Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans

Abstract

Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show for the first time in humans that theta-burst TUS selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition, that changes in TUS-mediated neuroplasticity last at least 50 minutes after stimulation, and that these effects may be state-dependent - a mechanism increasingly recognized to influence the brain's response to neuromodulation.

Personalized depth‐specific neuromodulation of the human primary motor cortex via ultrasound

“…Legon et al (2014) observed that the focal acoustic intensity during ultrasound transmission through the skull decreased by 3.7 to 4.1 times compared with transmission in free space. Yaakub, White, Roberts et al (2023) reported a reduction of approximately 58% in focal intensity in acoustic simulations through the skull compared with free-field conditions. Interestingly, Yaakub, White, Roberts et al (2023) demonstrated that continuous theta-burst TUS with an I SPPA of ∼15.07 W/cm 2 could affect the posterior cingulate cortex's excitability by reducing GABA ergic inhibition.…”

“…Yaakub, White, Roberts et al (2023) reported a reduction of approximately 58% in focal intensity in acoustic simulations through the skull compared with free-field conditions. Interestingly, Yaakub, White, Roberts et al (2023) demonstrated that continuous theta-burst TUS with an I SPPA of ∼15.07 W/cm 2 could affect the posterior cingulate cortex's excitability by reducing GABA ergic inhibition. In contrast, our research indicated that continuous theta-burst TUS at a lower I SPPA of ∼2.38 W/cm 2 decreased M1 excitability.…”

“…However, according to Yaakub, White, Roberts et al. (2023), such variations in the T1 MR protocol do not significantly affect the fidelity of converting MRI to pseudo‐CT images. These individualized pseudo‐CT images were calibrated by setting a threshold at 300 HU and limiting values exceeding 2000 HU to transform Hounsfield units (HU) into mass density (Yaakub, White, Kerfoot et al., 2023).…”

“…It is important to mention that the T1 MR protocol employed in our study differed slightly from the one used in the initial development of the pseudo-CT algorithm by Yaakub, White., Kerfoot et al (2023). However, according to Yaakub, White, Roberts et al (2023), such variations in the T1 MR protocol do not significantly affect the fidelity of converting MRI to pseudo-CT images. These individualized pseudo-CT images were calibrated by setting a threshold at 300 HU and limiting values exceeding 2000 HU to transform Hounsfield units (HU) into mass density (Yaakub, White, Kerfoot et al, 2023).…”

Kaleidoscope

“…For the psychiatrists in the room, ultrasound was probably last seen during an obstetrics placement in medical school, and it might seem an unexpected arrival in the neuroscience suite. However, Yaakub et al 6 propose that its ability to mediate neurochemical changes may make it an interesting and novel addition to the neuromodulatory toolkit. I was interested to learn that compared with the more established TMS and tDCS, TUS offers two potential advantages.…”