Brain Network Control Emerges over Childhood and Adolescence

network control

 

The developing human brain contains a cacophony of electrical and chemical signals from which emerge the powerful adult capacities for decision-making, strategizing, and critical thinking. These signals support the trafficking of information across brain regions, in patterns that share many similarities with traffic patterns in railway and airline transportation systems. Yet while air traffic is guided by airport control towers, and railway routes are guided by signal control rooms, it remains a mystery how the information traffic in the brain is guided and how that guidance changes as kids grow.

In part, this mystery has been complicated by the fact that, unlike transportation systems, the brain is not hooked up to external controllers. Control must happen internally. The problem becomes even more complicated when we think about the sheer number of routes that must exist in the brain to support the full range of human cognitive capabilities. Thus, the controllers would need to produce a large set of control signals or use different control strategies. Where internal controllers might be, how they produce large variations in routing, and whether those controllers and their function change with age are important open questions.

A recent paper published in Nature Communications – a product of collaboration among the Departments of Bioengineering and Electrical & Systems Engineering at the University of Pennsylvania and the Department of Psychiatry of Penn’s Perelman School of Medicine – offers some interesting answers. In their article, Danielle Bassett, Ph.D., Eduardo D. Glandt Faculty Fellow and Associate Professor in the Penn BE Department, Theodore D. Satterthwaite, M.D., Assistant Professor in the Penn Psychiatry Department, postdoctoral fellow Evelyn Tang, and their colleagues suggest that control in the human brain works in a similar way to control in man-made robotic and other mechanical systems. Specifically, controllers exist inside each human brain, each region of the brain can perform multiple types of control, and this control grows as children grow.

As part of this study, the authors applied network control theory — an emerging area of systems engineering – to explain how the pattern of connections (or network) between brain areas directly informs the brain’s control functions. For example, hubs of the brain’s information trafficking system (like Grand Central Station in New York City) show quite different capacities for and sensitivities to control than non-hubs (like Newton Station, Kansas). Applying these ideas to a large set of brain imaging data from 882 youths in the Philadelphia area between the ages of 8 and 22 years old, the authors found that the brain’s predicted capacity for control increases over development. Older youths have a greater predicted capacity to push their brains into nearby mental states, as well as into distant mental states, indicating a greater potential for diversity of mental operations than in younger youths.

The investigators then asked whether the principles of network control could explain the specific manner in which connections in the brain change as youths age. They used tools from evolutionary game theory – traditionally used to study Darwinian competition and evolving populations in biology – to ‘evolve’ brain networks in silico from their 8-year old state to their 22-year-old state. The results demonstrated that the optimization of network control is a principle that explains the observed changes in brain connectivity as youths develop over childhood and adolescence. “One of the observations that I think is particularly striking about this study,” Bassett says, “is that the principles of network controllability are sufficient to explain the observed evolution in development, suggesting that we have identified a quintessential rule of developmental rewiring.”

This research informs many possible future directions in scientific research. “Showing that network control properties evolve during adolescence also suggests that abnormalities of this developmental process could be related to cognitive deficits that are present in many neuropsychiatric disorders,” says Satterthwaite. The discovery that the brain optimizes certain network control functions over time could have important implications for better understanding of neuroplasticity, skill acquisition, and developmental psychopathology.

CIFAR Names Kording Associate Fellow

CIFAR
Konrad Kording, Ph.D.

Dr. Konrad Kording, a University of Pennsylvania PIK Professor in Bioengineering and Neuroscience, has been named an associate fellow by the Canadian Institute for Advanced Research (CIFAR), an advanced study institute headquartered in Toronto and partially funded by the government of Canada. Dr. Kording’s fellowship is in the institute’s Learning in Machines & Brains area, which has been one of CIFAR’s 14 interdisciplinary study fields since 2004. He joins 32 other fellows currently supported by the institute for their work in this area.

“The CIFAR program in Learning in Machines & Brains brings together many of the world’s leading deep learning scientists,” Dr. Kording says. “I look forward to collaborate with them to figure out how the brain learns.”

CIFAR was founded in 1982. Over the last 35 years, the institute has supported the work of scientists in 133 countries, including 18 Nobel Prize laureates.

Lagrange Goes to Dani Bassett

Lagrange
Danielle Bassett, Ph.D.

Danielle S. Bassett, Eduardo D. Glandt Faculty Fellow and Associate Professor in the University of Pennsylvania’s Department of Bioengineering, is the recipient of the 2017 Lagrange-CRT Foundation Prize. The prize, given by the Institute for Scientific Interchange Foundation in Turin, Italy, was created to encourage and honor researchers working in the field of complex systems.

Complex systems feature many interconnected parts whose individual behavior influences the outcomes of the whole. Examples include social media networks, ecological webs, stock markets, and in Bassett’s case, the brain. Her research maps and analyzes the networks of neurons that enable all manners of cognitive abilities, as well as how those networks evolve during development or malfunction in disease.

The prize comes with an award of €50,000, or roughly $60,000. It will be formally presented to Bassett at a ceremony in Turin next week. Bassett is the first woman to be the sole recipient of the prize since its inception in 2008. Lada Adamic won it alongside Xavier Gabaix in 2012.

Read more at the SEAS blog on Medium.

Chairs for BMES ’19 to Include Burdick

chairsJason Burdick, Ph.D., who is a professor in the University of Pennsylvania’s Department of Bioengineering, has been named one of the three chairs of the 2019 annual meeting of the Biomedical Engineering Society (BMES), which be held here in Philadelphia on October 16-19. Dr. Burdick will share this position with two other Philadelphians: Alisa Morss Clyne, Ph.D., an associate professor of mechanical engineering and mechanics at Drexel University; and Ruth Ochia, Ph.D., an associate professor of instruction in bioengineering at Temple University. Drs. Burdick, Clyne, and Ochia will share the responsibility for planning the meeting and chairing it once it is in session.

