Tag Archives: treatment

Electrical and computer engineering Professor Barry Van Veen wears an electrode net used to monitor brain activity via EEG signals. His research could help untangle what happens in the brain during sleep and dreaming.

Photo Credit: Nick Berard/UW-Madison

Stanford scientists seek to map origins of mental illness and develop noninvasive treatment

An interdisciplinary team of scientists has convened to map the origins of mental illnesses in the brain and develop noninvasive technologies to treat the conditions. The collaboration could lead to improved treatments for depression, anxiety and post-traumatic stress disorder.

BY AMY ADAMS


Over the years imaging technologies have revealed a lot about what’s happening in our brains, including which parts are active in people with conditions like depression, anxiety or post-traumatic stress disorder. But here’s the secret Amit Etkin wants the world to know about those tantalizing images: they show the result of a brain state, not what caused it.

This is important because until we know how groups of neurons, called circuits, are causing these conditions – not just which are active later – scientists will never be able to treat them in a targeted way.

“You see things activated in brain images but you can’t tell just by watching what is cause and what is effect,” said Amit Etkin, an assistant professor of psychiatry and behavioral sciences. Etkin is co-leader of a new interdisciplinary initiative to understand what brain circuits underlie mental health conditions and then direct noninvasive treatments to those locations.

“Right now, if a patient with a mental illness goes to see their doctor they would likely be given a medication that goes all over the brain and body,” Etkin said. “While medications can work well, they do so for only a portion of people and often only partially.” Medications don’t specifically act on the brain circuits critically affected in that illness or individual.

The Big Idea: treat roots of mental illness

The new initiative, called NeuroCircuit, has the goal of finding the brain circuits that are responsible for mental health conditions and then developing ways of remotely stimulating those circuits and, the team hopes, potentially treating those conditions.

The initiative is part of the Stanford Neurosciences Institute‘s Big Ideas, which bring together teams of researchers from across disciplines to solve major problems in neuroscience and society. Stephen Baccus, an associate professor of neurobiology who co-leads the initiative with Etkin, said that what makes NeuroCircuit a big idea is the merging of teams trying to map circuits responsible for mental health conditions and teams developing new technologies to remotely access those circuits.

“Many psychiatric disorders, especially disorders of mood, probably involve malfunction within specific brain circuits that regulate emotion and motivation, yet our current pharmaceutical treatments affect circuits all over the brain,” said William Newsome, director of the Stanford Neurosciences Institute. “The ultimate goal of NeuroCircuit is more precise treatments, with minimal side effects, for specific psychiatric disorders.”

“The connection between the people who develop the technology and carry out research with the clinical goal, that’s what’s really come out of the Big Ideas,” Baccus said.

Brain control

Etkin has been working with a technology called transcranial magnetic stimulation, or TMS, to map and remotely stimulate parts of the brain. The device, which looks like a pair of doughnuts on a stick, generates a strong magnetic current that stimulates circuits near the surface of the brain.

TMS is currently used as a way of treating depression and anxiety, but Etkin said the brain regions being targeted are the ones available to TMS, not necessarily the ones most likely to treat a person’s condition. They are also not personalized for the individual.

Pairing TMS with another technology that shows which brain regions are active, Etkin and his team can stimulate one part of the brain with TMS and look for a reaction elsewhere. These studies can eventually help map the relationships between brain circuits and identify the circuits that underlie mental health conditions.

In parallel, the team is working to improve TMS to make it more useful as a therapy. TMS currently only reaches the surface of the brain and is not very focused. The goal is to improve the technology so that it can reach structures deeper in the brain in a more targeted way. “Right now they are hitting the only accessible target,” he said. “The parts we really want to hit for depression, anxiety or PTSD are likely deeper in the brain.”

Technology of the future

In parallel with the TMS work, Baccus and a team of engineers, radiologists and physiologists have been developing a way of using ultrasound to stimulate the brain. Ultrasound is widely used to image the body, most famously for producing images of developing babies in the womb. But in recent years scientists have learned that at the right frequency and focus, ultrasound can also stimulate nerves to fire.

In his lab, Baccus has been using ultrasound to stimulate nerve cells of the retina – the light-sensing structure at the back of the eye – as part of an effort to develop a prosthetic retina. He is also teaming up with colleagues to understand how ultrasound might be triggering that stimulation. It appears to compress the nerve cells in a way that could lead to activation, but the connection is far from clear.

Other members of the team are modifying existing ultrasound technology to direct it deep within the brain at a frequency that can stimulate nerves without harming them. If the team is successful, ultrasound could be a more targeted and focused tool than TMS for remotely stimulating circuits that underlie mental health conditions.

