Tag: neuroscience

  • Enzyme released by immune cells may play role in depression

    Enzyme released by immune cells may play role in depression

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    Mount Sinai researchers have shown for the first time that immune cells called monocytes, derived in the bone marrow and released into the bloodstream, can be drawn during stress into sites in the brain that control emotional behaviors. There, they release an enzyme called matrix metalloproteinase 8 (MMP8) that breaks down proteins and restructures the brain to alter the function of neurons and, ultimately, impair social behavior and reward.

    These data establish a novel mechanism by which the immune system can affect central nervous system function and behavior in the context of stress, potentially opening the door to novel therapeutic targets for stress-related disorders. The study appears in the February 7 issue of Nature.

    Psychosocial stress is a major factor for developing major depressive disorder and post-traumatic stress disorder (PTSD) and has been shown to have profound effects on the body, including the immune system and the brain. These data are the first to show that immune cells derived in the bone marrow-;and not the brain-;can be recruited during stressful circumstances to the brain, setting off a cascade of other mechanisms that alter brain function and behavior.”


    Flurin Cathomas, MD, lead author, Instructor of Neuroscience and member of the Brain-Body Research Center at Mount Sinai

    To explore these mechanisms, the research team performed comparative cross-species analyses in mice and humans and found that MMP8 is elevated in the serum of study subjects with major depressive disorder, as well as in stress-susceptible mice following chronic social defeat stress, a model of social trauma. Studies in mice confirmed that peripheral MMP8 enters the brain through damaged blood vessels to restructure the brain’s extracellular tissue matrix, which leads to altered function of neurons that ultimately impairs social behavior and reward.

    Prior to this work, most hypotheses about the role of the immune system in stress disorders such as depression have centered on mechanisms related to the brain’s resident immune cells, called microglia, and their ability to release pro-inflammatory molecules such as interleukins to control neural function and behavior.

    Using single-cell RNA sequencing to look at gene expression profiles in circulating monocytes as compared to microglia, the team found that, contrary to popular belief, the microglia did not exhibit a pro-inflammatory gene signature. The team found no evidence that they upregulate genes that code for interleukins. This is in stark contrast to circulating monocytes found within the blood vessel lining of brain regions that control mood and emotion.

    “There are no existing medications to target MMP8, and while it’s not yet clear if such treatments will ultimately be effective in treating depression, my hope is that this study will lead to renewed effort in developing such drugs,” said Scott Russo, PhD, Mount Sinai Professor in Affective Neuroscience, Leon Levy Director of the Brain-Body Research Center, and Center for Affective Neuroscience at Mount Sinai. “It’s also possible that non-pharmacological ‘lifestyle’ strategies to promote positive immune health might be helpful in treating these stress-related disorders.”

    The disturbances in the immune system identified in this study were only found in a subset of patients, which highlights the heterogeneous nature of such illnesses in terms of etiology. Additionally, the studies performed in human subjects were purely correlative, so the team does not yet know if treatments targeting monocytes or MMP8 directly will be effective for human stress disorders. Importantly, there are several additional MMPs that can be derived directly in the brain and it remains unclear whether they play complementary or opposing roles.

    “The brain and the body are unequivocally connected and we are really at the precipice of a markedly deeper understanding of how the connections between the brain and peripheral organ systems like the immune system, cardiovascular system, and others can affect a person’s health,” said Dr. Russo. “Our work suggests that strategies to promote immune health can benefit one’s emotional well-being and possibly prevent stress-related illnesses like depression and PTSD. Additional research for continued understanding and potential treatment development is warranted.”

    The Mount Sinai research team is currently testing therapeutic strategies to inhibit MMP8 as novel antidepressants. They are also investigating MMP8 as a novel immune biomarker for depression patients.

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    Journal reference:

    Cathomas, F., et al. (2024). Circulating myeloid-derived MMP8 in stress susceptibility and depression. Nature. doi.org/10.1038/s41586-023-07015-2.

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  • This Small Wearable Device Reduces Parkinson’s Symptoms

    This Small Wearable Device Reduces Parkinson’s Symptoms

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    In 2015, Lucy Yung was a young industrial designer working on assistive devices for stroke victims, people with multiple sclerosis, and those with other conditions which meant they struggled with fine motor control. Her projects included a pen that used high-frequency vibrations to help Parkinson’s patients write more clearly.

    Then she was diagnosed with a brain tumor. “I really learned what it felt like to be a patient and that any kind of support or help can dramatically change the lives of people with long-term conditions,” she says. Once she had recovered and returned to work in 2018, she picked up her research on Parkinson’s, with the goal to improve the lives of those with the disease.

