University Times

Models of memory creation developed

Pitt researchers have developed a way to make neural networks more accessible for experimentation. By reproducing the brain’s complex electrical impulses in models made of living brain cells, the team facilitated an unprecedented view of the neuron activity behind memory formation.

The paper was co-authored by neurobiology faculty member Guo-Qiang Bi and former Pitt bioengineering faculty member Henry Zeringue.

The team fashioned ring-shaped networks of brain cells that not only were capable of transmitting an electrical impulse, but also remained in a state of persistent activity associated with memory formation, Zeringue said.

Unraveling the mechanics of this network communication is key to understanding the cellular and molecular basis of memory creation, he said.

Magnetic resonance images have suggested that working memories are formed when the cortex, or outer layer of the brain, launches into extended electrical activity after the initial stimulus. But the brain’s complex structure and the diminutive scale of neural networks mean that observing this activity in real time can be nearly impossible, he said.

The Pitt team, however, was able to generate and prolong this excited state in groups of 40-60 brain cells harvested from the hippocampus of embryonic rats. In addition, the researchers produced the networks on glass slides that allowed them to observe the cells’ interplay.

To produce the models, adhesive proteins were stamped onto silicon discs, cultured and dried. The brain cells then were fused to the proteins and given time to grow and connect. The researchers disabled the cells’ inhibitory response then excited the neurons with an electrical pulse.

The resulting burst of network activity was able to be sustained for 12 seconds. Compared to the natural duration of a quarter of a second at most, the model permitted an extensive observation of how the neurons transmitted and held the electrical charge, Zeringue said.

Bioengineering doctoral student Ashwin Vishwanathan conducted the work in Zeringue’s lab. The work most recently was reported in the Royal Society of Chemistry (UK) journal Lab on a Chip.

The work was conducted through the Center for the Neural Basis of Cognition, operated by Pitt and Carnegie Mellon.

Pitt profs question cell phone study

In a letter published May 25 in the Journal of the American Medical Association (JAMA), several faculty members from the Department of Physics and Astronomy questioned the design and conclusions of a study published Feb. 23 in JAMA that suggests a correlation between cell phone use and increased glucose metabolism in the brain.

In the study, researchers led by the National Institute on Drug Abuse (NIDA) reported that 50 minutes of cell phone exposure resulted in increased glucose metabolism in the brain region closest to the phone’s antenna, but that this burst of activity was of unknown clinical significance.

Pitt faculty members Arthur Kosowsky and Eric Swanson and professor emeritus Edward Gerjuoy wrote that the researchers’ analyses were inconsistent with their data; that their analysis method was prone to statistical biases, and that they did not use a model that realistically represents cell phone radiation and its propagation into the brain.

Kosowsky said, “The brain is not a symmetrical material that operates in a vacuum. It’s a complicated organ with intricate electrical properties that we think were not adequately considered in the analysis of this experiment, as it was described in JAMA.

“We want to illuminate some potential shortcomings in a study that has been presented as making a significant contribution to the question of whether cellular phones impact brain function and health.”

The Pitt faculty members noted that the Feb. 23 report oversimplified electromagnetic radiation by assuming that cellular phone antennas are simple dipoles in which electrons oscillate the length of a linear antenna, such as on a radio. Modern cellular antennas are more often fractal, consisting of complex, repeating shapes that can change the antenna’s electric field pattern.

The study authors also assumed that the resulting radiation field acted as it would in a vacuum, which ignores the complex interaction of electromagnetic fields and living tissue.

These factors could produce substantially different conclusions from those reported in JAMA, Kosowsky said.

The Pitt writers also faulted the report’s data analysis as inconsistent and incomplete. Graphs in the paper that illustrate brain glucose metabolism do not include error bars to indicate the influence of uncertainty and noise — factors unrelated to the experiment — on the researchers’ measurements.

As a result, Kosowsky said, the effect of cellular phones on glucose metabolism appears to be highly significant in the plotted data, yet the NIDA team stresses in their paper that phone use resulted in only a modest increase in metabolism. In short, it’s difficult to determine whether the study’s results are significant or marginal, Kosowsky said.

The NIDA team members also knew which brain scans were from active and inactive phones, making biases in data analysis more likely, according to the letter. At the same time, the researchers did not randomize the side of the head on which study participants placed the active phone, nor did they control for the possible effect of heat from an active phone.

The Pitt letter is available at http://jama.ama-assn.org/content/305/20/2066.1.full.

Nursing faculty projects funded

School of Nursing faculty members recently received funding:

•  Marilyn Davies received support from Pitt’s Central Research Development Fund for her project titled “Providing Health Information to Households with Preschoolers at Risk for Obesity.”

• John M. O’Donnell, director of the nurse anesthesia program, received a $32,628 award from the Health Resources and Services Administration to support nurse anesthesia students.

UPB learning research to be published

Wayne Brinda, a Pitt-Bradford education faculty member, will have two articles appearing in education journals this fall.

“Ladder to Literacy” will appear in the fall issue of Middle School Journal, the journal of the National Middle School Association. Brinda also will present the paper at the association’s annual conference in November.

