The neural structure we use to store and process information in verbal working memory is more complex than previously understood, finds a new study by NYU researchers–a discovery that has implications for the creation of artificial intelligence systems.
The neural structure we use to store and process information in verbal working memory is more complex than previously understood, finds a new study by researchers at New York University. It shows that processing information in working memory involves two different networks in the brain rather than one—a discovery that has implications for the creation of artificial intelligence (AI) systems, such as speech translation tools.
“Our results show there are at least two brain networks that are active when we are manipulating speech and language information in our minds,” explains Bijan Pesaran, an associate professor at New York University’s Center for Neural Science and the senior author of the research.
The work appears in the journal Nature Neuroscience.
Past studies had emphasized how a single “Central Executive” oversaw manipulations of information stored in working memory. The distinction is an important one, Pesaran observes, because current AI systems that replicate human speech typically assume computations involved in verbal working memory are performed by a single neural network.
“Artificial intelligence is gradually becoming more human like,” says Pesaran. “By better understanding intelligence in the human brain, we can suggest ways to improve AI systems. Our work indicates that AI systems with multiple working memory networks are needed.”
The paper’s first author was Greg Cogan, an NYU postdoctoral fellow at the time of the study and now a postdoctoral fellow at Duke University; other co-authors were Professor Orrin Devinsky, director of the Comprehensive Epilepsy Center at NYU Langone Medical Center, Werner Doyle, an associate professor at NYU Langone’s Department of Neurosurgery, Dan Friedman, an associate professor at NYU Langone’s Department of Neurology, and Lucia Melloni, an assistant professor at NYU Langone’s Department of Neurology.
The study focused on a form of working memory critical for thinking, planning, and creative reasoning and involves holding in mind and transforming the information necessary for speech and language.
The researchers examined human patients undergoing brain monitoring to treat drug-resistant epilepsy. Specifically, they decoded neural activity recorded from the surface of the brain of these patients as they were listening to speech sounds and speaking after a short delay. This method required the study’s subjects to use a rule provided by the researchers to transform speech sounds they heard into different spoken utterances—for example, the patients were told to repeat the same sound they had heard while at other times the researchers instructed the patients to listen to the sound and make a different utterance.
The researchers decoded the neural activity in each patient’s brain as the patients applied the rule to convert what they heard into what they needed to say. The results revealed that manipulating information held in working memory involved the operation of two brain networks. One network encoded the rule that the patients were using to guide the utterances they made (the rule network). Surprisingly, however, the rule network did not encode the details of how the subjects converted what they heard into what they said. The process of using the rule to transform the sounds into speech was handled by a second, transformation network. Activity in this network could be used to track how the input (what was heard) was being converted into the output (what was spoken) moment-by-moment.
Translating what you hear in one language to speak in another language involves applying a similar set of abstract rules. People with impairments of verbal working memory find it difficult to learn new languages. Modern intelligent machines also have trouble learning languages, the researchers add.
“One way we can enhance the development of more intelligent systems is with a fuller understanding of how the human brain and mind works,” notes Pesaran. “Diagnosing and treating working memory impairments in people involves psychological assessments. By analogy, machine psychology may one day be useful for diagnosing and treating impairments in the intelligence of our machines. This research examines a uniquely human form of intelligence, verbal working memory, and suggests new ways to make machines more intelligent.”
Mechanisms underlying direct programming of stem cells could eventually lead to cell-replacement therapies
A team of scientists has uncovered details of the cellular mechanisms that control the direct programming of stem cells into motor neurons. The scientists analyzed changes that occur in the cells over the course of the reprogramming process. They discovered a dynamic, multi-step process in which multiple independent changes eventually converge to change the stem cells into motor neurons.
“There is a lot of interest in generating motor neurons to study basic developmental processes as well as human diseases like ALS and spinal muscular atrophy,” said Shaun Mahony, assistant professor of biochemistry and molecular biology at Penn State and one of the lead authors of the paper. “By detailing the mechanisms underlying the direct programing of motor neurons from stem cells, our study not only informs the study of motor neuron development and its associated diseases, but also informs our understanding of the direct programming process and may help with the development of techniques to generate other cell types.”
The direct programming technique could eventually be used to regenerate missing or damaged cells by converting other cell types into the missing one. The research findings, which appear online in the journal Cell Stem Cell on December 8, 2016, show the challenges facing current cell-replacement technology, but they also outline a potential pathway to the creation of more viable methods.
“Despite having a great therapeutic potential, direct programming is generally inefficient and doesn’t fully take into account molecular complexity,” said Esteban Mazzoni, an assistant professor in New York University’s Department of Biology and one of the lead authors of the study. “However, our findings point to possible new avenues for enhanced gene-therapy methods.”