    Parkinson’s stems from a communication problem: Damage to neurons in the substantia nigra of the brain leads to decreased levels of dopamine and unusual electrical rhythms, making it harder for signals to move between neurons. The instructions the brain is trying to send to the body struggle to get through, resulting in the characteristic tremors, rigidity, and freezing of gait seen in sufferers.

    But through her prior work on the pen, Yung had identified a potential solution. In the 19th century, French neurologist Jean-Martin Charcot noticed that Parkinson’s symptoms seemed to be markedly better after patients had been on long carriage or train rides, and subsequent research has revealed that rhythmic auditory, visual, or physical stimulation can help Parkinson’s patients walk more fluidly through what’s known as “cueing.”

    In 2019, Yung founded Charco Neurotech, a Cambridge-based startup named after the French neurologist, which has developed a wearable device that promises to reduce the symptoms of Parkinson’s disease. Charco’s device, the CUE1, is a small plastic disc with an electric motor inside. It sits on the wearer’s sternum, where it vibrates at a high frequency in a pattern that’s been proven to reduce the symptoms of Parkinson’s through cueing.

    Unlike deep-brain stimulation implants, which have also been used to treat Parkinson’s symptoms, the CUE1 is noninvasive—it attaches to the skin using medical adhesive—and inexpensive. The £295 ($371) device is being used by more than 2,000 people in the UK, with a waiting list of almost 20,000 across 120 countries. Charco has raised more than $10 million in funding and grants and now employs 38 people in the UK, South Korea, and the United States, including Parkinson’s specialists, nurses, engineers, and data analysts. The goal is to get the device approved by regulators so that it can be prescribed by doctors through the National Health Service or Medicaid.

    An app enables users to tailor the pattern of the vibration to one that works best for them. Yung is hoping to develop a feedback system so that the device automatically adjusts based on how well someone is moving—amping up or dialing down the pattern of cueing as needed. “What we’re seeing is that people tend to use the device all day,” she says. “Some people even use it when they’re sleeping, and it helps with sleeping, too.”

    This article appears in the March/April 2024 issue of WIRED UK magazine.

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  • A neural circuit for navigation keeps flies on target

    A neural circuit for navigation keeps flies on target

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    Nature, Published online: 07 February 2024; doi:10.1038/d41586-024-00230-5

    Studies reveal how neuronal populations in the fruit fly brain work together to compare the direction of a goal with the direction that the fly is facing, and convert this into a signal that steers the fly towards its target.

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  • The brain area that lights up in prickly people

    The brain area that lights up in prickly people

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  • Mathematicians have finally proved that Bach was a great composer

    Mathematicians have finally proved that Bach was a great composer

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    Johann Sebastian Bach was a great composer – according to information theory

    The Granger Collection / Alamy Stock Photo

    Johann Sebastian Bach is considered one of the great composers of Western classical music. Now, researchers are trying to figure out why – by analysing his music with information theory.

    Suman Kulkarni at the University of Pennsylvania and her colleagues wanted to understand how the ability to recall or anticipate a piece of music relates to its structure. They chose to analyse Bach’s opus because he produced an enormous number of pieces with many different structures, including religious hymns called chorales and fast-paced, virtuosic toccatas.

    First, the researchers translated each composition into an information network by representing each note as a node and each transition between notes as an edge, connecting them. Using this network, they compared the quantity of information in each composition. Toccatas, which were meant to entertain and surprise, contained more information than chorales, which were composed for more meditative settings like churches.

    Kulkarni and her colleagues also used information networks to compare Bach’s music with listeners’ perception of it. They started with an existing computer model based on experiments in which participants reacted to a sequence of images on a screen. The researchers then measured how surprising an element of the sequence was. They adapted information networks based on this model to the music, with the links between each node representing how probable a listener thought it would be for two connected notes to play successively – or how surprised they would be if that happened. Because humans do not learn information perfectly, networks showing people’s presumed note changes for a composition rarely line up exactly with the network based directly on that composition. Researchers can then quantify that mismatch.

    In this case, the mismatch was low, suggesting Bach’s pieces convey information rather effectively. However, Kulkarni hopes to fine-tune the computer model of human perception to better match real brain scans of people listening to the music.

    “There is a missing link in neuroscience between complicated structures like music and how our brains respond to it, beyond just knowing the frequencies [of sounds]. This work could provide some nice inroads into that,” says Randy McIntosh at Simon Fraser University in Canada. However, there are many more factors that affect how someone perceives music – for example, how long a person listens to a piece and whether or not they have musical training. These still need to be accounted for, he says.

    Information theory also has yet to reveal whether Bach’s composition style was exceptional compared with other types of music. McIntosh says his past work found some general similarities between musicians as different from Bach as the rock guitarist Eddie Van Halen, but more detailed analyses are needed.

