Chapter 4. Development of the Brain

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by Josh Wilbur Jake Haendel was a hard-partying chef from a sleepy region of Massachusetts. When he was 28, his heroin addiction resulted in catastrophic brain damage and very nearly killed him. In a matter of months, Jake’s existence became reduced to a voice in his head. Jake’s parents had divorced when he was young. He grew up between their two homes in a couple of small towns just beyond reach of Boston, little more than strip malls, ailing churches and half-empty sports bars. His mother died of breast cancer when he was 19. By then, he had already been selling marijuana and abusing OxyContin, an opioid, for years. “Like a lot of kids at my school, I fell in love with oxy. If I was out to dinner with my family at a restaurant, I would go to the bathroom just to get a fix,” he said. He started culinary school, where he continued to experiment with opioids and cocaine. He hid his drug use from family and friends behind a sociable, fun-loving front. Inside, he felt anxious and empty. “I numbed myself with partying,” he said. After culinary school, he took a job as a chef at a local country club. At 25, Jake tried heroin for the first time, with a co-worker (narcotics are notoriously prevalent in American kitchens). By the summer of 2013, Jake was struggling to find prescription opioids. For months, he had been fending off the symptoms of opioid withdrawal, which he likened to “a severe case of the flu with an added feeling of impending doom”. Heroin offered a euphoric high, staving off the intense nausea and shaking chills of withdrawal. Despite his worsening addiction, Jake married his girlfriend, Ellen, in late 2016. Early in their relationship, Ellen had asked him if he was using heroin. He had lied without hesitation, but she soon found out the truth, and within months, the marriage was falling apart. “I was out of control, selling lots of heroin, using even more, spending a ridiculous amount of money on drugs and alcohol,” he said. In May 2017, Ellen noticed that he was talking funnily, his words slurred and off-pitch. “What’s up with your voice?” she asked him repeatedly.

Keyword: Consciousness; Drug Abuse
Link ID: 27595 - Posted: 11.27.2020

By Bethany Brookshire A hungry brain craves food. A lonely brain craves people. After spending a day completely isolated from anyone else, people’s brains perked up at the sight of social gatherings, like a hungry person’s brain seeing food, scientists report November 23 in Nature Neuroscience. Cognitive neuroscientist Livia Tomova, then at MIT, and her colleagues had 40 participants fast for 10 hours. At the end of the day, certain nerve cells in the midbrain fired up in response to pictures of pizza and chocolate cake. Those neurons — in the substantia nigra pars compacta and ventral tegmental area — produce dopamine, a chemical messenger associated with reward (SN: 8/27/15). On a different day, the same people underwent 10 hours of isolation (no friends, no Facebook and no Instagram). That evening, neurons in the same spot activated in response to pictures of people chatting or playing team sports. The more hunger or isolation the subject reported, the stronger the effect (SN: 10/4/17). In people who reported that they were generally more lonely, the social responses were blunted. “We don’t really know what causes that,” Tomova says. “Maybe being isolated doesn’t really affect them as much, because it’s something that is not that different, perhaps, from their everyday life.” The midbrain, which plays an important role in people’s motivation to seek food, friends, gambling or drugs, responds to food and social signals even when people aren’t hungry or lonely. After all, a person always could eat or hang out. But hunger and loneliness increased the reaction and made people’s responses specific to the thing they were missing. The findings “speak to our current state,” says Tomova, now at the University of Cambridge. COVID-19 has left many more socially isolated, putting mental as well as physical health at stake (SN: 3/29/20) and leaving people with cravings for more than food. “It’s important to look at the social dimension of this kind of crisis.” L. Tomova et al. Acute social isolation evokes midbrain craving responses similar to hunger. Nature Neuroscience. Published online November 23, 2020. doi: 10.1038/s41593-020-00742-z. = © Society for Science & the Public 2000–2020

