Benedict Carey

He decided to study laughter instead, taking his methods out into the world and, through a series of studies and popular books, helping to create the modern science of humor.

“My approach to understanding laughter is one that a visiting extraterrestrial might take,” he wrote later. “What would the visitor make of the large bipedal animals emitting paroxysms of sound from a toothy vent in their faces?”

Provine, a professor of psychology at the University of Maryland, Baltimore County, died at 76 on Oct. 17 in a hospital in Baltimore. His wife, Helen Weems, said the cause was complications of non-Hodgkins lymphoma.

Provine made his career pivot in 1990, at a time when theories explaining laughter’s purpose were still not fully formed. People laughed for a variety of reasons, it was thought: in response to the folly of others, as an expression of superiority; to release aggressive or sexual tension; or to register upended expectations — say, ordering a “small” cola and receiving a supersize half-gallon cup.

Provine dug in, measuring the different sounds of laughter, its varying cadences and loudness, its presence in primates. (Chimpanzees laugh, too.) He and a team of graduate students lurked for hours with their notebooks at shopping malls, student unions and other public spaces, recording and evaluating some 1,200 pre-laughter comments.

They found that, contrary to common wisdom, laughter is rarely a response to jokes, stories or a prank. “Most of the laughter seemed to follow rather banal remarks, such as ‘Look, it’s Andre,’ ‘Are you sure?’ and ‘It was nice meeting you, too,’” Provine wrote, in a 1996 issue of American Scientist. “Even our greatest hits, the funniest of the 1,200 pre-laugh comments, were not necessarily howlers: ‘You don’t have to drink, just buy us drinks’; ‘She’s got a sex disorder — she doesn’t like sex’; and ‘Do you date within your species?’”

Weems said her husband had called this work “sidewalk neuroscience,” a low-budget but rigorous exercise that was immediately relevant to people’s daily lives “He believed strongly that the lay person, the taxpayer, should be able to get something out of the work, and he was devoted to popular media, to getting the word out.”

He did just that in a 2000 book, “Laughter: A Scientific Investigation,” which spelled out a broader theory of laughter’s function — as a social signal that bonds people and sets the tone for group gatherings. Laughter, of the derisive kind, can also be a means of excluding people, Provine found. It wasn’t long before he was articulating his findings on public radio in the United States and Canada and in the The Washington Post.

Provine extended his study of such “nonverbal vocalizations” well beyond laughter. In 2012 he published “Curious Behavior: Yawning, Laughing, Hiccupping, and Beyond.” He argued, for instance, that yawning not only indicated sleepiness but could also signal social empathy with others who are yawning.

“Although it is ubiquitous, and something that if you’re lucky you do every day, laughter is truly a puzzling phenomenon” said Peter McGraw, director of the Humor Research Lab at the University of Colorado, Boulder, and co-author of “The Humor Code: A Global Search for What Makes Things Funny.” “His book, ‘Laughter,’ is really a go-to source in this field, and one reason is that he studied laughter out in the real world, not in the lab.”

Rod Martin, an emeritus professor of psychology at the University of Western Ontario said, by email: “Bob Provine’s main contribution to the field of research in the psychology of humor was to draw attention to laughter as a phenomenon of interest in itself. Until then, humor researchers had mainly seen laughter as an outward expression of the inner experience of humor.”

Robert Raymond Provine was born May 11, 1943, in Tulsa, Oklahoma, the first of two sons of Robert William Provine, a chemist for Sun Oil, and Thelma Fern (Morgan) Provine, a homemaker. His younger brother, William, died when he was a teenager.

Robert attended Thomas Edison Preparatory School in Tulsa, then entered Oklahoma State University, where he earned a bachelor’s degree in psychology in 1965. He completed a Ph.D. in the same subject in 1971, at Washington University, in St. Louis. He worked there as a research assistant until 1974, when he moved to the University of Maryland, Baltimore County. He spent the rest of his career there and, by all accounts, embodied the figure of a laughter researcher: a bearded, congenial, wisecracking presence whose own humor could straighten the spine at its wicked best.

Provine’s first marriage, to Helen Vona, who was known as Vivi, in 1967, ended in divorce in 1990. He married Weems in 1996. In addition to her, he is survived by two children from his first marriage, Kimberly Lourenco and Robert W. Provine; and three grandchildren.

In the same American Scientist article, Provine wrote that the science of laughter was still far from worked out. “All of us have encountered people with bizarre-sounding laughter,” he wrote. “Do these odd types of laughter run in families? If so, what is the nature of its development and heritability?

“In my otherwise forgettable high-school physics class,” he continued, “there was a kid who brayed like a donkey when he laughed. Where is Roger now that I need him?”

This article originally appeared in

Robert Provine, an Authority on Laughter, Is Dead at 76

Dr. Robert Provine was studying nerve cells for eight hours a day in a windowless lab when he made a keen observation that would alter his life, and the shape of social science: I am getting tired of this.

Many of these factors have been studied by scientists for decades. Here are answers to some of the most common questions about the causes of mass murder.

Can one mass shooting inspire another?

Yes. Police find abundant evidence that shooters have studied previous crimes, often mimicking gestures or killing tactics, as if in homage to previous killers. This is true both of younger shooters who mow down unarmed people in schools, or at random; and of older men who execute innocents in the name of an ideology — be it opposition to immigration, white supremacy, radical Islam or another extreme belief.

The boy who slaughtered elementary school children and teachers in Sandy Hook, Connecticut, had studied the Columbine massacre, among many others. The man who shot to death 50 people at the Pulse nightclub in Orlando, Florida, had studied a previous attack, in San Bernardino, California. In both cases, the murderers cited radical Islam as justification.

