Trigeminal nerve direct current stimulation causes sustained increase in neural activity in the rat hippocampus.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation method that can modulate many brain functions including learning and memory. Recent evidence suggests that tDCS memory effects may be caused by co-stimulation of scalp nerves such as the trigeminal nerve (TN), and not the electric field in the brain. The TN gives input to brainstem nuclei, including the locus coeruleus that controls noradrenaline release across brain regions, including hippocampus. However, the effects of TN direct current stimulation (TN-DCS) are currently not well understood. HYPOTHESIS: In this study we tested the hypothesis that stimulation of the trigeminal nerve with direct current manipulates hippocampal activity via an LC pathway. METHODS: We recorded neural activity in rat hippocampus using multichannel silicon probes. We applied 3 min of 0.25 mA or 1 mA TN-DCS, monitored hippocampal activity for up to 1 h and calculated spikes-rate and spike-field coherence metrics. Subcutaneous injections of xylocaine were used to block TN, while intraperitoneal and intracerebral injection of clonidine were used to block the LC pathway. RESULTS: We found that 1 mA TN-DCS caused a significant increase in hippocampal spike-rate lasting 45 min in addition to significant changes in spike-field coherence, while 0.25 mA TN-DCS did not. TN blockage prevented spike-rate increases, confirming effects were not caused by the electric field in the brain. When 1 mA TN-DCS was delivered during clonidine blockage no increase in spike-rate was observed, suggesting an important role for the LC-noradrenergic pathway. CONCLUSION: These results support our hypothesis and provide a neural basis to understand the tDCS TN co-stimulation mechanism. TN-DCS emerges as an important tool to potentially modulate learning and memory.

Sensory nerve conduction stimulus threshold measurements of the infraorbital nerve and its applicability as a diagnostic tool in horses with trigeminal-mediated headshaking.

BACKGROUND: To determine whether sensory nerve conduction stimulus threshold measurements of the infraorbital nerve are able to differentiate horses with idiopathic trigeminal-mediated headshaking (i-TMHS) from healthy horses and from horses with secondary trigeminal-mediated headshaking (s-TMHS). In a prospective trial, headshaking horses were examined using a standardized diagnostic protocol, including advanced diagnostics such as computed tomography and 3-Tesla-magnetic resonance imaging (MRI), to differentiate s-TMHS from i-TMHS. Clinically healthy horses served as controls. Within this process, patients underwent general anesthesia, and the minimal sensory nerve conduction stimulus threshold (SNCT) of the infraorbital nerve was measured using a bipolar concentric needle electrode. Sensory nerve action potentials (SNAP) were assessed in 2.5-5 mA intervals. Minimal SNCT as well as additional measurements were calculated. RESULTS: In 60 horses, SNAP could be recorded, of which 43 horses had i-TMHS, six had suspected s-TMHS, three horses had non-facial headshaking, and eight healthy horses served as controls. Controls had a minimal SNCT ≥ 15 mA, whereas 14/43 horses with i-TMHS and 2/6 horses with s-TMHS showed a minimal SNCT ≤ 10 mA. Minimal SNCT ≤ 10 mA showed 100% specificity to distinguish TMHS from controls, but the sensitivity was only 41%. CONCLUSION: A minimal SNCT of the infraorbital nerve ≤ 10 mA was able to differentiate healthy horses from horses with TMHS. Nevertheless, a higher minimal SNCT did not exclude i-TMHS or s-TMHS and minimal SNCT does not distinguish s-TMHS from i-TMHS.

A measure of the blink reflex to parametric variation of mechanical stimulation of the trigeminal nerve.