    “I would love to perform the same analysis for different composers and non-Western music,” says Kulkarni.

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  • what scientists think of first human trial

    what scientists think of first human trial

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    The logo for Neuralink on a smartphone screen in front of a portrait of Elon Musk.

    Neuralink, founded by Elon Musk, has launched a long-awaited clinical trial.Credit: CFOTO/Future Publishing via Getty

    Neuralink, the company through which entrepreneur Elon Musk hopes to revolutionize brain–computer interfaces (BCIs), has implanted a ‘brain-reading’ device into a person for the first time, according to a tweet posted by Musk on 29 January.

    BCIs record and decode brain activity, with the aim of allowing a person with severe paralysis to control a computer, robotic arm, wheelchair or other device through thought alone. Apart from Neuralink’s device, others are under development and some have already been tested in people.

    Neurotechnology researchers are cautiously excited about Neuralink’s human trial. “What I hope to see is that they can demonstrate that it is safe. And that it is effective at measuring brain signals — short term, but, most importantly, long term,” says Mariska Vansteensel, a neuroscientist at University Medical Centre Utrecht in the Netherlands and president of the international BCI Society.

    But there is frustration about a lack of detailed information. There has been no confirmation that the trial has begun, beyond Musk’s tweet. The main source of public information on the trial is a study brochure inviting people to participate in it. But that lacks details such as where implantations are being done and the exact outcomes that the trial will assess, says Tim Denison, a neuroengineer at the University of Oxford, UK.

    The trial is not registered at ClinicalTrials.gov, an online repository curated by the US National Institutes of Health. Many universities require that researchers register a trial and its protocol in a public repository of this type before study participants are enrolled. Additionally, many medical journals make such registration a condition of publication of results, in line with ethical principles designed to protect people who volunteer for clinical trials. Neuralink, which is headquartered in Fremont, California, did not respond to Nature’s request for comment on why it has not registered the trial with the site.

    Nature examines how Neuralink’s implants compare to other BCI technologies, how the trial will advance BCIs and researchers’ concerns.

    How is the chip different from other BCIs?

    Like Blackrock Neurotech in Salt Lake City, Utah, Neuralink targets the activity of individual neurons — an approach that requires electrodes that penetrate the brain. Other companies are developing electrodes that sit on the brain’s surface — some of which are easily removable — to record averaged signals produced by populations of neurons. Neuroscientists have long argued that data from individual neurons are needed for sophisticated thought-decoding. But recent research indicates that averaged signals can allow decoding of complex cognitive processes, such as inner speech1. And New York City-based company Synchron has shown that a low-bandwidth surface BCI can provide basic but reliable smartphone control2.

    Like the Synchron system, Neuralink’s is fully implanted and wireless. That’s a first for BCIs that record from individual neurons. Previous such systems had to be physically connected to a computer through a port in the skull. This poses an infection risk and limits real-world usage.

    One man attaches a device to the bare chest of another man.

    An engineer fits a brain–computer interface device produced by another company, Synchron.Credit: William West/AFP via Getty

    The Neuralink chip contains 64 flexible polymer threads, providing 1,024 sites for recording brain activity, according to the company’s study brochure. That is considerably more than Blackrock Neurotech’s BCIs, the only other single-neuron recording system to have been implanted long-term in humans. So the Neuralink device could increase the bandwidth of brain–machine communication — although some users have had several Blackrock devices implanted. Neuralink touts the flexibility of its threads, and says it is developing a robot to insert them into the brain.

    Denison says the spectrum of approaches is exciting. It is now a case of seeing which perform best, in terms of safety, signal quality and durability, and user experience. “We need to all play the long game for the good of patients,” he says.

    What will scientists learn from the Neuralink human trial?

    Neuralink has released little information about its trial’s goals and did not respond to Nature’s request for an interview. But experts expect safety to be paramount at this stage. That involves observing the immediate impact of the device, says Denison — “no strokes, no bleeds, no vasculature damage, anything like that” — as well as for infections, and long-term follow-up to check that it remains safe to have the device implanted.

    Neuralink’s study brochure says that volunteers will be followed for five years. It also indicates that the trial will assess the device’s functionality, with volunteers using it at least twice weekly to control a computer and feed back on the experience.

    Vansteensel would like to know whether the quality of the detected neuronal signals degrades over time, which is common in existing devices. “You’re not going to replace electrodes easily after implantation,” she says. “If, in a month from now, they demonstrate beautiful decoding results — impressive. But I will want to see long-term results.”

    Denison is also keen to learn how a wireless system that can be used in non-laboratory settings performs.

    What concerns do scientists have about the Neuralink BCI?

