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October 27, 2016

Research Notes

Pitt to lead trauma network

Pitt’s Schools of the Health Sciences have been awarded a U.S. Department of Defense (DOD) contract that could lead to $90 million in research over the next decade to improve trauma care for both civilians and military personnel.

The contract will launch with a $10.8 million project to create a nationwide network of trauma systems and centers capable of conducting detailed research to improve military trauma care. The Linking Investigations in Trauma and Emergency Services (LITES) Network will include extensive data collection to link information covering pre-hospital care through recovery after discharge on potentially thousands of trauma cases across the country.

Said Jason L. Sperry, principal investigator, faculty member in surgery and critical care medicine in the School of Medicine and UPMC trauma surgeon: “Our immediate goal is to characterize what our network can do by obtaining intensive data from the pre-hospital and in-hospital settings, which is beyond what is normally obtained by trauma centers across the country. Our sense is that after approximately two years of accruing large amounts of data, we’ll be able to launch subsequent projects at the DOD’s request — including the gold standard, randomized clinical trials — to find out what approach to care works best to keep people who are injured in a trauma from dying.”

In its initial project, the LITES Network is expected to provide epidemiological data on moderate and severe injuries in the U.S. and identify any regional variations in the types of injuries and the way they’re managed.

Said Frank X. Guyette, co-principal investigator of LITES, faculty member in emergency medicine in the School of Medicine and medical director of STAT MedEvac: “The LITES Network will allow us to study the continuum of trauma care from the first emergency medical services contact through the emergency department and on to the operating rooms and intensive care units. The lessons learned through this project will teach us how to better care for ill and injured civilians and protect our soldiers in the future.”

A recent National Academies of Sciences, Engineering and Medicine report determined that the lives of hundreds of U.S. service members likely could be saved in future wars if trauma care were optimal, and that those gains would lead to tens of thousands of civilian lives saved if such improvements were shared with U.S. trauma centers.

“That report set a bold goal to achieve zero preventable deaths after injury and minimal trauma-related disability,” said Sperry. “Serendipitously, the LITES Network has the potential to spur research that will lead to clinical advancements to achieve that ambitious goal.”

Pitt will lead the project with the University of Colorado and Oregon Health & Science University, and also involve trauma centers at the University of Texas-Houston, Vanderbilt University, the University of Louisville, Baylor College of Medicine and the University of Arizona. Additional trauma centers from across the country will be involved in subsequent studies, including Penn, the University of Utah, the University of Texas Southwestern and the University of Florida. Pitt’s Graduate School of Public Health’s Epidemiology Data Center will be the data coordinating center, while the Multidisciplinary Acute Care Research Organization will be the clinical coordinating center.

The Coalition for National Trauma Research, composed of six leading trauma-related organizations, will be a key partner in the project by providing expertise in advocacy and strategic planning.

Barbara Early will be the program administrator. Other Pitt researchers are Stephen R. Wisniewski and David Okonkwo.


Concussions can be treated effectively, researchers say

Mid-aged doctor examining football player after concussionConcussions, often viewed by the public as dire and perplexing, can be treated effectively despite their complexity, according to experts from around the U.S.

The recent experts’ statement stems from an October 2015, “Targeted Evaluation and Active Management” (TEAM) symposium of concussion clinicians and researchers at UPMC that focused on best practices, protocols and active therapies for treating concussions.

The conference discussions were led by chair Micky Collins, director of the UPMC sports medicine concussion program, along with co-directors Anthony Kontos, faculty member in orthopaedic surgery, and David Okonkwo, faculty member in neurological surgery. The meeting was funded by the NFL Foundation.

The U.S. Center for Disease Control estimates that as many as 4 million concussions occur each year in the U.S., and sport- and recreation-related concussions in particular have been increasing.

Concussion symptoms, which can be subtle and last days or weeks, include but are not limited to headache, confusion and nausea.

Said Collins: “There has been only limited evidence-based guidance, particularly for primary care providers, about the active treatment of concussion. This makes it difficult for clinicians to determine how best to treat patients with this injury. Many are treating patients with concussion using a uniform, rest-based approach today much the same way they did a decade ago.”

Doctors typically advise patients to rest — both the brain and body — until symptoms abate, which might require accommodations at school or work. If the injury was sustained during sports, the patient is instructed not to return to play on the same day and to gradually increase aerobic, exertion-based activity while symptoms are monitored.

But, as described at the symposium, research is beginning to show active rehabilitation can help people recover more quickly and safely than simply resting.

