brain-garden-blog

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Yikes!

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Tiny Lab-Grown 'Brains' Raise Big Ethical Questions

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Eye Test Could Help Diagnose Autism

A new study out in European Journal of Neuroscience could herald a new tool that helps physicians identify a sub-group of people with Autism spectrum disorders (ASD). The test, which consists of measuring rapid eye movements, may indicate deficits in an area of the brain that plays an important role in emotional and social development.

“These findings build upon a growing field of research that show that eye movement could serve as a window into a part of the brain that plays a role in a number of neurological and development disorders, such as Autism,” said John Foxe, Ph.D., director of the University of Rochester Medical Center Del Monte Neuroscience Institute and co-author of the study.  

ASD is characterized by a wide range of symptoms that can vary in severity from person to person. This unpredictability not only presents a challenge for diagnosis, but also how best to devise a course of treatment. Identifying the specific phenotype of the disorder is, therefore, an essential first step to providing effective care.

Eye movements and the mechanisms by which the brain controls and processes what we choose to look at have been a major focus of neuroscience researchers for decades. The rapid eye movements we make when we shift our attention from one object to another, known as saccades, are essential to navigating, understanding, and interacting with the world around us. In healthy individuals, these saccades are rapid, precise, and accurate, redirecting the line of sight from one point of interest to another.

The potential relevance of eye movement in individuals with Autism is the area of the brain that controls these actions, a densely-packed structure of neurons known as the cerebellum. Traditionally considered to play a role in motor control, the cerebellum is now known to be essential to emotion and cognition via its connections to the rest of the brain. There is growing evidence that the structure of the cerebellum is altered in a sub-population of individuals with ASD.

In a series of experiments, the authors of the current study tracked the eye movements of individuals with ASD. The participants were asked to track a visual target that appeared in different locations on the screen. The experiment was designed in a manner that often caused the participant’s focus to “overshoot” the intended target. In healthy individuals, the brain would correctly adjust eye movements as the task is repeated. However, the eye movements of individuals with ASD continued to miss the target suggesting that the sensory motor controls in the cerebellum responsible for eye movement were impaired.

The inability of the brain to adjust the size of eye movement may not only be a marker for cerebellum dysfunction, but it may also help explain the communication and social interaction deficits that many individuals with ASD experience.

“These finding suggest that assessing the ability of people to adapt saccade amplitudes is one way to determine whether this function of the cerebellum is altered in ASD,” said Edward Freedman, Ph.D. an associate professor in the URMC Department of Neuroscience and co-author of the study. “If these deficits do turn out to be a consistent finding in a sub-group of children with ASD, this raises the possibility that saccade adaptation measures may have utility as a method that will allow early detection of this disorder.”

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Sleep Deprived Brains May Be Asleep and Awake at the Same Time

For something that can occupy such a significant chunk of time, sleep still remains a mysterious part of our lives. Although it is known to play a role in mental and physical health, such as metabolism and memory, there is much that is still not well understood.

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Stop Taking Adderall, Start Playing Video Games

Doctors could soon prescribe screen time for children with ADHD.

In the video game Project: EVO, you navigate roiling river rapids while dodging rapidly shifting obstacles and connecting with friendly flying characters. To earn stars and advance to the next level, you have to demonstrate multitasking mastery. Unlike other games that reward these kinds of skills, in this one you must prove to the game’s algorithm that you have made a leap in neurological function.

This is no ordinary entertainment — it’s a video game designed to lessen the symptoms of ADHD. And one day soon, it may be available by prescription and reimbursed by your insurance company.

The creator of Project: EVO, a Boston-based tech company called Akili Interactive, is betting that video games, often blamed for exacerbating behavioral and mental conditions, could actually provide successful treatments for ADHD. And it won’t just be kids playing on doctors’ orders. People on the autism spectrum, seniors with Alzheimer’s, and patients recovering from brain injuries may also benefit from playing games targeted to their specific neurological deficiencies.

Akili is working with the University of California, San Francisco’s Neuroscape Lab to build on the success of a game called Neuroracer, developed by UCSF neuroscientist Adam Gazzaley, which was shown to be a powerful tool for cognitive enhancement in adults aged 60 to 85.

In a 2013 study featured on the cover of Nature, Neuroracer’s multitasking features were shown to lead to improvements in real-life tasks that required working memory and sustained attention. In that game, players steer a virtual car while carrying out other actions that challenge their executive functioning. After 12 hours of this training, seniors were able to consistently beat 20-year-old novice players. The results were so astonishing that Gazzaley, a strikingly fit and even-keeled 40-something, became a darling of the Silicon Valley self-optimization set, a sort of med-tech celebrity who regularly speaks at tech conferences and dazzles the media with his plain-spoken charisma.