    Now that human trials have begun, volunteer safety and well-being is a pressing question. The trial was approved by the US Food and Drug Administration (FDA), which rejected an earlier application from Neuralink. But some researchers are uncomfortable that the trial is not listed on ClinicalTrials.gov. “My assumption would be that the FDA and Neuralink are following the playbook to a certain extent,” says Denison. “But we don’t have the protocol. So we don’t know that.”

    Transparency is also important to the people whom BCIs are intended to help. Ian Burkhart, a co-founder of the BCI Pioneers Coalition based in Columbus, Ohio, was paralysed after breaking his neck in a diving accident and spent 7.5 years with a Blackrock array implanted in his brain. He’s excited about what Neuralink might achieve. But, he says, “they could do much better with how much information they are releasing, instead of having everyone speculate on it. Especially for the patients who are so eagerly waiting for this type of technology to be able to improve their lives.”



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  • Girls’ brains aged unusually rapidly during the covid-19 pandemic

    Girls’ brains aged unusually rapidly during the covid-19 pandemic

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    Adolescents’ brains underwent accelerated ageing during the covid-19 pandemic, and the effect was more pronounced in girls than in boys

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  • Why free will doesn’t exist, according to Robert Sapolsky

    Why free will doesn’t exist, according to Robert Sapolsky

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    Robert Sapolsky is one of the most revered scientists alive today. He made his name from his work studying wild baboons in Kenya, unpicking how their complex social lives lead to stress and how that affects their health.

    His most recent focus, however, has been on something rather different – a book that comprehensively argues that free will doesn’t exist in any shape or form.

    As he writes: “We are nothing more or less than the sum of that which we could not control – our biology, our environments, their interactions”.

    In this episode of CultureLab, Sapolsky outlines his case against free will and what a society without free will should look like.

    You can find New Scientist Podcasts on your favourite podcast platform or by clicking here.

    Determined: A Science of Life Without Free Will is out now.

    Transcript

    Timothy Revell: Many of our listeners, they will know you as someone who spent years studying wild baboons, and then, also, as an eminent neuroscientist, so what made you decide to then suddenly look at free will so closely, which is, I guess, more often associated with philosophy? Was there, like, an enticing incident? Did something get you onto it first?

    Robert Sapolsky: Yes. I turned fourteen years old, at one point, and had a somewhat existentially unnerving experience and, that night, woke up at around two in the morning and say, “Aha, I get it. There’s no God, there’s no purpose, and there’s no free will,” and it’s been, kind of, like that every since.

    More approximately, about five years ago, I published a book called, Behave, The Biology of Humans at our Best and Worst, and I did a lot of public lecturing about, sort of, the general subject in the years since. And you’d go through, sort of, an hour’s talk of telling people about, the events one second before behaviour and one minute, and one hour, and one thousand years and all these different influences. With some regularity, somebody in the audience, afterwards, with Q&A, would say something like, “Wow. All this stuff, kind of, makes one wonder about free will,” which I, in effect, would say, “You think?” and it just struck me that I needed to write something that, very expectantly, tackled how completely silly and bankrupt the notion of free will is, when you put all the relevant science together.

    Then dealing with the bigger issue, I know it seems very straightforward and simplistic by now to me that there’s no free will, but the massive issue of, “Ph my God, what are we supposed to do if people actually started believing this? How are we supposed to function?’

    Timothy Revell: It’s funny that you say it’s now so easy to say that free will doesn’t exist, but I think for many people it’s one of those things that, subjectively, it feels very real, but then, you know, a good argument against that is a tale feels solid, but it’s mostly empty space, so we can’t really trust what we think about the world, certainly not our own experience of it. For those that haven’t spent as much time thinking about free will and reached the conclusion that you have, that it doesn’t exist, what is the argument? What does science say about free will?

    Robert Sapolsky: Well, my essential song and dance, and I should add about 90-95 per cent of philosophers agree, that there’s free will, and steadfastly hold onto it, and these are folks, who classify themselves as compatibilists, which is to say they’re willing to admit there are things like atoms and molecules and cells out there, but somehow, despite that, can still pull free will out of the hat in their thinking.

    In terms of my orientation, my basic approach is you look at a behaviour and someone has just done something that’s wonderful or awful or ambiguously in-between or in the eyes of the beholder, but some behaviour has happened, and you ask, “Why did that occur?” and you’re asking a whole hierarchy of questions. You’re, of course, asking, “Which neurons did what, ten milliseconds before?” but you’re also asking, “What sensory stimuli in the previous minutes triggered that?” but you’re also asking, “What did this morning’s hormone levels have to do with how sensitive your brain would be to those stimuli?”