The young man accused of shooting to death more than 20 adults and children in a Walmart in El Paso over the weekend had seen the video posted by the man who gunned down unarmed worshippers at mosques in Christchurch, New Zealand.

Forensic psychologists say that many would-be mass killers see themselves as part of a brotherhood of like-minded, isolated and resentful boys and men. To them, previous mass murderers may be perceived as idols and pioneers.

Are video games to blame for mass shootings?

The results of studies attempting to clarify the relationship between violent video games and aggression have been mixed, with experts deeply divided on the findings. A just-published analysis of the research to date concludes that “in the vast majority of settings, violent video games do increase aggressive behavior” — but that “these effects are almost always quite small.”

The “aggression” in question falls well short of assault with a weapon, never mind mass murder. So the weight of scientific opinion is that video games are not a decisive factor when a spree killer decides to act.

Establishing a persuasive link between shooting digital figures from the couch and real people in a mall or school is a long shot. A huge proportion of males in the United States have played or are playing video games; only a handful commit mass murders. And video games are even more popular in Asian countries, where mass killings are far rarer.

How strong is the link between mental illness and mass shootings?

Tenuous, at best. People who blame mass shootings on “the mentally ill” are usually reasoning backward from the act itself: The person just shot 20 unarmed strangers, so he must be “crazy.”

In fact, scientists find that only a small fraction of people with persistent mental distress are more likely than average to commit violent acts: patients with paranoid schizophrenia, which is characterized by delusional thinking and often so-called command hallucinations — frightening voices identifying threats where none exist.

People living in this kind of misery are far more likely to be the victims of violence than perpetrators; but they can act violently themselves, especially when using drugs or alcohol. The clearest recent example is Jared Loughner, the college student who opened fire at an event in Tucson, Arizona, hosted by then-Rep. Gabrielle Giffords in 2011, killing six and wounding 13. Loughner’s online posts demonstrated increasing drug use and paranoid fantasies.

About 1 in 5 mass murderers shows evidence of psychosis, according to Dr. Michael Stone, a forensic psychiatrist who maintains data on some 350 murderers going back more than a century. The other 80% have many of the problems that nearly everyone has to manage at some point in life: anger, isolation, depressive moods, resentments, jealousy.

Would drugging or confining people showing “red flags” prevent massacres?

No one knows for certain. In his speech, Trump mentioned the teenager who in 2018 killed 17 people at a high school in Parkland, Florida. It’s a good example: Before his murder spree, the shooter talked of his intentions to such an extent that classmates joked that he was the student most likely to shoot up the school.

“Unfortunately, it is wishful thinking to believe that there is a simple set of warning signs, a phone app or a checklist which can be used to identify a mass shooter,” said Dr. Deborah Weisbrot, director of the outpatient clinic of child and adolescent psychiatry at Stony Brook University.

She has interviewed about 200 young people, mostly teenage boys, who have made threats.

“There is no specific ‘profile’ of a shooter, as is still often sometimes assumed — there have been both male and female shooters, and different socioeconomic backgrounds,” she said.

Red-flag policies, tracking threats and other signs of trouble, have been in place for years in some school districts around the country. Would-be shooters often reveal their intentions in dark asides or rants online. They may profess respect for past mass killers even as they stockpile weapons and ammunition.

Los Angeles County, in particular, has intervened in scores of such cases since its program was implemented in 2007. It has not had a major school shooting, though there is no way to know if the program has prevented any.

Still, such preventive measures get students into therapy, and alert parents and teachers to warning signs: They do not require forced drugging and confinement before any crime has been committed. Implementing that kind of policy would require a thoughtful reconsideration of individual rights in this country — which, given partisan gridlock, is not likely to happen.

This article originally appeared in <a href="https://www.nytimes.com/2019/08/05/health/mass-shootings-mental-health.html" id="b52cc121-4299-3fa6-aa22-59022bf331b3">The New York Times</a>.

On Monday morning, President Donald Trump made his first televised statement about the mass murders committed over the weekend in El Paso, Texas, and Dayton, Ohio. He called for action to “stop mass killings before they start,” citing what he said were a number of contributing factors: the contagious nature of mass murder; the glorification of violence in video games; and the need to act on “red flags” to identify and potentially confine the “mentally ill monsters” that he said commit the cri...

What Drives People to Mass Shootings?

The strangeness of the symptoms, and the spookiness of the proposed causes, have given the story a life of its own in the diplomatic corps, the Pentagon and in assorted pockets of the internet where conspiracy theories thrive.

Now, researchers are reporting results from the first brain-imaging studies of 40 of those diplomats, who were carefully examined by neurologists after returning home from Cuba. The study, appearing Tuesday in the medical journal JAMA, concludes that the diplomats experienced some kind of brain trauma. But the nature and cause of that trauma were not clear, as it did not resemble the signature of more familiar brain injuries such as repeated concussions or exposure to battlefield blasts.

“The main thing we can do with brain imaging is ask whether something happened to the brain,” said Dr. Ragini Verma, a professor of radiology at the University of Pennsylvania Perlman School of Medicine and lead author of the new report. “And the answer we found is that yes, it did.”

Based on the findings, Verma said that a wholly psychogenic or psychosomatic cause was very unlikely. “But I don’t know the cause,” she said. “The imaging by itself cannot tell us that.”

Outside experts were divided on the study’s conclusions. Some saw important new evidence; others say it is merely a first step toward an explanation and difficult to interpret given the small number of patients.

“It’s good work, but there’s just not enough here to come to any conclusion,” said Dr. Mark Rasenick, a neuroscientist at the University of Illinois Chicago School of Medicine. Rasenick is a member of the Cuban Academy of Science and has close ties to scientists there who have been skeptical that invisible weapons were involved. “I think the only reason it’s going in JAMA is that it’s such a politically charged topic.”