The primary goal of this study was to develop a parametric model that relates variation in stimulation of the trigeminal nerve to properties of the blink response. We measured blink responses in 17 healthy, adult participants to air puffs directed at the lateral canthus of the eye at five different, log-spaced intensities (3.5-60 PSI). Lid position over time was decomposed into amplitude and velocity components. We found that blink amplitude was systematically related to log stimulus intensity, with the relationship well described by a sigmoidal function. The parameters of the model fit correspond to the slope of the function and the stimulus intensity required to produce half of a maximal blink response (the half-response threshold). There was a reliable increase in the half-response threshold for the contralateral as compared to the ipsilateral blink response. This increase was consistent across participants despite substantial individual differences in the half-response threshold and slope parameters of the overall sensitivity function, suggesting that the laterality effect arises in the neural circuit subsequent to individual differences in sensitivity. Overall, we find that graded mechanical stimulation of the somatosensory trigeminal afferents elicits a graded response that is well described by a simple parametric model. We discuss the application of parametric measurements of the blink response to the detection of group differences in trigeminal sensitivity.

Giuseppe Dagnini (1866-1928): Discoverer of the Trigemino-Cardiac Reflex and Practical Implications in Neurosurgery and Other Medical Specialties.

The authors present the life and art of Giuseppe Dagnini, a renowned Italian physician who was born in Bologna in 1866. He was the chief of the Maggiore Hospital in Bologna and authored valuable scientific works on the trigemino-cardiac reflex which is still applied in modern clinical practice. Dr. Dagnini firstly described the reflex in 1908 postulating that stimulation of one of the 3 branches of the trigeminal nerve triggers the afferent pathway in lowering heart rate. The authors also provide a modern outlook on the clinical implications of the TCR in neurosurgery, neuroanesthesia, and other medical specialties.

Efficacy and safety of trigeminal parasympathetic pathway stimulation for dry eye: A systematic review and meta-analysis.

This study aimed to investigate the efficacy and safety of trigeminal parasympathetic pathway (TPP) stimulation in the treatment of dry eye. A comprehensive search for randomized clinical trials was performed in seven databases (MEDLINE, Embase, CENTRAL, etc.) up to 28 February 2023. After screening the suitable studies, the data were extracted and transformed as necessary. Data synthesis and analysis were performed using Review Manager 5.4, and the risk of bias and quality of evidence were evaluated with the recommended tools. Fourteen studies enrolling 1714 patients with two methods (electrical and chemical) of TPP stimulation were included. Overall findings indicate that TPP stimulation was effective in reducing subjective symptom score (standardized mean difference [SMD], -0.45; 95% confidence interval [CI], -0.63 to -0.28), corneal fluorescence staining (mean difference [MD], -0.78; 95% CI, -1.39 to -0.18), goblet cell area (MD, -32.10; 95% CI, -54.58 to -9.62) and perimeter (MD, -5.90; 95% CI, -10.27 to -1.53), and increasing Schirmer's test score (SMD, 0.98; 95% CI, 0.65 to 1.31) and tear film break-up time (SMD, 0.57; 95% CI, 0.19 to 0.95). Compared to inactive or low-activity stimulation controls, it has a higher incidence of adverse events. Therefore, TPP stimulation may be an effective treatment for dry eye, whether electrical or chemical. Adverse events are relatively mild and tolerable. Due to the high heterogeneity and low level of evidence, the current conclusions require to be further verified.

Extracranial transport of brain lymphatics via cranial nerve in human.

Extracranial waste transport from the brain interstitial fluid to the deep cervical lymph node (dCLN) is not extensively understood. The present study aims to show the cranial nerves that have a role in the transport of brain lymphatics vessels (LVs), their localization, diameter, and number using podoplanin (PDPN) and CD31 immunohistochemistry (IHC) and Western blotting. Cranial nerve samples from 6 human cases (3 cadavers, and 3 autopsies) were evaluated for IHC and 3 autopsies for Western blotting. The IHC staining showed LVs along the optic, olfactory, oculomotor, trigeminal, facial, glossopharyngeal, accessory, and vagus nerves. However, no LVs present along the trochlear, abducens, vestibulocochlear, and hypoglossal nerves. The LVs were predominantly localized at the endoneurium of the cranial nerve that has motor components, and LVs in the cranial nerves that had sensory components were present in all 3 layers. The number of LVs accompanying the olfactory, optic, and trigeminal nerves was classified as numerous; oculomotor, glossopharyngeal, vagus, and accessory was moderate; and facial nerves was few. The largest diameter of LVs was in the epineurium and the smallest one was in the endoneurium. The majority of Western blotting results correlated with the IHC. The present findings suggest that specific cranial nerves with variable quantities provide a pathway for the transport of wastes from the brain to dCLN. Thus, the knowledge of the transport of brain lymphatics along cranial nerves may help understand the pathophysiology of various neurological diseases.

