raw/papers/10.1101_2025.08.08.669288
biorxiv BIORXIV bioRxiv bioRxiv 2692-8205 Cold Spring Harbor Laboratory BIORXIV/2025/669288 10.1101/2025.08.08.669288 biorxiv;2025.08.08.669288v3 biorxiv;2025.08.08.669288 2025.08.08.669288 2025.08.08.669288 2025.08.08.669288 3.1 Regular Article New Results Neuroscience Inhibiting the right dorsolateral prefrontal cortex selectively enhances unsupervised statistical learning 1 INSERM; 2 Eotvos Lorand University; 3 Atlantico Medio University; 4 University of Greenwich; 5 Semmelweis University * Corresponding author; email: [email protected] Pesthy Orsolya 1 6 [email protected] Pesthy Zsuzsanna Viktoria 2 Vekony Teodora 3 Janacsek Karolina 4 Fabo Daniel 5 http://orcid.org/0000-0002-9629-5856 Nemeth Dezso 1 2026 8 8 2025 1 4 2026 8 8 2025 2025.08.08.669288 08 8 2025 01 4 2026 01 4 2026 © 2026, Posted by openRxiv 2026 This pre-print is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), CC BY-NC 4.0, as described at http://creativecommons.org/licenses/by-nc/4.0/ The brain must balance the automatic extraction of environmental regularities with top-down cognitive control, yet the causal neural mechanisms governing this interplay are debated. In particular, the hemispheric contributions of the dorsolateral prefrontal cortex (DLPFC) remain unresolved. Here, we applied inhibitory repetitive transcranial magnetic stimulation (rTMS) to the left, right, or bilateral DLPFC in 95 healthy adults during a probabilistic sequence learning task. We found that inhibiting the right and bilateral DLPFC significantly enhanced statistical learning compared to sham and left DLPFC stimulation. Contrary to the hypothesis that this competition is mediated by the suppression of existing knowledge, episodic memory performance was unaffected across all stimulation groups. These findings challenge a direct episodic gating mechanism and suggest the DLPFC’s influence on statistical learning is hemisphere-dependent. As an alternative, we propose that right DLPFC inhibition shifts cognitive processing toward a more exploratory information-sampling strategy, a view supported by our finding of significantly greater reaction time variability in the right and bilateral stimulation groups. Together, our results provide causal evidence for a right-lateralized suppressive influence of the DLPFC on unsupervised learning and suggest its modulatory role is linked to information processing style rather than direct competition with episodic memory systems. French National Grant Agency ANR-22-CPJ1-0042-01 ANR-24-CE37-5807 National Brain Research Program NAP2022-I-2/2022 citation_submitter_name Orsolya Pesthy citation_submitter_email [email protected] citation_submitter_id 300545 citation_submitter_institution INSERM special-property contains-inline-supplementary-material has-earlier-version yes Competing Interest Statement The authors have declared no competing interest. Summary of Updates: We improved the method description, added figures, changed the episodic memory task analysis, refined the interpretation of the results. https://osf.io/e2rzs/?view_only=88125069a7ad418f804374378bacc441 DC1 Supplementary Materials