Keyword: Stress; Obesity
Link ID: 27594 - Posted: 11.27.2020

By Katherine J. Wu For a rodent that resembles the love child of a skunk and a steel wool brush, the African crested rat carries itself with a surprising amount of swagger. The rats “very much have the personality of something that knows it’s poisonous,” says Sara Weinstein, a biologist at the University of Utah and the Smithsonian Conservation Biology Institute who studies them. In sharp contrast to most of their skittish rodent kin, Lophiomys imhausi lumber about with the languidness of porcupines. When cornered, they fluff up the fur along their backs into a tip-frosted mohawk, revealing rows of black-and-white bands that run like racing stripes down their flanks — and, at their center, a thicket of specialized brown hairs with a honeycomb-like texture. Those spongy hairs contain a poison powerful enough to bring an elephant to its knees, and are central to Dr. Weinstein’s recent research, which confirmed ideas about how this rat makes itself so deadly. Give them a chance and African crested rats will take nibbles from the branch of a poison arrow tree. It’s not for nutrition. Instead, they will chew chunks of the plants and spit them back out into their fur, anointing themselves with a form of chemical armor that most likely protects them from predators like hyenas and wild dogs. The ritual transforms the rats into the world’s only known toxic rodents, and ranks them among the few mammals that borrow poisons from plants. Dr. Weinstein’s research, which was published last week in the Journal of Mammalogy, is not the first to document the crested rats’ bizarre behavior. But the new paper adds weight to an idea described nearly a decade ago, and offers an early glimpse into the animals’ social lives. First documented in the scientific literature in 1867, the rarely-glimpsed African crested rat “has captured so much interest for so long,” said Kwasi Wrensford, a behavioral ecologist at the University of California, Berkeley who wasn’t involved in the study. “We’re now just starting to unpack what makes this animal tick.” © 2020 The New York Times Company

Keyword: Neurotoxins; Learning & Memory
Link ID: 27592 - Posted: 11.27.2020

By Abby Goodnough PHILADELPHIA — Steven Kelty had been addicted to crack cocaine for 32 years when he tried a different kind of treatment last year, one so basic in concept that he was skeptical. He would come to a clinic twice a week to provide a urine sample, and if it was free of drugs, he would get to draw a slip of paper out of a fishbowl. Half contained encouraging messages — typically, “Good job!” — but the other half were vouchers for prizes worth between $1 and $100. “I’ve been to a lot of rehabs, and there were no incentives except for the idea of being clean after you finished,” said Mr. Kelty, 61, of Winfield, Pa. “Some of us need something to motivate us — even if it’s a small thing — to live a better life.” The treatment is called contingency management, because the rewards are contingent on staying abstinent. A number of clinical trials have found it highly effective in getting people addicted to stimulants like cocaine and methamphetamine to stay in treatment and to stop using the drugs. But outside the research arena and the Department of Veterans Affairs, where Mr. Kelty is a patient, it is nearly impossible to find programs that offer such treatment — even as overdose deaths involving meth, in particular, have soared. There were more than 16,500 such deaths last year, according to preliminary data, more than twice as many as in 2016. Early data suggests that overdoses have increased even more during the coronavirus pandemic, which has forced most treatment programs to move online. Researchers say that one of the biggest obstacles to contingency management is a moral objection to the idea of rewarding someone for staying off drugs. That is one reason publicly funded programs like Medicaid, which provides health coverage for the poor, do not cover the treatment. Some treatment providers are also wary of giving prizes that they say patients could sell or trade for drugs. Greg Delaney, a pastor and the outreach coordinator at Woodhaven, a residential treatment center in Ohio, said, “Until you’re at the point where you can say, ‘I can make a good decision with this $50,’ it’s counterproductive.” © 2020 The New York Times Company

