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Rewriting Reactivated Memories? A Systematic Review of Transcranial Magnetic Stimulation and Memory Reactivation and Reconsolidation Paradigms

AI Summary
  • TMS can modulate reactivated memories in ways compatible with reconsolidation, but effects are memory-system dependent and methodologically heterogeneous.
  • Strongest evidence arises from tightly controlled laboratory paradigms, notably fear studies where postreactivation prefrontal stimulation reduced physiological fear and return of fear.
  • Only five human studies employed low frequency rTMS or cTBS, mainly targeting dorsolateral prefrontal cortex; risk of bias and translational null results limit certainty.
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Neuromodulation. 2026 Jun 17:S1094-7159(26)00619-7. doi: 10.1016/j.neurom.2026.05.016. Online ahead of print.

ABSTRACT

INTRODUCTION: Memory reconsolidation refers to the postreactivation restabilization process through which consolidated memories may become modifiable under specific boundary conditions. Transcranial magnetic stimulation (TMS) offers a causal method for perturbing cortical processing during this putative window of lability. However, whether human TMS studies truly support a reconsolidation-based interpretation, rather than broader postretrieval modulation, has not been systematically synthesized.

MATERIALS AND METHODS: We conducted a systematic review of human studies examining TMS in relation to explicit memory reactivation or reconsolidation-oriented interventions. The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020, was protocolized according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 and was registered in PROSPERO (CRD420261334930). PubMed/MEDLINE, Scopus, and Web of Science were searched without date restriction. Eligible studies were original human investigations using any TMS modality applied in relation to a recognizable reactivation procedure and reporting delayed changes in later memory expression or performance. Data extraction included methodologic variables and theory-based coding of reconsolidation-oriented inferences. Risk of bias was assessed using RoB 2.

RESULTS: Five studies met the inclusion criteria-three on fear memory, one on episodic memory, and one on procedural memory. Two low-frequency stimulation approaches were represented: 1 Hz repetitive TMS and continuous theta-burst stimulation. The dorsolateral prefrontal cortex was the predominant target, whereas one procedural-memory study stimulated the primary motor cortex. In fear paradigms, postreactivation prefrontal stimulation was generally associated with attenuation of physiologic fear expression, and in the strongest designs, it reduced return of fear. In episodic memory, right prefrontal stimulation was associated with enhanced delayed recall. In procedural memory, stimulation during reactivation was associated with blockade of subsequent offline memory modification. Four studies provided comparatively strong reconsolidation-oriented support through explicit reactivation, critical controls, and delayed testing; one translational clinical-analog study yielded a null primary effect and weaker mechanistic certainty. Risk of bias ranged from low to high, with the main concerns related to randomization reporting and prespecified analyses.

CONCLUSIONS: Current human evidence suggests that TMS can modulate postreactivation memory outcomes in ways that are, in some cases, compatible with a reconsolidation framework. However, effects are memory-system dependent, methodologically heterogeneous, and currently strongest in tightly controlled laboratory paradigms rather than in more naturalistic translational settings.

PMID:42536010 | DOI:10.1016/j.neurom.2026.05.016

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