In an editor’s note, two editors of the journal acknowledged the uncertainties in the findings but added: “These unique data provide additional information and contribute to a growing evidence base that may help in understanding the neurological signs and symptoms experienced by this group of individuals.”

The new study was an extension of examinations, conducted at the University of Pennsylvania Center for Brain Injury and Repair, of several dozen diplomats returning from Cuba. In 2018, the Penn team, which included Dr. Douglas Smith and Dr. Randel Swanson, reported on the first 21 of those patients and identified a range of peculiar and often shared symptoms.

“The unique circumstances of these patients, and the consistency of the clinical manifestations, raised concern for a novel mechanism of a possible acquired brain injury,” that report concluded.

In the new study, the research team focused on those 21 patients and 19 subsequent ones, examining brain areas known to support hearing, balance and motor control. It also measured each individual’s volume of gray matter, the overall population of neurons; and of white matter, the connective tissue between the neurons. Gray matter makes up the bulk of the brain’s distinct organs, specialized to manage functions like vision, hearing and movement. White matter comprises the wiring that connects cells and organs into wider circuits. Sharp deficits in either can compromise brain function.

Those measures were then compared to an identical battery of brain images from 48 healthy adults representing the same mix of ages, genders and educational attainment.

On average, the diplomats had a lower volume of white matter than individuals in the control group. They also showed clear differences in the volume, connectivity and tissue properties of the cerebellum, which is involved in maintaining balance, and lower connectivity among neurons in the auditory and visual-spatial areas of the brain. The analysis found no difference between the groups in so-called executive-control networks, which are involved in thinking and planning.

The researchers could not say for certain what these differences mean, except that they are consistent with the symptoms the diplomats have reported. The overall pattern was unlike anything found in studies of people with traumatic brain injuries, multiple sclerosis, stroke damage or other neural disorders.

“If you look at the totality of these findings — an increase in this, a decrease in that — and combine them all, you have a presentation that is very unique to this cohort,” Verma said.

Whether that presentation reflects a physical injury from an enigmatic weapon, or something else, is still far from clear, the authors acknowledged. Reaching a firm conclusion would likely require many more new cases, a situation that nobody is eager to see.

This article originally appeared in <a href="https://www.nytimes.com/2019/07/23/science/cuba-diplomats-health.html" id="8e64a0c1-1a18-36af-ad9b-68266b471943">The New York Times</a>.

Were U.S. Diplomats Attacked in Cuba? Brain Study Deepens Mystery.

In late 2016, dozens of U.S. diplomats working in Cuba and China began reporting odd mental symptoms: persistent headaches, vertigo, blurred vision, hearing phantom sounds. Since then, scientists and commentators have groped for plausible explanations. Deliberate physical attacks, involving microwaves or other such technology? Or were psychological factors, subconscious yet mind-altering, the more likely cause?

“The main thing we can do with brain imaging is ask whether something happened to the brain,” said Dr. Ragini Verma, a professor of radiology at the University of Pennsylvania Perelman School of Medicine and lead author of the new report. “And the answer we found is that yes, it did.”

The FDA singled out Ambien and two other popular sleep aids, Lunesta and Sonata, as well as three formulations of zolpidem, the generic name for Ambien. The boxed warnings — the most prominent form of warning required by the agency — must list side effects such as sleepwalking and sleep driving, in which people using the drugs take risks without being fully awake.

The agency said such reactions were rare but could lead to injuries or death; it advised doctors not to prescribe the drugs to people who have had such side effects in the past.

“Patients, stop taking your insomnia medicine and contact your health care professional right away if you experience a complex sleep behavior where you engage in activities while you are not fully awake,” the agency’s safety alert said, “or if you do not remember activities you have done while taking the medicine.”

Prescriptions for sleeping pills grew to more than 20 million in 2010 from 5.3 million in 1999, according to national estimates. About 1 in 8 people with sleeping difficulty report using the drugs; among people of retirement age, more than a third report taking a sleeping aid.

The FDA warned about such effects in 2007, after doctors reported that some patients were having strange nighttime experiences, mostly while taking zolpidem (Ambien), the first of the so-called z-drugs.

“I am surprised to see this warning come out now,” said Dr. Ilene Rosen, a professor of clinical medicine at the University of Pennsylvania’s school of medicine, and former president of the American Academy of Sleep Medicine. “This is something I’ve been telling my patients for the last 15 years, and in the sleep community this is well known. And I’d like to think we’ve done a good job putting the news out there, that these drugs have some risks.”

She added that the z-drugs were not on the hospital formulary at the University of Pennsylvania for inpatients, because of the link to sleepwalking, falls and other problems.

The overall risk of bizarre half-sleep behaviors is not well known, because incidents are rare, or rarely reported, and individuals do not always remember raiding the refrigerator at 3 a.m., or connect the behavior to the drugs.

The FDA, in making its determination, reviewed 66 cases over the past 26 years that led to serious injuries. The incidents were described in case reports in medical literature and in the agency’s spontaneous reporting database, where doctors, patients and others report cases.

“These cases included accidental overdoses, falls, burns, near drowning, exposure to extreme cold temperatures leading to loss of limb, carbon monoxide poisoning, drowning, hypothermia, motor vehicle collisions with the patient driving, and self-injuries such as gunshot wounds and apparent suicide attempts,” the agency reported. “Patients usually did not remember these events.”

In recent years, the agency has warned multiple times of next-day fogginess, or cognitive impairment, after the use of Ambien and other sleeping pills, but has not required a boxed warning.