“More research in large, multicenter trials is needed to figure out what kinds of treatments are most effective for a set of symptoms and for individual patients,” Collins said. “Most importantly, we believe concussions are treatable and patients can and do get better.”

A 2015 Harris Poll of more than 2,000 U.S. adults found that 71 percent did not recognize that concussions are treatable. In the same report, 1 in 3 patients who had been diagnosed with a concussion reported receiving no prescribed treatment.


iSchool gains two library grants
School of Information Sciences faculty members received two grants from the Institute of Museum and Library Services (IMLS) through its Laura Bush 21st century librarian program. Leanne Bowler was awarded a two-year grant for $109,399 for her research titled, “Exploring Data Worlds at the Public Library: Programs and Pedagogy in Support of Youth Data Literacy.” Matthew Burton and interim Doreen E. Boyce Chair Liz Lyon were awarded $97,911 for “The Data Scientist as the 21st Century Librarian?”

Bowler and a colleague from the University of Texas-Austin, with help from the Carnegie Library of Pittsburgh, will investigate youth data literacy in technology-supported programs for young people at the public library. This project aims to increase awareness of the data literacy needs of youth as well as to develop strategies for better training youth librarians. Said Bowler: “Data literacy is new to the world of libraries and its meaning is still open to negotiation. Although many have advocated for the education of a data-literate population, there is little consensus on what such educational programs should look like, particularly in the context of informal learning at the public library.”

Burton and Lyon are part of a multidisciplinary team that includes researchers from the Data & Society Research Institute in New York City and North Carolina State University.

The team will convene a national forum to create a vision and roadmap for using data science, an interdisciplinary field that extracts insights from various forms of data in libraries. The project’s goal is to bring together communities with an array of experiences and perspectives on data science to develop and maintain a national digital platform.


Brain Institute awarded $600,000 Hillman grant

Female Anatomy Brain FullA gift of $600,000 from the Henry L. Hillman Foundation will help the University of Pittsburgh Brain Institute (UPBI) launch interdisciplinary projects to advance research on normal brain function and its impairment in a range of disorders. With matching funds from internal sources, UPBI is distributing $925,000 to five projects managed by Pitt faculty that address paralysis, Parkinson’s disease, adolescent substance use, obsessive compulsive disorder and brain computation. The funding also will support the growth of a UPBI Brain Bank to further research.

Said Peter Strick, scientific director of UPBI and faculty member and Thomas Detre Endowed Chair in the School of Medicine Department of Neurobiology: “Collectively, these projects have the potential to significantly advance our understanding of brain function and shed light on disorders that affect millions of people. New therapies are urgently needed, and the road to these cures begins with this kind of fundamental research. These projects will enable us to better frame the national research agenda and compete more effectively for large-scale federal funding opportunities.”

Nathan Urban, associate director of the UPBI, neurobiology faculty member and vice provost for special projects, said: “Several of these projects represent integrated, interdisciplinary efforts that bring together computational and engineering approaches to the study of important questions about brain function. As recognized in the federal BRAIN initiative, progress in brain science and in the understanding of disease increasingly requires scientists to work together across disciplinary and departmental boundaries to bring new technological and analytic approaches to bear on questions of neuronal function and dysfunction.”

Selected through a competitive process, the projects are:

• Enhanced Neural Prosthetics Using Shared-Mode Control: This project builds on the program in brain-controlled robotic arms and hands for paralyzed individuals. Led by Andrew Schwartz, neurobiology faculty member in the School of Medicine, a group of scientists and engineers will enhance the performance of neural prosthetics, allowing a paralyzed person to manipulate an object. A prosthetic limb will operate under an individual’s brain control, with a boost from an artificial intelligence component designed to predict what the individual intends to do. This shared-mode control will enable people who have quadriplegia to dexterously handle objects with a robotic arm and hand, and thus increase their independence.

• Linking Circuit Dysfunction to Symptoms Across Movement Disorders: Robert Turner, neurobiology faculty member, and colleagues will focus on brain circuitry and the basal ganglia, a heavily interconnected set of deep brain nuclei involved in disorders of movement, such as Parkinson’s disease. His project will lay the groundwork for establishing a predictive model of how pathology in this brain circuit results in symptoms seen in patients and animal models.

• Impact of Sleep and Circadian Rhythms on the Vulnerability for Substance Use in Adolescents: Adolescence is a particularly vulnerable time when teenagers are more susceptible to developing drug addiction and sleep disorders, with an estimated 16 percent of young adults developing a substance abuse disorder. Teens are “wired” to be impulsive and reward-seeking, according to Colleen McClung, psychiatry faculty member. Her project will include preliminary studies in young teenagers to research the impact of sleep and circadian disruptions on behaviors that could lead to addiction.

