Transcutaneous Trigeminal Nerve Stimulation Research Articles

Short-term transcutaneous trigeminal nerve stimulation does not affect visual oddball task and paired-click paradigm ERP responses in healthy volunteers

Recent research suggests that transcutaneous trigeminal nerve stimulation (TNS) may positively affect cognitive function. However, no clear-cut evidence is available yet, since the majority of it derives from clinical studies, and the few data on healthy subjects show inconsistent results. In this study, we report the effects of short-term TNS on event-related potentials (ERP) recorded during the administration of a simple visual oddball task and a paired-click paradigm, both considered useful for studying brain information processing functions. Thirty-two healthy subjects underwent EEG recording before and after 20min of sham- or real-TNS, delivered bilaterally to the infraorbital nerve. The amplitude and latency of P200 and P300 waves in the simple visual oddball task and P50, N100 and P200 waves in the paired-click paradigm were measured before and after treatment. Our results show that short-term TNS did not alter any of the ERP parameters measured, suggesting that in healthy subjects, short-term TNS may not affect brain processes involved in cognitive functions such as pre-attentional processes, early allocation of attention and immediate memory. The perspective of having an effective, non-pharmacological, non-invasive, and safe treatment option for cognitive decline is particularly appealing; therefore, more research on the positive effects on cognition of TNS is definitely needed.

Short-term neurochemical effects of transcutaneous trigeminal nerve stimulation using 7T magnetic resonance spectroscopy.

The purpose was to explore the effects of transcutaneous trigeminal nerve stimulation (TNS) on neurochemical concentrations (brainstem, anterior cingulate cortex [ACC], dorsolateral prefrontal cortex [DLPFC], ventromedial prefrontal cortex [VMPFC], and the posterior cingulate cortex [PCC]) using ultrahigh-field magnetic resonance spectroscopy. This double-blinded study tested 32 healthy males (age: 25.4±7.3years) on two separate occasions where participants received either a 20-minute TNS or sham session. Participants were scanned at baseline and twice post-TNS/sham administration. There were no group differences in concentration changes of glutamate, gamma-aminobutyric acid, glutamine, myoinositol (mI), total N-acetylaspartate, total creatine (tCr), and total choline between the baseline scan and the first post-TNS/sham scan and between the first and second post-TNS/sham scan in the brainstem, ACC, DLPFC, VMPFC, and PCC. Between the baseline scan and the second post-TNS/sham scan, changes in tCr (mean difference=0.280mM [0.075 to 0.485], p=.026) and mI (mean difference=0.662mM [0.203 to 1.122], p=.026) in the DLPFC differed between groups. Post hoc analyses indicated that there was a decrease in tCr (mean change=-0.201mM [-0.335 to -0.067], p=.003) and no change in mI (mean change=-0.327mM [-0.737 to 0.083], p=.118) in the TNS group; conversely, there was no change in tCr (mean change=-0.100mM [-0.074 to 0.274], p=.259) and an increase in mI (mean change=0.347mM [0.106 to 0.588], p=.005) in the sham group. These data demonstrate that a single session of unilateral TNS slightly decreased tCr concentrations in the DLPFC region.

SPECT imaging of cerebral blood flow changes induced by acute trigeminal nerve stimulation in drug-resistant epilepsy. A pilot study

ObjectiveTo 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). MethodsTen 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). ResultsAt 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. ConclusionShort-term TNS is followed a global increase in cortical perfusion, namely in the temporal and limbic lobes. SignificanceThe TNS-induced perfusion increase may reflect neurons’ activity changes in cortical areas implicated in the epilepsy network.

Transcutaneous trigeminal nerve stimulation modulates the hand blink reflex

The hand-blink reflex (HBR) is a subcortical response, elicited by the electrical stimulation of the median nerve, whose magnitude is specifically modulated according to the spatial properties of the defensive peripersonal space (DPPS) of the face. For these reasons, the HBR is commonly used as a model to assess the DPPS of the face. Little is known on the effects induced by the activation of cutaneous afferents from the face on the DPPS of the face. Therefore, we tested the effect of non-painful transcutaneous trigeminal nerve stimulation (TNS) on the amplitude of the HBR. Fifteen healthy participants underwent HBR recording before and after 20 min of sham- and real-TNS delivered bilaterally to the infraorbital nerve in two separate sessions. The HBR was recorded bilaterally from the orbicularis oculi muscles, following non-painful median nerve stimulation at the wrist. The HBR amplitude was assessed in the “hand‐far” and “hand‐near” conditions, relative to the hand position in respect to the face. The amplitudes of the hand-far and hand-near HBR were measured bilaterally before and after sham- and real-TNS. Real-TNS significantly reduced the magnitude of the HBR, while sham-TNS had no significant effect. The inhibitory effect of TNS was of similar extent on both the hand-far and hand-near components of the HBR, which suggests an action exerted mainly at brainstem level.

