The sheer complexity of the human brain means that, despite the tremendous advances made in neuroscience, there is still much we don’t know about what goes on inside our heads and how it goes awry in mental disorders. Even with the most advanced techniques, much of what we’ve learned about the brain is descriptive — telling that something is different between health and unhealthy function — but not why that something is different or how we could change it.
Rat microglia and neurons stained for different proteins
Among the approaches that have provided important insights into these questions is network science, which seeks to understand the brain as a complex system of multiple interacting components. Now, in a review published recently in Neuron, Danielle Bassett, Ph.D., Eduardo D. Glandt Faculty Fellow and Associate Professor of Bioengineering, and Richard Betzel, Ph.D., a postdoc in Dr. Bassett’s lab, have collaborated with scientists from the University of Heidelberg in Germany. The review covers a broad range of discoveries and innovations, moving from earlier, two-dimensional approaches to understanding the brain, such as graph theory, to newer approaches including multilayer networks, generative network models, and network control theory.
“Stating what is different in brain networks of individuals with disorders of mental health is not the same as identifying why” says Bassett. “Here we propose that emerging tools from network science can be used to identify true mechanisms of mental health disorders, and bridge molecular and genetic mechanisms through brain physiology, thus informing interventions in the form of pharmacological manipulations and brain stimulation.”
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.
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.
A “wiring diagram of the human brain,” produced using diffusion MRI scans of the brain.
A group of four scholars from the University of Pennsylvania, including Bioengineering professor Danielle Bassett, have issued a call in the journal Nature Human Behaviour for greater safeguards for patients as treatments in the field of neuroscience evolve and come ever closer to resembling “mind control.”
“While we don’t believe,” Bassett said, “that the science-fiction idea of mind control, totally overriding a person’s autonomy, will ever be possible, new brain-focused therapies are becoming more specific, targeted and effective at manipulating individuals’ mental states. As these techniques and technologies mature, we need systems in place to make sure they are applied such that they maximize beneficial effects and minimize unwanted side effects.”
Danielle Bassett, Eduardo D. Glandt Faculty Fellow and Associate Professor in the departments of Bioengineering and Electrical and Systems Engineering, recently collaborated with colleagues from the Perelman School of Medicine on a study that looks at how brain networks change as children develop into adolescence. Bassett’s previous work on applying network science principles to neuroscience has suggested that the organization of these networks helps lead to “cognitive control” and that they reorganize as children age, improving executive function.
In a new paper published in Current Biology, Bassett and her colleagues delve deeper into the network changes that lead to this improvement.
“The work,” Bassett says, “significantly extends our understanding of the role of modular network organization in development, and its importance for executive function.”
Do not stop to think about the reasons for what you are doing, about why you are questioning. The important thing is not to stop questioning. Curiosity has its own reasons for existence. One cannot help but be in awe when he contemplates the mysteries of eternity, of life, of the marvelous structure of reality. It is enough if one tries merely to comprehend a little of this mystery each day. Never lose a holy curiosity.
–Albert Einstein1
This haunting passage prompts a series of difficult questions. Should we ever worry about where our curiosity goes? Is it true that curiosity is an end in itself? Or, are its justifications so obvious to us as to go unquestioned? Have we lost our sense of mystery? What makes curiosity holy? Einstein himself did not study curiosity, nor could he revolutionize the field of curiosity studies, which is just coming into its own today. But he does capture the compulsion of curiosity and its tantalizing promise.
Kushal Sacheti, Founder and Director of the Center for Curiosity
The Center for Curiosity was established in New York in 2014 by Kushal Sacheti, a diamond merchant who was formerly an engineer. Its mission is to advance both the academic study of curiosity and the public practice of curiosity. A year after its founding, the first of its satellite centers was established at the University of Pennsylvania, in the School for Social Policy and Practice, under the leadership of Dean John Jackson, Jr. It is here that Mr. Sacheti’s dream of uniting engineering and curiosity came alive.