• Identifying the Circuits Underlying Abnormal Anxiety and Reward Processing: Obsessive compulsive disorder (OCD) affects 2-3 percent of people worldwide, and the underlying causes of this lifelong disability remain unclear. Susanne Ahmari, psychiatry faculty member, and colleagues will combine analysis of brain activity in patients and animal models to better understand the nature of the abnormal brain activity that gives rise to OCD symptoms. The goal is to transform our understanding of OCD and drive the development of new and more effective treatments.

• The Impact of Variability on Neuronal Processing: Neurons are unpredictable, varying their response from moment to moment within any given experiment. They also generate large amounts of data. Coping with such large-scale data and characterizing variability across brain regions will be essential to constructing models of how the brain processes sensory signals, and ultimately for developing an overarching theory of cognition. Brent Doiron, mathematics faculty member in the Dietrich School of Arts and Sciences, and Matthew Smith, ophthalmology faculty member in the School of Medicine, will aim to understand the functional consequences of variability on specific brain computations and the behaviors they generate.

• Enriching a Brain Bank: A UPBI Brain Bank will expand an existing, substantial resource of more than 1,000 brains, according to Julia Kofler, director of the Brain Bank, and Clayton A. Wiley, director of the University’s neuropathology fellowship program, both pathology faculty members in the School of Medicine. The bank has one of the largest brain collections related to amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease. It extensively characterizes tissues and makes a large number of brain-region tissues available for study by research teams worldwide.


Paralyzed man regains feeling through robotic arm

A 28-year-old man, Nathan Copeland, who has been unable to feel any sensation in his arms and fingers due to an accident, has regained feeling a decade later through a mind-controlled robotic arm that is connected to his brain.

Following brain surgery, Copeland was connected to the Brain Computer Interface (BCI) developed by Pitt researchers. In a study published in Science Translational Medicine, a team led by Robert Gaunt, physical medicine and rehabilitation faculty member in the School of Medicine, demonstrated for the first time in humans a technology that allowed Copeland to experience the sensation of touch through a robotic arm that he controls with his brain.

Said study co-author Andrew B. Schwartz, neurobiology faculty member and chair in systems neuroscience in the School of Medicine and a member of the University of Pittsburgh Brain Institute: “The most important result in this study is that microstimulation of sensory cortex can elicit natural sensation instead of tingling. This stimulation is safe, and the evoked sensations are stable over months. There is still a lot of research that needs to be carried out to better understand the stimulation patterns needed to help patients make better movements.”

The way our arms naturally move and interact with the environment around us is due to more than just thinking and moving the right muscles. We are able to differentiate between a piece of cake and a soda can through touch, picking up the cake more gently than the can.

The constant feedback we receive from the sense of touch is of paramount importance as it tells the brain where to move and by how much.

Gaunt and the research team have refined their system so that inputs from the robotic arm are transmitted through a microelectrode array implanted in the brain where the neurons that control hand movement and touch are located.

The microelectrode array and its control system, which were developed by Blackrock Microsystems, along with the robotic arm, which was built by Johns Hopkins University’s Applied Physics Lab, formed all the pieces of the puzzle.

Said Copeland: “I can feel just about every finger — it’s a really weird sensation. Sometimes it feels electrical and sometimes it’s pressure, but for the most part, I can tell most of the fingers with definite precision. It feels like my fingers are getting touched or pushed.”

At this time, Copeland can feel pressure and distinguish its intensity to some extent, though he cannot identify whether a substance is hot or cold.

Gaunt explained that everything about the work is meant to make use of the brain’s natural, existing abilities to give people back what was lost but not forgotten. “The ultimate goal is to create a system which moves and feels just like a natural arm would,” he said.

Other Pitt investigators on the team were Elizabeth Tyler-Kabara, Jennifer Collinger, Sharlene N. Flesher, Stephen T. Foldes, Jeffrey M. Weiss and John E. Downey. A colleague from the University of Chicago also contributed to the research.

Primary support for the study was provided by the Defense Advanced Research Projects Agency’s revolutionizing prosthetics program.

Additional support came from the Office of Research and Development, Rehabilitation Research and Development Service, the U.S. Department of Veterans Affairs and the National Science Foundation Graduate Research Fellowship.


