Tag Archives: cognition

Research Roundup: Monkeys and face recognition, animals advance AI, sugar to treat heart disease, and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • New study challenges our current understanding of how the brain recognizes faces. We can often pick out a face or a person in a crowd (e.g., finding Wally/Waldo), but the cellular mechanism via which this occurs has remained poorly understood. Using rhesus macaques, these researchers investigated which neuronal cells are responsible for facial recognition. By varying aspects of the face systematically (e.g., shape, distance between the eyes) and measuring 205 neurons in 2 animals, researchers found that each neuron responded to a specific combination of facial parameters rather than the face itself, using fMRI. In other words “the neuron is not a face detector, it’s a face analyser”, says Leopold. The brain “is able to realize that there are key dimensions that allow one to say that this is Person A and this is Person B.” Subsequent replication and extension using more subjects is warranted, but these findings provide an exciting new avenue of research with regards to face processing. This research was published in the journal Cell.

    Macaque. Source: Kathy West. CNPRC.

  • Researchers are using animal cognition to make advances in artificial intelligence.  Harvard assistant professor David Cox and his team are studying the rat visual cortex by training rats to play a complex object discrimination video game. While the rats are learning the video game, a 2 photon excitation microscope images neural activity in the visual cortex. These images are then used in conjunction with microscopic images of brain tissue slices to make digital maps of of the visual cortex. The hope is that these neural circuits could become maps for artificial neural networks and next generation artificial intelligence. Check out this video on “How to Digitize a Rat Brain”!
  • Artificial intelligence system detects pain levels in sheep. Researchers at the University of Cambridge have developed an artificial intelligence (AI) system which uses five different facial expressions to recognize whether a sheep is in pain, and to estimate pain severity. Building on earlier work which teaches computers to recognize emotions and expressions in human faces, Dr. Krista McLennan developed the Sheep Pain Facial Expression Scale (SPFES) in 2016, which can recognize pain with high accuracy. In the current study, Dr. Peter Robinson and colleagues developed machine learning techniques to reduce the time required for humans to learn to use SPFES, as well as the confounds of human bias in interpreting facial expressions. Researchers trained the AI model with a small dataset of about 500 photographs of sheep, and early tests showed that the model could estimate pain levels with about 80% degree of accuracy, indicating the system is learning. The next steps for the researchers will be to train the system to detect and recognize sheep faces from moving images, and to train it to work when the sheep are in profile. Ultimately, this research will lead to better pain detection and faster medical attention. The research was presented June 1 at the IEEE International Conference on Automatic Face and Gesture Recognition in Washington, DC.

    Face detection in sheep. Source: Liu et al., 2017, University of Cambridge

  • Lifelong protection from allergies a possibility? When your body comes into contact with a foreign particle, for example, pollen, your immune system kicks into play, producing antibodies (Immunoglobulin E). These antibodies travel to these foreign cells, attempt to “neutralize” them and in this process – triggers an allergic reaction. In order to quickly identify and mount a response to foreign particles that your body has encountered before, the body uses “memory” T cells. However, in some cases, this “memory” may be an “overreaction” of the system and once this “memory” is formed it is virtually impossible to be removed. In the present study using
    mice
    , researchers tackled this issue and were able to desensitize these memory cells which overreact to allergens using therapeutic gene transfer. Approximately 50 million American suffer from some form of allergic disease and this research, which is in pre-clinical trials, provides some hope of treatment. This study was published in the journal JCI Insight.

