Modulating the default mode network with deep TMS: a proof-of-concept framework with potential relevance to circuits implicated in lack of awareness of cognitive decline.
Youssef Bellaali, Dominika Sulcova, Adriana Salatino, Laurence Dricot, Bernard Jimmy Hanseeuw, John L Woodard, Adrian Ivanoiu
Frontiers in Aging Neuroscience April 22, 2026 DOI: 10.3389/fnagi.2026.1742759 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized within-subject sham-controlled experiment Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Right-handed healthy adults aged 26–30 years |
| Topics | Default mode network |
| Keywords | Alzheimer disease FMRI Anosognosia Tms |
| Key findings | Deep TMS of the right PCC produced significantly decreased resting-state connectivity in eight whole-brain clusters, including six DMN hubs (bilateral precuneus, bilateral supramarginal gyri, right angular gyrus, left posterior superior temporal gyrus), compared with sham. The authors argue this supports a causal contribution of the right PCC to DMN synchrony, while noting no behavioral or metacognitive assessments were performed. |
Abstract
Introduction: Self-referential processes are suspected to rely on the default mode network (DMN), particularly the posterior cingulate cortex (PCC). The right PCC, has been implicated in self-awareness, with neuroimaging studies showing its involvement in anosognosia in Alzheimer’s disease. However, causal evidence linking right PCC activity to DMN synchrony in humans remains scarce. This study examined whether transient modulation of the right PCC using continuous theta-burst deep transcranial magnetic stimulation (deep TMS) alters DMN connectivity in healthy adults.
Aim: To assess whether transient inhibition of the right PCC using continuous theta-burst deep transcranial magnetic stimulation (deep TMS) modulates DMN functional connectivity in healthy adults.
Methods: Twelve right-handed healthy participants (aged 26–30 years) underwent two randomized sessions: deep TMS targeting the right PCC and a sham condition. Resting-state fMRI was acquired 10–20 min post-stimulation. Connectivity changes were assessed through (1) a correlation-matrix analysis between the right PCC and 78 regions of the Brainnetome atlas, and (2) a whole-brain seed-based paired t -test. For the whole-brain analysis, statistical significance was determined using cluster-level Monte-Carlo correction ( p < 0.05).
Results: The region-based correlation matrix showed reduced connectivity between the PCC and three DMN-related regions (right precuneus, right inferior parietal gyrus, left superior temporal gyrus), although these did not survive multiple-comparison correction. The whole-brain analysis revealed eight clusters with significantly decreased connectivity after stimulation compared to sham, including six key DMN hubs (bilateral precuneus, bilateral supramarginal gyri, right angular gyrus, left posterior superior temporal gyrus).
Conclusion: Deep TMS of the right PCC induced a transient desynchronization of DMN connectivity, supporting a causal contribution of the right PCC to large-scale self-referential network integrity. While no behavioral evaluation was performed at this stage, these results provide a proof-of-principle that transient modulation of the right PCC can alter DMN synchrony, opening the way for future studies combining deep TMS with metacognitive and self-awareness assessments to directly investigate awareness mechanisms in healthy aging and neurodegenerative disease.
Comparable studies
Other randomized controlled trials on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Healthy volunteers | 2012 | Within-subjects, placebo-controlled, task-free fMRI study | n = 30 |
| The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers | 2014 | Placebo-controlled study | |
| Ketamine Decreases Resting State Functional Network Connectivity in Healthy Subjects: Implications for Antidepressant Drug Action Healthy subjects | 2012 | Randomized, placebo-controlled, double-blind, crossover rsfMRI challenge | |
| Antidepressants Normalize the Default Mode Network in Patients With Dysthymia Subjects with dysthymic disorder and healthy control participants aged 18 to 53 years | 2013 | Randomized controlled trial | n = 41 |
| Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis of Early Psychosis Healthy volunteers | 2012 | Within-subject, placebo-controlled experimental study | n = 15 |