Scientific Meeting » The NIMH Director’s Innovation Speaker Series: Neural Decoding and Control of Multiscale Brain Networks to Treat Mood Disorders and Beyond

The NIMH Director’s Innovation Speaker Series: Neural Decoding and Control of Multiscale Brain Networks to Treat Mood Disorders and Beyond

Date/Time:

Location: Neuroscience Center
Conference Room C
6001 Executive Boulevard
Bethesda, MD
WebEx

Maryam Shanechi On November 21, 2019, Dr. Maryam M. Shanechi will present “Neural Decoding and Control of Multiscale Brain Networks to Treat Mood Disorders and Beyond,” as part of the National Institute of Mental Health (NIMH) Director’s Innovation Speaker Series.

In her lecture, Dr. Shanechi will first discuss recent work on modeling, decoding, and controlling multisite human brain activity underlying mood states. She will then present a multiscale dynamical modeling framework that allows researchers to decode mood variations and identify brain sites that are most predictive of mood. She will also describe how to develop a system identification approach to characterize brain network dynamics (output) in response to electrical stimulation (input) and enable closed-loop control of brain activity. Finally, she will demonstrate that this multiscale framework can identify a unified low-dimensional latent state from hybrid spike-field activity, allowing it to combine information about a brain state from multiple scales of activity and model their different time-scales and statistical profiles. These models, decoders, and controllers could facilitate future closed-loop therapies for neurological and neuropsychiatric disorders and help probe neural circuits.

Maryam M. Shanechi is Assistant Professor and Viterbi Early Career Chair in Electrical and Computer Engineering at the Viterbi School of Engineering, University of Southern California (USC). She is also a faculty member in the Neuroscience Graduate Program and Biomedical Engineering at USC. She received her B.A.Sc. degree in Engineering Science from the University of Toronto in 2004 and her S.M. and Ph.D. degrees in Electrical Engineering and Computer Science from Massachusetts Institute of Technology (MIT) in 2006 and 2011, respectively. She held postdoctoral positions at Harvard Medical School and University of California, Berkeley from 2011-2013. She directs the Neural Systems Engineering Lab at USC. Her research is focused on developing closed-loop neurotechnologies through mathematical decoding and control of brain networks to treat neurological and neuropsychiatric disorders. She is the recipient of various awards including the National Science Foundation Faculty Early Career Development (CAREER) Program Award, the MIT Technology Review’s top 35 innovators under the age of 35 (TR35), the Popular Science Brilliant 10, an Army Research Office Multidisciplinary University Research Initiative (MURI) award, and the Office of Naval Research Young Investigator award.

Registration and Parking

This event is open without prior registration to all National Institutes of Health (NIH) staff and the public. Parking is available at a nominal fee. A government-issued photo identification card (such as an NIH ID or driver's license) is required to enter the building. The audio of this event will be available over WebEx.

Background

The NIMH Director’s Innovation Speaker Series was started to encourage broad, interdisciplinary thinking in the development of scientific initiatives and programs, and to press for theoretical leaps in science over the continuation of incremental thinking. Innovation speakers are encouraged to describe their work from the perspective of breaking through existing boundaries and developing successful new ideas, as well as working outside their initial area of expertise in ways that have pushed their fields forward. We encourage discussions of the meaning of innovation, creativity, breakthroughs, and paradigm-shifting.

More Information:

WEB EX

Meeting number: 621 521 377

Meeting password: INNOVSHAN

https://nih.webex.com/nih/j.php?MTID=m507d5e8aa9e442f8d09ebab071c58324

Video address: Dial 621521377@nih.webex.com You can also dial 173.243.2.68 and enter your meeting number.

Audio connection: 1-650-479-3208 Call-in toll number (US/Canada)

Sign Language Interpreters will be provided. Individuals with disabilities who need reasonable accommodations to participate in this program should contact Dawn Smith 301-451-3957 and/or the Federal Relay (1-800-877-8339).