Over the past 12 years, Gazzaley and his team have collaborated with designers and artists to develop a range of video games that might be able to treat a wide range of brain disorders. Now with investment backing from PureTech Health, an R&D and venture creation firm, Gazzaley and the Akili team are charging into unknown terrain: securing approval from the Food and Drug Administration for a video game.

It’s a slow, deliberate process that’s at odds with the shoot-first way tech is usually developed. The FDA requires any kind of drug or medical device to go through multiple phases of large-scale, randomized, double-blind clinical trials that must all succeed. There are hundreds, if not thousands, of legal and procedural details that must be airtight, so Akili has 11 full-time employees working in its compliance department. Now in the final Phase 3 trial, the Project: EVO game is close to becoming the first prescription-based video game.

If it gets approved, the implications are big. Prescription video games could become an enormous market even though they face the perception that screen time is generally not beneficial. And they could give children with ADHD an intriguing alternative to the stimulants that are prescribed for them with astonishing regularity.

Safeguards

Matt Omernick heads up product development for Akili, and was recruited by Gazzaley while he was executive art director at LucasArts. Omernick says the rigorous FDA approval process will assure medical professionals that the game is beneficial. “Get to market fast is not the strategy, and our investors know that,” he says. “Hopefully we will be the first to define a very new industry — digital medicine.”

Aside from a company called Posit Science, which is in talks with the FDA about using video games to treat various cognitive disorders, competition is virtually non-existent. However, persuading doctors and regulators is a steep uphill climb because several companies, including Lumosity and Neurocore — which counts Education Secretary Betsy DeVos as chief investor — have come under attack for making false claims about their benefits. Gazzaley himself has been among the critics.

The very idea of using video games therapeutically goes against the “you’ll rot your brain” conventional wisdom that is in fact validated by numerous studies. While some research has shown that playing video games consistently can lead to significant improvements in vision and attentiveness, even more studies demonstrate the negative effects of screen time, including serious addiction — particularly for those with ADHD, attention problems, and anti-social tendencies.

It’s a slow, deliberate process that’s at odds with the shoot-first way tech is usually developed.

Omernick says that Project: EVO has built-in safeguards to ensure that it’s only used for one 30-minute session per day, so kids can’t get addicted to it. It stops functioning entirely after the daily session. He stays away from the swirl of controversy surrounding kids and screen time by taking a very pragmatic approach: “No matter what, video games are not going away, and this is one that is actually beneficial for your brain,” he says.

Kids who are prescribed the game will go through behavioral and neurological assessments first. Then, they’ll play the game on an iPad for half an hour a day, five days a week, for four weeks. The game is entertaining and visually immersive, offering up the kind of rewards that kids are familiar with from other video games. At the start of the training, a cartoon character in a lab coat explains the session’s objectives. Players learn to position and tilt the tablet to control an avatar traveling through outdoor environments while hitting targets and avoiding distractors. Even for me, a neurotypical 39-year-old, the game is fun, challenging, and hard to put down.

Unlike an over-the-counter game, in which all players have to do the same things to advance to higher levels or earn rewards, Project: EVO is a completely individualized tool for each player. It measures neurological skills such as perceptual discrimination, visuomotor tracking, and multitasking ability, says Omernick, and players move on only “once you demonstrate that you’ve actually changed something neurologically. So the game pushes you to improve a part of your brain, like a personal trainer.”

After the four weeks of gaming, the players are once again thoroughly assessed for attention, processing speed, and reaction times. The clinical team asks parents to report kids’ symptoms, observes how the children behave during the month, and interviews the kids themselves about how they are feeling and how they believe they might have progressed. The Project: EVO pilot study results released last April showed significant improvement in attention abilities for all participants, and sustained effects for up to nine months.

Other possibilities

The Akili team is also setting up similar studies with autism spectrum disorder, depression, Alzheimer’s disease, and traumatic brain injury. Last December, Akili announced promising results in a study of a digital screening platform that detects biomarkers of Alzheimer’s disease. The device, called AD Screen, is also in late-stage clinical trials.

