Transcranial focused ultrasound to the posterior cingulate cortex modulates default mode network and subjective experience: an fMRI pilot study

Abstract

Background: Transcranial focused ultrasound (TFUS) is an emerging neuromodulation tool for temporarily altering brain activity and probing network functioning. The effects of TFUS on the default mode network (DMN) are unknown.

Objective: The study examined the effects of transcranial focused ultrasound (TFUS) on the functional connectivity of the default mode network (DMN), specifically by targeting the posterior cingulate cortex (PCC). Additionally, we investigated the subjective effects of TFUS on mood, mindfulness, and self-related processing.

Methods: The study employed a randomized, single-blind design involving 30 healthy subjects. Participants were randomly assigned to either the active TFUS group or the sham TFUS group. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted before and after the TFUS application. To measure subjective effects, the Toronto Mindfulness Scale, the Visual Analog Mood Scale, and the Amsterdam Resting State Questionnaire were administered at baseline and 30 min after sonication. The Self Scale and an unstructured interview were also administered 30 min after sonication.

Results: The active TFUS group exhibited significant reductions in functional connectivity along the midline of the DMN, while the sham TFUS group showed no changes. The active TFUS group demonstrated increased state mindfulness, reduced Global Vigor, and temporary alterations in the sense of ego, sense of time, and recollection of memories. The sham TFUS group showed an increase in state mindfulness, too, with no other subjective effects.

Conclusions: TFUS targeted at the PCC can alter DMN connectivity and cause changes in subjective experience. These findings support the potential of TFUS to serve both as a research tool and as a potential therapeutic intervention.

Keywords: default mode network; fMRI; mindfulness; neuromodulation; non-invasive brain stimulation; transcranial focused ultrasound.

Figure 1

Timeline of MRI data acquisition and TFUS application. Data were gathered before and after TFUS application.

Figure 2

Acoustic intensity measurements. (A) Skull attenuation and geometric deformation of acoustic temporal peak pressure recorded in water and through a sample of cadaver parietal bone (“skull”). Center of the beam and FWHM are displayed. Lateral shift displayed in (A) and axial shift in (C). The periodic variation in peak intensity in the axial plane in panel C is thought to be due to standing waves created by the annular geometry of the transducer. (B) Skull-attenuated ultrasound intensity map is overlaid on a single subject’s MRI. Estimation of peak focus was determined using recorded neuronavigation coordinates from that subject’s TFUS session. (D) Spatial distribution of temporal peak intensity of the ultrasound beam in water (top) and through a cadaver parietal skull piece (bottom). Left panel shows lateral spatial topography of temporal peak intensity of the beam at the axial peak; right panel displays axial topography.

Figure 3

ROI-to-ROI functional connectivity changes from baseline to average of t₁ and t₂. (A) Sagittal, coronal, and axial views of significant ROI-to-ROI functional connectivity changes in active TFUS condition, all of which were decreases in functional connectivity (represented by blue connecting lines, with the affected ROIs highlighted in yellow) within and along the midline of the DMN and cingulate cortex. (B) No significant ROI-to-ROI functional connectivity changes found in the sham TFUS condition.

Figure 4

ROI-to-ROI functional connectivity changes from baseline to t₁ and t₂ in active condition. Sagittal and axial views of significant ROI-to-ROI functional connectivity changes in each timepoint compared to baseline for each condition, all of which were decreases in functional connectivity (represented by blue connecting lines, with the affected ROIs highlighted in yellow). (A) Contrast of t₁ to baseline in active condition. (B) Contrast of t₂ to baseline in active condition. (C) Contrast of t₁ to baseline in sham condition. (D) Contrast of t₂ to baseline in sham condition.

Figure 5

Effects of TFUS on Toronto Mindfulness Scale. Boxplots depicting changes measured by the Toronto Mindfulness Scale. (A) Changes in total mindfulness score between pre and post for each active and sham condition. (B) Changes in the “Decentering” subscale. (C) Changes in the “Curiosity” subscale. ***p < 0.001, **p < 0.01, *p < 0.05.

Figure 6

Effects of TFUS on Visual Analog Mood Scale. Boxplots depicting changes measured by the Visual Analog Mood Scale. (A) Changes in Global Affect score between pre and post for each active and sham condition. (B) Changes in the Global Vigor score between pre and post for each active and sham condition. A significant difference was found in the active condition. *p < 0.05.

Figure 7

Effects of TFUS on Self Scale. Individual item responses to the Self Scale. *p < 0.05.