Original Article

Blog Post » Harnessing the Power of Technology for Mental Health

It’s 90 degrees Fahrenheit out. Sweat is pouring down my forehead. I look down at my cyclocomputer: 6 miles to go. I stop my furious pedaling, pull over to the side of the path, take a calming breath, and look around as I open a bottle of water. The landscape is full of rolling sand dunes like something out of Lawrence of Arabia. It should be. I’m cycling on Al Qudra bicycle track, a serpentine loop purpose-built into the desert in Dubai, UAE. Arriving half a day early for the annual meeting of the World Economic Forum (WEF) Global Futures Councils, I took the opportunity to engage in bicycle tourism, one of my favorite activities.

Qudra Desert, Dubai

Qudra Desert, Dubai

My smartphone and its apps, my cyclocomputer and its sophisticated software — these are technologies that help me plan and get the most out of my cycling experiences. They provide solutions to myriad problems and democratize these solutions. I didn’t pore over maps for hours or constantly stop to ask for directions to plan my next cycling adventure. I just pulled out my smartphone and consulted a few of my apps. In the palm of my hand, I planned out a cycling route, searched for a bike rental shop on a web mapping service, found a lunch spot — and I was on my way.

Imagine if we had such easy technological solutions to help guide our forays into mental health. How might devices and software help with mental health screening, diagnosis, and prevention? How might they connect individuals who have mental illnesses to providers or enhance access to care in remote and under-resourced settings? How might these technologies enable the use of relevant data for research and quality improvement? These were the very questions I contemplated as my computer guided me back to the bike shop; these were the questions I was in Dubai to address.

The WEF is best known for its annual meeting in Davos, Switzerland, where world leaders, academics, and international affairs experts gather to discuss global issues and strive to improve “the state of the world.” Much of the work of the WEF, however, is done by its Global Futures Councils. The Technology for Mental Health Council is one of these workgroups, aimed at fostering international collaborations to develop technological approaches that address mental health.

The idea that technology can be harnessed for mental health is not a new one. There are thousands of apps aimed at maintaining or improving mental health. Some facilitate connections to mental health professionals; others provide stand-alone treatment approaches or help individuals record their symptoms and monitor their progress. Newer tech approaches are also proving incredibly useful for research purposes. For example, NIMH-funded research groups and startup companies are examining the potential of using a combination of activity monitors, digital keyboards, and phone usage in addition to in-the-moment surveys to detect the onset of depression or mania more quickly.

In Dubai, ensconced in a white board-festooned pod in a modern conference center, WEF’s Technology for Mental Health Council discussed how our group might contribute to these efforts. In the room, we had academics, leaders of foundations and scientific societies, individuals with lived experience, global mental health advocates, tech and health care corporate representatives, a journal editor, and a neuroethicist. We debated approaches and priorities, and, at the end of the first day, we settled on a focus: tech approaches to reducing youth suicide, a growing problem around the world. The second day was spent discussing concrete plans for what we might accomplish as a group, including: a series of blogs, webinars, and conferences aimed at increasing the dialogue among technology companies, scientists, and those living with mental illnesses; and tools to understand the responsible use of technology aimed at identifying youth at risk for suicide. The resources of the WEF, the members of the council, and affiliated organizations will be brought to bear on fulfilling these plans over the coming year.

The World Economic Forum (WEF) Technology and Mental Health Council discusses approaches for harnessing technology for mental health.

The World Economic Forum (WEF) Technology for Mental Health Council discusses approaches for harnessing technology for mental health.

One significant issue with mental health-related technologies such as smartphone apps is the need for rigorous scientific studies to demonstrate that such technologies actually work. For most smartphone apps, the consequences of failure are minimal. If your restaurant app search for a vegetarian restaurant sends you to a Korean barbecue joint, you check a different app instead. But ineffective technological solutions may have much more severe consequences for an individual living with a mental illness — particularly for someone experiencing suicidal thoughts. Getting these solutions right is crucial, and that means we need rigorously designed clinical trials to show that they work. Unlike some tech solutions, which are released with a consumer goods mindset, NIMH supports research aimed at demonstrating clinical efficacy — a crucial step for technologies that are designed to solve clinical problems.