But unlike with ADHD, this space is a bit more well-traveled. Posit Science has offered a cognitive enhancement game, BrainHQ, for five years. The Southern California branch of AAA offers older drivers a chance to complete 10 hours of training in the game in exchange for a discount on their auto insurance, says Posit Science CEO Henry Mahncke; he believes that health insurance discounts for patients who complete brain training will soon follow. Some of the exercises in BrainHQ, when combined with other treatments, have been shown to reduce the risk for dementia and even to help people with early Alzheimer’s.

Gazzaley says that most of the Akili games in development offer preventive potential as well, possibly protecting kids from developing ADHD, or lessening cognitive decline in adults. In fact, he maintains that the games could enhance cognitive abilities in everyone. The Neuroscape team is now working with school systems in the San Francisco Bay Area to train students to perform better academically using its video games.

But it’s not yet clear what the overall experience would be like for people who just pick up the game on their own, without a prescription for a certain condition. Among the details that haven’t been nailed down: Would non-prescription users have access to Akili’s clinical team as well? Would it be prohibitively expensive?

Cutting back on meds

It’s clear that parents and medical professionals are looking for an alternative way to treat ADHD. Diagnoses of hyperactivity disorder have skyrocketed in the past decade, affecting an estimated 11 percent of kids ages 4–17. About half of these kids take powerful drugs to lessen their symptoms and make them more amenable to classroom learning, following rules, and staying still.

Prescriptions of Adderall, Ritalin, and related drugs are up 28 percent since 2007. These drugs often present side effects, ranging from loss of appetite and weight to cardiac irregularities and slowed growth. They’re also widely used illegally off-label for their stimulant effects among the college set. It’s not yet fully understood how these drugs affect the developing brain, making each child a walking experiment. Adding to this, concern is growing that the ADHD diagnosis — which has criteria that are subjectively determined by clinicians — is incorrect about a third of the time, leading millions of kids to take drugs that they don’t really need. So Project: EVO offers a completely new framework for helping ADHD kids.

The idea that a video game could replace or reduce pharmaceutical treatments makes more sense when you consider that social, rather than behavioral and neurodevelopmental factors, frequently influence diagnosis. It’s the youngest kids in a classroom cohort who are more likely to be labeled hyperactive. Black and brown kids are diagnosed more often than their white classmates. To put it in historical perspective, hyperactivity wasn’t even acknowledged before compulsory schooling began in the 19th century. In many respects, children have become the target of modification because — let’s face it — fundamentally changing the social and environmental structures that negatively influence their behavior is more than a bit daunting. It’s widely acknowledged that in less rigid environments, children appear to evidence ADHD symptoms much less.

It’s clear that parents and medical professionals are looking for an alternative way to treat ADHD.

Emory University physician and anthropologist Mel Konner has proposed that ADHD is a matter of what’s known as evolutionary mismatch. The trait of short attention may have once provided survival advantages, but in the modern context it has become maladaptive because our environment is so different from the context in which Homo sapiens evolved, and our genes haven’t caught up. “These kids have hunter-gatherer brains in the modern context,” he says. “The testing regime in schools, coupled with the cutbacks in outdoor recess and art programs means that we are making the mismatch worse.”

Some solid research has found that kids with ADHD show significant improvement after getting regular outdoor play in natural settings, essentially recreating the hunter-gatherer lifestyle in small doses. And adventure sports disproportionately attract people who can successfully channel their ADHD energies into mountain climbing or paragliding. Similarly, Posit Science CEO Mahncke says that cognitive decline in seniors could be caused by lifestyle factors. Most people in the developed world are now sedentary, and our professional lives involve becoming narrowly focused on one type of task, in one place. Even if that task is intellectually demanding, that intensity is not what keeps our brains sharp. “Humans are one of the most adaptable animals — we can live anywhere — and what sustains us and maintains our brain health is constant new learning and adapting to environments,” Mahncke says.

But health professionals find it hard to write a prescription for an environment or a lifestyle. Take the idea of outdoor play — how much is effective? What kind of play is best? Are some spaces more beneficial than others? And what about the majority of people who don’t have easy access to wilderness?

That’s why Gazzaley thinks a video game prescription will likely be the most reliable treatment alternative for ADHD — and eventually for other disorders. “With almost 100% of newly diagnosed cases of ADHD, parents are asking: ‘Is there anything else I can do for my child besides drugs?’” Gazzaley says. “Our goal is to be on the pharmacy shelf next to Adderall. Any doctor will have the ability to prescribe our video game, which has a delivery system that is better than any drug.”

