Search bioRxiv⌕ Search

bioRxiv · 10.64898/2026.03.10.710890

Facilitating Mindfulness Training with Ultrasonic Neuromodulation

Abstract

Systematic focus training is increasingly recognized for its therapeutic benefits, with equanimity, the ability to maintain an open and accepting attitude towards all experience, identified as a critical mechanism for improving well-being. Physiologically, experienced meditators demonstrate reduced activity in the posterior cingulate cortex (PCC), a hub of the default mode network (DMN), and increased segregation between the DMN and the central executive network (CEN). This study investigated whether non-invasive neuromodulation could facilitate these neural and behavioral shifts in novice practitioners. We conducted a single-blind, randomized controlled trial with 24 meditation-naive participants who engaged in a two-week "Body Focus" mindfulness training program. Participants were randomized to receive either active (n=16) or sham (n=8) suppressive transcranial focused ultrasound (tFUS) targeting the PCC during four in-person meditation sessions. Resting-state fMRI analysis revealed a robust Condition x Session interaction in functional connectivity. While the sham group showed a trend toward increased coupling, the active tFUS group demonstrated significant decoupling (increased segregation) between the DMN and CEN, a pattern characteristic of advanced meditators. Subnetwork analysis indicated these effects were driven primarily by the decoupling of the core self-referential system in DMN (DMNA) from the external-oriented control system of the CEN (CENB). Behaviorally, greater reductions in DMN-CEN connectivity within the active group predicted larger increases in self-reported acceptance and longer duration of voluntary meditation practice. These findings suggest that tFUS targeting the PCC can acutely redirect neuroplastic trajectories during early mindfulness training, potentially accelerating the acquisition of equanimity and distinct network configurations associated with effortless awareness. Significance StatementThis study demonstrates that transcranial focused ultrasound (tFUS) targeting the posterior cingulate cortex (PCC) can synergistically enhance mindfulness training in novices. By inducing a robust decoupling between the default mode and central executive networks - a neural signature typically acquired only after hundreds of hours of practice - this intervention effectively redirected the neural trajectory of novice practitioners toward that of experienced meditators in just two weeks. These findings suggest that targeted neuromodulation can bypass early obstacles in meditation practice, offering a promising "precision wellness" avenue for accelerating the acquisition of equanimity and its associated well-being benefits.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lord, B., Lord, E. N., Schachtner, J. N., Beaman, L., Young, S., Allen, J. J., Sanguinetti, J. L.. 2026-03-13. Facilitating Mindfulness Training with Ultrasonic Neuromodulation. https://doi.org/10.64898/2026.03.10.710890

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