This article originally appeared in <a href="https://www.nytimes.com/2019/04/30/health/sleep-drugs-ambien-side-effects.html" id="cd698218-870c-3646-a538-72d0403672d6">The New York Times</a>.

Federal health regulators announced on Tuesday that they would require manufacturers of sleeping pills such as Ambien and related drugs to post strongly worded warnings in boxes on labels and patient guides. The Food and Drug Administration, in what it called a safety announcement, noted that the drugs’ side effects included risky behaviors, such as sleepwalking and sleep driving, that can lead to injury and even death.

Drug Agency Calls for Strong Warning Labels on Popular Sleep Aids

Thousands of people are reduced to similarly painstaking means of communication as a result of injuries suffered in accidents or combat, of strokes, or of neurodegenerative disorders like amyotrophic lateral sclerosis, or ALS, that disable the ability to speak.

Now, scientists are reporting that they have developed a virtual prosthetic voice, a system that decodes the brain’s vocal intentions and translates them into mostly understandable speech, with no need to move a muscle, even those in the mouth. (The physicist and author Stephen Hawking used a muscle in his cheek to type keyboard characters, which a computer synthesized into speech.)

“It’s formidable work, and it moves us up another level toward restoring speech” by decoding brain signals, said Dr. Anthony Ritaccio, a neurologist and neuroscientist at the Mayo Clinic in Jacksonville, Florida, who was not a member of the research group.

Researchers have developed other virtual speech aids. Those work by decoding the brain signals responsible for recognizing letters and words, the verbal representations of speech. But those approaches lack the speed and fluidity of natural speaking.

The new system, described on Wednesday in the journal Nature, decipher the brain’s motor commands guiding vocal movement during speech — the tap of the tongue, the narrowing of the lips — and generates intelligible sentences that approximate a speaker’s natural cadence.

Experts said the new work represented a “proof of principle,” a preview of what may be possible after further experimentation and refinement. The system was tested on people who speak normally; it has not been tested in people whose neurological conditions or injuries, like common strokes, could make the decoding difficult or impossible.

For the new trial, scientists at the University of California, San Francisco, and UC Berkeley recruited five people who were in the hospital being evaluated for epilepsy surgery.

Many people with epilepsy do poorly on medication and opt to undergo brain surgery. Before operating, doctors must first locate the “hot spot” in each person’s brain where the seizures originate; this is done with electrodes that are placed in the brain, or on its surface, and listen for telltale electrical storms.

Pinpointing this location can take weeks. In the interim, patients go through their days with electrodes implanted in or near brain regions that are involved in movement and auditory signaling. These patients often consent to additional experiments that piggyback on those implants.

The five such patients at UCSF agreed to test the virtual voice generator. Each had been implanted with one or two electrode arrays: stamp-size pads, containing hundreds of tiny electrodes, that were placed on the surface of the brain.

As each participant recited hundreds of sentences, the electrodes recorded the firing patterns of neurons in the motor cortex. The researchers associated those patterns with the subtle movements of the patient’s lips, tongue, larynx and jaw that occur during natural speech. The team then translated those movements into spoken sentences.

Native English speakers were asked to listen to the sentences to test the fluency of the virtual voices. As much as 70 percent of what was spoken by the virtual system was intelligible, the study found.

“We showed, by decoding the brain activity guiding articulation, we could simulate speech that is more accurate and natural sounding than synthesized speech based on extracting sound representations from the brain,” said Dr. Edward Chang, a professor of neurosurgery at UCSF and an author of the new study. His colleagues were Gopala K. Anumanchipalli, also of UCSF, and Josh Chartier, who is affiliated with both UCSF and Berkeley.

Previous implant-based communication systems have produced about eight words a minute. The new program generates about 150 words a minute, the pace of natural speech.

The researchers also found that a synthesized voice system based on one person’s brain activity could be used, and adapted, by someone else — an indication that off-the-shelf virtual systems could be available one day.

The team is planning to move to clinical trials to further test the system. The biggest clinical challenge may be finding suitable patients: strokes that disable a person’s speech often also damage or wipe out the areas of the brain that support speech articulation.

Still, the field of brain-machine interface technology, as it is known, is advancing rapidly, with teams around the world adding refinements that might be tailored to specific injuries.

“With continued progress,” wrote Chethan Pandarinath and Yahia H. Ali, biomedical engineers at Emory University and Georgia Institute of Technology, in an accompanying commentary, “we can hope that individuals with speech impairments will regain the ability to freely speak their minds and reconnect with the world around them.”

This article originally appeared in <a href="https://www.nytimes.com/2019/04/24/health/artificial-speech-brain-injury.html" id="c43a6eac-2346-3492-a89b-41de406becdd">The New York Times</a>.

Scientists Create Speech From Brain Signals

“In my head, I churn over every sentence ten times, delete a word, add an adjective, and learn my text by heart, paragraph by paragraph,” Jean-Dominique Bauby wrote in his memoir, “The Diving Bell and the Butterfly.” In the book, Bauby, a journalist and editor, recalled his life before and after a paralyzing spinal injury that left him virtually unable to move a muscle; he tapped out the book letter by letter, by blinking an eyelid.

“We showed, by decoding the brain activity guiding articulation, we could simulate speech that is more accurate and natural sounding than synthesized speech based on extracting sound representations from the brain,” said Dr. Edward Chang, a professor of neurosurgery at University of California, San Francisco and an author of the new study. His colleagues were Gopala K. Anumanchipalli, also of UCSF, and Josh Chartier, who is affiliated with both UCSF and UC Berkeley.

Thousands of people are reduced to painstaking means of communication as a result of injuries suffered in accidents or combat, of strokes, or of neurodegenerative disorders such as amyotrophic lateral sclerosis, or ALS, that disable the ability to speak.