How repair protein finds DNA damage

Researchers at the School of Medicine and University of Pittsburgh Cancer Institute (UPCI) have demonstrated how Rad4, a protein involved in DNA repair, scans the DNA in a unique pattern of movement called “constrained motion” to efficiently find structural faults in DNA.

The findings, reported in Molecular Cell, could lead to therapies that boost existing drug treatments and counter drug-resistance.

Said senior author Bennett Van Houten, Richard M. Cyert Professor of Molecular Oncology in the School of Medicine and co-leader of UPCI’s molecular and cellular cancer biology program: “Rad4 is like the cop who is the first responder at an accident. The cop can move quickly to recognize where the incident is and regulate traffic while directing the paramedics arriving in an ambulance.”

Constrained motion allows Rad4 to be fast enough to scan large lengths of DNA quickly, yet slow enough that it does not miss structural errors in DNA that could be caused by chemicals or ultraviolet (UV) light.

Mutations in Rad4, called XPC in humans, and other proteins in the DNA repair machinery are known to cause a genetic condition called xeroderma pigmentosum, where individuals have sensitivity to sunlight and are at an extremely high risk for developing skin cancer.

Muwen Kong, a graduate student in Van Houten’s laboratory, along with his collaborators, tagged normal and mutant Rad4 molecules with light-emitting quantum dots.

They then watched them move across strands of DNA suspended between beads using a fluorescence microscope.

The results suggest that the first responder, consisting of Rad4 and another protein, Rad23, quickly scans the DNA for accidents by attempting to bend it. Alterations in the structure of DNA, such as those caused by chemicals or UV light, change the ease with which DNA can be bent. Once a potential accident is recognized, the Rad4-Rad23 first-responder team slows down to a constrained motion pattern to more carefully examine a smaller region of 500-1,000 base pairs in the DNA.

When structural damage is confirmed, Rad4-Rad23 stays near the scene and flags down the “paramedics,” comprised of the rest of the DNA repair machinery, to fix the damage. This mechanism, which Van Houten calls recognition-at-a-distance, allows Rad4 to be near the error without impeding the rest of the DNA repair crew.

Though much work is needed before these results can be translated to the clinic, they provide new avenues to improve treatment methods, especially in cancer. Resistance is a major problem with current treatments, such as cisplatin, which kills cancer cells by introducing DNA crosslinks similar to UV light. By developing drugs that target Rad4/XPC or other repair proteins, it could be possible to enhance the effects of current treatments when they are used together, and also reduce the chances of tumor cells developing resistance, Van Houten said.

Pitt co-investigators were Lili Liu, Stefanie Böhm, Simon C. Watkins and Kara A. Bernstein.
Also contributing were colleagues from the University of Illinois-Chicago, Washington State University and the University of Kent, U.K.

The research was funded by the National Institutes of Health (NIH) and the National Science Foundation.


BRAIN Initiative grant to study speech

A grant from NIH will help to fund advanced research focused on deeper understanding of how speech is controlled in the brain. The research team will study patients with Parkinson’s disease (PD) while they undergo deep brain stimulation (DBS) surgery.

The $3.3 million, three-year grant is among the third round of awards in the NIH’s BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative launched by President Barack Obama in 2013 as a large-scale effort to understand the brain and apply the knowledge to treating a variety of brain disorders including Alzheimer’s, schizophrenia, autism and traumatic brain injury.

A multidisciplinary team from Pitt, Carnegie Mellon University and Johns Hopkins University will be led by Mark Richardson, neurological surgery faculty member in the School of Medicine, director of the epilepsy and movement disorders surgery program at UPMC and member of the Brain Institute.

Since DBS produces predictable improvements in most motor symptoms of PD but does not result in consistent improvement in speech — it may have a negative impact on language function — Richardson’s team developed a novel method to record activity from different parts of the brain’s speech circuit.

Evidence from previous studies has suggested that the basal ganglia, a group of structures in the base of the brain, play an important role in the speech motor system. However, there is no neurophysiological model for how it actually modulates speech, which is a barrier to developing specific treatments to address deficits that can significantly reduce patients’ abilities to communicate.

Said Richardson: “Our overall goals are to determine how motor and linguistic speech information is encoded in the brain, and to understand how this information can be used to treat speech disorders.”

The study will aim to understand which neuronal activity in the subthalamic nucleus (STN) — a component of the basal ganglia — is responsible for different aspects of speech, including articulation, volume, pitch and efficiency, along with identifying how the STN interacts with the cortex to modulate speech. To do this, researchers will record the brain activity of PD patients during DBS surgery as they are asked to perform a variety of speech tasks.