    You’re also asking, “What have the previous months been, trauma, stimulation, whatever, in terms of neuroplasticity?” and before you know it, you’re back to adolescents and your last gasp of constructing your frontal cortex, and childhood and foetal environment and it’s epigenetic consequences, and of course, genes. Amazingly, at that point, you have to push further back. What sort of culture were your ancestors inventing and what sort of ecosystems prompted those inventions, because that was influencing how your mother was mothering you within minutes of birth, and then, you know, some evolution thrown in for good measure.

    What you see at that point is, not just saying, “Wow, when you look at all these different disciplines, collectively, they’re showing we’re just biological machines,” but they’re not all these different disciplines. They’re all one continuous one. If you’re talking about genes, by definition, genes and behaviour, by definition, you’re talking about evolution and you’re talking about neurobiology and genetic variance and neuronal function. If you’re talking about, you know, early trauma in life, you’re talking about epigenetics and you’re talking about adult propensity. So, they’re all one continuous seam of influences, and when you look at it that way, there’s not a damn crack anywhere in there to shoehorn in a notion of free will.

    Timothy Revell: You talk about this in your book, but I think, for many people, they still feel like maybe there’s room. You know, with each individual step, it feels like those are influences rather than the 100 per cent determining factor. Is there, when people come to you and say, “Oh, but there’s still a little bit of room,” you know, “These are all things that influence me on a given day. of course, if it’s hot, I’m more likely to go outside and enjoy the sun, but it’s still my decision,” how do you go from that, from influences, to, “It’s not just influences, everything we do is dictated in one way or another, by this whole combination of factors’?

    Robert Sapolsky: Well, the jerky, sort of, challenge that I lay down at that point is, “Okay, so you’re still holding out for free will somewhere in there, just because it seems so counter-intuitive if that is all we are,” but look at some behaviour, you just pulled the trigger on a gun, like something very consequential, and you could probably even identify the three-and-a-half neurons in the motor cortex that sent that command to your muscles.

    Show me, let’s examine those three-and-a-half neurons that just did that. Show me that what they did was completely impervious to what was going on in any other neuron surrounding them, but at the same time, show me that it was impervious to whether you were tired, stressed, sleepy, happy, well-fed, at that moment. Show me that it’s impervious and would’ve done the exact same thing no matter what your hormone levels were this morning, no matter what your childhood was, no matter what your genome is, the epigenetics. Show me that it would’ve done the exact same thing after changing any of those or all of those variables, and as far as I’m concerned, you’ve just proven free will, and they can’t, because there’s absolutely nothing any of your, like, molecules making you up just did to generate a behaviour that’s independent of every second before.

    It is impossible to show that we can act freely of everything that came before.

    Timothy Revell: Do you think there’s a reason why we seem so wired to think that free will does exist? Is there some evolutionary benefit to us believing that? If we just accepted it from the beginning, that it doesn’t exist, would that maybe actually be better for us, overall?

    Robert Sapolsky: Oh, well, at first pass, it’s depressing as hell and alarming and unsettling and all of that, and all sorts of wise evolutionary biologists have thought about the evolution of self-deception, and by the time you’re as smart of a primate as we are, we had to have developed a robust capacity for not believing in what might be the case, because otherwise, it would be all too overwhelming and despairing and just existential void and all that stuff.

    You know, there’s a very, very strong emotional incentive to feel agency, and endless aspects of experimental psychology has shown that you stress people or frazzle them or give them an unsolvable problem, and they get a way distorted sense of agency, at that point, as a defence. The really critical issue there though is the assumption that believing there’s no free will, okay, there’s no free will and you better believe it, and that’s about as appealing as, like, swallowing cod liver oil or something but, you know, suck it up, that’s the way the world works.

    My overwhelmingly emphasis is, if you suddenly are convinced there’s no free will, and that’s a total bummer for you, because that makes your, like, egregiously privileged salary seem like something you did not necessarily earn and your prestigious degrees and your circle of loving friends and all the other things that you feel like you, in some manner, earn, deserve, you’re entitled to, oh, bummer, if that’s not the case. If that’s your response to the idea of there being no free will, by definition, you were one of the lucky ones.

    For most people on earth, who were dealing with far less privilege, the notion that we are not the captains of our fate is, like, wildly liberating and humane. I mean, just ask someone who’s genetic profile and metabolism dooms them to obesity and being subject to a lifelong of unhappiness and societal stigma over that, and that’s just one of the billion ways in which the discovery that we’re nothing more or less than the biology over which we had no control and the environment over-, is great news, and is the most humane thing on Earth. All we spent is the last 500 years of scientific insights into seeing that people are not responsible for all sorts of things for which they used to be blamed or made to feel like they are inadequate or burnt at the stake for, and this is wonderfully liberating.