Early returns from this research are promising. A couple of examples: Jukka-Pekka Onnela, Ph.D., of the Harvard T. H. Chan School of Public Health is studying a smartphone-based approach to predicting relapse of schizophrenia symptoms. Smartphone data collected in a pilot study showed that participants’ patterns of behavior changed noticeably in the 2 weeks before they relapsed. Although more work is needed, this kind of technology could eventually allow clinicians to detect symptoms and intervene before relapse occurs. Meanwhile, software solutions for care delivery are achieving results. Findings suggest that PRIME — a digital motivation booster being studied by Sophia Vinogradov, M.D., of the University of Minnesota Medical School and Danielle Schlosser, Ph.D., of the University of California, San Francisco — can reduce depressive symptoms in individuals with schizophrenia.

This careful work is worthwhile for many reasons, but chief among them is the potential reach of technology. What I heard from my fellow council members in Dubai echoed what I’ve learned from visiting our research sites in Nepal, Kenya, and India, not to mention rural Louisiana and upstate New York. Access to mental health care is limited by resources, including a lack of qualified providers as well as insufficient funding and facilities. Effective technological solutions could help make up for this shortfall, helping guide people along their own serpentine paths through health care deserts to oases of recovery.

References

Barnett, I., Torous, J., Staples, P., Sandoval, L., Keshavan, M., & Onnela, J.- P. (2018). Relapse prediction in schizophrenia through digital phenotyping: A pilot study. Neuropsychopharmacology, 43, 1660-1666. doi:10.1038/s41386-018-0030-z

Schlosser, D. A., Campellone, T. R., Truong, B., Etter, K., Vergani, S., Komaiko, K., & Vinogradov, S. (2018). Efficacy of PRIME, a mobile app intervention designed to improve motivation in young people with schizophrenia. Schizophrenia Bulletin, 44(5), 1010-1020. doi:10.1093/schbul/sby078

Original Article

Science News » Side Effects Mild, Brief with Single Antidepressant Dose of Intravenous Ketamine

 

Read transcript.

National Institutes of Health researchers found that a single, low-dose ketamine infusion was relatively free of side effects for patients with treatment-resistant depression. Elia Acevedo-Diaz, M.D., Carlos Zarate, M.D., and colleagues at the NIH’s National Institute of Mental Health (NIMH) report their findings in the Journal of Affective Disorders.

Studies have shown that a single, subanesthetic-dose (a lower dose than would cause anesthesia) ketamine infusion can often rapidly relieve depressive symptoms within hours in people who have not responded to conventional antidepressants, which typically take weeks or months to work. However, widespread off-label use of intravenous subanesthetic-dose ketamine for treatment-resistant depression has raised concerns about side effects, especially given its history as a drug of abuse.

“The most common short-term side effect was feeling strange or loopy,” said Acevedo-Diaz, of the Section on the Neurobiology and Treatment of Mood Disorders, part of the NIMH Intramural Research Program (IRP) in Bethesda, Maryland. “Most side effects peaked within an hour of ketamine administration and were gone within two hours. We did not see any serious, drug-related adverse events or increased ketamine cravings with a single-administration.”

The researchers compiled data on side effects from 163 patients with major depressive disorder or bipolar disorder and 25 healthy controls who participated in one of five placebo-controlled clinical trials conducted at the NIH Clinical Center over 13 years. While past studies have been based mostly on passive monitoring, the NIMH IRP assessment involved active and structured surveillance of emerging side effects in an inpatient setting and used both a standard rating scale and clinician interviews. In addition to dissociative (disconnected, unreal) symptoms, the NIMH IRP assessment examined other potential side effects – including headaches, dizziness, and sleepiness. The study did not address the side effects associated with repeated infusions or long-term use.

Out of 120 possible side effects evaluated, 34 were found to be significantly associated with the treatment. Eight occurred in at least half of the participants: feeling strange, weird, or bizarre; feeling spacey; feeling woozy/loopy; dissociation; floating; visual distortions; difficulty speaking; and numbness. None persisted for more than four hours. No drug-related serious adverse events, cravings, propensity for recreational use, or significant cognitive or memory deficits were seen during a three-month follow-up.

To overcome the limitations associated with side effects and intravenous delivery, ongoing research efforts seek to develop a more practical rapid-acting antidepressant that works in the brain similarly to ketamine. These NIMH researchers, in collaboration with the National Institute on Aging, and the National Center for Advancing Translational Science, are planning a clinical trial of a ketamine metabolite that showed promise as a potentially more specific-acting treatment in pre-clinical studies. Meanwhile, the U.S. Food and Drug Administration earlier this year approved an intranasal form of ketamine called esketamine, which can be administered to adults with treatment-resistant depression in a certified doctor’s office or clinic.

