Newswise – Neuromodulation includes a range of therapeutic approaches to relieve symptoms, such as pain or tremors, or to restore movement or function. Therapeutic stimulation of neurons with electrical energy or chemicals – and potentially with acoustic waves – can amplify or attenuate neural impulses in the brain or body. Acoustic signals in the form of ultrasound offer a promising class of neuromodulation that would be a particularly interesting approach because it is non-invasive – no surgical procedure to implant stimulation electrodes is required. Ultrasound provides temporary modulation that can be adjusted for a desired effect. Now, researchers have shown that it has the potential to be targeted to 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), demonstrated the potential of a neuromodulation approach which uses low intensity ultrasound energy, called transcranial focused ultrasound or tFUS. In an article published in the May 4, 2021 issue of Nature Communications, the authors describe tFUS in rodent experiments that demonstrate the alternative of non-invasive neuromodulation.
“Transcranial focused 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. “Under conditions where symptoms include debilitating pain, externally generated pulses of ultrasound at controlled frequencies and intensity could inhibit pain signals.”
For their studies, he and his team designed a kit that included an ultrasound transducer and a device that records signal data from neurons, called a multi-electrode array. During experiments with anesthetized rodents, the researchers entered the skull and brain with various 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 network.
When a signal is sent from one neuron to another, whether by engaging the senses or controlling movement, the triggering 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 ultrasound stimulation directly to excitatory neurons, they observed a high pulse rate, or spike. They observed that inhibitory neurons subjected to the same tFUS energy did not exhibit a significant disturbance of the spike rate. The study demonstrated that the ultrasound signal can be transmitted through the skull to selectively activate subpopulations of specific neurons, in effect targeting neurons with different functions.
“Our research addresses an unmet need to develop non-toxic, non-addictive, non-pharmacological therapies for human use,” said He. “We hope to further develop the tFUS approach with variation in ultrasound frequencies and to deepen knowledge about neural activity so that this technology has the optimum chance of benefiting brain health.”
The application of this research has broad implications; it is not limited to a single disease. For many people with pain, depression, and drug 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 myriad of neurological and psychiatric illnesses and conditions,” he said.
Nature Communications editors selected the article for a special feature, titled “From Brain to Behavior [sic]Which includes some of the most exciting brain work published this year by the journal.
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).