Individual susceptibility to TMS affirms the precuneual role in metamemory upon recollection

Background A recent virtual-lesion study using inhibitory repetitive transcranial magnetic stimulation (rTMS) confirmed the causal behavioral relevance of the precuneus in the evaluation of one’s own memory performance (aka mnemonic metacognition). Objective This study’s goal is to elucidate how these TMS-induced neuromodulatory effects might relate to the neural correlates and be modulated by individual anatomical profiles in relation to meta-memory. Methods In a within-subjects design, we assessed the impact of 20-min rTMS over the precuneus, compared to the vertex, across three magnetic resonance imaging (MRI) neuro-profiles on 18 healthy subjects during a memory versus a perceptual task. Results Task-based functional MRI revealed that BOLD signal magnitude in the precuneus is associated with variation in individual meta-memory efficiency, and such correlation diminished significantly following TMS targeted at the precuneus. Moreover, individuals with higher resting-state functional connectivity (rs-fcMRI) between the precuneus and the hippocampus, or smaller grey matter volume in the stimulated precuneal region exhibit considerably higher vulnerability to the TMS effect. These effects were not observed in the perceptual domain. Conclusion We provide compelling evidence in outlining a possible circuit encompassing the precuneus and its mnemonic midbrain neighbor the hippocampus at the service of realizing our meta-awareness during memory recollection of episodic details. Highlights TMS on precuneus reduces meta-memory ability during memory retrieval. TMS disrupts the correlation between BOLD activity and meta-memory ability. TMS effect is modulated by rs-fcMRI between precuneus and hippocampus. Individuals with greater precuneal grey matter volume more immune to TMS effect.