Neuromodulation encompasses a variety of therapeutic approaches to relieve symptoms, such as pain or tremor, or to restore movement or function. Therapeutic stimulation of neurons with electrical energy or chemicals (and potentially with acoustic waves) can amplify or dampen neuronal impulses in the brain or body. Acoustic signals in the form of ultrasound offer a promising class of neuromodulation that would be an especially valuable approach because it is non-invasive: no surgical procedure is required to implant electrodes for stimulation. Ultrasound offers temporal modulation that can be adjusted to obtain the desired effect. Now researchers have shown that it has the potential to target neurons with specific functions.
A team led by Bin He, Ph.D., professor of biomedical engineering at Carnegie Mellon University, and funded in part by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), has demonstrated the potential of a neuromodulation approach that uses low-intensity ultrasound energy, called transcranial focused ultrasound, or tFUS. In an article published in the May 4, 2021 issue of Nature CommunicationsThe authors describe tFUS in rodent experiments demonstrating the non-invasive neuromodulation alternative.
“Focused transcranial ultrasound is a promising approach that could be used to treat forms of chronic pain, among other applications,” said Moria Bittmann, Ph.D., director of the NIBIB program in Biorobotic Systems. “In conditions where symptoms include debilitating pain, externally generated ultrasound pulses at controlled frequencies and intensity could inhibit pain signals.”
For their studies, He and his team designed an array that included an ultrasound transducer and a device that records data from neural signals, called a multi-electrode array. During experiments with anesthetized rodents, the researchers penetrated the skull and brain with several brief pulses of acoustic waves, targeting specific neurons in the cerebral cortex. They simultaneously recorded the change in electrophysiological signals of different types of neurons with the multi-electrode array.
If we can locate and target areas of the brain using acoustic and ultrasonic energy, I believe we can potentially treat a wide variety of neurological and psychiatric diseases and conditions. —Bin He
When a signal is sent from one neuron to another, either activating the senses or controlling movement, the emission of that signal through the synapse or junction between neurons is called a spike. Two types of neurons observed by researchers are excitatory and inhibitory neurons. When the researchers used tFUS to deliver repeated bursts of ultrasonic stimulation directly to excitatory neurons, they observed a high burst frequency, or spike. They observed that inhibitory neurons subjected to the same tFUS energy did not show a significant alteration in spike rate. The study demonstrated that the ultrasound signal can be transmitted through the skull to selectively activate specific subpopulations of neurons, in effect targeting neurons with different functions.
“Our research addresses an unmet need to develop non-toxic, non-addictive and non-pharmacological therapies for human use,” He said. “We hope to further develop the tFUS approach with variation in ultrasound frequencies and seek insights into neural activity so that this technology has the optimal opportunity to benefit brain health.”
The application of this research has broad implications; It is not limited to just one disease. For many people suffering from pain, depression and addiction, he believes non-invasive tFUS neuromodulation could be used to facilitate treatment. “If we can locate and target areas of the brain using acoustic and ultrasound energy, I think we can potentially treat a wide variety of neurological and psychiatric diseases and conditions,” he said.
The editors of Nature Communications selected the role for a special featurecalled “From brain to behavior [sic]”, which comprises some of the most interesting work on the brain published this year by the magazine.
This work was supported, in part, by NIH grants from NIBIB (EB029354, EB021027), the National Institute of Mental Health (MH114233), the National Center for Advancing Translational Sciences (AT009263), and the National Institute of Neurological Disorders and Stroke (NS096761).
Read the article: Kai Yu, Xiaodan Niu, Esther Krook-Magnuson, Bin He. Intrinsic functional neuronal type selectivity of transcranial focused ultrasound neuromodulation. Nature Communications2021; 12 (1) DOI: 10.1038/s41467-021-22743-7
This Science Highlight describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is critical to promoting new and better ways to prevent, diagnose, and treat diseases. Science is an unpredictable and incremental process: each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without knowledge of fundamental basic research.