The researchers had shown previously that they can transform mouse embryonic stem cells into motor neurons by expressing three transcription factors — genes that control the expression of other genes — in the stem cells. The transformation takes about two days. In order to better understand the cellular and genetic mechanisms responsible for the transformation, the researchers analyzed how the transcription factors bound to the genome, changes in gene expression, and modifications to chromatin at 6-hour intervals during the transformation.
“We have a very efficient system in which we can transform stem cells into motor neurons with something like a 90 to 95 percent success rate by adding the cocktail of transcription factors,” said Mahony. “Because of that efficiency, we were able to use our system to tease out the details of what actually happens in the cell during this transformation.”
“A cell in an embryo develops by passing through several intermediate stages,” noted Uwe Ohler, senior researcher at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin and one of the lead authors of the work. “But in direct programming we don’t have that: we replace the gene transcription network of the cell with a completely new one at once, without the progression through intermediate stages. We asked, what are the timing and kinetics of chromatin changes and transcription events that directly lead to the final cell fate?”
The research team found surprising complexity — programming of these stem cells into neurons is the result of two independent transcriptional processes that eventually converge. Early on in the process, two of the transcription factors — Isl1 and Lhx3 — work in tandem, binding to the genome and beginning a cascade of events including changes to chromatin structure and gene expression in the cells. The third transcription factor, Ngn2, acts independently making additional changes to gene expression. Later in the transformation process, Isl1 and Lhx3 rely on changes in the cell initiated by Ngn2 to help complete the transformation. In order for direct programming to successfully achieve cellular conversion, it must coordinate the activity of the two processes.
“Many have found direct programming to be a potentially attractive method as it can be performed either in vitro — outside of a living organism — or in vivo — inside the body and, importantly, at the site of cellular damage,” said Mazzoni. “However, questions remain about its viability to repair cells — especially given the complex nature of the biological process. Looking ahead, we think it’s reasonable to use this newly gained knowledge to, for instance, manipulate cells in the spinal cord to replace the neurons required for voluntary movement that are destroyed by afflictions such as ALS.”
Learn more: How to Make a Motor Neuron
In a small double-blind study, Johns Hopkins researchers report that a substantial majority of people suffering cancer-related anxiety or depression found considerable relief for up to six months from a single large dose of psilocybin — the active compound in hallucinogenic “magic mushrooms.”
The researchers cautioned that the drug was given in tightly controlled conditions in the presence of two clinically trained monitors and said they do not recommend use of the compound outside of such a research or patient care setting.
The Johns Hopkins team released its study results, involving 51 adult patients, concurrently with researchers from New York University Langone Medical Center, who conducted a similarly designed study on 29 participants. Both studies are published in the Journal of Psychopharmacology on Dec. 1.
The Johns Hopkins group reported that psilocybin decreased clinician- and patient-rated depressed mood, anxiety and death anxiety, and increased quality of life, life meaning and optimism. Six months after the final session of treatment, about 80 percent of participants continued to show clinically significant decreases in depressed mood and anxiety, with about 60 percent showing symptom remission into the normal range. Eighty-three percent reported increases in well-being or life satisfaction. Some 67 percent of participants reported the experience as one of the top five meaningful experiences in their lives, and about 70 percent reported the experience as one of the top five spiritually significant lifetime events.
“The most interesting and remarkable finding is that a single dose of psilocybin, which lasts four to six hours, produced enduring decreases in depression and anxiety symptoms, and this may represent a fascinating new model for treating some psychiatric conditions,” says Roland Griffiths, Ph.D., professor of behavioral biology in the Departments of Psychiatry and Behavioral Sciences and of Neuroscience at the Johns Hopkins University School of Medicine. He notes that traditional psychotherapy offered to people with cancer, including behavioral therapy and antidepressants, can take weeks or even months, isn’t always effective, and in the case of some drugs, such as benzodiazepines, may have addictive and other troubling side effects.
Griffiths says his team’s new study grew out of a decade of research at Johns Hopkins on the effects of psilocybin in healthy volunteers, which found that psilocybin can consistently produce positive changes in mood, behavior and spirituality when administered to carefully screened and prepared participants. The study was designed to see if psilocybin could produce similar results in psychologically distressed cancer patients.
“A life-threatening cancer diagnosis can be psychologically challenging, with anxiety and depression as very common symptoms,” says Griffiths. “People with this kind of existential anxiety often feel hopeless and are worried about the meaning of life and what happens upon death.”
For the study, the investigators recruited 51 participants diagnosed with life-threatening cancers, most of which were recurrent or metastatic. They were chosen from a total of 566 individuals reached through flyers, web advertisements and physician referrals. Most participants had breast, upper digestive, GI, genitourinary or blood cancer, and each had been given a formal psychiatric diagnosis, including an anxiety or depressive disorder.
Half of the participants were female with an average age of 56. Ninety-two percent were white, 4 percent were African-American and 2 percent were Asian.