- by Jessica Carew Kraft

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Neuroscientists creating games for dogs

1. I want to be a part of this lab.

2. These scientists get to work with the sweetest research participants.

3. I need this for my dog.

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   How your mind protects you against hallucinations

More than 300 years ago, the philosopher René Descartes asked a disturbing question: If our senses can’t always be trusted, how can we separate illusion from reality? We’re able to do so, a new study suggests, because our brain keeps tabs on reality by constantly questioning its own past expectations and beliefs. Hallucinations occur when this internal fact-checking fails, a finding that could point toward better treatments for schizophrenia and other psychiatric disorders.

The study is “very elegant,” and an important step toward identifying the brain regions that produce hallucinations—and keep them in check, says Georg Northoff, a neuroscientist at the University of Ottawa who was not involved with the work.

We don’t always perceive the world as we see—or hear—it. In an experiment devised at Yale University in the 1890s, for example, researchers repeatedly showed volunteers an image paired with a tone. When the scientists stopped playing the tone, participants still “heard” it when the image appeared. A similar auditory hallucination occurs in daily life: when you think you hear your cellphone ring or buzz, only to find it’s turned off. “People come to expect the sound so much that the brain hears it for them,” says Albert Powers, a psychiatrist at Yale University and an author of the new study.

These examples suggest hallucinations arise when the brain gives more weight to its expectations and beliefs about the world than to the sensory evidence it receives, says study author and Yale psychiatrist Philip Corlett. To test that idea, he, Powers, and colleagues decided to apply a version of the 1890s experiment to four different groups: healthy people, people with psychosis who don’t hear voices, people with schizophrenia (a subtype of psychosis) who do, and people—such as self-described psychics—who regularly hear voices but don’t find them disturbing.

The researchers trained everyone to associate a checkerboard image with a 1-kilohertz, 1-second-long tone. As the team changed the intensity of the tone and sometimes tuned it out entirely, participants were asked to press a button when they heard it, increasing or decreasing pressure to indicate their level of confidence. Using magnetic resonance imaging scanners, the researchers captured a snapshot of the participants’ brain activity as they made their choices.

The team hypothesized that people who hear voices would be more likely to “believe” in auditory hallucinations. That’s precisely what they found: Both the schizophrenics and self-described psychics were nearly five times more likely to say they heard the nonexistent tone than healthy controls. They were also about 28% more confident that they had heard the tone when none was there, the researchers report today in Science.

Both self-described psychics and people with schizophrenia also showed abnormal neuronal activity in several brain regions responsible for monitoring our internal representations of reality. The more severe a person’s hallucinations were, for example, the less activity they displayed in the cerebellum, a wrinkled nodule at the back of the brain. The cerebellum plays a critical role in planning and coordinating future movements, a process that requires constantly updating one’s perception of the outside world.

The findings confirm that, when it comes to how we perceive the world, our ideas and beliefs can easily overpower our senses, Powers says. The work also suggests that the cerebellum is a key checkpoint against this distortion, he adds.

Northoff says future experiments should investigate whether there are any telling differences between the psychotic and healthy brain at rest. Such studies could guide still-experimental therapies such as transcranial magnetic stimulation, which aims to suppress or boost brain activity in targeted areas through electrical currents. Even more promising, says Corlett, is the prospect that studies like this one will help clinicians predict who is likely to develop schizophrenia, allowing them to seek early treatment.

By Emily Underwood at Science

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The concept of schizophrenia is coming to an end – here’s why

The concept of schizophrenia is dying. Harried for decades by psychology, it now appears to have been fatally wounded by psychiatry, the very profession that once sustained it. Its passing will not be mourned.

Today, having a diagnosis of schizophrenia is associated with a life-expectancy reduction of nearly two decades. By some criteria, only one in seven people recover. Despite heralded advances in treatments, staggeringly, the proportion of people who recover hasn’t increased over time. Something is profoundly wrong.

Part of the problem turns out to be the concept of schizophrenia itself.

Arguments that schizophrenia is a distinct disease have been “fatally undermined”. Just as we now have the concept of autism spectrum disorder, psychosis (typically characterised by distressing hallucinations, delusions, and confused thoughts) is also argued to exist along a continuum and in degrees. Schizophrenia is the severe end of a spectrum or continuum of experiences.

Jim van Os, a professor of psychiatry at Maastricht University, has argued that we cannot shift to this new way of thinking without changing our language. As such, he proposes the term schizophrenia “should be abolished”. In its place, he suggests the concept of a psychosis spectrum disorder.