Thousands of people are reduced to similarly painstaking means of communication as a result of injuries suffered in accidents or combat, of strokes, or of neurodegenerative disorders such as amyotrophic lateral sclerosis, or ALS, that disable the ability to speak.

Experts said the new work represented a “proof of principle,” a preview of what may be possible after further experimentation and refinement. The system was tested on people who speak normally; it has not been tested in people whose neurological conditions or injuries, such as common strokes, could make the decoding difficult or impossible.

Five such patients at UCSF agreed to test the virtual voice generator. Each had been implanted with one or two electrode arrays: stamp-size pads, containing hundreds of tiny electrodes, that were placed on the surface of the brain.

“With continued progress,” wrote Chethan Pandarinath and Yahia J. Ali, biomedical engineers at Emory University and Georgia Institute of Technology, in an accompanying commentary, “we can hope that individuals with speech impairments will regain the ability to freely speak their minds and reconnect with the world around them.”

“In my head, I churn over every sentence ten times, delete a word, add an adjective, and learn my text by heart, paragraph by paragraph,” wrote Jean-Dominique Bauby in his memoir, “The Diving Bell and the Butterfly.” In the book, Bauby, a journalist and editor, recalled his life before and after a paralyzing spinal injury that left him virtually unable to move a muscle; he tapped out the book letter by letter, by blinking an eyelid.

On Saturday, a team of scientists reported a glimmer of hope. Using an implant that stimulates activity in key areas of the brain, they restored near-normal levels of brain function to a middle-aged woman who was severely injured in a car crash 18 years ago.

Experts said the woman was a test case, and that it was far from clear whether the procedure would prompt improvements for others like her. That group includes an estimated 3 million to 5 million people, many of them veterans of the wars in Iraq and Afghanistan, with disabilities related to traumatic brain injuries.

The woman, now in her early 40s, was a student when the crash occurred. She soon recovered sufficiently to live independently. But she suffered from persistent fatigue and could not read or concentrate for long, leaving her unable to hold a competitive job, socialize much or resume her studies.

She and her family asked to remain anonymous.

“Her life has changed,” said Dr. Nicholas Schiff, a professor of neurology and neuroscience at Weill Cornell Medicine and a member of the study team. “She is much less fatigued, and she’s now reading novels. The next patient might not do as well. But we want to keep going to see what happens.”

A lack of research funding and interest has made that difficult, he added. “We’ve not been able to do so because there’s an incredible drag on doing anything for this population,” he said

The woman improved gradually, and by three months was consistently scoring about 15% better than she had previously on standardized tests of attention, planning and executive function. She also reported 70% less fatigue on a standard measure, and no longer took daily afternoon naps, as she had before, the researchers reported.

About 1 in 5 people with similar injuries receive some continuing treatment. This often includes cognitive therapy — typically, computer-based training for attention and memory, an hour a week for 12 weeks — and many see gradual improvements. But that therapy is not easy to access, and insurers don’t always pay for it.

This article originally appeared in <a href="https://www.nytimes.com/2019/04/13/health/implant-brain-injury.html" id="a2746fba-f614-3270-a38b-1c3fdc0eaae7">The New York Times</a>.

More than 3 million Americans live with disabling brain injuries. The vast majority of these individuals are lost to the medical system soon after their initial treatment, to be cared for by family or to fend for themselves, managing fatigue, attention and concentration problems with little hope of improvement.

Doctors Use Electrical Implant to Aid Brain-Damaged Woman

“This is a pilot study,” said Dr. Steven Flanagan, chairman of the department of rehabilitation medicine at NYU Langone Health, who was not part of the research team. “And we certainly cannot generalize from it. But I think it’s a very promising start, and there is certainly more to come in this work.”

She and her family asked to remain anonymous, and the researchers did not reveal further details other than to remark on her improvement.

Schiff and another team leader, Dr. Joseph Giacino, director of rehabilitation neuropsychology at Spaulding Rehabilitation Hospital and an associate professor at Harvard Medical School, presented the case at a brain-science convention in Washington, D.C., in an informal, public session.

The two collaborated with clinical centers at Stanford and the University of Utah, and with researchers at the Cleveland Clinic. Dr. Jaimie Henderson, a neurosurgeon at Stanford, performed the surgery, and the team is recruiting other candidates in the Bay Area to see if the procedure is viable for other people with mild to moderate traumatic brain injuries.

In the surgery, performed this past summer, Henderson threaded two electrodes into the thalamus, a switching center deep in the brain. Precision was critical. Before the surgery, the team did extensive work to identify specific regions in the brain that support activation of the frontal cortex, which is involved in thinking and planning, and the basal ganglia, which supports learning and memory.

“Operating on the thalamus is pretty routine,” Henderson said in an email. “This is a different target, though, and difficult to hit because of its size and shape. So a bit of extra precision is called for.”

The electrodes were connected to a pacemaker device, implanted in the woman’s chest wall, that produced active current for 12 hours a day, from morning to evening.

At one point during her rehabilitation, the pacemaker accidentally failed, and her gains tapered off. Doctors quickly restored the current, and her ability improved.

“Getting a 10% improvement is considered excellent, and they broke right through it to 15%,” said Dr. Joseph Ricker, director of psychology at New York University’s Rusk Rehabilitation center.

In 2006, members of the same research team performed a similar surgery on a 38-year-old man with severe brain damage; he was living in a partially conscious state, only periodically aware and virtually mute and immobile. The procedure allowed him to recover some movement and speech, gains he maintained until his death some years later. But no similar procedures have been reported since then, the researchers said.