“I am very happy to be appointed as a program chair for the 2019 BMES meeting in Philadelphia, along with Alisa Morss Clyne of Drexel University and Ruth Ochia of Temple University,” Dr. Burdick said when asked about the honor. “The three of us felt that it was important to represent the various biomedical engineering research and education programs within the city of Philadelphia, since the meeting will be held here.  There is such a wealth of biomedical engineering efforts in Philly that provides great opportunities to engage in outreach and interaction with both the community and local industry during the meeting.”

New Faculty: Interview With Joel Boerckel

Boerckel
Joel Boerckel, Ph.D.

Continuing with our series of interviews with new faculty members, we feature this interview with Dr. Joel Boerckel, who has a dual appointment in the Department of Bioengineering at Penn and the Perelman School of Medicine’s Department of Orthopaedic Surgery.  Dr. Boerckel’s research concerns the mechanobiology of development and regeneration. Here, he speaks with Andrew Mathis about his career to this point and where he sees the fields of tissue engineering and regenerative medicine heading over the future. Enjoy!

Phillips-Cremins Research Identifies Protein Involved in Brain Development

Phillips-Cremins
Jennifer Phillips-Cremins, Ph.D.

The vast majority of genetic mutations that are associated with disease occur at sites in the genome that aren’t genes. These sequences of DNA don’t code for proteins themselves, but provide an additional layer of instructions that determine if and when particular genes are expressed. Researchers are only beginning to understand how the non-coding regions of the genome influence gene expression and might be disrupted in disease.

​​​​​​​​​​​​Jennifer Phillips-Cremins, assistant professor in the Department of Bioengineering in the University of Pennsylvania’s School of Engineering and Applied Science, studies the three-dimensional folding of the genome and the role it plays in brain development. When a stretch of DNA folds, it creates a higher-order structure called a looping interaction, or “loop.” In doing so, it brings non-coding sites into physical contact with their target genes, precisely regulating gene expression in space and time during development.

Phillips-Cremins and lab member Jonathan Beagan have led a new study identifying a new protein that connects loops in embryonic stem cells as they begin to differentiate into types of neurons. Though the study was conducted in mice, these findings inform aspects of human brain development, including how the genetic material folds in the 3-D nucleus and is reconfigured as stem cells become specialized. Better understanding of these mechanisms may be relevant to a wide range of neurodevelopmental disorders.

Cremins lab members Michael Duong, Katelyn Titus, Linda Zhou, Zhendong Cao, Jingjing Ma, Caroline Lachanski and Daniel Gillis also contributed to the study, which was published in the journal Genome Research.​​​​​​

Continue reading at the SEAS blog.

Burdick Recognized by NIH in Two Programs

Burdick
Jason Burdick, Ph.D.

Jason Burdick, Ph.D., professor in the Department of Bioengineering, was among the recent recipients of a grant from Sharing Partnership for Innovative Research in Translation (SPIRiT), a pilot grant program awarded by the Clinical and Translational Science Award (CTSA) division of the National Institutes of Health (NIH).

Dr. Burdick’s research, undertaken with Albert Sinusas, MD, of Yale, concerns the development of a noninvasive treatment to limit the damage to the heart caused by heart attacks, which are suffered annually by almost 750,000 Americans. Using single-photo emission computed tomography (SPECT), the technique identifies the damaged heart muscle on the basis of enzymes activated by damage, followed by the targeted administration of bioengineered hydrogels for the delivery of therapeutics

Dr. Burdick says, “This research has the potential to advance treatments for the many individuals with heart attacks who have few current options. Our approach uses injectable materials and advanced imaging techniques to address the changes in protease levels after heart attacks that can lead to tissue damage.”

In other news, Dr. Burdick was one of 12 researchers named by the NIH’s Center for Engineering Complex Tissues to lead collaborative projects aimed at generating complex tissues for several parts of the body.

Organ-on-a-Chip Earns Big CRI Grant for Huh Lab

CRI grant Huh
Dan Huh, Ph.D.

As we reported earlier, Dan Huh, Wilf Family Term Chair & Assistant Professor in the Department of Bioengineering, has been awarded a $1 million grant from the Cancer Research Institute (CRI), along with its first CRI Technology Impact Award.

Recently, the Penn Engineering Blog featured a story on Dr. Huh’s grant and the research it will support for the next three years. You can read the story at the SEAS blog.

Congratulations again to Dr. Huh!

New Faculty: Interview With Mike Mitchell

Mitchell
Mike Mitchell, Ph.D.

Here’s the promised interview with new faculty member Mike Mitchell, who starts as assistant professor of bioengineering at Penn in the Spring 2017 semester. Mike and editor Andrew E. Mathis discuss Mike’s background and education, where cancer research is now and where it’s heading, and just how big the radius is on the cheesesteak zone of impact around Philadelphia.

Enjoy!

Macrophages Engineered Against Cancer Cells

macrophages Discher
Dennis Discher, Ph.D.

Dennis E. Discher, Ph.D., Robert D. Bent Professor in the Department of Chemical and Biomolecular Engineering and a secondary faculty member in the Department of Bioengineering, was the lead author on a recent study that showed that engineered macrophages (a type of immune cell) could be injected into mice, circulate through their bodies, and invade solid tumors in the mice, engulfing human cancers cells in the tumors.

According to Cory Alvey, a graduate student in pharmacology who works in Professor Discher’s lab and the first author on the paper, said, “Combined with cancer-specific targeting antibodies, these engineered macrophages swarm into solid tumors and rapidly drive regression of human tumors without any measurable toxicity.”

Read more here.