Another problem is that schizophrenia is portrayed as a “hopeless chronic brain disease”. As a result, some people given this diagnosis, and some parents, have been told cancer would have been preferable, as it would be easier to cure. Yet this view of schizophrenia is only possible by excluding people who do have positive outcomes. For example, some who recover are effectively told that “it mustn’t have been schizophrenia after all”.

Schizophrenia, when understood as a discrete, hopeless and deteriorating brain disease, argues van Os, “does not exist”.

Breaking down breakdowns

Schizophrenia may instead turn out to be many different things. The eminent psychiatrist Sir Robin Murray describes how::

I expect to see the end of the concept of schizophrenia soon … the syndrome is already beginning to breakdown, for example, into those cases caused by copy number [genetic] variations, drug abuse, social adversity, etc. Presumably this process will accelerate, and the term schizophrenia will be confined to history, like “dropsy”.

Research is now exploring the different ways people may end up with many of the experiences deemed characteristic of schizophrenia: hallucinations, delusions, disorganised thinking and behaviour, apathy and flat emotion.

Indeed, one past error has been to mistake a path for the path or, more commonly, to mistake a back road for a motorway. For example, based on their work on the parasite Toxoplasma gondii, which is transmitted to humans via cats, researchers E. Fuller Torrey and Robert Yolken have argued that “the most important etiological agent [cause of schizophrenia] may turn out to be a contagious cat”. It will not.

Evidence does suggest that exposure to Toxoplasma gondii when young can increase the odds of someone being diagnosed with schizophrenia. However, the size of this effect involves less than a twofold increase in the odds of someone being diagnosed with schizophrenia. This is, at best, comparable to other risk factors, and probably much lower.

For example, suffering childhood adversity, using cannabis, and having childhood viral infections of the central nervous system, all increase the odds of someone being diagnosed with a psychotic disorder (such as schizophrenia) by around two to threefold. More nuanced analyses reveal much higher numbers.

Compared with non-cannabis users, the daily use of high-potency, skunk-like cannabis is associated with a fivefold increase in the odds of someone developing psychosis. Compared with someone who has not suffered trauma, those who have suffered five different types of trauma (including sexual and physical abuse) see their odds of developing psychosis increase more than fiftyfold.

Other routes to “schizophrenia” are also being identified. Around 1% of cases appear to stem from the deletion of a small stretch of DNA on chromosome 22, referred to as 22q11.2 deletion syndrome. It is also possible that a low single digit percentage of people with a schizophrenia diagnosis may have their experiences grounded in inflammation of the brain caused by autoimmune disorders, such as anti-NMDA receptor encephalitis, although this remains controversial.

All the factors above could lead to similar experiences, which we in our infancy have put into a bucket called schizophrenia. One person’s experiences may result from a brain disorder with a strong genetic basis, potentially driven by an exaggeration of the normal process of pruning connections between brain cells that happens during adolescence. Another person’s experiences may be due to a complex post-traumatic reaction. Such internal and external factors could also work in combination.

Either way, it turns out that the two extreme camps in the schizophrenia wars – those who view it as a genetically-based neurodevelopmental disorder and those who view it as a response to psychosocial factors, such as adversity – both had parts of the puzzle. The idea that schizophrenia was a single thing, reached by a single route, contributed to this conflict.

Implications for treatment

Many medical conditions, such as diabetes and hypertension, can be reached by multiple routes that nevertheless impact the same biological pathways and respond to the same treatment. Schizophrenia could be like this. Indeed, it has been argued that the many different causes of schizophrenia discussed above may all have a common final effect: increased levels of dopamine.

If so, the debate about breaking schizophrenia down by factors that lead to it would be somewhat academic, as it would not guide treatment. However, there is emerging evidence that different routes to experiences currently deemed indicative of schizophrenia may need different treatments.

Preliminary evidence suggests that people with a history of childhood trauma who are diagnosed with schizophrenia are less likely to be helped by antipsychotic drugs. However, more research into this is needed and, of course, anyone taking antipsychotics should not stop taking them without medical advice. It has also been suggested that if some cases of schizophrenia are actually a form of autoimmune encephalitis, then the most effective treatment could be immunotherapy (such as corticosteroids) and plasma exchange (washing of the blood).

Yet the emerging picture here is unclear. Some new interventions, such as the family-therapy based Open Dialogue approach, show promise for a wide range of people with schizophrenia diagnoses. Both general interventions and specific ones, tailored to someone’s personal route to the experiences associated with schizophrenia, may be needed. This makes it critical to test for and ask people about all potentially relevant causes. This includes childhood abuse, which is still not being routinely asked about and identified.