The feasibility and technical aspects of trigemino-cervical reflex elicitation in humans under general anesthesia.

OBJECTIVE: To analyze the feasibility, neurophysiological aspects, stimulation patterns, and topographic distribution of trigemino-cervical reflex (TCR) components in humans under general anesthesia. METHODS: This prospective observational study enrolled 20 participants who underwent posterior fossa surgery, surgical proceduresin thecraniovertebral junction,or spinal cord surgery. TCR responses were simultaneously recorded in the sternocleidomastoid (SCM) and trapezius muscles after electrical stimulation of the supraorbital and infraorbital nerves. TCR responses were recorded preoperatively and intraoperatively using single-pulse and multipulse (trains of 2-7 electrical stimuli) stimulation, respectively. Two stimulus duration patterns were evaluated: 0.2-0.5 ms and 0.5-1.0 ms. RESULTS: Intraoperatively, short- and long-latency TCR components were obtained in the SCM ipsilateral to the stimulation with variable recordability. Short-latency responses were the most commonly recorded components. A longer stimulus duration (0.5-1.0 ms) seems to favor the elicitation of TCR responses under general anesthesia. CONCLUSIONS: Short-latency components recorded in the SCM ipsilateral to the stimulation could be regularly elicited under general anesthesia when a larger stimulus duration (0.5-1.0 ms) was applied. SIGNIFICANCE: This is the first study to demonstrate the elicitation of TCR components in humans under general anesthesia. This neurophysiological technique can potentially optimize intraoperative neurophysiological monitoring during brainstem surgery.

Assessment of Intranasal Function of the Trigeminal Nerve in Daily Clinical Practice.

BACKGROUND: The trigeminal nerve is a mixed cranial nerve responsible for the motor innervation of the masticatory muscles and the sensory innervation of the face, including the nasal cavities. Through its nasal innervation, we perceive sensations, such as cooling, tingling, and burning, while the trigeminal system mediates the perception of airflow. However, the intranasal trigeminal system has received little attention in the clinical evaluation of patients with nasal pathology. SUMMARY: Testing methods that enable the clinical assessment of intranasal trigeminal function have recently been developed. This study aims to present the current clinical methods that can be utilised in everyday practice, as described in the literature. These methods include four assessment techniques: (1) the quick screening test of trigeminal sensitivity involves patients rating the intensity of ammonium vapour presented in a lipstick-like container. (2) The lateralisation test requires subjects to identify which nasal cavity is being stimulated by a trigeminal stimulus, such as eucalyptol or menthol, while the other side receives an odourless stimulus. (3) The trigeminal sticks test evaluates the trigeminal function similarly to the olfactory function using sticks filled with trigeminal stimulant liquids. (4) The automated CO2 stimulation device is used for measuring trigeminal pain thresholds, utilising intranasal CO2 stimuli to define the pain threshold. KEY MESSAGES: Assessing intranasal trigeminal function clinically may prove useful in evaluating rhinology patients, particularly those who encounter nasal obstruction without anatomical blockage and those experiencing olfactory disorders with suspected trigeminal dysfunction. Despite their limitations, the presented methods may provide useful information about nasal patency, chemosensitivity, and pain sensation in the daily clinical practice of such patients, leading to better therapeutic decisions.