Given her work on the network neuroscience of human learning, Dr. Danielle Bassett, Associate Professor of Bioengineering, was one of the first faculty spotlighted in Penn’s Center for Curiosity seminar series. Her talk, “Flexible Brain Network Dynamics During Learning,” so perfectly represented the Center’s mission that she was quickly appointed to its advisory board. Shortly thereafter, Dr. Bassett invited the Center’s two postdoctoral fellows, Dr. Arjun Shankar and Dr. Perry Zurn, to lead curiosity workshops at the 2016 Penn Network Visualization program. This program provides young artists the opportunity to understand and creatively reimagine network science. Dr. Zurn’s seminar on structural models of curiosity, coupled with Dr. Shankar’s workshop on the affective elements of curiosity, inspired program fellows to explore curiosity not only in network science, but also in their own artistic praxis.
Dr. Arjun Shankar, Center for Curiosity, Postdoctoral FellowDr. Perry Zurn, Center for Curiosity, Postdoctoral FellowDr. Danielle Bassett (left) and Dr. Susan Engel (right) at the Curiosity Across the Disciplines Symposium, December 9, 2016
Behind Dr. Bassett’s Network Visualization program is a passion for thinking between the arts and sciences and a conviction that they are richer enterprises together. An even broader commitment to interdisciplinarity energizes Penn’s Center for Curiosity. Last December, Drs. Zurn and Shankar organized the Curiosity Across the Disciplines symposium. This day-long event explored the concept of curiosity across major academic disciplines (history, medicine, ecology, neuroscience, psychology, education, anthropology, comparative literature, ethnic studies, political philosophy, and film). As presenters (including Dr. Bassett) reflected on their fields’ contributions to curiosity studies, as well as the role of curiosity in their own scholarship, a deeper, shared conversation emerged about how curiosity can help us to collectively navigate the scientific, educational, and political challenges of our times.
The collaboration between Penn’s Center for Curiosity and the Department of Bioengineering has really only begun. This fall, Drs. Zurn and Bassett are co-organizing a symposium on The Network Neuroscience of Curiosity. Speakers will include Dr. Danielle Bassett, Dr. David Danks (Carnegie Mellon University), Dr. Jacqueline Gottlieb (Columbia University), and Dr. Celeste Kidd (University of Rochester). And, as a long-term project, they have started a conversation about reinvigorating the Bioengineering curriculum with an emphasis on student curiosity and creativity. Sharing Penn’s commitment to community outreach, moreover, the Center for Curiosity and Department of Bioengineering are also in conversation with Westtown School about building an art- and science-centered curiosity initiative there.
If indeed one cannot help but be curious about life and its mysterious design, that journey is perhaps best undertaken together—Einstein’s fabled solipsism notwithstanding. This exciting new partnership at Penn is yet another step in that direction.
1 Albert Einstein, Statement to William Miller, as quoted in LIFE magazine (2 May 1955); reprinted in Joseph S. Willis, Finding Faith in the Face of Doubt: A Guide for Contemporary Seekers (Quest Books, 2001), 58; and William Hermanns, Einstein and the Poet: In Search of the Cosmic Man (1983; Brandon Books, 2013), 138.
Faculty members in the Department of Bioengineering at the University of Pennsylvania are among the recipients of a major $9.25 million grant from the Paul G. Allen Family Foundation to study the mechanism underlying concussion and to investigate possible interventions.
David Meaney, PhD, Solomon R. Pollack Professor and Chair of the Bioengineering Department (above left), is one of two principal investigators, with Douglas H. Smith, MD, professor of neurosurgery at Penn’s Perelman School of Medicine (above right). In addition, Danielle S. Bassett, PhD, Eduardo D. Glandt Faculty Fellow and Associate Professor (below left), Dongeun (Dan) Huh, PhD, Wilf Family Term Assistant Professor (below center), and David Issadore, PhD, assistant professor (below right), all of BE Department, are co-investigators. The Allen Foundation grant also involves investigators from Columbia University (Barclay Morrison, Ph.D.), Duke University (Cameron Bass, Ph.D.), and Children’s Hospital of Philadelphia (Akiva Cohen, Ph.D.).