Keyword: Drug Abuse; Learning & Memory
Link ID: 27556 - Posted: 10.28.2020

R. Douglas Fields As I opened my copy of Science at home one night, an unfamiliar word in the title of a new study caught my eye: dopaminylation. The term refers to the brain chemical dopamine’s ability, in addition to transmitting signals across synapses, to enter a cell’s nucleus and control specific genes. As I read the paper, I realized that it completely upends our understanding of genetics and drug addiction. The intense craving for addictive drugs like alcohol and cocaine may be caused by dopamine controlling genes that alter the brain circuitry underlying addiction. Intriguingly, the results also suggest an answer to why drugs that treat major depression must typically be taken for weeks before they’re effective. I was shocked by the dramatic discovery, but to really understand it, I first had to unlearn some things. “Half of what you learned in college is wrong,” my biology professor, David Lange, once said. “Problem is, we don’t know which half.” How right he was. I was taught to scoff at Jean-Baptiste Lamarck and his theory that traits acquired through life experience could be passed on to the next generation. The silly traditional example is the mama giraffe stretching her neck to reach food high in trees, resulting in baby giraffes with extra-long necks. Then biologists discovered we really can inherit traits our parents acquired in life, without any change to the DNA sequence of our genes. It’s all thanks to a process called epigenetics — a form of gene expression that can be inherited but isn’t actually part of the genetic code. This is where it turns out that brain chemicals like dopamine play a role. All genetic information is encoded in the DNA sequence of our genes, and traits are passed on in the random swapping of genes between egg and sperm that sparks a new life. Genetic information and instructions are coded in a sequence of four different molecules (nucleotides abbreviated A, T, G and C) on the long double-helix strand of DNA. The linear code is quite lengthy (about 6 feet long per human cell), so it’s stored neatly wound around protein bobbins, similar to how magnetic tape is wound around spools in cassette tapes. All Rights Reserved © 2020

Keyword: Drug Abuse; Epigenetics
Link ID: 27555 - Posted: 10.28.2020

By Jane E. Brody Do you have the heart to safely smoke pot? Maybe not, a growing body of medical reports suggests. Currently, increased smoking of marijuana in public, even in cities like New York where recreational use remains illegal (though no longer prosecuted), has reinforced a popular belief that this practice is safe, even health-promoting. “Many people think that they have a free pass to smoke marijuana,” Dr. Salomeh Keyhani, professor of medicine at the University of California, San Francisco, told me. “I even heard a suggestion on public radio that tobacco companies should switch to marijuana because then they’d be selling life instead of selling death.” But if you already are a regular user of recreational marijuana or about to become one, it would be wise to consider medical evidence that contradicts this view, especially for people with underlying cardiovascular diseases. Well: Get the best of Well, with the latest on health, fitness and nutrition. Compared with tobacco, marijuana smoking causes a fivefold greater impairment of the blood’s oxygen-carrying capacity, Dr. Keyhani and colleagues reported. In a review of medical evidence, published in January in the Journal of the American College of Cardiology, researchers described a broad range of risks to the heart and blood vessels associated with the use of marijuana. The authors, led by Dr. Muthiah Vaduganathan, cardiologist at Brigham and Women’s Hospital in Boston, point out that “marijuana is becoming increasingly potent, and smoking marijuana carries many of the same cardiovascular health hazards as smoking tobacco.” Edible forms of marijuana have also been implicated as a possible cause of a heart attack, especially when high doses of the active ingredient THC are consumed. © 2020 The New York Times Company

Keyword: Drug Abuse
Link ID: 27550 - Posted: 10.26.2020

By Scott Barry Kaufman Do you get excited and energized by the possibility of learning something new and complex? Do you get turned on by nuance? Do you get really stimulated by new ideas and imaginative scenarios? If so, you may have an influx of dopamine in your synapses, but not where we traditionally think of this neurotransmitter flowing. In general, the potential for growth from disorder has been encoded deeply into our DNA. We didn’t only evolve the capacity to regulate our defensive and destructive impulses, but we also evolved the capacity to make sense of the unknown. Engaging in exploration allows us to integrate novel or unexpected events with existing knowledge and experiences, a process necessary for growth. Dopamine production is essential for growth. But there are so many misconceptions about the role of dopamine in cognition and behavior. Dopamine is often labeled the “feel-good molecule,” but this is a gross mischaracterization of this neurotransmitter. As personality neuroscientist Colin DeYoung (a close colleague of mine) notes, dopamine is actually the “neuromodulator of exploration.” Dopamine’s primary role is to make us want things, not necessarily like things. We get the biggest rush of dopamine coursing through our brains at the possibility of reward, but this rush is no guarantee that we’ll actually like or even enjoy the thing once we get it. Dopamine is a huge energizing force in our lives, driving our motivation to explore and facilitating the cognitive and behavioral processes that allow us to extract the most delights from the unknown. If dopamine is not all about feeling good, then why does the feel-good myth persist in the public imagination? I think it’s because so much research on dopamine has been conducted with regard to its role in motivating exploration toward our more primal “appetitive” rewards, such as chocolate, social attention, social status, sexual partners, gambling or drugs like cocaine. © 2020 Scientific American