The group has been working together for about five years, and in 2012 got funding from Bio-X NeuroVentures, which eventually gave rise to the Stanford Neurosciences Institute, to pursue this technology. Baccus said that before merging with Etkin’s team they had been focusing on the technology without specific brain diseases in mind. “This merger really gives a target and a focus to the technology,” he said.

Etkin and Baccus said that if they are successful, they hope to have both a better understanding of how the brain functions and new tools for treating disabling mental health conditions.

Source: Stanford News

Engineering new bone growth

Coated tissue scaffolds help the body grow new bone to repair injuries or congenital defects.

By Anne Trafton


 

CAMBRIDGE, MA — MIT chemical engineers have devised a new implantable tissue scaffold coated with bone growth factors that are released slowly over a few weeks. When applied to bone injuries or defects, this coated scaffold induces the body to rapidly form new bone that looks and behaves just like the original tissue.

This type of coated scaffold could offer a dramatic improvement over the current standard for treating bone injuries, which involves transplanting bone from another part of the patient’s body — a painful process that does not always supply enough bone. Patients with severe bone injuries, such as soldiers wounded in battle; people who suffer from congenital bone defects, such as craniomaxillofacial disorders; and patients in need of bone augmentation prior to insertion of dental implants could benefit from the new tissue scaffold, the researchers say.

“It’s been a truly challenging medical problem, and we have tried to provide one way to address that problem,” says Nisarg Shah, a recent PhD recipient and lead author of the paper, which appears in the Proceedings of the National Academy of Sciences this week.

Paula Hammond, the David H. Koch Professor in Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Department of Chemical Engineering, is the paper’s senior author. Other authors are postdocs M. Nasim Hyder and Mohiuddin Quadir, graduate student Noémie-Manuelle Dorval Courchesne, Howard Seeherman of Restituo, Myron Nevins of the Harvard School of Dental Medicine, and Myron Spector of Brigham and Women’s Hospital.

Stimulating bone growth

Two of the most important bone growth factors are platelet-derived growth factor (PDGF) and bone morphogenetic protein 2 (BMP-2). As part of the natural wound-healing cascade, PDGF is one of the first factors released immediately following a bone injury, such as a fracture. After PDGF appears, other factors, including BMP-2, help to create the right environment for bone regeneration by recruiting cells that can produce bone and forming a supportive structure, including blood vessels.

Efforts to treat bone injury with these growth factors have been hindered by the inability to effectively deliver them in a controlled manner. When very large quantities of growth factors are delivered too quickly, they are rapidly cleared from the treatment site — so they have reduced impact on tissue repair, and can also induce unwanted side effects.

“You want the growth factor to be released very slowly and with nanogram or microgram quantities, not milligram quantities,” Hammond says. “You want to recruit these native adult stem cells we have in our bone marrow to go to the site of injury and then generate bone around the scaffold, and you want to generate a vascular system to go with it.”

This process takes time, so ideally the growth factors would be released slowly over several days or weeks. To achieve this, the MIT team created a very thin, porous scaffold sheet coated with layers of PDGF and BMP. Using a technique called layer-by-layer assembly, they first coated the sheet with about 40 layers of BMP-2; on top of that are another 40 layers of PDGF. This allowed PDGF to be released more quickly, along with a more sustained BMP-2 release, mimicking aspects of natural healing.

The scaffold sheet is about 0.1 millimeter thick; once the growth-factor coatings are applied, scaffolds can be cut from the sheet on demand, and in the appropriate size for implantation into a bone injury or defect.

Effective repair

The researchers tested the scaffold in rats with a skull defect large enough — 8 millimeters in diameter — that it could not heal on its own. After the scaffold was implanted, growth factors were released at different rates. PDGF, released during the first few days after implantation, helped initiate the wound-healing cascade and mobilize different precursor cells to the site of the wound. These cells are responsible for forming new tissue, including blood vessels, supportive vascular structures, and bone.

BMP, released more slowly, then induced some of these immature cells to become osteoblasts, which produce bone. When both growth factors were used together, these cells generated a layer of bone, as soon as two weeks after surgery, that was indistinguishable from natural bone in its appearance and mechanical properties, the researchers say.

“Using this combination allows us to not only have accelerated proliferation first, but also facilitates laying down some vascular tissue, which provides a route for both the stem cells and the precursor osteoblasts and other players to get in and do their jobs. You end up with a very uniform healed system,” Hammond says.

Another advantage of this approach is that the scaffold is biodegradable and breaks down inside the body within a few weeks. The scaffold material, a polymer called PLGA, is widely used in medical treatment and can be tuned to disintegrate at a specific rate so the researchers can design it to last only as long as needed.

Hammond’s team has filed a patent based on this work and now aims to begin testing the system in larger animals in hopes of eventually moving it into clinical trials.

This study was funded by the National Institutes of Health.

Source: MIT News Office