  • Type of sugar may treat atherosclerosis, mouse study shows. Researchers at the Washington University School of Medicine in St. Louis worked with mice prone to atherosclerosis, clogged arteries due to the buildup of plaque, and found that when injecting trehalose, a natural sugar, the immune system “cleans up” this plaque.  Babak Razani, MD, PhD, an assistant professor of medicine, and his colleagues showed that trehalose activates TFEB, a molecule that then.goes into the nucleus of macrophages and binds to DNA. This turns on specific genes and leads to additional organelles that act as “housekeeping machinery.”  Babak says, “Trehalose is not just enhancing the housekeeping machinery that’s already there,” Razani said. “It’s triggering the cell to make new machinery..”  Trehalose is a mild sweetener and FDA approved for human consumption.  Plaque degradation is not seen when administered orally.  Researchers hope to study trehalose as a potential therapy for atherosclerosis in hopes to find a way to protect its  housekeeping properties when given orally.

    Cross section of mouse aorta with a large plaque. Source: Ismail Sergin

 

 

 

Research Roundup: An artificial womb for preemie lambs, umbilical cord protein enhances cognition, smartphones to control diabetes, and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • An artificial womb has successfully kept premature lambs alive. Extreme prematurity — infants born at 22 to 23 weeks gestation — is a leading cause of infant mortality, and infants who do survive often have serious disabilities like cerebral palsy or major cognitive deficits. Researchers at the Children’s Hospital of Pennsylvania have developed a first-of-its kind artificial womb that mimics the uterine environment, and have found in studies of lambs that this womb allows the premature lambs to grow normally inside the womb for 3-4 weeks. The thought is that treating the preemies more like fetuses than newborns by extending normal gestation may give them a better chance of survival. The artificial womb, pictured below, is a fluid-filled transparent container that simulates how fetuses float in amniotic fluid inside the mother’s uterus. The womb is attached to a mechanical placenta that keeps blood oxygenated for the fetus. Over the four weeks of study, the lamb fetuses grew to open their eyes, grow wool, breathe, and swim. Human trials are still several years away, though the research team is already in discussions with the Food and Drug Administration. The study was published in Nature Communications and is freely available for download.

  • New research finds that at least one third of all gut nerve cells are replaced weekly. The gut contains the second largest nervous system in the body, the enteric nervous system. Similarly to the number of viable eggs that a woman is born with, it was a once held scientific belief that the gut nerve cells we’re born with are the same ones that we die with. Using healthy adult you mice, and a variety of modern techniques, this study confirmed previous research findings of ongoing neuronal cell loss because of apoptosis (cell death) — although total neuronal numbers remain constant. This observed neuronal homeostasis was found to be maintained from dividing precursor cells that are located within myenteric ganglia. Mutation of these adult precursors led to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Since gut nerve cells were thought to remain unchanged across time, it has limited our understanding and treatment of diseases which affect the gut. These results “enable a new understanding of the pathogenesis of enteric neuromuscular diseases as well as the development of novel regenerative therapies.” This study was published in the Proceedings of the National Academy of Sciences.

  • A new study finds that protein found in human blood makes mice smarter. Previous research investigating the effects of young blood on aging animals has generally focused on within (same) species comparisons. In this study, researchers investigated the role of a human umbilical cord plasma and its effects on aged mice — in particular with respect to hippocampus and behavioral measures of cognition. These particular measures were investigated as impairment is observed in older individuals. They found that human plasma, injected in mice, was associated with revitalization of the hippocampus with increased levels of gene expression there. Additionally, they found that behavioral measures of cognition were also improved. The protein tissue inhibitor of metalloproteinases 2 (TIMP2), was found to be implicated with these positive changes. This study has been published in Nature.

    hippocampus

    Schematic of the hippocampus. Source.

