Temporal patterning of trigeminal nerve stimulation gates hippocampal plasticity across species
Chen, L.; Sun, Q.; Guo, X.; Wu, H.; Asamoah, B.; Ye, W.; Seminck, N.; Huang, H.; Laughlin, M. M.
Show abstract
Non-invasive neuromodulation can influence memory, but whether peripheral stimulation can engage hippocampal plasticity through a defined mechanism and translate across species remains unclear. Here we provide, to our knowledge, the first cross-species evidence linking trigeminal nerve stimulation to sustained hippocampal plasticity, direct human hippocampal engagement and associative-memory benefit. In rats, intermittent 200 Hz TNS produced persistent CA1 fEPSP potentiation and prolonged neuronal firing despite substantially lower cumulative charge than continuous 100-Hz stimulation. LC inhibition strongly suppressed these responses. In patients undergoing stereo-EEG monitoring, i200-TNS evoked prominent hippocampal and thalamic responses and increased hippocampal theta-gamma coupling. In a randomized active-sham crossover study, i200-TNS was associated with improved delayed occupation recall and accompanying EEG changes. These results link patterned trigeminal stimulation to hippocampal physiology across species and support its potential for engaging human memory-related networks.
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