New method offers platform for brain treatment

June 11, 2010

The ability to diagnose and treat brain dysfunction without surgery may rely on a new method of non-invasive brain stimulation using pulsed ultrasound developed by a team of scientists, led by William “Jamie” Tyler, a neuroscientist at Arizona State University. The approach, published in the journal Neuron on June 9, shows that pulsed ultrasound not only stimulates action potentials in intact motor cortex in mice, but it also “elicits motor responses comparable to those only previously achieved with implanted electrodes and related techniques,” said Yusuf Tufail, the lead author from ASU’s School of Life Sciences.

Other techniques such as transcranial magnetic and deep brain stimulation, electroconvulsive shock therapy and transcranial direct current stimulation are used to treat a range of brain dysfunctions, including epilepsy, Parkinson’s disease, chronic pain, coma, dystonia, psychoses and depression. However, most of these approaches suffer from “critical weaknesses,” Tyler said, including requirements for surgery, low-spatial resolution or genetic manipulations. Optogenetics, for example, is one state-of-the-art technology that merges genes from plants and other organisms with the intact brains of animals to offer control of neural circuitry. Download Full Image

“Scientists have known for more than 80 years that ultrasound can influence nerve activity,” Tufail said. “Pioneers in this field transmitted ultrasound into neural tissues prior to stimulation with traditional electrodes that required invasive procedures. Those studies demonstrated that ultrasound pre-treatments could make nerves more or less excitable in response to electrical stimulation.

“In our study, however, we used ultrasound alone to directly stimulate action potentials and drive intact brain activity without doing any kind of surgery.”

“It is fascinating to witness these effects firsthand,” he added. Tufail is one of four doctoral students in ASU’s School of Life Sciences who worked with Tyler on the project. The team also included Alexei Matyushov, a physics undergraduate student in ASU’s Barrett Honors College working with Tyler, and Nathan Baldwin, a doctoral student in bioengineering, and Stephen Helms Tillery, an assistant professor, with ASU’s Ira A. Fulton Schools of Engineering.

"We knew from some of our previous work that ultrasound could directly stimulate action potentials in dishes containing slices of brain tissue,” Tyler said. “Moving to transmit ultrasound through the skin and skull to stimulate the intact brain inside a living animal posed a much greater challenge.”

Despite such challenges, the study shows how ultrasound can be used to stimulate brain circuits with millimeter spatial resolution.

“We’ve come a long way from the observations of Scribonius Largus, a Roman physician in the 1st century A.D. who placed electric torpedo fish on headache sufferers’ foreheads to ease their pain,” Tyler said. “Our method paves the way for using sound waves to study and manipulate brain function, as well as to diagnose and treat its dysfunction.”

In addition to advancing hope for noninvasive treatments of brain injury and disease, the groups’ experiments in deeper subcortical brain circuits also revealed that ultrasound may be useful for modifying cognitive abilities.

"We were surprised to find that ultrasound activated brain waves in the hippocampus known as sharp-wave ripples,” Tufail said. “These brain activity patterns are known to underlie certain behavioral states and the formation of memories.”

The scientists also found that ultrasound stimulated the production of brain-derived neurotrophic factor (BDNF) in the hippocampus – one of the most potent regulators of brain plasticity.

Tyler said the fact that ultrasound can be used to stimulate action potentials, meaningful brain wave activity patterns, and BDNF leads him to believe that, in the future, ultrasound will be useful for enhancing cognitive performance; perhaps even in the treatment of cognitive disabilities such as mental retardation or Alzheimer's disease.

Tyler’s students also have collected data that suggests that repeated exposure to low-intensity ultrasound does not pose a health risk to rodents.

"We examined many aspects of brain health following stimulation and found that low-intensity ultrasound is safe for repeatedly stimulating the brains of mice," said Anna Yoshihiro, a neuroscience doctoral student in ASU’s College of Liberal Arts and Sciences and co-author of the journal article. Yoshihiro works to treat Parkinsonian monkeys and has achieved some early success in treating epileptic seizures in mice using ultrasonic neuromodulation.

Monica Li Tauchmann, Yoshihiro’s contemporary and co-author on the article, recalls the first time the method worked: "I was helping with experiments. We were trying to stimulate the brain of a living mouse with ultrasound. Not a whole lot was happening at first. Then, Dr. Tyler changed some of the ultrasound waveform parameters and the mouse started moving. We spent the rest of that day repeating the stimulation and the mouse was perfectly fine. It recovered from anesthesia as if nothing had happened. I think we were all astonished."

