The development of a technique to precisely control the activity of neurons nestled deep in the brain and usher in the next-generation of noninvasive brain stimulation earned Shuo Chen the 2019 Science & PINS Prize for Neuromodulation.
"Noninvasive, remote manipulation of deep brain activity stands at the frontier of neuroscience, and has great potential to be used in medical applications," said Chen, who expanded on his findings in his grand prize-winning essay, "Optical modulation goes deep in the brain." "Such technologies are urgently needed, considering that one-third of people have reported mental disorders at some time in their life."
In the next 10 years alone, the number of patients affected by a neurological disorder is expected to reach 1.1 billion worldwide, yet safe and effective treatments for such diseases are lacking. Deep brain stimulation (DBS) has proved to be one of the most effective therapies to date for conditions like Parkinson's disease and obsessive-compulsive disorder.
However, DBS requires implantation of electrodes in hard-to-reach areas of the brain to electrically stimulate the neurons thought to be involved in the underlying illness. In addition to the procedure involving surgical and follow-up costs that can reach up to $35,000, the electrical stimulation can fail to reach the intended neuron targets, and implantation is risky — potentially leading to complications like brain bleeding or infection.
In search of a more precise and minimally invasive way to conduct DBS, Chen, currently a postdoctoral fellow at the University of California, Berkeley, turned to optogenetics — the use of light to control neurons — rather than electrode stimulation of neurons. To accomplish this, he shifted the existing optogenetic technology into the near-infrared (NIR) wavelength, which is recognized for its tissue-penetrating capability, in contrast to highly scattered and absorbed blue-green wavelengths.
He used nano-sized "light bulbs" called upconversion nanoparticles as a way to convert invisible NIR light into visible blue-green light to activate nearby neurons. "Our approach transforms the tissue-penetrating NIR signal by a local convertor to a different signal — the visible light — capable of triggering ion channels for the modulation of neuronal activity," said Chen.
In his essay published in the August 2 issue of Science, Chen demonstrated the potential of this method by stimulating various deep structures in the mouse brain by NIR delivered from outside of the skull. He successfully triggered neurons residing in an area of the brain suspected to be linked to major depression to release dopamine.
While the technique pioneered by Chen holds promise, two key challenges need to be addressed, he noted. "The first is improving the development of biocompatible energy converters and noninvasive gene delivery technologies. The second is further optimizing the efficacy of neuron stimulation. When combined, truly noninvasive high-precision deep brain stimulation without surgical intervention may be realized," said Chen.
"Shuo Chen researches minimally invasive methods for deep brain stimulation to treat neurological disorders including Parkinson's disease. Chen used tissue-penetrating near-infrared light to stimulate nanoparticles implanted deep within a mouse brain. The nanoparticles emitted visible light, which activated targeted ion channels in neurons," said Science Translational Medicine editors Caitlin Czajka and Mattia Maroso. "The PINS Prize for Neuromodulation encourages such innovative research to drive translational developments that help patients."
"It is too soon to predict which technique will emerge at the forefront of next-generation noninvasive brain stimulation technology. However, we believe that achievements such as NIR upconversion optogenetics are rapidly unlocking numerous development routes and paving the way toward a bright therapeutic future," said Chen.
Established in 2016, the Science & PINS Prize for Neuromodulation is a highly competitive prize which honors scientists for their excellent contributions to neuromodulation research — awarded annually for outstanding research performed in the past three years as described in a 1,500-word essay. The winner is awarded $25,000 and publication of his or her essay in Science. PINS provides financial support to allow the grand prize winner and finalist to attend an August 31 ceremony in China.
Chen and finalist Bozhi Tian will be recognized during the ceremony that will be held at the beginning of the 2019 Annual Meeting of Chinese Neuromodulation Society & The 10th Neuromodulation Congress in China's Kunming, Yunnan Province. A ceremony dinner will also be held the same day.
Chen received his undergraduate and master's degrees in chemical engineering from Tsinghua University and his Ph.D. in chemistry from the University of Tokyo. He then completed a Japan Society for the Promotion of Science postdoctoral fellowship in neuroscience at the RIKEN Center for Brain Science. He is now a Human Frontier Science Program postdoctoral fellow at UC Berkeley. His research interests include the development of minimally invasive methods to record and manipulate brain activity and how long-term memory is formed, stored and recalled.
Bozhi Tian was recognized as a prize finalist for his essay "Nongenetic neural control with light." Tian received his undergraduate and master's degrees from Fudan University, and his Ph.D. degree from Harvard University. After postdoctoral training at Massachusetts Institute of Technology and Harvard Medical School, Tian started his lab in the department of chemistry at the University of Chicago in 2012. His current research involves bioelectronics, semiconductor-enabled probing of subcellular biophysics, and the chemical dynamics at soft-hard interfaces.
The award co-sponsor Beijing PINS Medical Co. Ltd. is a company from China. Since the first Deep Brain Stimulation initiative of Tsinghua University in 2000, PINS Medical has gradually established a multinational corporation with headquarters based in Beijing and an international business center in Singapore. As an innovative high-tech enterprise with focus on neuromodulation, a variety of clinical products have been developed to date, which include stimulators for deep brain, vagus nerve, spinal cord and sacral nerve stimulation therapies. PINS Medical devotes itself to providing cutting-edge treatments for patients who suffer from neurological disorders such as Parkinson's disease, epilepsy, overactive bladder and chronic pain.