Keyword: Attention; Drug Abuse
Link ID: 27549 - Posted: 10.26.2020

By Rachel Nuwer With their bright saucer eyes, button noses and plump, fuzzy bodies, slow lorises — a group of small, nocturnal Asian primates — resemble adorable, living stuffed animals. But their innocuous looks belie a startling aggression: They pack vicious bites loaded with flesh-rotting venom. Even more surprising, new research reveals that the most frequent recipients of their toxic bites are other slow lorises. “This very rare, weird behavior is happening in one of our closest primate relatives,” said Anna Nekaris, a primate conservationist at Oxford Brookes University and lead author of the findings, published Monday in Current Biology. “If the killer bunnies on Monty Python were a real animal, they would be slow lorises — but they would be attacking each other.” Even before this new discovery, slow lorises already stood out as an evolutionary oddity. Scientists know of just five other types of venomous mammals: vampire bats, two species of shrew, platypuses and solenodons (an insectivorous mammal found in Cuba, the Dominican Republic and Haiti). Researchers are just beginning to untangle the many mysteries of slow loris venom. One key component resembles the protein found in cat dander that triggers allergies in humans. But other unidentified compounds seem to lend additional toxicity and cause extreme pain. Strangely, to produce the venom, the melon-sized primates raise their arms above their head and quickly lick venomous oil-secreting glands located on their upper arms. The venom then pools in their grooved canines, which are sharp enough to slice into bone. “The result of their bite is really, really horrendous,” Dr. Nekaris says. “It causes necrosis, so animals may lose an eye, a scalp or half their face.” © 2020 The New York Times Company

Keyword: Aggression; Neurotoxins
Link ID: 27539 - Posted: 10.21.2020

By John Horgan One of the most impressive, disturbing works of science journalism I’ve encountered is Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America, published in 2010. In the book, which I review here, award-winning journalist Robert Whitaker presents evidence that medications for mental illness, over time and in the aggregate, cause net harm. In 2012, I brought Whitaker to my school to give a talk, in part to check him out. He struck me as a smart, sensible, meticulous reporter whose in-depth research had led him to startling conclusions. Since then, far from encountering persuasive rebuttals of Whitaker’s thesis, I keep finding corroborations of it. If Whitaker is right, modern psychiatry, together with the pharmaceutical industry, has inflicted iatrogenic harm on millions of people. Reports of surging mental distress during the pandemic have me thinking once again about Whitaker’s views and wondering how they have evolved. Below he answers some questions. —John Horgan
 Horgan: When and why did you start reporting on mental health? Whitaker: It came about in a very roundabout way. In 1994, I had co-founded a publishing company called CenterWatch that covered the business aspects of the “clinical trials industry,” and I soon became interested in writing about how financial interests were corrupting drug trials. Risperdal and Zyprexa had just come to market, and after I used a Freedom of Information request to obtain the FDA’s review of those two drugs, I could see that psychiatric drug trials were a prime example of that corruption. In addition, I had learned of NIMH-funded research that seemed abusive of schizophrenia patients, and in 1998, I co-wrote a series for the Boston Globe on abuses of patients in psychiatric research. My interest was in that broader question of corruption and abuse in research settings, and not specific to psychiatry. © 2020 Scientific American

Keyword: Depression; Schizophrenia
Link ID: 27531 - Posted: 10.19.2020

By Eddie Jacobs How would you feel about a new therapy for your chronic pain, which—although far more effective than any available alternative—might also change your religious beliefs? Or a treatment for lymphoma that brings one in three patients into remission, but also made them more likely to vote for your least preferred political party? These seem like idle hypothetical questions about impossible side effects. After all, this is not how medicine works. But a new mental health treatment, set to be licensed next year, poses just this sort of problem. Psychotherapy assisted by psilocybin, the psychedelic compound in “magic mushrooms,” seems to be remarkably effective in treating a wide range of psychopathologies, but also causes a raft of unusual nonclinical changes not seen elsewhere in medicine. Although its precise therapeutic mechanisms remain unclear, clinically relevant doses of psilocybin can induce powerful mystical experiences more commonly associated with extended periods of fasting, prayer or meditation. Arguably, then, it is unsurprising that it can generate long-lasting changes in patients: studies report increased prosociality and aesthetic appreciation, plus robust shifts in personality, values and attitudes to life, even leading some atheists to find God. What’s more, these experiences appear to be a feature, rather than a bug, of psilocybin-assisted psychotherapy, with the intensity of the mystical experience correlating with the extent of clinical benefit. © 2020 Scientific American,