Technical Aspects of Eliciting Trigeminocervical and Trigeminospinal Reflexes in Humans: A Scoping Review.

SUMMARY: This scoping review aims to summarize the technical strategies for obtaining trigeminocervical reflex (TCR) and trigeminospinal reflex (TSR) responses. Studies published on TCR or TSR elicitation in humans through electrical stimulation of trigeminal nerve branches were eligible for this scoping review. The data of interest included stimulation parameters, site of stimulation, recording parameters, and the feasibility of TCR and TSR elicitation, in healthy participants. Short-latency TCR responses were regularly obtained in both anterior and posterior neck muscles after electrical stimulation of the supraorbital and infraorbital nerves under voluntary muscle activation. However, without voluntary muscle activation, we found evidence of elicitation of short-latency TCR components only in the posterior neck muscles after supraorbital or infraorbital nerve stimulation. Long-latency TCR responses were regularly obtained in the anterior and posterior neck muscles in studies that evaluated this technique, regardless of the trigeminal branch stimulation or muscle activation status. Short-latency TSR components were not obtained in the included studies, whereas long-latency TSR responses were regularly recorded in proximal upper limb muscles. This scoping review revealed key heterogeneity in the techniques used for TCR and TSR elicitation. By summarizing all the methodological procedures used for TCR and TSR elicitation, this scoping review can guide researchers in defining optimized technical approaches for different research and clinical scenarios.

Multimodal acoustic-electric trigeminal nerve stimulation modulates conscious perception.

Multimodal stimulation can reverse pathological neural activity and improve symptoms in neuropsychiatric diseases. Recent research shows that multimodal acoustic-electric trigeminal-nerve stimulation (TNS) (i.e., musical stimulation synchronized to electrical stimulation of the trigeminal nerve) can improve consciousness in patients with disorders of consciousness. However, the reliability and mechanism of this novel approach remain largely unknown. We explored the effects of multimodal acoustic-electric TNS in healthy human participants by assessing conscious perception before and after stimulation using behavioral and neural measures in tactile and auditory target-detection tasks. To explore the mechanisms underlying the putative effects of acoustic-electric stimulation, we fitted a biologically plausible neural network model to the neural data using dynamic causal modeling. We observed that (1) acoustic-electric stimulation improves conscious tactile perception without a concomitant change in auditory perception, (2) this improvement is caused by the interplay of the acoustic and electric stimulation rather than any of the unimodal stimulation alone, and (3) the effect of acoustic-electric stimulation on conscious perception correlates with inter-regional connection changes in a recurrent neural processing model. These results provide evidence that acoustic-electric TNS can promote conscious perception. Alterations in inter-regional cortical connections might be the mechanism by which acoustic-electric TNS achieves its consciousness benefits.

Mesencephalic trigeminal nucleus neurons with collaterals to both eyelid and masseter muscles shown by fluorescent double-labeling, revealing a potential mechanism for Marcus Gunn Syndrome.

Poking palpebral conjunctiva evoked upper-eyelid retraction during ophthalmic surgery. Iatrogenic eyelid ptosis occurred if eyelid branch of lachrymal nerve was sectioned. Mesencephalic trigeminal nucleus (Vme) neurons were labeled when tracer injected into lachrymal nerve innervating eyelid Mueller's muscle. Masseter afferent Vme neurons projecting to oculomotor nucleus (III) was observed in toad and rat, which helps amphibians to stare prey when they open mouth widely to prey. We hypothesized single Vme neurons may have peripheral collaterals to both eyelid and masseter muscles. WGA-594 was injected into upper eyelid, and WGA-488 was simultaneously delivered into ipsilateral masseter muscle in the same rat. Then, double labeled Vme neurons were found under both conventional and confocal microscope. Meanwhile, contact of WGA-594 positive eyelid afferent Vme neurons with WGA-488 labeled masseter afferent ones were observed sometimes. Combined with our previous observation of oculomotor projection Vme neurons, we thought WGA-594/488 double labeled Vme cells, at least some of them, are oculomotor projecting ones. Contact between eyelid and masseter afferent Vme neurons are supposed to be electrotonically coupled, based on a line of previous studies. If exogenous or genetic factors make these Vme neurons misinterpret masseter input as eyelid afferent signals, these Vme neurons might feedforward massages to eyelid retractor motoneurons in the III. Besides, oculomotor projecting Vme neurons might be co-fired by adjacent masseter afferent Vme neurons through electrotonic coupling once the masseter muscle is activated. In these cases, Marcus Gunn Syndrome might occur. This finding leads to a new hypothesis for the Syndrome.