Reference:

Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression. Acevedo-Diaz EE, Cavanaugh GW, Greenstein D, Kraus C, Kadriu B, Zarate CA Jr, Park LT. https://doi.org/10.1016/j.jad.2019.11.028, Nov. 10, 2019, Journal of Affective Disorders.

Funding:

MH002857

About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

NIH…Turning Discovery Into Health®

Original Article

Video » Discover NIMH: Personalized and Targeted Brain Stimulation Therapies

Discover NIMH: Personalized and Targeted Brain Stimulation Therapies

 

Watch on YouTube.

Transcript

>> DR. JOSH GORDON: Brain stimulation therapies are important and effective treatments for people with depression and other mental disorders. The National Institute of Mental Health, NIMH, is supporting studies exploring how to make brain stimulation therapies like electroconvulsive therapy or ECT and transcranial magnetic stimulation or TMS more personalized and effective while reducing side effects.

>> DR. SARAH LISANBY: And I learned about ECT because one of my patients had to receive it. She was severely depressed and had a form of depression called catatonia. This can be life-threatening. And after her first ECT treatment, she was able to talk, she was able to move, she was able to eat. It really was life-saving for her.

>> DR. MATTHEW RUDORFER: Dr. Lisanby has done groundbreaking work in neurostimulation. She has brought ECT closer to the mainstream in the development of new and exciting neurostimulation treatments that offer options for people, especially with resistant depression. She has shown how we can optimize existing treatments such as electroconvulsive therapy and using magnetic stimulation, develop totally new approaches which did not exist a generation ago.

>> DR. SARAH LISANBY: Transcranial magnetic stimulation, or TMS, is the noninvasive way of stimulating the brain. It's a tool that we can use to study brain function but really excitingly, it's now a treatment that we can use for depression. We are seeking to develop new tools to improve the potency of TMS, how we can optimize, make it more effective for every person with depression by figuring out how to personalize the treatment. Finally, we have a tool that can not only teach us about depression and other serious illnesses but actually do something about it.

>> DR. JOSH GORDON: ECT and TMS both stimulate the brain with electricity but unlike ECT in which electrical stimulation is more generalized, TMS can be targeted to a specific site in the brain. TMS is a tool that is widely used to study complex aspects of brain function. NIMH-supported studies are exploring TMS's potential as a novel therapeutic treatment for mental disorders.

>> DR. SARAH LISANBY: We're seeking to improve the safety of our most effective treatments, including electroconvulsive therapy. TMS has a better safety profile. It doesn't affect memory. And one of the things that we're doing right now is coupling TMS with therapy. We're using the therapy to activate the circuits of the brain that are important for responding to treatment, and we stimulate using TMS to enhance the learning process during therapy.

>> DR. MATTHEW RUDORFER: Dr. Lisanby has taken essentially a 20th-century treatment, ECT, and brought it into the 21st century using modern neuroscience. We can get the therapeutic effect we want but avoid many of the adverse effects which has plagued treatments like electroconvulsive therapy in the past.

>> DR. JOSH GORDON: TMS is an FDA-approved treatment used for depression and obsessive-compulsive disorder. NIMH-funded research is now seeking to understand the mechanisms underlying its effects and to develop TMS treatments for conditions like anxiety disorders and post-traumatic stress disorder where it has shown some promising results.

>> DR. MATTHEW RUDORFER: Patients used to feel that if they were referred for ECT, that was their last resort, that was the end of the line, and, in fact, that's not the case.

>> DR. SARAH LISANBY: TMS has gone from a research tool to something that is really making a difference in peoples' lives. There's nothing more rewarding than seeing a person respond, seeing a person go from the depths of depression, hopelessness, even having thoughts of wanting to end their life, and to have that melt away and have them return to the person that they were before the serious disease of depression had affected them.

>> DR. JOSH GORDON: Through these and many other research projects, NIMH is striving to bring hope, therapies, and treatments to individuals and families affected by mental disorders.

