Julia C Lobo, Alba Gutiérrez-Menéndez, Marta Mendez, Candela Zorzo
In animal models, TMS consistently improved spatial learning and memory under pathological conditions, including neurodegenerative, vascular, stress-related, and injury models. These effects were associated with convergent mechanisms, including restoration of hippocampal long- term potentiation, modulation of neurotrophic signaling, reduced apoptosis and neuroinflammation, enhanced synaptic plasticity, and recovery of hippocampal network function. In contrast, findings in healthy animals were mixed and strongly dependent on stimulation parameters. Human findings were similarly variable. Improvements were observed in some clinical populations, whereas results in healthy individuals were inconsistent and task dependent. Neurophysiological evidence indicated modulation of oscillatory activity and hippocampal-cortical connectivity, although these changes did not always translate into measurable behavioral effects.
INTRODUCTION: Spatial memory relies on distributed hippocampal-cortical networks that are highly sensitive to modulation of excitability, connectivity, and synaptic plasticity. Transcranial magnetic stimulation (TMS) has emerged as a promising tool to experimentally probe and therapeutically modulate these networks, although its effects on spatial memory remain heterogeneous.
METHODS: We conducted a PRISMA-guided systematic review synthesizing evidence from rodent and human studies examining the effects of TMS on spatial memory. A total of 35 studies (23 animal, 12 human) identified through searches of Scopus, Web of Science, and PubMed were included, encompassing a broad range of stimulation protocols, behavioral paradigms, and neurophysiological outcomes.
RESULTS: In animal models, TMS consistently improved spatial learning and memory under pathological conditions, including neurodegenerative, vascular, stress-related, and injury models. These effects were associated with convergent mechanisms, including restoration of hippocampal long- term potentiation, modulation of neurotrophic signaling, reduced apoptosis and neuroinflammation, enhanced synaptic plasticity, and recovery of hippocampal network function. In contrast, findings in healthy animals were mixed and strongly dependent on stimulation parameters. Human findings were similarly variable. Improvements were observed in some clinical populations, whereas results in healthy individuals were inconsistent and task dependent. Neurophysiological evidence indicated modulation of oscillatory activity and hippocampal-cortical connectivity, although these changes did not always translate into measurable behavioral effects.
DISCUSSION: Overall, TMS effects on spatial memory appear to be strongly state-dependent, reflecting interactions between stimulation parameters and underlying circuit integrity. Further research should prioritize multimodal approaches integrating behavioral and neurophysiological measures, particularly in clinical populations, to improve mechanistic understanding and translational applicability.
SYSTEMATIC REVIEW REGISTRATION: https://osf.io/, identifier 10.17605/OSF.IO/32VWN.