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Objective To explore the cortical areas targeted by acute transcutaneous trigeminal nerve stimulation (TNS) in patients with drug-resistant epilepsy (DRE) using single photon emission computed tomography (SPECT). Methods Ten patients with DRE underwent brain SPECT at baseline and immediately after a 20-minute TNS (0.25 ms; 120 Hz; 30 s ON and 30 s OFF) applied bilaterally to the infraorbital nerve. The French Color Standard International Scale was used for qualitative analyses and z-scores were used to calculate the Odds Ratio (OR). Results At baseline global hypoperfusion (mainly in temporo-mesial, temporo-parietal and fronto-temporal and temporo-occipital areas) was detected in all patients. Following TNS, a global increase in cortical tracer uptake and a significant decrease in median hypoperfusion score were observed. A significant effect favoring a general TNS-induced increase in cortical perfusion (OR = 4.96; p = 0.0005) was detected in 70% of cases, with significant effects in the limbic (p = 0.003) and temporal (p = 0.003) lobes. Quantitative analyses of z-scores confirmed significant TNS-induced increases in perfusion in the temporal (+0.59 SDs; p = 0.001), and limbic (+0.43 SDs; p = 0.03) lobes. Conclusion Short-term TNS is followed a global increase in cortical perfusion, namely in the temporal and limbic lobes. Significance The TNS-induced perfusion increase may reflect neurons’ activity changes in cortical areas implicated in the epilepsy network.

Trigeminal nerve stimulation (TNS) is a non-invasive neuromodulation method which is increasingly used for its beneficial effects on symptoms of several neuropsychiatric disorders such as drug-resistant epilepsy. Sites and mechanisms of its action are still unknown. The present study was aimed at investigating the physiological effects of acute TNS on rest electroencephalographic (EEG) activity. EEG was recorded with a 19-channel EEG system from 18 healthy adults who underwent 20 min of sham- and real-TNS (cycles of 30 s ON and 30 s OFF) in two separate sessions. EEG was continuously acquired in the 10-min preceding TNS, during TNS in the "OFF" period and throughout 10 min after TNS. Mean frequency, total power over the 0.5-48 Hz frequency range and absolute power for delta, theta, alpha, beta and gamma bands were analyzed by a discrete Fast Fourier Transform algorithm. Interhemispheric and intrahemispheric coherences were also analyzed for each band at different time points. Intra- and interhemispheric coherences were significantly reduced for the beta frequencies only during real-TNS (p = 0.002 and p = 0.006, respectively). No TNS effect on the power spectra of any band was detected. A trend of increase in the mean EEG frequency total power during real-TNS (p = 0.03) and of decrease in interhemispheric gamma coherence after real-TNS (p = 0.01) was observed. Acute TNS may induce a spatially diffuse desynchronization of fast EEG rhythms in healthy adults, this desynchronization may underpin the antiepileptic effect of TNS described by clinical studies.

Background Transcutaneous trigeminal nerve stimulation (TNS) has antiepileptic effects in patients with drug-resistant epilepsy (DRE). However, whether and how TNS is able to modulate the electroencephalogram (EEG) background activity in patients with DRE is still unknown. Objectives To investigate the effect of short-term TNS on EEG background activity in DRE by qualitative and quantitative analyses. Methods Twenty-nine DRE patients participated in the study. Twenty-two were randomly divided into a “sham-TNS” or “real-TNS” group; seven patients underwent stimulation of the median nerve (MNS) at the wrist. Real-TNS was delivered bilaterally to the infraorbital nerve (trains of 1–20 mA, 120 Hz, cyclic modality for 20 min). The sham-TNS protocol mimicked the real-TNS one but at a zero intensity. For MNS, the same parameters as real-TNS were used. EEG was continuously acquired for 40 min: 10′ pre, 20′ during and 10′ post stimulation. EEG was visually inspected for interictal epileptiform discharge (IEDs) changes and processed by spectral analysis for changes in mean frequency and absolute power of each frequency band. Results A significant increase of EEG absolute alpha power was observed during real-TNS compared with the sham-TNS (F34,680 = 1.748; p = 0.006). Conversely, no significant effects were noticed either for quantitative analysis of other frequency bands or for IEDs detection. MNS proved unable to modulate EEG activity. Conclusions Short-term TNS induces an acute and specific effect on background EEG of DRE by increasing the absolute alpha band power. EEG alpha rhythm enhancement may index a cortical functional inhibition and act as a seizure-preventing mechanism.