Keyword: Drug Abuse; Emotions
Link ID: 27521 - Posted: 10.12.2020

By Linda Searing U.S. deaths from overdoses of cocaine, a powerfully addictive stimulant, numbered 14,666 in 2018, the most recent year tallied, according to a new report from the Centers for Disease Control and Prevention. The rate of overdose deaths remained stable from 2009 through 2013, the report found, but then headed upward at about 27 percent each year from 2013 through 2018. That rate increase represents about 2½ times more cocaine-related deaths in 2018 than in 2014. Although the report does not address potential causes of the increase in cocaine overdose deaths, the Drug Enforcement Administration has said increased availability of the drug, “in large part due to record levels of coca cultivation and cocaine production in Colombia,” has led to increased usage in the United States. The CDC report says that the rate of overdose deaths from cocaine was higher among men than women and more common among middle-aged people (35 to 44 years old), those living in urban rather than rural areas, and people residing in the Northeast region. In addition, the rate of overdose deaths attributed to cocaine laced with a synthetic opioid such as fentanyl increased faster in recent years than did overdose deaths from purely cocaine. Cocaine overdoses can cause breathing problems, high blood pressure, hallucinations and extreme agitation, as well as seizures, heart attacks and strokes.

Keyword: Drug Abuse
Link ID: 27520 - Posted: 10.12.2020

By Matt Richtel VALLEJO, Calif. — The adolescent patient turned sullen and withdrawn. He hadn’t eaten in 13 days. Treatment with steroids, phenobarbital and Valium failed to curb the symptoms of his epilepsy. Then, on Sept. 18, he had a terrible seizure — violently jerking his flippers and turning unconscious in the water. Cronutt, a 7-year-old sea lion, had to be rescued so he didn’t drown. His veterinarian and the caretakers at Six Flags Discovery Kingdom began discussing whether it was time for palliative care. “We’d tried everything,” said Dr. Claire Simeone, Cronutt’s longtime vet. “We needed more extreme measures.” On Tuesday morning, Cronutt underwent groundbreaking brain surgery aimed at reversing the epilepsy. If successful, the treatment could save increasing numbers of sea lions and sea otters from succumbing to a new plague of epilepsy. The cause is climate change. As oceans warm, algae blooms have become more widespread, creating toxins that get ingested by sardines and anchovies, which in turn get ingested by sea lions, causing damage to the brain that results in epilepsy. Sea otters also face risk when they consume toxin-laden shellfish. The animals who get stranded on land have been given supportive care, but often die. Cronutt may change that. “If this works, it’s going to be big,” said Mariana Casalia, a neuroscientist at the University of California, San Francisco, who helped pioneer the techniques that led to a procedure that took place a vet surgery center in Redwood City, Ca. © 2020 The New York Times Company