Original Article

Science News » NIH Awards Funding for Early Autism Screening

The National Institutes of Health (NIH) has awarded more than four million dollars in FY 2019 to support seven research projects aimed at developing and validating screening tools to detect signs of autism spectrum disorder in the first year of life. Approximately 19 million dollars is projected to be awarded to these projects by NIH over the duration of the funded projects.

“Early detection and treatment of children with autism spectrum disorder are two of the most important factors for optimizing children’s outcomes,” said Dr. Joshua Gordon, director of the National Institute of Mental Health (NIMH). “It is critical that we develop screening tools that can pick up on early emerging signs of autism risk so that doctors can be vigilant in tracking children’s development and ensure they get intervention services as early as possible.”

It is estimated that autism spectrum disorder (ASD)—a developmental disorder that affects social communication and behavior—affects 1 in 59 children in the United States. Reliably detecting autism in young children is difficult, and the average age of diagnosis for ASD hovers around four years of age. Delays in diagnosis can have profound and long-lasting effects on children, since early intervention has been demonstrated to improve cognitive and behavioral outcomes for young children with ASD.

Because early treatment is so critical for children with ASD, efforts have been made to try to reduce the age of diagnosis by universally screening all children for signs of autism. Children who are found to be at high risk for developing autism can then be connected with intervention services as soon as possible. Although well-validated instruments exist to screen toddlers for ASD between 18 and 24 months of age, there is evidence that many infants at risk for ASD show differences in the way social attention and early forms of communication develop over the first year of life.

The seven projects—supported jointly by the NIH’s NIMH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Neurological Disorders and Stroke, and the National Institute on Deafness and Other Communication Disorders—seek to translate findings related to early-emerging signs of autism into practical ASD screening tools that can be implemented in the general population and in community settings.

The grants awarded include:

Community-Viable Screening for ASD in 9-month-old Infants Using Quantitative Eye-Tracking Assays of Social Visual Engagement
Warren Jones, Ph.D., Emory University
In this study, researchers will measure the ability of an eye-tracking-based assessment of social visual engagement performed during children’s 9-month well-child visits to screen for ASD and other actionable developmental delays.

Validation of the Social Communication CheckUp and Autism Risk Indicator in the First Year of Life
Amy Wetherby, Ph.D., Florida State University
The goal of this study is to validate the effectiveness of a new automated online screening tool—the Social Communication (SoCo) CheckUp—to screen for communication delay and autism at well-child visits at 9, 12, 15, 18, 21, and 24 months of age.

Novel Approaches to Infant Screening for ASD in Pediatric Primary Care
Geraldine Dawson, Ph.D., Duke University
The overall goal of this project is to develop and validate a novel screening tool, called SenseToKnow, for use in a primary care setting. This tool identifies risk for ASD in infants based on patterns of attention, orienting, affect, vocalizations, and motor behavior.

Neonatal Cry Acoustics and Neurobehavioral Characteristics as Early Markers of Risk for Autism Spectrum Disorder
Stephen Sheinkopf, Ph.D., Women and Infants Hospital—Rhode Island
This project seeks to identify children at risk for autism in infancy by developing and validating a novel tool/process that analyzes features of crying and neurobehavior that preliminary evidence has shown may be atypical in infants at risk for autism.

Novel Video-Based Approaches for Detection of Autism Risk in the First Year of life
Sally Ozonoff, Ph.D., University of California at Davis
In this study, the researchers aim to investigate and validate the Video-referenced Infant Rating System for Autism, a brief web-based instrument that utilizes video depictions rather than written descriptions of behavior to detect signs of ASD.

Novel Computer Vision-Based Assessment of Infant-Caregiver Synchrony as an Early Level II Screening Tool for Autism
Robert Thomas Schultz, Ph.D., Children’s Hospital of Philadelphia
This project tests a new method of screening for ASD in infancy by detecting alterations in the dynamic social coordination between infants and caregivers during brief, play-based interactions.

Development of a Telehealth Screener and Assessment for Infants At-Risk for ASD in Diverse Communities
Meagan Ruth Talbott, Ph.D., University of California at Davis
The goal of this project is to develop a telehealth screener to assess infants' early ASD symptoms that will improve families' access to specialized screening and decrease the significant wait time for an expert evaluation.

Original Article