Selected from a large national pool of applicants, the Allen Foundation grant will bring together new technology platforms developed by Drs. Huh and Issadore to study how concussions occur at the microtissue scale and release markers of rewiring during recovery. Network theory models from Dr. Bassett’s group will provide an entirely new view on how concussion recovery occurs at all scales in the brain. The overall impact of the project will be to move away from the widely held perspective that all concussions should be treated identically and towards a view that concussions can follow several recovery pathways, some of which must be monitored closely in the days to weeks following injury.
When someone talks about using “your network” to find a job or answer a question, most people understand that to mean the interconnected web of your friends, family, and acquaintances. But we all have another key network that shapes our life in powerful ways: our brains.
In the brain, impulses whiz from one brain region to another, helping you formulate all of your thoughts and decisions. As science continues to unlock the complexities of the brain, a group of researchers has found evidence that brain networks and social networks actually influence and inform one another.
It found that people who show greater changes in connectivity in their mentalizing system during social exclusion compared to inclusion tend to have a less tightly knit social network — that is, their friends tend not to be friends with one another. By contrast, people with more close-knit social networks, in which many people in the network tend to know one another, showed less change in connectivity in their mentalizing regions.
In high school, Rebecca Kellner (right) always had a dual love of art and science. When she entered the University of Pennsylvania as a freshman, she thought that her interest in art would always be separate from her pursuit of science. “I’ve always loved art and science and I wondered how I would integrate my passions into one area of study,” Rebecca says. “Then I heard about the Network Visualization Program run by Dr. Danielle Bassett . In this program, the intersection of art and science is celebrated, and this intersection is a place where I feel right at home.”
The Penn Network Visualization Program, begun in 2014, had long been a dream of Dr. Bassett. She wanted a forum where young artists and research scientists could interact with each other. “Science and art are often perceived to be at odds with each other, two fundamentally different ways of understanding the world. As a scientist, I’ve learned that the visual impact of the information I present is crucially important. Networks are visually intuitive,” says Bassett, “and represent an opportunity to foster a common language between scientists and artists.”
In this six-week summer program, young artists spend time with scientists at Penn who are performing cutting-edge research in network science as applied to social systems, human biology, and physical materials, with the underlying goal of advancing bioengineering. Faculty from the Warren Center for Network and Data Science who have volunteered their time and creativity to the project include Eleni Katifori, Erol Akcay, and Randy Kamien of the School of Arts and Sciences; Robert Ghrist and Victor Preciado of the School of Engineering and Applied Sciences; Sandra Gonzalez-Bailon of the Annenberg School of Communications; and Francis Diebold of the Wharton School of Business. During the course of the internship, the artists produce works of art interpreting and capturing the intricacies of these networks in novel ways. Artistic supervision and project advice are provided by local artists affiliated with the program. The goal of the internship is to provide scientists with new conceptualizations of their research and to provide the intern with new knowledge in scientific art applications.
Rebecca was thrilled when she was accepted into the program. During her internship she worked with a variety of scientists. Her final artwork focused on the research of Dr. Ann Hermundstad (Janelia), the postdoctoral researcher in the Physics of Living Matter Group, University of Pennsylvania Department of Physics and Astronomy. Dr. Hermundstad’s research focuses on what and how the brain sees. Fascinated by these networks, Rebecca created a painting and a laser-etched acrylic book.
Nicholas Hanchak
The program also invites six high school students who have exhibited creativity and academic achievement. Nicholas Hanchak (right) from Westtown School participated during the summer of 2016. “I love art, science and baseball and I am thinking about architecture as a possible career,” Nicholas says. “The Penn program challenged me to find new ways to combine these interests.” For his final project, Nicholas created a Plinko Game Board showing the difference between the networks in a healthy brain and in a brain damaged by stroke.
“Artists and scientists are kindred spirits because they both are interested in observing what is in front of them,” says Dr. Bassett. “The Network Visualization program offers an opportunity for scientists and artists to inform each other in very tangible ways.”
The program runs every other summer. During the fall, several of the artists’ pieces are showcased in Philadelphia-area middle and high schools, particularly in disadvantaged areas. These efforts are enabled by ongoing collaborations with the Netter Center for Community Partnerships and Penn’s Center for Curiosity, and they are partially funded by the National Science Foundation. Bassett hopes this outreach effort will encourage children to explore intersections between the arts and sciences, while instilling a growing appreciation of their networked world.
