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Alterations in large-scale resting-state network nodes following transcranial focused ultrasound of deep brain structures

Stephanie M. Gorka, Jagan Jimmy, Katherine Koning, K. Luan Phan, Natalie Rotstein, Bianca Hoang-Dang, Sabrina Halavi, Norman Spivak, Martin M. Monti, Nicco Reggente, Susan Y. Bookheimer, Taylor P. Kuhn

Frontiers in Human Neuroscience 2024 · 10.3389/fnhum.2024.1486770

human healthyhealthyfmri

Abstract

Background Low-intensity transcranial focused ultrasound (tFUS) is a brain stimulation approach that holds promise for the treatment of brain-based disorders. Studies in humans have shown that tFUS can successfully modulate perfusion in focal sonication targets, including the amygdala; however, limited research has explored how tFUS impacts large-scale neural networks. Objective The aim of the current study was to address this gap and examine changes in resting-state connectivity between large-scale network nodes using a randomized, double-blind, within-subjects crossover study design. Methods Healthy adults ( n = 18) completed two tFUS sessions, 14 days apart. Each session included tFUS of either the right amygdala or the left entorhinal cortex (ErC). The inclusion of two active targets allowed for within-subjects comparisons as a function of the locus of sonication. Resting-state functional magnetic resonance imaging was collected before and after each tFUS session. Results tFUS altered resting-state functional connectivity (rsFC) within and between rs-network nodes. Pre-to-post sonication of the right amygdala modulated connectivity within nodes of the salience network (SAN) and between nodes of the SAN and the default mode network (DMN) and frontoparietal network (FRP). A decrease in SAN to FPN connectivity was specific to the amygdala target. Pre-to-post sonication of the left ErC modulated connectivity between the dorsal attention network (DAN) and FPN and DMN. An increase in DAN to DMN connectivity was specific to the ErC target. Conclusion These preliminary findings may suggest that tFUS induces neuroplastic changes beyond the immediate sonication target. Additional studies are needed to determine the long-term stability of these effects.

Abstract via europepmc.

Specieshuman
Subjects20 participants
Sessions per subject2
Randomisedyes
Blindingdouble
Sham / controlactive control site
Auditory controlnot reported
Readout timingoffline
Anaesthesianot applicable
Readoutsfmri — pre/post resting-state BOLD ROI-to-ROI functional connectivity
Direction of effectmixed or unclearPre-to-post amygdala sonication changed connectivity within the salience network and between salience and default-mode and frontoparietal nodes (decrease in SAN-FPN specific to amygdala); ErC sonication increased dorsal attention to default-mode and frontoparietal connectivity.
Adverse eventsnone observedParticipants were followed for three continuous days; no adverse events or negative reactions were reported.

Exposures

Exposure 1: Right amygdala (inhibitory protocol)

Target: amygdala — “right amygdala”
Device: BrainSonix · BrainSonix Corp. ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)650✓✓✓
Pulse duration (ms)5✓✓✓
Pulse repetition frequency (Hz)10✓✓✓
Duty cycle (%)5pulse duration × PRF gives 5%✓✓✓
Sonication duration (s)30✓✓✓
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 estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)0.72✓✓✓
Protocol, in the paper’s words

5% duty cycle, 10 cycles of 30 s on and 30 s off for a total of 5 min of non-consecutive tFUS; 5 ms pulse width at 10 Hz PRF.

Exposure 2: Left entorhinal cortex (excitatory protocol, active control target)

Target: entorhinal cortex — “left entorhinal cortex (ErC)”
Device: BrainSonix · BrainSonix Corp. ✓

Pulse timing
Waveformpulsed
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✓✓✓
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 estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)0.72✓✓✓
Protocol, in the paper’s words

5% duty cycle, 10 cycles of 30 s on and 30 s off for a total of 5 min of non-consecutive tFUS; 0.5 ms pulse width at 100 Hz PRF.

Flags from extraction

  • exposures[0].unspecified_domain.ispta_w_cm2 — Stated as Ispta.3 = 720 mW/cm2 without saying whether measured in water or in tissue; converted to 0.72 W/cm2 and left in the unspecified domain.
  • exposures[1].unspecified_domain.ispta_w_cm2 — Stated as Ispta.3 = 720 mW/cm2 without saying whether measured in water or in tissue; converted to 0.72 W/cm2 and left in the unspecified domain.
  • n_subjects — 20 enrolled; 18 completed the amygdala session and 19 the ErC session; 17 completed both. Abstract says n = 18.
  • exposures[0].device.model — Transducer model not named; BrainSonix named as the maker in the focal-depth sentence.
  • provenance — Participants are the same as in Kuhn et al. 2023 ('previously published study of these participants'); this paper reanalyses resting-state connectivity from the already-reported exposure.