Keyword: Epilepsy; Neurotoxins
Link ID: 27516 - Posted: 10.10.2020

Ken Solt & Oluwaseun Akeju The state of dissociation is commonly described as feeling detached from reality or having an ‘out of body’ experience. This altered state of consciousness is often reported by people who have psychiatric disorders arising from devastating trauma or abuse. It is also evoked by a class of anaesthetic drug, and can occur in epilepsy. The neurological basis of dissociation has been a mystery, but writing in Nature, Vesuna et al.1 describe a localized brain rhythm that underlies this state. Their findings will have far-reaching implications for neuroscience. The authors first recorded brain-wide neuronal activity in mice using a technique called widefield calcium imaging. They studied changes in these brain rhythms in response to a range of drugs that have sedative, anaesthetic or hallucinogenic properties, including three that induce dissociation — ketamine, phencyclidine (PCP) and dizocilpine (MK801). Only the dissociative drugs produced robust oscillations in neuronal activity in a brain region called the retrosplenial cortex. This region is essential for various cognitive functions, including episodic memory and navigation2. The oscillations occurred at a low frequency, of about 1–3 hertz. By contrast, non-dissociative drugs such as the anaesthetic propofol and the hallucinogen lysergic acid diethylamide (LSD) did not trigger this rhythmic retrosplenial activity. Vesuna et al. examined the active cells in more detail using a high-resolution approach called two-photon imaging. This analysis revealed that the oscillations were restricted to cells in layer 5 of the retrosplenial cortex. The authors then recorded neuronal activity across multiple brain regions. Normally, other parts of the cortex and subcortex are functionally connected to neuronal activity in the retrosplenial cortex; however, ketamine caused a disconnect, such that many of these brain regions no longer communicated with the retrosplenial cortex. © 2020 Springer Nature Limited

Keyword: Drug Abuse; Consciousness
Link ID: 27481 - Posted: 09.19.2020

Jon Hamilton Scientists used light to control the firing of specific cells to artificially create a rhythm in the brain that acted like the drug ketamine enjoynz/Getty Images Out-of-body experiences are all about rhythm, a team reported Wednesday in the journal Nature. In mice and one person, scientists were able to reproduce the altered state often associated with ketamine by inducing certain brain cells to fire together in a slow, rhythmic fashion. "There was a rhythm that appeared, and it was an oscillation that appeared only when the patient was dissociating," says Dr. Karl Deisseroth, a psychiatrist and neuroscientist at Stanford University. Dissociation is a brain state in which a person feels separated from their own thoughts, feelings and body. It is common in people who have some mental illnesses or who have experienced a traumatic event. It can also be induced by certain drugs, including ketamine and PCP (angel dust). The study linking dissociation to brain rhythms represents "a big leap forward in understanding how these drugs produce this unique state," says Dr. Ken Solt, an anesthesiologist at Harvard Medical School and Massachusetts General Hospital. Solt is the co-author of an article that accompanied the study but was not involved in the research. The finding also could be a step toward finding non-drug methods to control states of consciousness, Solt says. Deisseroth's lab made the discovery while studying the brains of mice that had been given ketamine or other drugs that cause dissociation. The team was using technology that allowed them to monitor the activity of cells throughout the brain. © 2020 npr

Keyword: Drug Abuse; Consciousness
Link ID: 27480 - Posted: 09.19.2020

By John Horgan I interviewed psychologist Susan Blackmore 20 years ago while doing research for my book Rational Mysticism. Here, lightly edited, is my description of her: “Her hair was dyed orange, red, and yellow, dark-rooted, cut short as a boy’s, with sideburns plunging like daggers past each multi-ringed ear. Words spewed from her pell-mell, accompanied by equally vigorous hand signals and facial expressions. She was keen on onomatopoeic sound effects: Ahhhhh (to express her pleasure at finding other smart people when she entered Oxford); DUN da la DUN da la DUN (the galloping noise she heard as she sped down a tree-lined tunnel in her first out-of-body experience); Zzzzzzt (the sound of reality dissolving after her second toke of the psychedelic dimethyltryptamine). We were talking in the dining room of the inn where she was staying, and twice we had to move to a quieter spot when employees or patrons of the inn started talking near us. One side effect of her spiritual practice, she explained, is that she has a hard time ignoring stimuli. ‘I think it is one of the bad effects of practicing mindfulness. I'm so aware of everything all the time.’” Blackmore began her career as a parapsychologist, intent on finding evidence for astral projection and extrasensory perception. Her investigations transformed her into a materialist and Darwinian (one of her best-known books describes humans as “meme machines”) who doesn’t believe in ESP, God or free will. And yet she is a mystic, too, who explores consciousness via meditation and psychedelics. In other words, Blackmore pulls off the trick of being both a hard-nosed skeptic and an open-minded adventurer. What more can one ask of a mind scientist? Curious about how her thinking has evolved in our mind-boggling era, I e-mailed her a few questions. An edited transcript of the interview follows. © 2020 Scientific American

Keyword: Consciousness; Drug Abuse
Link ID: 27475 - Posted: 09.16.2020