One challenge to developing new treatments for traumatic brain injuries is that candidates are hard to find. “We are targeting here the heart of the problem, mild to moderate traumatic brain injury,” Giacino said. “But finding people and accessing them is difficult. They are really isolated.”

Dr. Flora Hammond, who leads the Physical Medicine and Rehabilitation Department at Indiana University School of Medicine, said: “Recovery from these deficits is challenged by a sparsity of proven treatments and lack of access to rehabilitative care. These observations are a positive step toward improving life after brain injury.”

Anyone above a certain age who has drawn a blank on the name of a favorite uncle, a friend’s phone number or the location of a house key understands how fragile memory is. Its speed and accuracy begin to slip in one’s 20s and keep slipping. This is particularly true for working memory, the mental sketch pad that holds numbers, names and other facts temporarily in mind, allowing decisions to be made throughout the day.

On Monday, scientists reported that brief sessions of specialized brain stimulation could reverse this steady decline in working memory, at least temporarily. The stimulation targeted key regions in the brain and synchronized neural circuits in those areas, effectively tuning them to one another, as an orchestra conductor might tune the wind section to the strings.

The findings, reported in the journal Nature Neuroscience, provide the strongest support yet for a method called transcranial alternating current stimulation, or tACS, as a potential therapy for memory deficits, whether from age-related decline, brain injury or, perhaps, creeping dementia.

In recent years, neuroscientists have shown that memory calls on a widely distributed network in the brain, and it coordinates those interactions through slow-frequency, thrumming rhythms called theta waves, akin to the pulsing songs shared among humpback whales. The tACS technology is thought to enable clearer communication by tuning distant circuits to one another.

The tACS approach is appealing for several reasons, perhaps most of all because it is noninvasive; unlike other forms of memory support, it involves no implant, which requires brain surgery. The stimulation passes through the skull with little sensation. Still, a widely available therapy is likely years away, as the risks and benefits are not fully understood, experts said.

“This study suggests that age-related impairment in one particular form of short-term memory largely reflects a failure of synchronization,” said Michael Kahana, a brain scientist at the University of Pennsylvania who was not involved in the research. If the technique can boost other forms of memory, “it could be a game changer for the treatment of age-related memory decline and possibly even dementia,” Kahana said.

In the new study, Robert M.G. Reinhart and John A. Nguyen, neuroscientists at Boston University, invited two groups of subjects, young adults and people in their 60s and 70s, to the lab for baseline measures of their neural firing rhythms. The scientists tailored the tACS program to optimize rhythmic “coupling” between frontal and temporal cortex areas in each individual’s brain. These brain regions specifically support working memory.

After 25 minutes of gentle stimulation, delivered by electrodes built into a skullcap, the older subjects performed just as well on memory tests as young adults.

The participants tested their own working memories repeatedly, completing 10 sessions on a computer-based program that mimicked the old Highlights magazine game: stare at an image, then decide if subsequent images are identical or have subtle differences.

They performed under several conditions, including without stimulation; with “sham” stimulation, as a placebo control; and with the targeted tACS. The results were striking. Young people reliably outperformed their elders in the no-stimulation and sham conditions. But with the aid of the tACS, the older participants did just as well as their younger counterparts. And their working memory remained sharp for as long as the researchers continued testing it, for 50 minutes.

“We show here that working-memory decline in people in their 60s and 70s is due to brain circuits becoming uncoupled, or disconnected,” said Reinhart, in a call with reporters. He added that the findings “show us that negative, age-related changes in working memory are not unchangeable. We can bring back the superior function you had when you were much younger.”

The tACS tuning prompted greater improvements in older people than in younger ones, the study found, which suggests that the tool is more a corrective than an enhancer of memory. In another experiment, Reinhart and Nguyen found that, by using the tACS technology to decouple key brain regions, they could temporarily muddle the working memory of young participants.

The new findings come at a time when increasing numbers of people are experimenting with brain stimulation at home, placing electrodes on different areas of their skulls, depending on how they’re feeling. They share tips online about how best to use stimulation when feeling depressed, or impulsive, or mentally foggy — with mixed results. Experts said that the sort of stimulation used in the new study is far from a do-it-yourself approach.

“Reinhart and Nguyen use a very complex, sophisticated system here in a very carefully controlled environment,” Bradley Voytek, a neuroscientist at the University of California, San Diego, said in an email. “Do not try this at home!This is a promising start, not a panacea for memory problems.”

This article originally appeared in <a href="https://www.nytimes.com/2019/04/08/health/aging-brain-memory.html" id="dbfc4160-c46a-3f0e-ae4c-6587ba17f60a">The New York Times</a>.

(Mind)

To Improve Memory, Tune It Like an Orchestra

They performed under several conditions, including without stimulation; with “sham” stimulation, as a placebo control; and with the targeted tACS. Young people reliably outperformed their elders in the no-stimulation and sham conditions. But with the aid of the tACS, the older participants did just as well as their younger counterparts. And their working memory remained sharp for as long as the researchers continued testing it, for 50 minutes.

Reinhart said the findings “show us that negative, age-related changes in working memory are not unchangeable.”

Anyone above a certain age who has drawn a blank on the name of a favorite uncle, a friend’s phone number or the location of a house key understands how fragile memory is. Its speed and accuracy begin to slip in one’s 20s and keep slipping. This is particularly true for working memory, the mental sketch pad that holds numbers, names and other facts temporarily in mind, allowing decisions to be made throughout the day.

On Wednesday afternoon, former vice president and potential presidential candidate Joe Biden released a video in which he discussed the importance of personal space. “Social norms have begun to change,” he said. “They’ve shifted, and boundaries of protecting personal space have been reset — and I get it.”

