Sustained modulation of primate deep brain circuits with focused ultrasonic waves
Taylor D. Webb, Matthew G. Wilson, Henrik Odéen, Jan Kubanek
Brain Stimulation 2023, 16, 798-805 · 10.1016/j.brs.2023.04.012
Abstract
Background Transcranial focused ultrasound has the potential to noninvasively modulate deep brain circuits and impart sustained, neuroplastic effects. Objective Bring the approach closer to translations by demonstrating sustained modulation of deep brain circuits and choice behavior in task-performing non-human primates. Methods Low-intensity transcranial ultrasound of 30 s in duration was delivered in a controlled manner into deep brain targets (left or right lateral geniculate nucleus; LGN) of non-human primates while the subjects decided whether a left or a right visual target appeared first. While the animals performed the task, we recorded intracranial EEG from occipital screws. The ultrasound was delivered into the deep brain targets daily for a period of more than 6 months. Results The brief stimulation induced effects on choice behavior that persisted up to 15 minutes and were specific to the sonicated target. Stimulation of the left/right LGN increased the proportion of rightward/leftward choices. These effects were accompanied by an increase in gamma activity over visual cortex. The contralateral effect on choice behavior and the increase in gamma, compared to sham stimulation, suggest that the stimulation excited the target neural circuits. There were no detrimental effects on the animals' discrimination performance over the months-long course of the stimulation. Conclusion This study demonstrates that brief, 30-s ultrasonic stimulation induces neuroplastic effects specifically in the target deep brain circuits, and that the stimulation can be applied daily without detrimental effects. These findings encourage repeated applications of transcranial ultrasound to malfunctioning deep brain circuits in humans with the goal of providing a durable therapeutic reset.
Abstract via europepmc.
Exposures
Exposure 1: Sonication of left/right lateral geniculate nucleus (LGN) with varying pressure/intensity/duty cycle/PRF
Target: lateral geniculate nucleus — “left or right lateral geniculate nucleus (LGN)”
Device: custom-built · Doppler Electronic Technologies · 256-element ultrasound transducer array (Remus phased-array system) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 480 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 0.6, 1.2, 4.8swept | ✓✓✓⚑ |
| Duty cycle (%) | 1.8, 3.6, 14.4swept | ✓✓✓⚑ |
| 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) | 500, 700, 1,000, 1,400swept | ✓✓✓ |
| In-situ Isppa (W/cm²) | 8, 14, 31, 59, 64swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | 1, 2swept | ✓✓✓ |
Each neuromodulation sonication lasted 30 s and consisted of a train of 30 ms pulses at 480 kHz, delivered into left or right LGN interleaved across sessions (left LGN sonicated in 55 sessions: 35 in subject B, 20 in subject E; right LGN in 55 sessions: 36 in B, 19 in E), with sham (unfocused, randomized-phase) sonications also collected; behavioural/EEG effects were analysed in the five-minute windows following sonication offset. In a separate anatomical safety test, the left LGN was insonated for 1 minute total duration (1.5 MPa, 30 ms pulse duration, 10% duty cycle) immediately followed by gadolinium contrast injection.
Flags from extraction
exposures[0].in_situ.method— Text is internally inconsistent: it states the estimated pressure at focus was 46% of the free-field value, then states the Table 1/2 values 'assume that the in-situ intensity is de-rated by a factor of 21%' relative to free field; these two derating factors (46% vs 21%) do not match.n_sessions_per_subject— Total sessions differed substantially by subject (a total of 79 sessions in subject B and 45 sessions in subject E, including sham), so no single n_sessions_per_subject value applies.exposures[0].timing.pulse_repetition_frequency_hz— Values pooled from Table 1 (subject B) and Table 2 (subject E) parameter sweeps across multiple named stimulation settings (B1-B5, E1-E3); the pairing between individual PRF/duty-cycle/pressure/intensity combinations per named setting is lost when each field is listed independently.exposures[0].timing.duty_cycle_pct— Values pooled from Table 1 and Table 2; see note on pulse_repetition_frequency_hz regarding loss of per-setting pairing.sham_type— The active sham delivered the same acoustic energy but with randomized element phases (unfocused beam) rather than powering off, blocking or moving the transducer, so it does not cleanly match a listed sham_type category.auditory_control— The paper controls for auditory/vestibular confounds via post-offset-only analysis windows, hemisphere-specific effects, and an active (unfocused) sham rather than any of the listed auditory_control categories.