The umbrella of brain restoration research extends beyond cellular approaches, like the research efforts driven by H. Isaac Chen, MD, an assistant professor of Neurosurgery at the Perelman School of Medicine, as seen in the first part of this science-fiction inspired series. Experts are also utilizing advanced computer and imaging technology to push the boundaries of neuroscience care.
Melding Brain, Computer, and Behavior
Progress has been made in recent years on brain-machine interfaces (BMI) — technology that provides a direct communication link between a brain and an external device. Elon Musk, for one, has been making headlines in the BMI world for Neuralink. At Penn, Timothy H. Lucas, MD, PhD, an associate professor of Neurosurgery at the Perelman School of Medicine and co-director of the Translational Neuromodulation Lab, helped create Penn's first BMI device.
Illustration of a fully integrated brain computer interface system. Source: Neurosurgery
Lucas’ research focuses on developing implantable devices that can restore function to patients with paralysis after brain injury or disease. Think of Christopher Reeve and Stephen Hawking — their brains stopped talking to their bodies. Lucas and his lab are trying to restore that normal communication pathway using implantable computers.
“When you have a telephone call, two people have equal measure, it’s two-way communication — the same is true for moving an arm or leg. Motor signals from the brain move to the leg to make it contract, or sensory signals from your fingertips when holding a pen send a signal to the brain on how much pressure to apply and when. That second connection is called sensory, and the devices we’re working on tackle that side of the equation,” Lucas explained.
Most of Lucas’ current work is trying to provide that sensory reanimation to the hand, bypassing damaged neural connections. He and his team developed a suite of implants that go in the fingers. The implants communicate with a device one wears like a smartwatch, which sends information to a brain implant.
“There’s really only a handful of groups that are looking at the sensory side of this equation, and we’re far along in the pathway,” Lucas said. “We anticipate to be in human clinical trials in the next few years.”
Lucas isn’t the only Penn scientist melding technology with the brain. Brian Litt, MD, a professor of Neurology, Neurosurgery, and Bioengineering, is working towards developing implanted machines that are responsive to what is happening in the brain. He recently won a Pioneer Award from the NIH for this work to develop a new generation of autonomous neurodevices that can question us, record, and combine learning algorithms based on neurological signals and feedback to act and alter human behavior on the fly.
In epilepsy, for example, these devices could predict and prevent seizures. Or an implant might improve psychiatric symptoms by querying patient perceptions and altering stimulation patterns algorithmically to improve them. This new research builds upon Litt’s background in neurology, engineering, neuroscience, and his track record of building new medical devices to treat neurological diseases.
“Our behavior is what affects our health most, but we don’t get any feedback on how our actions impact us, because there currently isn’t a way for implantables to communicate freely with us. We are working to solve that problem,” Litt said. This represents a paradigm shift from current devices, which gather data over time and then give feedback to physicians, who convey it to patients often months after important health-changing events. Unfortunately, this time scale is usually too long for patients to act or even remember what they might have done to impact their well-being, Litt said.
Litt sees this technology being applicable to all types of devices, not just for the brain — insulin pumps for diabetes, defibrillators for heart disease, or devices for blood pressure. His aim is to build a generation of responsive implants that can collaborate with their human hosts in real-time, linking a patient’s feelings, experience and perception to machine algorithms and specific therapy, even predicting and preventing events like seizures before they start.
“Suppose your doctor just gave you a new antibiotic, and you took it, but it actually increased your risk of seizures. The device could recognize that from your brainwaves, and ask ‘What just happened? Your risk of seizure just went up,” Litt explained. “You could then text the device that you took a new antibiotic. Then the device might respond with a recommendation to take a rescue medication, or warn you in an hour if it gets worse.” This interaction would not only prevent you from having a seizure, but warn you so you won’t make the same mistake in the future.
Visualizing What Can’t Be Seen
Kathryn A. Davis, MD, medical director of the Epilepsy Monitoring Unit and an assistant professor of Neurology, is leading an effort to advance imaging in order to detect hard-to-find parts of the brain responsible for epilepsy seizures.
More than 3 million people in the United States have epilepsy, and about 1 million of those cases are drug resistant, meaning medication is failing to keep them seizure free. This can have a huge impact on someone’s life, dictating if or how they work and in what environment, or whether they can drive.
Advanced imaging shows abnormalities in white matter tracts of patient with a rare genetic form of epilepsy (top) compared to healthy control (bottom). Source: Epilepsia Open
This population is the one Davis most wants to help. “Of these patients, many — about half — don’t have identifiable abnormalities on their brain imaging, and we’ve been working on developing advanced imaging approaches to find these hidden lesions noninvasively,” Davis said.
If epilepsy is drug resistant, it’s important to be seen by an epilepsy specialist at a comprehensive epilepsy center, like the one at Penn, to evaluate why, and if there are better treatment options. Key to this evaluation is advanced imaging, since identifying the region in the brain where the seizure is coming from can dictate the right treatment option.
Some of the patients with “hidden” seizure locations that can’t be seen via traditional neuroimaging often require invasive neurosurgery to determine their best care options. This involves the placement of electrodes in the brain to record seizure activity prior to deciding if they are a good candidate for a surgical or device treatment. In pioneering new approaches to find hidden hotspots with noninvasive neuroimaging, Davis and her team aim to find the best treatment for patients, whether that be seizure control devices, resective surgery, or continued medical management, without invasive testing.
Davis and her colleagues developed a technique called GluCEST, which provides the ability to see seizures that other scans have missed by looking at levels of glutamate, the most common excitatory neurotransmitter in the brain. Davis has also shown that network-based analyses of imaging techniques looking at blood flow in the brain and the structural connections within the brain uncover seizure onset regions. These new imaging approaches will open doors for many patients who were previously not considered candidates for additional treatments — making it possible to find the hotspots in their brains causing seizures once and for all.
Stimulating the Brain for Sight
“The next frontier of neurosurgery is all about technology,” said Daniel Yoshor, MD, chair of Neurosurgery. “In the future, neurosurgery will increasingly use technology to actually interface with the brain in order to restore function.”
Yoshor’s lab taps exactly into that future-forward philosophy. His lab is working to understand how visual information is processed in the human brain. Specifically, Yoshor is working on developing new methods and technologies for inputting information directly into the brain.
In most patients with acquired blindness, the problem is caused by damage to their eyes or optic nerve, rather than the part of the brain that supports vision. Yoshor’s strategy is to bypass the eyes and instead, direct information straight to the brain. Yoshor recently made a big step toward this goal by way of a brain implant which allowed test subjects to visualize the shape of letters in order to identify them.
“What’s happening in the neurosciences today is extraordinary — there’s been tremendous advances in the past few years and there’s an avalanche of innovation ahead,” Yoshor said. “Our efforts are ambitious, but with the ongoing developments in neuroscience, engineering, and computer technology, it is no longer science fiction.”