    Timothy Revell: Yes, so I want to get into some of those implications, because, as you say, it’s, sort of, liberating to think, “Well, we’re just the products of our biology,” but at the same time, we’ve built a whole society around responsibility. That you have responsibilities to do certain things, but also, we have responsibility as society to hold people accountable for the decisions that they make, and these words are all, sort of, loaded with an intrinsic understanding of free will being baked into it.

    Robert Sapolsky: Yes.

    Timothy Revell: If everyone read your book overnight and agreed with you 100 per cent, what does a society look like where we accept this principle that free will does not exist?

    Robert Sapolsky: Well, I think the first thing to emphasise is the roof isn’t going to cave in, because over and over and over, we have subtracted responsibility out of our views of human behaviour in the natural world, and it’s been okay. People haven’t run amok, society hasn’t, you know, gone to hell, at that point, because 400 years ago, we figured out hailstorms are not caused by witches and, like, old crones would not be held responsible for hailstorms and burnt at the stake. About 200 years ago, people figured out, definitely, that an epileptic seizure is not a sign of demonic possession. Responsibility is subtracted out.

    About 50 years ago, the damn physiatrics, sort of, old boy oligarchy figured out that schizophrenia is not caused by mothers with psychodynamic hatred of their child, and instead, it’s a neurogenetic disorder. 30 years ago, we figured out that kids at school that simply are not learning to read, it’s not because they’re lazy and unmotivated, it’s because their cortical abnormalities are making them reverse letters that have, like, closed loops in them or whatever. We’ve done it over and over and over, and things have been just fine, and in fact, things have gotten much better and much more humane.

    So, the challenge is to just imagine what things people a century from now will be saying about our time period and things we still thought were volitional and things that we punished people for and things that we rewarded people for, where there was absolutely no basis for it. More practically, like, how are we supposed to function? It seems like the first, sort of, thing to get off the table is, “Oh my God, we’re all going to run amok, because people will be unconstrained by, you know, “I can’t be held responsible.”

    Really careful studies suggest that people won’t run amok. Some pretty superficial ones say that, as soon as you prime people physiologically to believe less in free will, they start cheating like mad on their economic games, two minutes later, but, sort if, deeper studies show that that’s really not the case, and there’s a great parallel example. Instead of thinking, “Wow, I can do whatever I want, because I’m not responsible for my actions,” thinking, “Wow, I can do whatever I want because I won’t be held responsible in an ultimate sense.” Atheists are, if anything, more ethical in their behaviour than the highly religious. The running amok thing is not a worry.

    The next one that’s got to be disposed of is, like nonetheless, dangerous people need to be contained and, yes, absolutely. Just because someone is not responsible for them being a damaging person, because they’ve been damaged as hell, like all of the rotten luck they’ve gotten, adversity in life, that doesn’t mean, you know, you shouldn’t constrain them from damaging. What people emphasise more and more is a quarantine model. Like, if somebody is infectious, through no fault of their own, they’re quarantined.

    If a car’s breaks don’t work and it will run you over, keep it in a garage. If a person’s frontal cortex has been so done in by childhood trauma that they can’t regulate their emotional behaviours, make sure they can’t damage people. Make sure if all of that can strain them with the absolute minimum needed to prevent that and not an inch more in the name of retribution or rotten souls or anything that they deserve. And, as the flip side of it, like recognise that some people are better brain surgeons are better basketball players or something than others and that’s great. We really do want to have competent brain surgeons and I presume basketball players out there and they should be doing that stuff but don’t tell that they’re entitled to a greater salary than anyone else and don’t give them a greater salary. The meritocracy makes as little sense as does the criminal justice system when you really think about this.

    Timothy Revell: Yes, it’s very interesting that as you present the things from history and you reel through them. Things like the not believing that people are influencing hail storms or that you’re-, in some way it’s a sign of the devil if you have epilepsy or the same with dyslexia. Those things feel so obvious to us now sitting here and I think that the vast majority of people will go of course it’s ridiculous we ever thought anything else but yet when you say for the criminal justice system it needs to be reframed so that it is no longer about responsibility but instead about quarantine I think there are lots of people who maybe have a harder time reaching that same conclusion. Is that what you find? That when you talk to people-, so historical examples that all makes sense but maybe the next step just seems almost unfathomable.

