Elisa Konofagou, Ph.D. – ek2191@columbia.edu
Department of Biomedical Engineering
Columbia University
351 Engineering Terrace, mail code 8904
1210 Amsterdam Avenue
New York, NY 10027

Popular version of paper 1pBA6
Presented Monday morning, May 7, 2018
175th ASA Meeting, Minneapolis, MN

Stimulation of the brain has been a topic of curiosity of humans since the beginning of time. Being able to selectively stimulate the brain to enhance performance such as think deeper and remember faster remains, a formidable challenge. Mapping the circuitry of the entire healthy human brain remains an equally unattainable goal. Brain mapping entails the study of biological functions of different regions in the brain. Although many regions of the brain have already been identified, there is very little known as to how the different regions communicate and whether activation patterns observed during specific behaviors are causally related to those behaviors. Such a brain map would not only further the understanding of the brain itself, but also potentially lead to novel cures or treatments for neurological conditions. One way to aid the progress in brain mapping is neurostimulation, a technique used to stimulate or activate neurons in the brain, usually by means of an electrode. When the electrode delivers a stimulus pulse to a targeted brain region, the biological response associated with that area will occur. Ultrasound has been consistently reported for neuronal stimulation for several decades in both animals and humans including eliciting brain activity detected by functional MRI and electroencephalography. In addition, this knowledge can be used to understand the differences between normal and pathological brains to treat patients.

In the peripheral nervous system, ultrasound has been reported since 1929 to stimulate nerves in excised frog muscle fibers and to this day the majority of the studies so far have entailed stimulation of excised nerves. The leading technique to treat peripheral neurological disorders is implantation of electrodes along the peripheral nerve and stimulating the nerve with electrical current. A noninvasive alternative that could treat neuropathic pain and suppress nerve activity constitutes thus an important challenge in interventional neurology.

i) ii)
iii)neurons iv)

Figure 1: i) FUS setup for neuromodulation, cameras recording hind limb and tail movements and pupil dilation and eye movement. ii) Recorded left hind paw movement (before (purple) after (green) movement), iii) FUS-induced motor response elicitation: EMG of the right hind limb during contralateral evoked response for different acoustic pressure levels with the success rate increasing at larger pressures and iv) contralateral paw movement elicited by FUS neurostimulation.

Our group has been studying the noninvasive stimulation or inhibition of both the central and peripheral nervous system in live animals. In the brain, we have shown that focused ultrasound is capable of noninvasively stimulating paw movement as well as sensory responses such as pupil dilation and eye movement when different brain regions are targeted, showing for the first time that ultrasound can tap into both the motor and sensory brain regions (Fig. 1). In the periphery, when the ultrasound beam is focused on the sciatic nerve in a live, anesthetized animal, the thigh muscle becomes activated and muscle twitches can be induced at low ultrasonic intensities while the same twitches can be inhibited at higher intensities due to associated temperature rise that inhibits nerve firing. Cellular and fiber responses in excised tissue have confirmed the live animal responses (Fig. 2).


Figure 2:  FUS compared to electrical modulation: a) Ex vivo measurements of action potentials in a nerve bundle through FUS (red) and electrical stimulation; b) in vivo EMG responses in murine leg muscle at different FUS pressures and duty cycles. FUS elicits very similar motor responses as electrical stimulation (E.S.; dashed horizontal line), especially at higher pressures and duty cycles.

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