Biden was responding to allegations by two women that he made them uncomfortable by coming too close and by being too familiar and hands-on. His video was, in part, an acknowledgment that the rules of social engagement can change over time — along with perceptions of how much physical contact is appropriate, and where the boundaries of personal space lie.

The dynamics of both social space and touching have been well explored by scientists. In the 1960s, U.S. anthropologist Edward Hall laid out the basics of social space, based on field work in Europe, Asia and elsewhere.

We each reserve around us a zone of about 18 inches — “intimate space,” he called it — for close friends and family. “Personal space,” from 18 inches to about 4 feet, is open to acquaintances and colleagues. And “social space,” from 4 feet to 12 feet, is the appropriate orbit for strangers or new colleagues.

These zones appear to be wired into the brain’s evolved sense of spatial safety. Brain regions such as the amygdala, which registers threats, activate automatically when a boundary has been crossed.

In 2009, brain scientists at the California Institute of Technology reported the case of a woman with a genetic condition that had badly damaged her amygdala. Her social space was a fraction of the normal range, and strangers could approach within a foot and not provoke discomfort.

Those zones are averages, and they vary by individual, by culture and, likely, over generations. In some South American countries, such as Argentina and Peru, strangers are allowed a closer approach, and social space is more like 2 feet. Personal experience matters, too; someone who has been subjected to harassment or violence may well monitor the borders of contact more closely.

Biden, a temperamentally affectionate politician, plowed right into the intimate space of people he encountered, at a time, in the #MeToo era, when the discussion of inappropriate contact has gained volume and the need to acknowledge consent has grown acute.

People who develop a hands-on style, who are free with hugs and touches, generally do so because they have learned what a powerful bonding mechanism such nonverbal communication can be. In just the past decade, psychologists have conducted scores of studies on the effects of touching.

“Touch is the basic language of affection,” said Dacher Keltner, a psychologist at the University of California, Berkeley. “It is one of most reassuring modes of communication. An embrace or encouraging shoulder nudge from the right person is more powerful than words in relieving anxiety.”

Even small touches from lovers or friends have a powerful effect on the brain and body, instantly reducing physical signs of stress and activating areas of the brain known to be involved in tamping down fear and anxiety.

Perhaps the most dramatic example comes from work led by James Coan, a psychologist at the University of Virginia, who has tested how hand-holding affects the anticipation of an electric shock.

In a 2017 study, a team led by Coan and Karen Hasselmo, of the University of Arizona, recruited 110 men and women of diverse backgrounds. Each was paired with a spouse, a lover or a friend, and was seated in an MRI scanner with electrodes on an ankle, prepared for a slight electric shock.

The research team measured each subject’s levels of physiological distress and brain activity under several conditions, including while holding the hand of the friend or partner, while holding a stranger’s hand, and while facing the shock alone.

“The main finding on partnered hand-holding is that, when someone close to you is holding your hand, your reaction to the threat of electric shock is much lower” than when alone, said Coan. “Hand-holding from a stranger had no effect.”

Cross-cultural surveys have shown that almost any touch from a lover is agreeable, as are many expressions of physical contact from a friend. But, universally, strangers are allowed to do little more than touch a person’s hands. Contact most anywhere else is off-limits; the touch is received uncertainly or as an intrusion.

The accusations against Biden seem to describe situations that fall somewhere between those extremes. The news coverage has put many women in mind of unsolicited shoulder massages at the office or unasked-for hugs and arms around the shoulder. The touchers aren’t strangers; they are familiar colleagues, often valued ones, and not always men.

“My sense is that the first reaction of women who are touched in the workplace without invitation is what teenagers these days call ‘cringy,’” said Laura Kray, a professor at UC Berkeley’s school of business, in an email. “Not only is it uncomfortable, but it generates a kind of a panic at the thought of what is to come next and how we are going to navigate this tricky situation.”

She added: “Obviously, having an established relationship of trust alters the meaning of an appreciative hug or a pat on the shoulder in a more positive direction. Arm around lower back or kiss on head are boundary violations, as a general rule.”

One question with no clear answer is how supportive touching gradually becomes more affectionate and, for some people, sexual and mutual.

“What we don’t know after all this time is how you get from one place to the other,” Coan said. “Nobody does. There’s no simple answer, in psychological research or in life. That trajectory is going to include all kinds of signaling errors. As people zigzag toward love or affection, they’re blowing it all the time.”

A blank stare, a cold shoulder, or a few flinty words can correct many, perhaps most, of those errors. But far from all of them — in part because of vast differences in the way individuals perceive touches from colleagues or co-workers.

For instance, research suggests that young children typically are encouraged and reassured by a friendly touch on the shoulder, not only from parents but also from teachers. But that uniformity changes by young adulthood.

Some people recoil at any touch intended as affectionate that does not come from someone close; others can find the same touch, in the same circumstances, a comfort.

A similar variability likely exists among those doing the touching. A 2012 study led by Paul Piff of the University of California, Irvine, and Amanda Purcell of Yale found that people prone to hypomania, who are highly energetic and social, were exquisitely tuned to the comfort from touches intended to be supportive.

But there was a catch: They also were measurably numbed to intrusive or brusque touches. The research suggests that such people, by extension, also may be oblivious to the effect of their attempts at physical contact and perhaps blind to the cringes of someone they’re trying to reassure or support.

Placing an arm around the shoulders of the wrong co-worker can invite a push, a slap, a formal grievance — or a viral video.

However the allegations against Biden play out politically or in the press, the boundaries of personal space will always remain somewhat fluid and, except in the most obvious cases, open to interpretation. If you aren’t sure, ask first.