    Robert Sapolsky: Exactly, and the real challenge is to think back that somewhere, I don’t know, 400 years ago there was some very learned, reflective, compassionate, empathic, introspective smart guy who is some sort of judge or something, and he believed in helping the underdog. And if there had been national public radio then to contribute money to, he would’ve done that and gotten a little button saying, “I support, like, everything they believe in.” He would’ve been like a total bleeding heart liberal of the time, and he’d come home at the end of the day and say, “Wow, tough day. We had this guy. Had to burn him at the stake. Had seizures. He obviously welcomed in Satan, I mean, kids. He had a wife, kids who were really upset. It was, like, hard to do but what can you do?” Nobody told him to welcome in Satan, so of course, we had to burn him at the stake, but tough day. And that would’ve been a compassionate liberal at the time and it would’ve been inconceivable then in the same way that it’s inconceivable now that somebody’s IQ or somebody’s capacity to master tough difficult things or somebody’s inability to regulate their emotions and thus be really damaging makes just as little sense.

    Timothy Revell: Can you talk us through a little bit about that because quite a lot of those historical examples there about-, sort of, parts of the human condition becoming medicalized, us appreciating that their diseases or conditions that are really affecting things that happened to people. For example them having seizures but when it comes to crime I think some people will not see the immediate link there. So if you have someone who has committed a crime, how does the medical side of this, the neuroscience, all of that, fit into the point where they commit a crime?

    Robert Sapolsky: Well, the examples you bring up first are the easy ones or the edge cases. Society is pretty good at recognising, at least in the American legal system, that if somebody has a sufficiently low IQ they shouldn’t be held legally responsible for a violent act or whatever. There’s, like, a cut off and people fight over what the cut off should be and all of that. If someone has had massive damage to their frontal cortex or a tumour there, I don’t know, about half the states in the United States are willing to say, in this edge case, there was not actually responsibility.

    But yes, then we get to the normative range of like people doing awful stuff or people doing commendable stuff, where there isn’t an obvious whatever that presents, you know, this is a special mitigating case. There’s no special mitigating cases because it’s a continuum of the exact same biology. The second you can show stuff like what a paper a couple of years ago showed which is brain imaging on fetuses that by the time you’re a third trimester fetus the social economic status of your parents are already influencing the rate in which your brain is growing. By the time you can take kids and adolescence and show like a formal checklist of childhood adversaries and traumas, what somebody’s score is on this scale.

    The ace score, adverse child experience score. Like, we had a score from zero to ten depending on just how unlucky and awful your childhood was and for every additional point you get on the scale there’s about a 35 per cent increase chance that a guy by age 20 will have done something antisocial and violent. There’s about 35 per cent increase change that a female will have had a teen pregnancy of either unsafe sex, of by adulthood, a major mood disorder like anxiety or depression. If you can show that one extra step, whoa. Not only were they sexually abused as a kid but somebody in the family was incarcerated. That one extra point makes him 35 per cent more likely to be that way as an adult. You’re looking at what has to come into any of these factors which is we’ve just scratched the service on the things that move you from a 35 per cent chance of a particular outcome to a 100 per cent chance. And what I endlessly go on about is, like, ace scores adverse childhood experience scores.

    You can have the exact same conclusion if there was such a thing as, like, RLCE ridiculously lucky child who experiences and you can get a whole scale on that. Did your parents read books to you? Did you, like, play and laugh a lot? Did you never wonder where your next meal was coming from? And no doubt for every one of those a 35 per cent increase chance that you’re going to have the corner office in some corporation some day. Like, you look at those and any of these myths of somebody being responsible ultimately for the bad or the good just isn’t supportable and eventually is morally repugnant as well.

    Timothy Revell: I think for many-, like for me certainly when reading the book, I can accept all of that but part of me also wants to think but I’m different. There’s a certain sense of-, like, I totally understand that if you’ve gone through these horrible life experiences that is of course going to affect you later in life but it’s so hard to drop that idea that maybe I would make different choices but I think it is quite compelling that argument you put forward that I think would it be fair to say it boils down to if you had the same life experiences and you had the same biology you would do the same things.

    Robert Sapolsky: Exactly. And feel the same sense of agency and captain of your fate, sort of, delusions. Something I try to emphasise though throughout the book is this is incredibly difficult to think this way. Like, I’ve believed this since I was, like, early adolescence and 99 per cent of the time I can’t manage to pull this off.

    I think I recount in there a few years back there was some, like, appalling hate crime. Some guy showed up with an automatic weapon in a place of worship and killed a bunch of people and listening to the radio that next Monday morning saying whoever is being arraigned and is going to be charged with a federal hate crime as well which makes him eligible for the death penalty. I thought, “Yes. Fry the bastard.” Wait. I’m working on death penalty cases right now to convince juries that-, yet no one says this is going to be easy.