The potential for different treatments to work for different people further explains the schizophrenia wars. The psychiatrist, patient or family who see dramatic beneficial effects of antipsychotic drugs naturally evangelically advocate for this approach. The psychiatrist, patient or family who see drugs not working, but alternative approaches appearing to help, laud these. Each group sees the other as denying an approach that they have experienced to work. Such passionate advocacy is to be applauded, up to the point where people are denied an approach that may work for them.

What comes next?

None of this is to say the concept of schizophrenia has no use. Many psychiatrists still see it as a useful clinical syndrome that helps define a group of people with clear health needs. Here it is viewed as defining a biology that is not yet understood but which shares a common and substantial genetic basis across many patients.

Some people who receive a diagnosis of schizophrenia will find it helpful. It can help them access treatment. It can enhance support from family and friends. It can give a name to the problems they have. It can indicate they are experiencing an illness and not a personal failing. Of course, many do not find this diagnosis helpful. We need to retain the benefits and discard the negatives of the term schizophrenia, as we move into a post-schizophrenia era.

What this will look like is unclear. Japan recently renamed schizophrenia as “integration disorder”. We have seen the idea of a new “psychosis spectrum disorder”. However, historically, the classification of diseases in psychiatry has been argued to be the outcome of a struggle in which “the most famous and articulate professor won”. The future must be based on evidence and a conversation which includes the perspectives of people who suffer – and cope well with – these experiences.

Whatever emerges from the ashes of schizophrenia, it must provide better ways to help those struggling with very real experiences.

Originally published by The Conversation

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Settlement Reached in C.I.A. Torture Case

A settlement in the lawsuit against two psychologists who helped devise the Central Intelligence Agency’s brutal interrogation program was announced on Thursday, bringing to an end an unusual effort to hold individuals accountable for the techniques the agency adopted after the Sept. 11 attacks.

Lawyers for the three plaintiffs in the suit, filed in 2015 in Federal District Court in Spokane, Wash., said the former prisoners were tortured at secret C.I.A. detention sites. The settlement with the psychologists, Dr. Bruce Jessen and Dr. James Mitchell, came after a judge last month urged resolving the case before it headed to a jury trial in early September.

The plaintiffs — two former detainees and the family of a third who died in custody — had sought unspecified punitive and compensatory damages. The terms of the settlement are confidential, and it is unclear whether a financial payout was involved. The parties agreed to a joint statement in which the psychologists said that they had advised the C.I.A. and that the plaintiffs had suffered abuses, but that they were not responsible.

In a phone interview, one of the plaintiffs, Mohamed Ben Soud, said through a translator: “I feel that justice has been served. Our goal from the beginning was justice and for the people to know what happened in this black hole that was run by the C.I.A.’s offices.”

Dror Ladin, a lawyer with the American Civil Liberties Union, which helped bring the suit, called the case “a historic victory for our clients and for the rule of law.”

The plaintiffs said that Drs. Jessen and Mitchell, former military psychologists, profited from their work as contractors for the C.I.A. The men received up to $1,800 a day and later formed a company that was paid about $81 million to help operate the interrogation program over several years.

The United States government also agreed to indemnify the men and their company, including paying legal fees, judgments and settlements up to $5 million. Some of those funds were used to cover legal bills during Justice Department investigations. As of November 2011, there was close to $4 million left, according to a document made public in the lawsuit.

James T. Smith, the psychologists’ lead counsel, said in a statement that his clients were “public servants whose actions in regard to the interrogation of suspected terrorists were authorized by the U.S. government, legal and done in an effort to protect innocent lives.”

In an interview, Dr. Mitchell said he found it “regrettable that one guy died and those other guys were treated badly,” adding: “We had nothing to do with it. We’re not responsible for it. They say we are, but in my view they’re wrong.”

The psychologists produced a memo in 2002 proposing harsh techniques to be used on terrorism suspects thought to be resisting interrogations. The C.I.A. adopted nearly all of these methods, including waterboarding, stuffing prisoners into small boxes, forcing them to hold painful positions for hours and slamming them into plywood walls.

The so-called enhanced interrogation techniques were based on those used in military survival schools to simulate what service members might undergo if captured by regimes violating the laws of war. They were later condemned as illegal under United States and international law and were ultimately banned. The American Psychological Association consequently prohibited its members from participating in national security interrogations.

As a candidate, President Trump said he would bring back waterboarding “and a hell of a lot worse,” but later said he would defer to Defense Secretary Jim Mattis’s strong opposition — widespread in the military — to torture and prisoner mistreatment.