Immunotherapy aids head, neck cancers

The immunotherapy nivolumab significantly increases survival and causes fewer adverse side effects in patients with recurrent head and neck cancer, according to a randomized trial co-led by investigators at UPCI, partners with UPMC CancerCenter.

The results of the international CheckMate-141 phase III clinical trial were reported in the New England Journal of Medicine, following preliminary presentations at the annual American Society of Clinical Oncology and American Association for Cancer Research meetings. Patients on nivolumab were doing so much better than those receiving standard therapy that the trial was stopped early to allow all patients to receive it.

Said lead author and trial co-chair Robert Ferris, UPMC Endowed Professor, chief of the Division of Head and Neck Surgery and co-leader of the cancer immunology program at UPCI: “Due to our clinical trial, anti-PD-1 therapies like nivolumab are now the recommended treatment for patients with this very difficult, devastating cancer.”

Worldwide, more than 600,000 cases of squamous-cell carcinoma of the head and neck are diagnosed annually, and the cancer recurs in more than half the patients within three years. The cancer typically returns because it has evaded the immune system and become resistant to chemotherapy.

Alcohol and tobacco use are the two main risk factors for head and neck cancers. Infection with the human papillomavirus (HPV) also is a risk factor, and rates of head and neck cancer attributable to HPV infection have increased 250 percent over the past several decades.

Nivolumab, which belongs to a class of drugs known as immunotherapeutics, enables the body’s immune system to destroy cancer cells. It currently is approved to treat certain types of cancers, including melanoma and lung cancer.

The CheckMate-141 trial enrolled 361 patients receiving care at 64 locations worldwide for recurrent head and neck cancer that had progressed within six months of chemotherapy. From June 2014 through August 2015, the researchers randomly assigned 240 patients to receive nivolumab and 121 to receive standard therapy, which consisted of one of three chemotherapy drugs.

On average, the patients on nivolumab survived 7.5 months, versus 5.1 months for the patients on standard therapy. At one year, 36 percent of the nivolumab patients were still living, compared with 16.6 percent of the standard-care patients.

Additionally, only 13.1 percent of the patients receiving nivolumab suffered serious, quality-of-life-disrupting side effects, compared with 35.1 percent of those receiving standard therapy.

“For the vast majority of patients, nivolumab isn’t a cure and more research is needed to find one,” said Ferris. “Perhaps even more important, we need to prevent this cancer from ever occurring. We have to help people to stop smoking or chewing tobacco, and encourage them to never start. We also need to continue to encourage children to be vaccinated against HPV.”

The trial was co-chaired by a researcher at Ohio State University. Additional U.S. institutions that participated in the trial were the University of Texas MD Anderson Cancer Center, Stanford Cancer Institute, the University of Chicago, the University of Michigan, Emory University, the Dana-Farber Cancer Institute and Bristol-Myers Squibb.

International collaborators were located at Centre Leon Berard, Centre Antoine Lacassagne, and Institut Gustave Roussy, all in France; Fondazione IRCCS Istituto Nazionale Tumori in Italy; the Institute of Cancer Research in the U.K.; University Hospital Essen in Germany; Hospital Universitario 12 de Octubre in Spain; University Hospital Zurich in Switzerland; and National Cancer Center Hospital East and Kobe University Hospital, both in Japan.

The trial was funded by Bristol-Myers Squibb, which now is seeking U.S. Food and Drug Administration approval for the use of nivolumab in head and neck carcinoma.


Nurturing improves kids’ emotional and mental health

Nurturing caregiving from a few consistent individuals helps to minimize the potential emotional and mental health development issues that can arise from spending the early years of a child’s life in an institution. Within such facilities, infants and toddlers reared in daily contact with responsive and warm professionals display better physical, cognitive and social development. After they are placed into families, they have less aggressive and defiant tendencies and show fewer externalizing behaviors.

These are the primary findings of a study led by researchers within the School of Education’s Office of Child Development. A follow-up report to previous research, the study acknowledges that infants and toddlers who reside in traditional institutions for extended periods are more likely to exhibit internalizing and externalizing behavioral problems even after being placed into families for some years. The study sought to determine whether positive interventions in these institutions would be associated with improvements in their behavior after transitioning into family care.