  • The European Ombudsman rejected a complaint by the “Stop Vivisection” European Citizens Initiative that they had not received adequate reasoning behind the decision by the European Commission to reject the initiative in July 2015. “Stop Vivisection” wanted to repeal the European animal research regulation, Directive 2010/63/EU and replace it with a proposal to speed a ban on such practices. The ombudsman noted that the Commission has complied with its duty to explain, in a clear, comprehensible and detailed manner, its position and political choices regarding the objectives of the ECI “Stop Vivisection””.
  • A new study uses your smartphone to control symptoms of diabetes. In a good example of multi-disciplinary translational medicine, and using “a multidisciplinary design principle coupling electrical engineering, software development, and synthetic biology” researchers based at the Shanghai Key Laboratory of Regulatory Biology “engineered a technological infrastructure enabling smartphone-assisted semiautomatic treatment of diabetes in mice.” Hydrogel capsules, containing cells that could produce “mouse insulin” in vivo and which contained wirelessly powered infrared LEDs were implanted in mice. Smartphones were then used to control this implant causing it to secrete “mouse insulin” as needed. Researchers were able to maintain glucose homeostasis over several weeks in the diabetic mice. This study provides a step toward translating cell-based therapies into the clinic. It also highlights that even though this technique was developed in vitro, safety and efficacy trials in animals are needed before they can be used in humans. This study was published in the journal Science.
Apr27_2017_ShanghaiKeyLabOfRegulatoryBiology_DiabeticMouseSmartPhone2447847722.jpg

Photo courtesy of Shanghai Key Laboratory of Regulatory Biology

Understanding the animal, not just its parts

A recent article in the Atlantic, “How Brain Scientists Forgot That Brains Have Owners” is making headlines. The journalist claims that in an article published in early February, titled “Neuroscience Needs Behavior: Correcting Reductionist Bias”, fancy new technologies have led the field of neuroscience astray. The original scientific publication does draw attention to an area of neuroscience that neglects behavior, and outlines the importance of measuring behavior and the brain. However, behavior is not necessary in all areas of neuroscience, and adding behavior to some neuroscience studies could be problematic. Furthermore, the overall goal of the scientific publication was only to suggest that the field of neuroscience is lacking in scientists interested in studying the whole brain rather than the just studying the sum of its parts.

The field of neuroscience is diverse. Take for example the 9 themes at the Society for Neuroscience Conference in 2016:

  1. Development
  2. Neural Excitability, Synapses, and Glia [Neurophysiology]
  3. Neurodegenerative Disorders and Injury
  4. Sensory Systems
  5. Motor Systems
  6. Integrative Physiology and Behavior
  7. Motivation and Emotion
  8. Cognition
  9. Techniques [Technologies]

Glancing over these themes it is apparent that many scientists specialize in different types of neuroscience. Thus, some neuroscientists may study behavior and some may not need to study behavior. For example, neuroscientists investigating questions about technologies or neurophysiology may not need to study behavior at all — it depends on the question. Those only interested in the integration of physiology and behavior would study both the brain and behavior. And those studying cognition or motor systems might conduct experiments on behavior without directly measuring the brain. Whether neuroscientists study brain and/or behavior depends on the research questions they are asking.

Although both publications neglected to discuss the diversity of neuroscience, the main theme of the scientific publication was to change the way scientists interested in the integration of physiology and behavior approach their research questions. Too many neuroscientists focus on using as many new technologies as possible, and then use behavior as an afterthought. The issue here is that some of these new technologies are not yet well understood. Thus, scientists’ research questions using these technologies could be misguided.

Furthermore, behavior is a separate area of research on its own and should never be treated as an afterthought. Thus, the authors suggest that neuroscience needs more interdisciplinary scientists who understand and study the relationships between brain and behavior. It needs scientists that can merge all areas of the field.

All neuroscientists however, no matter their specific question, will help advance the field in different ways. And all neuroscientists do not need to study behavior. However, Interdisciplinary scientists in particular may set the stage for understanding the whole animal and how the brain operates within it. Furthermore, these scientists may help increase the translation of research from animal to human.