Each participant had two treatment sessions scheduled five weeks apart, one with a very low psilocybin dose (1 or3 milligrams per 70 kilograms) taken in a capsule and meant to act as a “control” placebo because the dose was too low to produce effects. In the other session, participants received a capsule with what is considered a moderate or high dose (22 or 30 milligrams per 70 kilograms).
To minimize expectancy effects, the participants and the staff members supervising the sessions were told that the participants would receive psilocybin on both sessions, but they did not know that all participants would receive one high and one low dose. Blood pressure and mood were monitored throughout the sessions. Two monitors aided participants during each session, encouraging them to lie down, wear an eye mask, listen to music through headphones and direct their attention on their inner experience. If anxiety or confusion arose, the monitors provided reassurance to the participants.
In addition to experiencing changes in visual perception, emotions and thinking, most participants reported experiences of psychological insight and often profound, deeply meaningful experiences of the interconnectedness of all people.
The researchers assessed each participant’s mood, attitude about life, behaviors and spirituality with questionnaires and structured interviews before the first session, seven hours after taking the psilocybin, five weeks after each session and six months after the second session. Immediately after the sessions, participants completed questionnaires assessing changes in visual, auditory and body perceptions; feelings of transcendence; changes in mood; and more.
Structured clinical interviews, such as the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale, and patient questionnaires, like the Beck Depression Inventory and the State-Trait Anxiety Inventory, assessed depression and anxiety. Other questionnaires assessed quality of life, death acceptance, meaningful existence, optimism and spirituality — generally defined as a search for the meaning of life and a connection to something bigger than one’s self. To measure the changes in attitudes, moods and behavior over time, the researchers administered a questionnaire that assessed negative or positive changes in attitudes about life, mood and behavior.
With regard to adverse effects, Griffiths says 15 percent of participants were nauseated or vomited, and one-third of participants experienced some psychological discomfort, such as anxiety or paranoia, after taking the higher dose. One-third of the participants had transient increases in blood pressure. A few participants reported headaches following the session.
“Before beginning the study, it wasn’t clear to me that this treatment would be helpful, since cancer patients may experience profound hopelessness in response to their diagnosis, which is often followed by multiple surgeries and prolonged chemotherapy,” says Griffiths. “I could imagine that cancer patients would receive psilocybin, look into the existential void and come out even more fearful. However, the positive changes in attitudes, moods and behavior that we documented in healthy volunteers were replicated in cancer patients.”
Up to 40 percent of people with cancer suffer from a mood disorder, according to the National Comprehensive Cancer Network.
Anticipating wide interest in the psilocybin research from scientists, clinicians and the public, the journal solicited 11 commentaries to be co-published with the study results written by luminaries in psychiatry, palliative care and drug regulation, including two past presidents of the American Psychiatric Association, a past president of the European College of Neuropsychopharmacology, the former deputy director of the U.S. Office of National Drug Control Policy, and the former head of the U.K. Medicines and Healthcare Products Regulatory Authority. In general, the commentaries were supportive of the research and of using these drugs in a clinical setting as tools for psychiatry.
Taking a page from Jonathan Swift’s “Gulliver’s Travels”, a team of scientists has created malleable and microscopic self-assembling particles that can serve as the next generation of building blocks in the creation of synthetic materials.
“Our work turns the tiniest of particles from inflexible, Lego-like pieces into ones that can transform themselves into a range of shapes,” explains Stefano Sacanna, an assistant professor in NYU’s Department of Chemistry and the senior author of the paper, which appears in the journal Nature Communications. “With the ability to change their contours, these particles mimic alterations that occur in nature.”
The research focused on engineering particles a micrometer in width—about 1/200th the width of a strand of human hair.
Specifically, it aimed to enhance the adaptability of colloids—small particles suspended within a fluid medium. Such everyday items such as paint, milk, gelatin, glass, and porcelain are composed of colloidal dispersions, but it’s their potential to control the flow of light that has scientists focused on creating exotic colloidal geometries.
New York University (NYU) is a private, nonsectarian American research university based in New York City.
Founded in 1831, NYU is now one of the largest private universities in the United States. Its main campus is situated at Washington Square in Greenwich Village, and it also has campuses located overseas.
NYU was the founding member of the League of World Universities, an international organization consisting of rectors and presidents from urban universities across six continents. The league and its 47 representatives gather every two years to discuss global issues in education. L. Jay Oliva formed the organization in 1991 just after he was inaugurated president of New York University.
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A team of scientists has developed an algorithm that captures our learning abilities, enabling computers to recognize and draw simple visual concepts that are mostly indistinguishable from those created by humans.
The work, which appears in the latest issue of the journal Science, marks a significant advance in the field—one that dramatically shortens the time it takes computers to “learn” new concepts and broadens their application to more creative tasks.
“Our results show that by reverse engineering how people think about a problem, we can develop better algorithms,” explains Brenden Lake, a Moore-Sloan Data Science Fellow at New York University and the paper’s lead author. “Moreover, this work points to promising methods to narrow the gap for other machine learning tasks.”