Structural-Functional Brain Network Modulation using Transcranial Focused Ultrasound Stimulation: Implications on the Default Mode Network in Humans

Chang-hyun Park, Song E. Kim, Yun Seo Choi, Jihye Lee, Seo Young Lee, Ju Hyeong Kang, Seongeun Hwang, Young Goo Kim, Hyang Woon Lee

NeuroImage 2025 · 10.1016/j.neuroimage.2025.121540

human healthyhealthyfmriother mri

Abstract

Transcranial focused ultrasound (tFUS) has emerged as a promising noninvasive technique for brain stimulation due to its precise focusing and deep penetration capabilities. However, its potential to modulate brain networks beyond the stimulation site and optimal sonication parameters required for such modulation remain unclear. In light of this knowledge gap, this study investigates the effects of tFUS targeted at the medial prefrontal cortex (mPFC), a key component of the default mode network (DMN), to determine whether varying the sonication parameters could specifically modulate the DMN. Specifically, in this study, 21 healthy participants were divided into groups that received excitatory, suppressive, or sham tFUS stimulation targeting the mPFC. To assess the effects, diffusion-weighted MRI and resting-state functional MRI were employed to assess the correspondence between structural and functional brain connectomes before and after tFUS. Subsequently, changes following tFUS were compared among the three groups. Our results showed that while tFUS generally increased coupling between structure and function near the stimulation site after both excitatory and suppressive stimulation, a significant enhancement in structure-function correspondence was specifically observed within the DMN connected to the stimulation site under excitatory stimulation. Based on these observations, the findings highlight the potential of specific tFUS protocols to effectively modulate the DMN, thereby offering insights into optimizing tFUS for brain network modulation and its potential as a non-invasive therapeutic intervention.

Abstract via europepmc.

Specieshuman

Subjects7, 7swept participants

Sessions per subject1

Randomisedyes

Blindingsingle

Sham / controlundescribed

Auditory controlpost hoc check

Readout timingoffline

Anaesthesianot applicable

Readoutsfmri, other mri — Resting-state fMRI (GSA, ReHo, FC); diffusion MRI structure-function correspondence (R2)

Direction of effectmixed or unclearBoth protocols increased structure-function coupling near the mPFC; a significant increase across the default mode network occurred only after the excitatory protocol.

Adverse eventsnone observedSkin temperature monitored and held at 35.4 C; no participants reported auditory confounding or other side effects.

Exposures

Exposure 1: Excitatory and suppressive tFUS protocols to mPFC

Target: ventromedial prefrontal cortex — “medial prefrontal cortex (mPFC)”
Device: Neurosona · Neurosona · NS-US100 ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	250	✓✓✓
Pulse duration (ms)	0.5	✓✓✓
Pulse repetition frequency (Hz)	1,400, 100swept	✓✓✓⚑
Duty cycle (%)	70, 5swept	✓✓✓
Sonication duration (s)	0.3	✓✓✓⚑

Pressure and intensity, by domain
Free-field pressure (kPa)	not reported
Free-field Isppa (W/cm²)	not reported
Free-field Ispta (W/cm²)	not reported
In-situ estimate	not reportedsingle value
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	0.75	✓✓✓⚑
In-situ Ispta (W/cm²)	0.525, 0.038swept	✓✓✓⚑

Protocol, in the paper’s words

Excitatory: 0.5 ms pulses at 1400 Hz (70% DC) in 300 ms pulse trains (420 pulses) separated by 5 s. Suppressive: 0.5 ms pulses at 100 Hz (5% DC) in 300 ms trains (30 pulses) with no inter-train interval (continuous pulsing). Trains repeated over a 20-min session.

Flags from extraction

exposures[0].timing.pulse_repetition_frequency_hz — Two protocols at the same target and frequency are recorded as lists in order [excitatory, suppressive]; same order for duty cycle and in situ Ispta.
exposures[0].timing.sonication_duration_s — Pulse train duration 300 ms; the whole session was 20 min of repeated trains.
exposures[0].in_situ.isppa_w_cm2 — Table labels Isppa 'in situ' but the text says only 'determined based on acoustic calibration'; method of derivation not stated, so method is not_reported.
exposures[0].in_situ.ispta_w_cm2 — Values 525 and 38 mW/cm2 converted to W/cm2; ordered [excitatory, suppressive], not a min-max range.
sham_type — Sham stimulation is described only as a sham tFUS group; mechanism not stated.
auditory_control — Participants were reported afterwards as having no auditory confounding; no control during the experiment.
direction_of_effect — Excitatory protocol increased structure-function correspondence in the default mode network; suppressive effect on the DMN was unclear; whole-brain activity tended to increase after excitatory and decrease after suppressive.