The case against the psychologists proceeded despite multiple attempts by their lawyers to have it dismissed. They argued that the men acted solely under the authority of the government and were entitled to the same immunity as government officials. The judge, Justin L. Quackenbush, also denied motions by both sides requesting that he rule summarily in their favor before a trial.

Although there will be no public trial, the case — over its nearly two-year course — expanded public knowledge about the C.I.A.’s torture program. Previously secret documents were declassified, including C.I.A. cables from the covert prisons known as black sites. And the two psychologists, along with the former C.I.A. officials Jose Rodriguez and John Rizzo, were subjected to lengthy questioning by opposing lawyers in video depositions. Their sometimes sterile description of the techniques contrasted with the emotional accounts, in separate depositions, of the men who underwent them.

The plaintiffs and some of their experiences are described in the executive summary of the 6,700-page Senate Intelligence Committee Report on Torture. The report, published in December 2014 and based on a five-year review of over six million pages of documents, lists 38 men known to have been subjected to the techniques in C.I.A. prisons. It denounced the methods as brutal and criticized the C.I.A. for providing false and misleading information to federal officials about the interrogation program’s effectiveness.

The psychologists came into direct contact with only one of the three detainees, Gul Rahman, who died in C.I.A. custody in Afghanistan in 2002, probably of hypothermia, according to an agency investigation into his death.

The judge ruled last week that a trial could also proceed on behalf of the two other former prisoners — Mr. Ben Soud and Suleiman Salim — whose lawyers argued that the psychologists had aided and abetted their torture.

Mr. Ben Soud, a Libyan detained by the C.I.A. in 2003 and held in Afghanistan, was locked in small boxes, slammed against a wall and doused with buckets of ice water while naked and shackled. Mr. Salim, a Tanzanian also captured in 2003 and held by the C.I.A. in Afghanistan, was beaten, isolated in a dark cell for months, doused with water and deprived of sleep.

The A.C.L.U. and the Gibbons law firm of Newark brought the lawsuit under the Alien Tort Statute, which allows foreign citizens to seek justice in United States courts for violations of their rights under international law or United States treaties.

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If you're having co-author problems, I feel bad for you son. I've got 99 problems, but single-authored papers are the norm in my discipline.

Shit Academic Say

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In 2011, Claudio Aspesi, a senior investment analyst at Bernstein Research in London, made a bet that the dominant firm in one of the most lucrative industries in the world was headed for a crash. Reed-Elsevier, a multinational publishing giant with annual revenues exceeding £6bn, was an investor’s darling. It was one of the few publishers that had successfully managed the transition to the internet, and a recent company report was predicting yet another year of growth. Aspesi, though, had reason to believe that that prediction – along with those of every other major financial analyst – was wrong.                    

The core of Elsevier’s operation is in scientific journals, the weekly or monthly publications in which scientists share their results. Despite the narrow audience, scientific publishing is a remarkably big business. With total global revenues of more than £19bn, it weighs in somewhere between the recording and the film industries in size, but it is far more profitable. In 2010, Elsevier’s scientific publishing arm reported profits of £724m on just over £2bn in revenue. It was a 36% margin – higher than Apple, Google, or Amazon posted that year.

But Elsevier’s business model seemed a truly puzzling thing. In order to make money, a traditional publisher – say, a magazine – first has to cover a multitude of costs: it pays writers for the articles; it employs editors to commission, shape and check the articles; and it pays to distribute the finished product to subscribers and retailers. All of this is expensive, and successful magazines typically make profits of around 12-15%.

The way to make money from a scientific article looks very similar, except that scientific publishers manage to duck most of the actual costs. Scientists create work under their own direction – funded largely by governments – and give it to publishers for free; the publisher pays scientific editors who judge whether the work is worth publishing and check its grammar, but the bulk of the editorial burden – checking the scientific validity and evaluating the experiments, a process known as peer review – is done by working scientists on a volunteer basis. The publishers then sell the product back to government-funded institutional and university libraries, to be read by scientists – who, in a collective sense, created the product in the first place.

It is as if the New Yorker or the Economist demanded that journalists write and edit each other’s work for free, and asked the government to foot the bill. Outside observers tend to fall into a sort of stunned disbelief when describing this setup. A 2004 parliamentary science and technology committee report on the industry drily observed that “in a traditional market suppliers are paid for the goods they provide”. A 2005 Deutsche Bank report referred to it as a “bizarre” “triple-pay” system, in which “the state funds most research, pays the salaries of most of those checking the quality of research, and then buys most of the published product”.