Brinda said that the paper is based on the research he did for his doctoral thesis at Duquesne University.  He worked with two groups of reluctant and struggling middle-school-age readers, 10 in an urban area and 10 in a rural area.

Brinda interviewed each of the students and teachers and worked with them over four months to develop a system of introducing information before it is read. The system also supports students’ reading during the exploration of a novel in a way that increases comprehension and interest.

He said he was interested in the area because as a middle and high school student, he was himself a struggling reader.

Reluctant readers played a role in Brinda’s second publication for this fall as well.

His article, “Bringing Literature to Life for Urban Adolescents: Artistic, Dramatic Instruction and Live Theatre,” will appear in the Journal of Aesthetic Education. Brinda and co-author Janine Certo of Michigan State University conducted a yearlong study in two sixth-grade classrooms in a high-poverty, urban, western Pennsylvania middle school.

In addition to reading young adult novels, students attended theatrical productions of the novels put on by a semi-professional theatre company that produces adaptations of literature and designs instructional support materials to meet literacy challenges.

The study demonstrated the positive impact artistic and dramatic instructional strategies have as pathways to comprehension, engagement and enjoyment.

“These results are essential to urban learners who often receive the worst kinds of instructional activities tied to standardized test scores and lack opportunities with the arts,” Brinda said. “Transformation occurred with a series of activities designed to guide the process of reading and make it enjoyable.

“Artistic and dramatic pedagogy supported by live theatre has a significant effect on addressing the needs of urban and all reluctant adolescent readers. Our hope is that administrators will see the importance of continuing field trips to theatrical events; teachers will draw on local theatres as resources for building enjoyment and excitement with reading, and theatres will see themselves as literacy resources.”

In addition to teaching at  Pitt-Bradford, Brinda is the artistic director and co-founder of Prime Stage Theatre in Pittsburgh, which blends education with theatre for adolescents, teachers and families.

Oncology research presented

Researchers from the University of Pittsburgh Cancer Institute (UPCI) and the School of Medicine recently presented findings from their projects at the American Society of Clinical Oncology annual meeting.

Among them were:

Patients willing to share health info

Ellen Beckjord, a psychiatry faculty member affiliated with UPCI Behavioral Medicine, and her colleagues found that cancer patients are eager to share their electronic health information to improve quality of care.

The  researchers  analyzed  a  2010  survey  of  more than 7,400 cancer patients by LIVESTRONG and the National Cancer Institute’s 2007 survey Health Information National Trends Survey to determine patient perspectives on electronic health information.

“Nearly all people affected by cancer think that privacy is important with regards to electronic health information, and more than 70 percent want information-sharing with providers to be more convenient. In comparison, almost 50 percent of the American population find it very important that providers share data,” Beckjord said. “Most compelling to me, as a researcher, is the willingness of almost 60 percent of the cancer patient respondents to have their information de-identified to support research activities. This finding could lead to further research using electronic health records.”

Breast cancer chemo combo tested

Adam Brufsky, a faculty member in medicine and associate director of clinical investigation at UPCI, and his colleagues analyzed data from a subset of patients in a larger trial called RIBBON-2, which added bevacizumab, or Avastin, to chemotherapy regimens for second-line treatment of metastatic breast cancer.

They found that among the 159 patients with triple-negative breast cancers, meaning the tumors do not carry estrogen, progesterone or human epidermal growth factor 2 (HER2) receptors, adding bevacizumab lengthened progression-free survival, improved treatment response rate, and potentially increased overall survival by nearly six months.

Brufsky said, “We await the final analysis of this trial later this year to see if the benefit is sustained in this subset of patients who have few other effective treatment options.”

Brain cancer vaccine tested

Hideho Okada, a faculty member in neurological surgery, with colleagues tested a novel brain cancer vaccine they developed for safety and ability to generate an immune response.

They found that among patients with recurrent malignant glioma, the vaccine was well tolerated; the most common side effects were skin reactions at the injection site and transient fever and chills. About 80 percent of the participants developed an immune response against the tumor antigens.

“Nearly half of the recurrent glioblastoma patients and two-thirds of the anaplastic glioma patients had shrinkage of their tumors or stable disease,” Okada said. Further trials are underway.

Habits, women’s cancers analyzed

Stephanie Land, a Graduate School of Public Health faculty member and director of the ReSET Center, and her colleagues examined the associations between lifestyle behaviors and cancer incidence in women enrolled in the breast cancer prevention trial conducted by the Pittsburgh-based National Surgical Adjuvant Breast and Bowel Project.

The prospective study analyzed the risk of common cancers in 13,388 healthy women at high risk of breast cancer, based on the participants’ baseline self-reported smoking, alcohol use and physical activity.

Land’s study showed that compared to women who never smoked, the incidence of invasive breast cancer was 60 percent higher for women who smoked at least 35 years and 35 percent higher for women who smoked 15-35 years.

Also, the incidence of colon cancer was significantly higher for women with longer histories of cigarette smoking. Endometrial cancer incidence was significantly higher in women with low levels of leisure-time physical activity, which may be due to the association between fitness and obesity.

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