmiak salt, or ammonium chloride.

Scientists have for decades recognised that the tongue responds strongly to ammonium chloride. However, despite extensive research, the specific tongue receptors that react to it remained elusive.

Liman and the research team thought they might have an answer. In recent years, they uncovered the protein responsible for detecting sour taste. That protein, called OTOP1, sits within cell membranes and forms a channel for hydrogen ions moving into the cell.

Hydrogen ions are the key component of acids, and as foodies everywhere know, the tongue senses acid as sour, such as the citric acid in lemon juice. Hydrogen ions from these acidic substances move into taste receptor cells through the OTOP1 channel.

Because ammonium chloride can affect the concentration of acid – that is, hydrogen ions – within a cell, the team wondered if it could somehow trigger OTOP1.

To answer this question, they introduced the Otop1 gene into lab-grown human cells so the cells produce the OTOP1 receptor protein. They then exposed the cells to acid or to ammonium chloride and measured the responses.

“We saw that ammonium chloride is a really strong activator of the OTOP1 channel,” Liman said. “It activates as well or better than acids.”

Ammonium chloride gives off small amounts of ammonia, which moves inside the cell and raises the pH, meaning fewer hydrogen ions.

“This pH difference drives a proton influx through the OTOP1 channel,” explained Ziyu Liang, a PhD student in Liman’s lab and first author on the study.

To confirm that their result was more than a laboratory artifact, they turned to a technique that measures electrical conductivity, simulating how nerves conduct a signal. Using taste bud cells from normal mice and from mice the lab previously genetically engineered to not produce OTOP1, they measured how well the taste cells generated electrical responses called action potentials when ammonium chloride is introduced.

Taste bud cells from wildtype mice showed a sharp increase in action potentials after ammonium chloride was added while taste bud cells from the mice lacking OTOP1 failed to respond to the salt. This confirmed their hypothesis that OTOP1 responds to the salt, generating an electrical signal in taste bud cells.

The same was true when another member of the research team, Courtney Wilson, recorded signals from the nerves that innervate the taste cells. She saw the nerves respond to addition of ammonium chloride in normal mice but not in mice lacking OTOP1.

Then the team went one step further and examined how mice react when given a choice to drink either plain water or water laced with ammonium chloride. For these experiments, they disabled the bitter cells that also contribute to the taste of ammonium chloride. Mice with a functional OTOP1 protein found the taste of ammonium chloride unappealing and did not drink the solution, while mice lacking the OTOP1 protein did not mind the alkaline salt, even at very high concentrations.

“This was really the clincher,” Liman said. “It shows that the OTOP1 channel is essential for the behavioral response to ammonium.”

But the scientists weren’t done. They wondered if other animals would also be sensitive to and use their OTOP1 channels to detect ammonium. They found that the OTOP1 channel in some species seems to be more sensitive to ammonium chloride than in other species. And human OTOP1 channels were also sensitive to ammonium chloride.

So, what is the advantage in tasting ammonium chloride and why is it evolutionarily so conserved?

Liman speculates that the ability to taste ammonium chloride might have evolved to help organisms avoid eating harmful biological substances that have high concentrations of ammonium.

“Ammonium is found in waste products – think of fertiliser – and is somewhat toxic,” she explained, “so it makes sense we evolved taste mechanisms to detect it. Chicken OTOP1 is much more sensitive to ammonium than zebra fish.” Liman speculates that these variations may reflect differences in the ecological niches of different animals. “Fish may simply not encounter much ammonium in the water, while chicken coops are filled with ammonium that needs to be avoided and not eaten.”

But she cautions that this is very early research and further study is needed to understand species differences in sensitivity to ammonium and what makes OTOP1 channels from some species sensitive and some less sensitive to ammonium.

Towards this end, they have made a start. “We identified a particular part of the OTOP1 channel – a specific amino acid – that’s necessary for it to respond to ammonium,” Liman said. “If we mutate this one residue, the channel is not nearly as sensitive to ammonium, but it still responds to acid.”

Moreover, because this one amino acid is conserved across different species, there must have been selective pressure to maintain it, she says. In other words, the OTOP1 channel’s ability to respond to ammonium must have been important to the animals’ survival.

In the future, the researchers plan to extend these studies to understand whether sensitivity to ammonium is conserved among other members of the OTOP proton family, which are expressed in other parts of the body, including in the digestive tract.

And who knows? Perhaps ammonium chloride will join the other five basic tastes to bring the official count to six.

Source: University of Southern California