Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans
Taylor Kuhn, Norman M. Spivak, Bianca H. Dang, Sergio Becerra, Sabrina E. Halavi, Natalie Rotstein, Benjamin M. Rosenberg, Sonja Hiller, Andrew Swenson, Luka Cvijanovic, Nolan Dang, Michael Sun, David Kronemyer, Rustin Berlow, Malina R. Revett, Nanthia Suthana, Martin M. Monti, Susan Bookheimer
Frontiers in Neural Circuits 2023, 17 · 10.3389/fncir.2023.1120410
Abstract
Background Low intensity, transcranial focused ultrasound (tFUS) is a re-emerging brain stimulation technique with the unique capability of reaching deep brain structures non-invasively. Objective/hypothesis We sought to demonstrate that tFUS can selectively and accurately target and modulate deep brain structures in humans important for emotional functioning as well as learning and memory. We hypothesized that tFUS would result in significant longitudinal changes in perfusion in the targeted brain region as well as selective modulation of BOLD activity and BOLD-based functional connectivity of the target region. Methods In this study, we collected MRI before, simultaneously during, and after tFUS of two deep brain structures on different days in sixteen healthy adults each serving as their own control. Using longitudinal arterial spin labeling (ASL) MRI and simultaneous blood oxygen level dependent (BOLD) functional MRI, we found changes in cerebral perfusion, regional brain activity and functional connectivity specific to the targeted regions of the amygdala and entorhinal cortex (ErC). Results tFUS selectively increased perfusion in the targeted brain region and not in the contralateral homolog or either bilateral control region. Additionally, tFUS directly affected BOLD activity in a target specific fashion without engaging auditory cortex in any analysis. Finally, tFUS resulted in selective modulation of the targeted functional network connectivity. Conclusion We demonstrate that tFUS can selectively modulate perfusion, neural activity and connectivity in deep brain structures and connected networks. Lack of auditory cortex findings suggests that the mechanism of tFUS action is not due to auditory or acoustic startle response but rather a direct neuromodulatory process. Our findings suggest that tFUS has the potential for future application as a novel therapy in a wide range of neurological and psychiatric disorders associated with subcortical pathology.
Abstract via europepmc.
Exposures
Exposure 1: Amygdala tFUS (disruptive paradigm)
Target: amygdala — “right amygdala”
Device: BrainSonix · BrainSonix Corp. ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.72 | ✓✓✓ |
Both paradigms used a 5% duty cycle, in 10 cycles of 30 s on, 30 s off, for a total of 5 min of non-consecutive tFUS. The amygdala paradigm used a 5 ms pulse width at 10 Hz PRF, hypothesized to disrupt/inhibit amygdala activity.
Exposure 2: Entorhinal cortex (ErC) tFUS (excitatory paradigm)
Target: entorhinal cortex — “left entorhinal cortex (ErC)”
Device: BrainSonix · BrainSonix Corp. ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.72 | ✓✓✓ |
Both paradigms used a 5% duty cycle, in 10 cycles of 30 s on, 30 s off, for a total of 5 min of non-consecutive tFUS. The ErC paradigm used a 0.5 ms pulse width at 100 Hz PRF, hypothesized to increase/excite ErC activity.
Flags from extraction
exposures[0].device.model— Device is attributed to BrainSonix Corp but no specific model number is given in the main text.exposures[0].timing.sonication_duration_s— Recorded as the 30-s active block length; the paper separately reports a total of 5 min of non-consecutive tFUS across 10 such blocks (see protocol_description).n_sessions_per_subject— Inferred as 2 from the two-session crossover design (one per target); not stated as a bare number.