    I’m terrible at it 99 per cent of the time. Not only am I violating my intellectual beliefs but my moral beliefs as well because these are really strong reflexes to both get pissed off at people who do awful things but in addition probably more fundamentally to feel, kind of, good about yourself if someone says well nice job on that. Yes. I did a nice job. I’m entitled to that praise. This is going to be incredibly hard but we’ve done it over and over and over again and it’s not that hard to identify the corners of society where it’s most important to make that emphasis first.

    Timothy Revell: You hinted at it there but can you talk a little bit about your direct experience with the criminal justice system where you have appeared as a, sort of, expert on the brain. What has your role been there and how does it play into all of this?

    Robert Sapolsky: Oh, this has been this little, minor hobby of working with what are called public defenders, who are the people who are assigned when some defendant can’t afford their own attorney, and this is a whole world of, like, liberal, do-gooder attorneys who lose 95 per cent of their cases. I’ve been working on a bunch of these, and what has always been the scenario is this is someone who has done something very, very bad. And where, initially, they were threatened and did something that could pass as self-defence, they stabbed the guy before the other guy could stab them who came at them first and they’re then lying there on the ground incapacitated and ten seconds later they come back and stab the guy an additional 72 times.

    At which point the jury says well, you know, the first stab was self defence but 10 seconds that was enough time to premeditate and figure out that the threat was over with. But whoa, 72 additional times. That counts as premeditated murder and it’s always that, sort of, scenario and it is always somebody who was already virtually guaranteed to do this by the time they were 5 years old. Substance abuse at home, psychological abuse, physical abuse, sexual abuse, prenatal exposure drugs of abuse, shuttled through foster homes. Stabbed for the first time at age 10, you know, that repeated concussive head traumas from people abusing them, all of that and you look at someone like that and this is screamingly this is a broken machine.

    The thing that I always do with these juries is take them through, like, what’s going on in the brain when you make a decision and how we’re much more likely neurobiologically to make an awful decision if we’re under a whole lot of stress. Like somebody coming at us with a knife and we’re a gazillion times more likely to make the wrong decision during that 10 seconds if we have a brain that’s been pickled in adversity from day one because your brain would’ve been constructed in a way where you’re going to make a terrible impulsive decision at that point and then I dramatically look at the jury and say the same thing you said before which is if they had gone through this fetal life childhood etc, etc, all the things that-, they would’ve done the exact same thing and the juries all nod and look like they’re following and then they go into the jury room and they look at the pictures of the corpse with the head almost decapitated from stabs number 36 through 43 or something out of the 72 and they vote to convict the guy. I’ve done 12 of these trials by now over the years and we’ve lost 11 of them and that’s even arguing, like, the edge cases. Wow, this is a guy whose frontal cortex was destroyed in a car accident when he was eight.

    He spent two months in a coma, came out of it, no prior history whatever and did his first murder at age 12 and here you guys have just convicted him of his 8th and 9th murders and he’s a broken machine. And you know, they go and sit about it for a while and they come back with the death penalty so it’s a real uphill battle even with these edge cases of, whoa, traumatic examples of, like, terrible like or then look at like, Ivy League students or my undergrads at Stanford and look at their histories and you know by age 5 they already had their paths set to have a higher of an average income sometime later and would go to a prestigious college and the same exact thing. It’s very hard to just work with the gears that made them who they are.

    Timothy Revell: Alright, one last question for you. What are you planning on tackling next? Is it the meaning of life?

    Robert Sapolsky: Oh, I don’t know. I hope something interesting comes along, building on-, not to get all preachy and stuff, but at the end of the day this stops being an issue for neuroscientists or behaviour geneticists or early childhood develop-, and it becomes a social justice issue. It’s really great, philosophically, if people believe less in free will and all of that. The number of people on earth who are made to suffer because of the miserable luck in their life, starting with their ancestors picking the wrong, god-awful corner of the planet to live in, and centuries later, that has something to do with this person’s cerebral malaria when they were five.

    The social justice aspects of this, at the end of the day, are really the things that matter most about this, because we have a constructed a world with an awful lot of myths of free will, and culpability and responsibility. And most people who don’t have the corner office in their, like, fancy corporation, most people have mostly suffered because of this so that’s, kind of, the end that is galvanising me the most at this point. At the end of the day, that’s what this stuff is really about.

    Timothy Revell: So, what did you think? It’s a pretty compelling case that Sapolsky built I think that free will doesn’t exist and as he puts it in the book “We are not captains of our ships. Our ships never had captains.” And if we could really accept that the implications that would have for our society would be profound. If you have any thoughts on this do please get in touch at podcasts at new scientist.com. We would love to hear from you and if you enjoy our podcast do please leave a review on whatever platform you’re listening to us on. It does really help us out .That’s it for this episode of culture lab. We’ll be back in a couple of weeks time with some more. That’s bye for now. 

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