Tyler believes that there are a host of potential applications for ultrasound in brain manipulation. Besides basic science and medical uses, ultrasound represents a core platform around which future brain-machine interfaces can also be designed for gaming, entertainment and communication purposes because of its noninvasive nature.

“Space travel, hand-held computers, the Internet, and global positioning – not even a lifetime ago these things were mere science fiction. Today, they are commonplace,” Tyler said. “Maybe the next generation of social entertainment networks will involve downloading customized information or experiences from personalized computer clouds while encoding them into the brain using ultrasound. I see no reason to rule out that possibility.”

"To be honest,” he adds, “we simply don’t know yet how far we can push the envelope. That is why many refer to the brain as the last frontier – we still have a lot to learn."

Margaret Coulombe, margaret.coulombe">">
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School of Life Sciences

Johnson named dean of Fulton Schools of Engineering

June 13, 2010

Paul Johnson, executive dean of the Ira A. Fulton Schools of Engineering and professor in the School of Sustainable Engineering and the Built Environment, has been named dean of the Fulton Engineering Schools, effective Jan. 1, 2011. Johnson has been a faculty member at ASU since 1994 and has previously served as the university’s associate vice president for research and as interim dean of Fulton.

He succeeds Dean Deirdre Meldrum, who has been promoted to senior scientist for ASU, also effective Jan. 1, 2011. In this new capacity Meldrum will report to ASU President Michael M. Crow and Elizabeth D. Capaldi, provost and executive vice president, providing leadership on the scientific direction for the university as well as spearheading major national science and engineering initiatives. Download Full Image

“Paul Johnson has been an outstanding senior administrator at ASU, both in engineering and the office of research,” Crow said. “He is ideally positioned to advance the transformation of the Fulton Schools of Engineering from a traditional school of engineering to a new model of education and research that is taking on the national grand challenges facing our world.”

“Paul has received strong and enthusiastic support among the engineering faculty to take over the leadership of the Fulton Schools of Engineering,” Capaldi said. “He has gained the confidence of all by his ability to take the decisive action necessary to build quality and move engineering forward while listening well and incorporating thoughts of others.  He is a highly effective leader who embodies the academic and personal excellence that he inspires in others and is the ideal person to lead engineering.”

“I'm honored to be offered this position and excited by the challenges and opportunities that lie ahead,” Johnson said. “This is a critical time in the evolution of our schools of engineering. Decisions and investments made in the next few years will likely define our trajectory for decades. Dean Meldrum has bravely started us down this new grand challenge-focused path and attracted national attention to the revolutionary transformation of our schools. We will continue on that path to design and build unique schools of engineering distinguished by a commitment to attract and prepare the next generation of engineers, and by the impact of our research and the quality of our faculty, staff and students.”

Johnson received a bachelor's degree in chemical engineering from the University of California-Davis in 1983, and a master's degree and doctorate in chemical engineering from Princeton University in 1984 and 1987, respectively.

He came to ASU as an associate professor in 1994, rising to the rank of full professor in 2003. He later served as associate dean of research at Fulton, university associate vice president of research, and executive dean of Fulton, a position he has held since 2006. His teaching, research and professional activities focus on the application of contaminant fate and transport fundamentals to subsurface remediation and risk assessment problems. He is an expert in soil and groundwater remediation and risk assessment.

Johnson serves as the editor-in-chief for the National Ground Water Association's journal Ground Water Monitoring and Remediation, and on the National Research Council Committee for Future Options for Management in the Nation’s Subsurface Remediation Effort. He is a consultant to industry and federal and state agencies. Before joining ASU, he was a senior research engineer at the Shell Oil Westhollow Technology Center.

The Ira A. Fulton Schools of Engineering at Arizona State University serve more than 4,000 undergraduates and 2,000 graduate students, providing skills and knowledge for shaping careers marked by innovation and societal impact. Ranked nationally in the top 10 percent among accredited engineering programs, the schools engage in use-inspired research in a multidisciplinary setting for the benefit of individuals, society and the environment.

The schools’ 200-plus faculty members teach and pursue research in areas of electrical, chemical, mechanical, aerospace, civil, environmental and sustainable engineering, as well as bioengineering, computer science and engineering, informatics, decision systems and construction management. The schools of engineering also work in partnership with the School of Arts, Media and Engineering and the School of Earth and Space Exploration, and faculty work collaboratively with the Biodesign Institute at ASU, the School of Sustainability and the Global Institute of Sustainability.

Sharon Keeler