The problem of neuroscience without interdisciplinary scientists

A possible issue with scientists only studying one part of the animal (i.e. the brain) is that they neglect the rest of the animal. The authors suggest many neuroscientists only interested in the brain use a top-down approach (brain-behavior) to infer how behavior operates — and this is problematic. A recent experiment on understanding a simple computer demonstrates the potential flaws in a top-down approach. Briefly, computer scientists tested whether the processes of three classic videogames could be inferred by only studying the microprocessor that operated the videogames. In contrast to the brain, the scientists already understood how this computer system operates. After much investigation of the hardware of the microprocessor and how it functions, it remained unclear how the processes in the videogames operated. Thus, by using a top-down approach to understand behavior we will not be able to understand the brain

The bigger problem with measuring the brain and inferring behavior without studying behavior is that you are only studying one part of the animal. Consider the blind men and the elephant:

blind-men-and-the-elephant

Quite simply, if I am blind-folded and given an elephant’s ear then I may think it is a fan. For me to understand and determine that I am holding an elephant’s ear, I would need to investigate the whole elephant — beyond a small part and beyond all parts individually. Interdisciplinary scientists study the “whole elephant.”

However, only studying the ear of an elephant isn’t completely problematic. I can measure what it is composed of, stick electrodes in it to see how it responds, pour different chemicals on it to see how it reacts, measure how it grows over time, test it in different scenarios etc. Thus, I can learn many different aspects about this so called fan. However, what I cannot do is infer its function or purpose without considering the whole elephant. Also, I may be unable to determine which findings are related to the potential functions, and which findings are not related to the potential functions.

The elephant and the blind men, also apply to all experiments using animal models for understanding human biology. If I do not investigate or consider the whole “elephant” I may never determine that the “ear” I am looking at has a similar function to “ears” in many other animals. More generally, if I only study neural circuitry in a mouse without considering the mouse as a whole (anatomy, organs, cells, behavior, environment, development, evolution, etc.) then it won’t help me determine how — or if – the neural circuitry may function similarly in the human.

Development is particularly important — and often forgotten — ­when studying the whole animal. You cannot just study the “ear” of the “elephant” at a specific time point in a specific environment because the structure or function may change over time. Consider the development of a frog:

development-of-a-frog

In the tadpole stage the frog has a long tail for swimming and gills for breathing underwater. As it develops into an adult frog, however, the tail is reabsorbed and the frog exchanges its gills for lungs. Developmental context is necessary for understanding the whole animal.

The necessity of neuroscience with interdisciplinary scientists

Interdisciplinary scientists study both neural circuitry and behavior to understand the processes of the brain. However, this does not mean that they study parts of the brain, then study some behaviors, and understand the system. It also does not mean that they take a top-down approach (brain to behavior) or bottom-up approach (behavior to brain) — the choice here should depend on the specific research question. Interdisciplinary scientists study both brain and behavior at the same time. By studying both at the same time they can see how behavior emerges from neural circuitry and how neural circuitry emerges from behavior. The two are dependent on one another, they are not separate.

Consider this optical illusion:

optical-illusion-face-and-candlestick

If I just look at the picture on the left, I might only see a chalice and begin describing all of its visual properties and then infer its function. However, if I look at the picture on the right then it might become apparent that the picture is both a chalice and two people looking at each other. If I have too narrow of a focus — only studying the chalice — then I completely miss understanding that this is an optical illusion. Understanding the whole is important, and one part is not the greater than the other.

However, as mentioned earlier when trying to identify the function of an elephant’s ear, if I do not have a starting point for inferring function or mechanism then I could be asking the wrong questions. This is the point that the authors in the original scientific publication also make. If you do not study the behavior of the animal or process that you are interested in, then you will be asking all the wrong questions concerning neural circuitry. One cannot understand the game of chess by just analyzing all the pieces and the board. You must first observe how the game is played, and then you can determine what makes the pieces and the board important.

This is example of watching chess being played first and then analyzing the pieces and the board, represents a top-down approach. However, as already mentioned, the approach you take is particular to the question you are interested in. Different approaches give you different answers. And in the unknown world of brain and behavior, we may really not know enough to properly infer how something functions.