Effect of a 10-day transcutaneous trigeminal nerve stimulation (TNS) protocol for depression amelioration: A randomized, double blind, and sham-controlled phase II clinical trial

BackgroundMajor depressive disorder (MDD) is one of the leading causes of disability in the world. However, treatment options are still limited, and marked by high refractoriness rates, new approaches are needed to optimize clinical improvement. Trigeminal nerve stimulation (TNS) is an innovative neuromodulation strategy consisting on the application of an electric current over the trigeminal nerve that propagates stimuli towards brain areas involved in mood control. ObjectiveWe examined the effects of TNS in MDD after a 10-day experimental protocol. MethodsThis was a randomized, double blind, and sham-controlled phase II study with 24 patients with severe MDD. Patients underwent a 10-day intervention protocol and were assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17) at following three observation points: baseline (T1), after 10 days (T2), and after one month of the last stimulation session (T3). Main clinical outcome analysis of variance (ANOVA) was performed. ResultsPatients in the active group presented a mean reduction of 36.15% in depressive symptoms after the stimulation protocol. There was a significant interaction between group and time regarding HDRS-17 scores (F = 3.18; df = 2; p = 0.0456). Post hoc analyses exhibited a statistically significant difference between active and sham group symptoms at T2 (p = 0.040) and T3 (p = 0.026), which highlights the sustained amelioration of depressive symptoms. ConclusionThe present study found amelioration of depressive symptoms for patients undergoing a 10-day stimulation protocol of TNS, and this was sustained after one month of follow-up.

Effect of short-term transcutaneous trigeminal nerve stimulation on EEG activity in drug-resistant epilepsy

BackgroundTranscutaneous 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. ObjectivesTo investigate the effect of short-term TNS on EEG background activity in DRE by qualitative and quantitative analyses. MethodsTwenty-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. ResultsA 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. ConclusionsShort-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.

62. Transcutaneous trigeminal nerve stimulation (TNS) induces a long-term potentiation (LTP)-like plasticity of the blink reflex (BR) in patients with blepharospasm (BS)

TNS induces a long-term depression (LTD)-like plasticity of the BR in healthy subjects (controls). BS have an hyperexcitability of the BR recovery cycle (BRRC) and an altered brainstem plasticity [2;3]. TNS effects on BR and BRRC of BS was investigated in the present study. Seven BS and seven controls underwent BR and BRRC (inter-stimulus intervals: 200, 300, 500 ms) assessment before and at 0 (T0), 15 (T15) and 30 (T30) min after TNS delivery (120 Hz; 30 s ON, 30 s OFF for 20 min). R2 areas of the BR were similar in BS and controls at baseline but were significantly different (p < 0.001) following TNS administration, with a significant facilitation in BS at T15 (p = 0.006) and a significant inhibition in controls at T15 and T30 (p < 0.05). At baseline, the BRCC was significantly enhanced in BS compared with controls (p < 0.05) and appeared unchanged after TNS, in both groups. The BRRC was unaffected by TNS in both controls and BS, while the TNS-induced LTD of R2 circuits observed in controls was inverted into a LTP-like effect in BS. These preliminary data suggest that TNS may be a useful tool to evaluate an altered brainstem plasticity of brainstem circuits.

ID 215 – Transcutaneous trigeminal nerve stimulation induces a long-term depression-like plasticity of the human blink reflex

Objective To test the after-effects of 20-min, cyclic transcutaneous trigeminal nerve stimulation (TNS) on the excitability of the blink reflex (BR). Methods The areas of the R1 and R2 components of the BR were measured in 20 healthy subjects before and at 0–5, 15, 20, 30 and 45 min after TNS (asymmetric biphasic square wave pulses: duration 250 μ s, intensity 1–20 mA, frequency 120 Hz, alternating 30s ON, 30s OFF for 20 min) delivered bilaterally to the infraorbitary nerve. Results The areas of the R2 components of the BR were significantly suppressed at each time interval tested after TNS ( p Conclusions 20-min TNS did not affected the R1 component of the BR, while inducing a long lasting inhibition of the R2 component, possibly through a long-term depression (LTD)-like mechanism. The different effect on the two components of the BR suggests that only polysynaptic brainstem pathways may be modulated by TNS. Key message TNS is a useful tool to investigate the LTD-like plasticity of brainstem polysynaptic circuits in healthy subjects.

Trigeminal nerve stimulation modulates brainstem more than cortical excitability in healthy humans.

Multiple sites in the central nervous system (CNS) have been hypothesized to explain the beneficial effects of transcutaneous trigeminal nerve stimulation (TNS) on several disorders. This work investigated the acute effects of TNS on the excitability of brainstem and intracortical circuits, as well as on sensorimotor integration processes at cortical level in physiological conditions. Brainstem excitability was evaluated in seventeen healthy subjects measuring the R1 and R2 areas of the blink reflex (BR) and its recovery cycle, with cortical excitability and sensorimotor integration assessed by probing short-interval (SICI) and long-interval (LICI) intracortical inhibition, with short-interval (SICF), intracortical facilitation (ICF), short-latency (SAI) and long-latency (LAI) inhibition measuring motor potentials evoked in the first dorsal interosseous muscle by TMS of the contralateral motor cortex. Neurophysiological parameters were assessed, in seventeen healthy subjects, before and after cyclic 20-min TNS delivered bilaterally to the infraorbital nerve. After TNS, the area of the R2 was significantly reduced (p=0.018). By contrast, R1 area and R2 recovery cycle were unaffected. Similarly, SICI, ICF, LICI, SICF, SAI and LAI appeared unaltered after TNS. These data suggest that, in normal subjects, TNS mainly acts on brainstem polysynaptic circuits mediating the R2 component of the BR and plays a minor role in modifying the activity of higher-level structures involved in the R2 recovery cycle and in modulation of cortical excitability. A further investigation of a chronic TNS-induced effect may disclose a higher potential for TNS in producing measurable after effects on its CNS targets.