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Closing the loop between engineering and medical science.

A Neurosurgeon and an Electrical Engineer Walk into a Lab

In Penn State’s newest and most advanced research building, a new program is taking shape that, if successful, will revolutionize the ways in which we interact with the human brain. Led by Srinivas Tadigadapa, an electrical engineer, and Steve Schiff, a neurosurgeon with a background in physics and control engineering, this ambitious project exemplifies the convergence of research fields that are typically separated by distinct disciplinary boundaries.

In 2013, the Obama White House laid out a grand challenge to “accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought.” Called the BRAIN Initiative, it is a 12-year plan to fund research into understanding the brain on multiple levels, using a variety of new and developing technologies. With these tools, it is hoped that the many diseases and malfunctions that afflict the brain can be controlled or eliminated. Schiff and Tadigadapa recently won one of Penn State’s two exploratory BRAIN awards.

A transdisciplinary team to solve a monumental problem

Steve Schiff has the soothing voice and gentle manner of someone who has spent a large part of his career dealing with children, and frequently, children of materials scientists, electrical and mechanical engineers, and nanotechnologists, who occupy the north wing of the building, with medical and biological researchers, who occupy the building’s west wing.

Schiff is director of the Penn State Center for Neural Engineering, a lab that takes up an entire floor of the Life Sciences wing of the Millennium Science Complex on Penn State’s University Park campus. A series of card-swipe controlled laboratories make up the 11,000-square-foot Center, with facilities for the construction of custom electronics, live animal imaging, surgery, and advanced computerized microscopy. His Center colleagues include medical doctors, engineers and biomedical engineers, and the graduate students they are training.

In the Materials wing of the building in a basement micro and nanoscale devices laboratory, Tadigadapa’s group is developing microelectromechanical systems (MEMS) that miniaturize device arrays for sensing and actuating, some of which the team hopes will one day be implanted into the human skull in order to explore the brain on a cell-by-cell basis.

Penn State’s Millennium Science Complex was built with the concept of integrating the expertise of materials scientists, electrical and mechanical engineers, and nanotechnologists, who occupy the north wing of the building, with medical and biological researchers, who occupy the building’s west wing.

“This building we are in reflects this interaction, because we are half materials science and half life sciences,” Schiff said. “We will literally build these technologies on one side and walk them up the stairs to our lab where we do experiments on neurons. We will use individual neurons that we will be recording from and stimulating to see how far we can push this technology. We are, to our knowledge, the only center at present that is in a position to manufacture these high density arrays for sensing and stimulation in a nanofabrication facility and then literally transition them to an operating room.”

The team also includes, as a consultant, John Wikswo of Vanderbilt University, who is one of the world’s leading experts on magnetic fields in neurons. “John provides some of the key physics expertise that no one else in the world has,” Schiff said.

In short, Schiff and Tadigadapa, with Wikswo’s help, propose to develop a technology capable of measuring the activity of individual cells of the brain and to stimulate those cells at room temperature with a MEMS device capable of being implanted above the inner table of the skull for long-term human use.

Why stimulate the brain?

For the past 70 to 80 years, scientists have been using electrodes on the surface of the brain to measure electrical currents, and, since the 1950s, to stimulate the brain. In recent times, an approach called deep brain stimulation (DBS) was developed as a means to treat the tremors associated with Parkinson’s disease. Now, DBS is being studied experimentally as a method to treat major depression, along with a variety of other ailments. In DBS, a pair of electrodes is implanted in the brain and a generator is surgically implanted in the patient’s chest wall. A pattern of electrical pulses is used to stimulate portions of the brain. The treatment seems to work for a proportion of patients with major depression, although the exact mechanism is still unknown. Another use of such sensing and stimulation is to run robotics for patients with disabilities. However, bleeding, stroke and infection are potential side effects.

“If I put electrodes into the brain, which I have done a great deal in my career, there is a measurable risk of hemorrhage and damage, and there is always a few percent risk of infection,” Schiff said. “If I’m studying a child for epilepsy, I need to take those things out by two weeks, definitely by three weeks, or I have to go in and free them from the scar that’s already formed.

“Imagine you are trying to run an artificial hand,” posited Schiff. “You want to pick up signals from the hand area of the cortex to give you the intention of the individual to move such a hand. We can only do that now by implanting arrays of electrodes into the hand area of the brain itself.”

Because the bone of the skull is a good insulator, electrical signals from neurons in the brain cannot easily pass through it into the outside world. So the skull has to be opened up to place electrodes on the surface or deeper into the brain. This can and often does damage brain tissue and can cause infection in the cerebral fluid, potentially leading to meningitis. Furthermore, electrodes tend to corrode or be scarred over within weeks to a few years, necessitating more surgery.