This article originally appeared in <a href="https://www.nytimes.com/2019/04/04/health/psychology-metoo-biden.html" id="678bf89a-6430-3fc1-a45b-be249173872b">The New York Times</a>.

Beyond Biden: How Close Is Too Close?

The new drug, esketamine, made by Janssen Pharmaceuticals, won approval from the Food and Drug Administration on Tuesday for people who have received little or no relief from other antidepressants. The FDA’s decision followed months of anticipation; esketamine, which will be marketed under the name Spravato, is the first prescription for depression derived from ketamine, an old and widely used anesthetic.

The recommended course of the newly approved drug is twice a week, for four weeks, with boosters as needed, in conjunction with one of the commonly used oral antidepressants. But both esketamine and ketamine have side effects, including out-of-body sensations and hallucinations, and have the potential for abuse. The FDA issued strict safety requirements: Doses must be taken in a doctor’s office or clinic, with patients monitored for at least two hours, the experience must be entered in a registry, and patients should not drive on the day of treatment.

“These issues raise barriers,” said Dr. Erick Turner, a psychiatrist at Oregon Health &amp; Science University. “People have to come in twice a week to the hospital and stick around for two hours being monitored. So you’ve got to have space for them, and the question is, where? The waiting room’s not going to work — in the clinic somewhere, which can be hard to find. And then someone’s got to drive them home.”

The cost of Spravato is also a concern, some doctors said. The wholesale price of the one-month initial treatment will range from $4,720 to $6,785, depending on dosage, according to Janssen. Follow-up treatment will cost an additional $2,360 to $3,540. That makes the overall cost comparable to existing treatments like electroconvulsive therapy and transcranial magnetic stimulation.

The retail price of esketamine, with added hospital costs, is steeper than treatment with intravenous ketamine, the generic anesthetic. Hundreds of clinics around the country already provide a course of intravenous treatments, usually six over a couple of weeks, for about $500 per infusion, plus booster infusions as needed. The cost comes out of pocket, since the generic anesthetic is not approved for depression.

Insurers are more likely to cover at least a portion of the cost of esketamine nasal spray, but the industry does not always follow the government’s lead.

“It’s expensive, and I’m skeptical, but we do intend to set up treatment here,” said Dr. Mark George, a professor of psychiatry and neurology at the Medical University of South Carolina, in Charleston. He said his electroconvulsive therapy clinic has space for esketamine treatment, but that he will have to hire a nurse and perhaps other personnel.

“I have spent 30 years investigating depression, and I am massively aware of how devastating depression can be,” he added. “So for now I am grateful to have a new tool in the tool kit.”

Dr. Carolyn Rodriguez, an assistant professor and associate chair in the psychiatry and behavioral sciences at Stanford’s medical school, said the safety requirements were crucial, and that patients should also be informed of the drug’s risks.

“Ketamine’s effects are transient, and we don’t know the long-term effects of repeated dosing” of either the anesthetic or esketamine, said Rodriguez, who is studying the generic anesthetic as a possible treatment for obsessive-compulsive disorder. “We do know that people who abuse the drug, using it at higher doses, and frequently, have bladder toxicity and cognitive problems. Patients will need to be fully informed.”

Psychiatrists also said they have been thinking about which patients are ideal candidates for the new drug. The data presented by Janssen to the FDA were mixed, and suggested that esketamine provided lasting relief for a subset of people with treatment-resistant depression.

Doctors administering the intravenous generic anesthetic also have reported mixed results, with some reporting very high improvement across the board, and others much less so.

Dr. John Lauriello, chair of psychiatry at the University of Missouri School of Medicine, in Columbia, said that his clinic already administers intravenous ketamine for some patients, with good results. The new drug, he said, likely would appeal most to people with deep depression who are skittish about being hooked up to an IV and respond slowly to other treatment.

“I’ve got a guy, he eventually got better on standard antidepressants,” Lauriello said. “But it took three weeks; they were the worst three weeks of his life, and mine. That’s the sort of person I might give the esketamine spray, to buy time until the standard treatment works.”

George, the South Carolina psychiatrist, said that patient selection may be crucial to getting the most out of the newly approved medication. “If it turns out the new drug helps even one of 10 people with this disease, and we can figure out who those people are, then it’s very much worth it.”

This article originally appeared in <a href="https://www.nytimes.com/2019/03/08/health/depression-drugs-ketamine.html" id="05043a1b-0ce5-3025-a4c0-fa2366adb86c">The New York Times</a>.

Doctors welcomed federal approval this week of a new, fast-acting nasal spray for depression. But also they expressed concerns about its cost and long-term effects, as well as the logistics of administering it in accordance with safety requirements.

Doctors Welcome New Depression Drug, Cautiously

His son Dr. Jeffrey Rubin confirmed the death.

Rubin, a psychiatrist who spent most of his long career in private practice in Manhattan, was a young analyst in the late 1950s when he found his calling: He wrote a novella about troubled boy, based in part on a child being assisted by his wife, a special-education teacher. He followed that book, “Jordi,” with “Lisa and David,” which examined the inner lives of two young people with severe mental distress.

“Lisa and David” was made into the popular 1962 movie “David and Lisa,” directed by Frank Perry and starring Keir Dullea and Janet Margolin, with Howard da Silva as a psychiatrist. (The two names were switched to avoid confusion with another movie of the time called simply “Lisa.”)

Dr. Theodore Rubin, a psychoanalyst and a prolific writer whose short novel “Lisa and David,” about two teenagers finding love at a therapeutic school, was made into an Academy Award-nominated movie, and who became the public face of psychotherapy in postwar American popular culture, died Saturday in a nursing home in Manhattan. He was 95.

Benedict Carey

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