Said Robert B. McCall, one of the study’s lead researchers and a co-director of the child development office: “Unfortunately, many children around the world are reared in a regimented fashion by a large number of individuals who provide only the basics of care and support in a businesslike fashion with very little else — no response to crying, no conversation, no play, no hugs. The typical neglectful institutional method minimizes sensitive and responsive caregiver-child relationships and produces chronic stress, which leads to higher rates of deficient development and behavioral patterns. Conversely, improved caregiver-child interactions and relationships might be expected to minimize such adverse outcomes, leading to happier and more well-adjusted children. We believe these findings are potentially significant to professionals seeking to improve alternative care facilities and train their staff to care for the children in their care.”

Christina J. Groark, lead researcher and a co-director of the office, said: “This research shows that the characteristics of typical family life are important contributors to the development of infants and toddlers, even when implemented in an institution. The quality and consistency of early caregiver-child interactions appear to be the most important elements of childcare, regardless of whether the children live in an institution or a family.”

The study, conducted with Russian colleagues, observed the children, facilities and personnel of three separate institutions — also known as Russian baby homes—in St. Petersburg. Researchers followed 135 children who had spent at least three months in one of the three institutions. Participating children departed for domestic families either during the study or up to six years later and resided in those families for at least one year. The children were between 18 months and 10 years of age.

For the study, one institution was allowed to conduct business practices as usual — a representative of the status quo — while the other two were asked to install specific childcare interventions. Staff members within the second facility were instructed to interact with the children in a “parent-like” manner — expressing warm, caring and sensitive mannerisms — the same as they would with their own children. The third institution was asked to implement the same parent-like mannerism intervention as well as a series of caregiver-child policy changes. These changes included cutting the number of different caregivers the child experienced regularly and having those same one or two professionals consistently playing a role in the child’s daily life. In essence, the policy changes implemented in the second and third facilities looked to mimic parent-child relations as much as possible; in addition, the third facility was made more “family-like” in operation.

When transferred into domestic families, children from the intervention-implemented institutions were rated as being less indiscriminately friendly with strangers. The children also displayed fewer incidences of aggressive behavior, especially when compared to children who experienced longer stints in the status quo group home.

Pitt psychologists Jennifer L. Salaway and Megan M. Julian also contributed to the research. Their paper was published online in the American Psychological Association’s International Perspectives in Psychology.


Insomnia linked to altered brain activity

Beautiful woman lying on bed sleepless at night. Anxiety, stressSpecific brain regions, including those involved in awareness of self and tendency to ruminate, show altered activity in patients with insomnia when compared to good sleepers, according to a School of Medicine study published in the journal Sleep.

A research group led by Daniel Buysse, faculty member in psychiatry and clinical and translational science and the UPMC Professor of Sleep Medicine, identified differences in brain activity between states of sleep and wakefulness in 44 patients diagnosed with insomnia and 40 good sleepers.

Said Buysse, senior author on the study: “While patients with insomnia often have their symptoms trivialized by friends, families and even physicians, the findings in this study add strong evidence to the emerging view that insomnia is a condition with neurobiological as well as psychological causes.”

The study also shows that brain activity during sleep is more nuanced than previously thought, with different brain regions experiencing varying depths of sleep.

The findings may help improve current treatments for insomnia such as transcranial magnetic stimulation, and increase understanding of why treatments such as mindfulness meditation are effective in some patients.

Researchers used positron emission tomography (PET) scans during which participants were injected with a solution of glucose molecules tagged with a tracer. Brain regions with higher activity took up a proportionally higher amount of the radioactively tagged glucose and were more metabolically active on the PET scans.

Data from the scans revealed relative activity differences in specific brain regions between states of sleep and wakefulness in patients with insomnia and good sleepers. The differences can be attributed to either decreased activity during wakefulness or heightened activity during sleep, the researchers report.

Dysfunction in the brain regions identified in the study may correlate to specific symptoms in patients with insomnia, including impairments in self-awareness and mood, memory deficits and rumination, according to the authors.

Though the study design did not allow authors to discern whether brain activity changes were the cause or consequence of insomnia, the results do indicate that sleep is not uniform across different parts of the brain, contradicting the prevailing view that the entire brain is “on” while awake and “off” while asleep.

Other Pitt authors on the study were Daniel B. Kay, Helmet T. Karim, Adriane M. Soehner, Brant P. Hasler, Kristine A. Wilckens, Jeffrey A. James, Howard J. Aizenstein, Julie C. Price, Bedda L. Rosario, David J. Kupfer, Anne Germain, Martica H. Hall, Peter L. Franzen and Eric A. Nofzinger.

The research was funded by grants from NIH and support from Sepracor Inc.



—Compiled by Marty Levine

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