Scientists are well aware that they seem to be getting a bad deal. The publishing business is “perverse and needless”, the Berkeley biologist Michael Eisen wrote in a 2003 article for the Guardian, declaring that it “should be a public scandal”. Adrian Sutton, a physicist at Imperial College, told me that scientists “are all slaves to publishers. What other industry receives its raw materials from its customers, gets those same customers to carry out the quality control of those materials, and then sells the same materials back to the customers at a vastly inflated price?” (A representative of RELX Group, the official name of Elsevier since 2015, told me that it and other publishers “serve the research community by doing things that they need that they either cannot, or do not do on their own, and charge a fair price for that service”.)

Many scientists also believe that the publishing industry exerts too much influence over what scientists choose to study, which is ultimately bad for science itself. Journals prize new and spectacular results – after all, they are in the business of selling subscriptions – and scientists, knowing exactly what kind of work gets published, align their submissions accordingly. This produces a steady stream of papers, the importance of which is immediately apparent. But it also means that scientists do not have an accurate map of their field of inquiry. Researchers may end up inadvertently exploring dead ends that their fellow scientists have already run up against, solely because the information about previous failures has never been given space in the pages of the relevant scientific publications. A 2013 study, for example, reported that half of all clinical trials in the US are never published in a journal.

According to critics, the journal system actually holds back scientific progress. In a 2008 essay, Dr Neal Young of the National Institutes of Health (NIH), which funds and conducts medical research for the US government, argued that, given the importance of scientific innovation to society, “there is a moral imperative to reconsider how scientific data are judged and disseminated”.

Aspesi, after talking to a network of more than 25 prominent scientists and activists, had come to believe the tide was about to turn against the industry that Elsevier led. More and more research libraries, which purchase journals for universities, were claiming that their budgets were exhausted by decades of price increases, and were threatening to cancel their multi-million-pound subscription packages unless Elsevier dropped its prices. State organisations such as the American NIH and the German Research Foundation (DFG) had recently committed to making their research available through free online journals, and Aspesi believed that governments might step in and ensure that all publicly funded research would be available for free, to anyone. Elsevier and its competitors would be caught in a perfect storm, with their customers revolting from below, and government regulation looming above.

In March 2011, Aspesi published a report recommending that his clients sell Elsevier stock. A few months later, in a conference call between Elsevier management and investment firms, he pressed the CEO of Elsevier, Erik Engstrom, about the deteriorating relationship with the libraries. He asked what was wrong with the business if “your customers are so desperate”. Engstrom dodged the question. Over the next two weeks, Elsevier stock tumbled by more than 20%, losing £1bn in value. The problems Aspesi saw were deep and structural, and he believed they would play out over the next half-decade – but things already seemed to be moving in the direction he had predicted.

Over the next year, however, most libraries backed down and committed to Elsevier’s contracts, and governments largely failed to push an alternative model for disseminating research. In 2012 and 2013, Elsevier posted profit margins of more than 40%. The following year, Aspesi reversed his recommendation to sell. “He listened to us too closely, and he got a bit burned,” David Prosser, the head of Research Libraries UK, and a prominent voice for reforming the publishing industry, told me recently. Elsevier was here to stay.

Aspesi was not the first person to incorrectly predict the end of the scientific publishing boom, and he is unlikely to be the last. It is hard to believe that what is essentially a for-profit oligopoly functioning within an otherwise heavily regulated, government-funded enterprise can avoid extinction in the long run. But publishing has been deeply enmeshed in the science profession for decades. Today, every scientist knows that their career depends on being published, and professional success is especially determined by getting work into the most prestigious journals. The long, slow, nearly directionless work pursued by some of the most influential scientists of the 20th century is no longer a viable career option. Under today’s system, the father of genetic sequencing, Fred Sanger, who published very little in the two decades between his 1958 and 1980 Nobel prizes, may well have found himself out of a job.

Even scientists who are fighting for reform are often not aware of the roots of the system: how, in the boom years after the second world war, entrepreneurs built fortunes by taking publishing out of the hands of scientists and expanding the business on a previously unimaginable scale. And no one was more transformative and ingenious than Robert Maxwell, who turned scientific journals into a spectacular money-making machine that bankrolled his rise in British society. Maxwell would go on to become an MP, a press baron who challenged Rupert Murdoch, and one of the most notorious figures in British life. But his true importance was far larger than most of us realise. Improbable as it might sound, few people in the last century have done more to shape the way science is conducted today than Maxwell.

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