Regardless, this example of chess also applies to all experiments using animal models. For example, I might have learned how to play chess on a large and heavy wooden board with specially molded iron pieces. And as long as I understand the rules and processes of chess, then I can play chess on any board — be it big or small, plastic or wood, physical or virtual. But if I spend all my time studying the chess pieces and never watching how the game is played, then it might be difficult for me to identify which chess piece does what on a different chess set. Just like it would be difficult for me to determine which brain areas of a mouse might be analogous to which brain areas in a human without measuring behavior.

The authors also explain that multiple neural circuits may be responsible for a single behavior, and a single neural circuit may be responsible for multiple behaviors. This further complicates the issue of studying one part of the animal over the other. Thus, one specific neural circuit does not map to one specific behavior.

neural-activity-in-animals-and-the-behaviours-associated

In conclusion, the neuroscientists who published the original scientific article are correct: behavior is necessary and you must study it if you want to understand the brain. However, all the fancy techniques neuroscientists have developed, independent of behavior, help us ask specific questions about neural circuitry and about behavior. Also, all scientists experimenting on animals —not just neuroscientists — should understand the arguments used in this paper and apply it to their own experiments. This will help us better understand how findings in one species might relate to findings in another, and thus help the translation of all science using animal models.

Justin Varholick

The moral relevance of human intelligence

Animal rights proponents often assert that “sentience” is the only morally relevant characteristic. In their view, we owe the same moral consideration to all sentient living beings, which must include the same basic rights to life and freedom.

The animal rights philosopher asks — Why does it matter if humans can compose a violin concerto or prove complex mathematical theorems?  After all, animals also have unique abilities that no human possess.  Birds can fly unassisted, dolphins use sonar, and mice have an exquisite sense of smell. In what way does human intelligence makes us different from other living beings in any morally relevant way?

As an example, one of these philosophers, Prof. Gary Francione, writes:

“[…] cognitive characteristics beyond sentience are morally irrelevant […] being “smart” may matter for some purposes, such as whether we give someone a scholarship, but it is completely irrelevant to whether we use someone as a forced organ donor, as a non-consenting subject in a biomedical experiment.”

Sentience, according to the dictionary, is the “ability to feel and perceive things.”  However, to Prof. Francione it clearly means something more:

[…] sentience is a necessary as well as sufficient characteristic for a being to have interests (preferences, desires, or wants) in the first place. A rock is not sentient; it does not have any sort of mind that prefers, desires, or wants anything. A plant alive but has no sort of mind that prefers, desires, or wants anything.

Having preferences, desires, beliefs, interests and acting purposely to achieve them is to attribute a living being with mental states that go beyond the mere ability to feel and perceive things.  It goes beyond the accepted definition of “sentience”.  Yet, it seems obvious that not all species possess these attributes in equal degrees.

A human mother that is contemplating death due to cancer, will suffer beyond her physical pain when thinking that her children will grow up without a her, that she will never see them marry or have children of their own, that she will leave her spouse alone to take care of the family.

It is her cognitive abilities that allow her to suffer in ways other animals cannot.  Thus, if we agree that suffering is morally relevant, the type of suffering this mother experiences must count too.  And because such suffering is enabled to beings with the cognitive abilities that allow them to pose such questions, one must conclude that human cognitive abilities are morally relevant too.

Human cognitive abilities enable us to suffer in ways no other animals find possible.

There is a second important way in human intelligence becomes morally relevant.  It is the fact that our cognitive skills give rise to the scientific edifices of mathematics, physics and life sciences, which allows us, humans, to combat suffering in the world.

Humans have relied on our science to develop vaccines, screening tests and diagnostic devices, therapies and cures for many diseases.  These developments have saved billions lives, both human and non-human, and eliminated much suffering.

In contrast, while it is true that birds fly, dolphins use sonar and mice have a terrific sense of smell, none of these abilities allow them to battle suffering.

Rejecting our ability to confront suffering is to reject our human condition. Rejecting the moral responsibility that results from our cognitive abilities, as proposed by animal rights activists, would be wrong.