Diagnostic Value of Blink Reflex Combined with Trigeminal Somatosensory Evoked Potential in Trigeminal Neuralgia.

Objective: To explore the diagnostic value of blink reflex combined with trigeminal somatosensory evoked potential (TSEP) in trigeminal neuralgia. Methods: A total of 147 patients with trigeminal neuralgia were enrolled as the research objects between February 2022 and February 2023. After admission, all underwent blink reflex on affected/healthy sides and TSEP examinations. The diagnostic value of the blink reflex combined with TSEP was analyzed. Results: The latency of R1, R2, and R2' waves (refers to the different nerve signal waveforms that are recorded when a facial nerve conduction speed test is performed) on the affected side was significantly longer than that on the healthy side (t = 26.324, 18.391, 20.801,Ps < .001), and latency of W1, W2 and W3 waves was also significantly longer than that on the healthy side (t = 16.045, 10.814, 10.349, P < .001). The results of Pearson correlation analysis showed that the latency of R1, W1, W2, and W3 waves was positively correlated with the VAS score (r = 0.539, 0.611, 0.577, 0.586, P < .001). The results of receiver operating characteristic (ROC) curves analysis showed that area under the curve (AUC) values of R1, R2, R2', W1, W2, and W3 waves latency on the affected side in the diagnosis of trigeminal neuralgia were 0.753, 0.634, 0.651, 0.748, 0.756 and 0.736, respectively. The AUC of combined detection was 0.926, significantly greater than that of the single index (P < .001). Conclusion: Blink reflex combined with TSEP monitoring can improve the diagnostic value of trigeminal neuralgia, and the latency is related to pain.

Intranasal trigeminal sensitivity to mechanical stimuli is associated with the perception of nasal patency.

PURPOSE: The aim of this prospective study was to examine the characteristics of a clinical test for the assessment of nasal trigeminal sensitivity to mechanical stimuli and its association with the perception of nasal patency. METHODS: Thirty-two normosmic healthy subjects participated (17 women and 15 men; age = 26 ± 3 years). Precisely defined air puffs were used with a flow rate of 2L/min for mechanical stimulation. They were presented to the nasal vestibule, nasal septum, and inferior turbinate with various stimulus durations. Thresholds were measured by single-staircase stimuli with changes in stimulus duration in steps of 10 ms. Trigeminal suprathreshold intensity was rated by subjects for stimulus durations of 200, 300, 400, and 500 ms. Test-retest reliability was examined by intraclass correlations (ICCs) and Bland-Altman plot with limits of agreement. Pearson's correlations were calculated between self-rated nasal patency and nasal trigeminal sensitivity. RESULTS: As indicated by trigeminal threshold and suprathreshold intensities, the nasal vestibule is the most sensitive area among the three locations, followed by the nasal septum and the inferior turbinate (p < 0.001). Coefficients of correlations between test and retest were 0.76 for thresholds, and 0.56 suprathreshold intensities (p < 0.001). The Bland-Altman analysis showed a good agreement between test-retest values. In addition, significant positive associations between trigeminal suprathreshold intensities and self-rated nasal obstruction were found at the inferior turbinate (r = 0.4, p < 0.05). CONCLUSION: Reliable assessment of nasal trigeminal sensitivity for air puffs appears to be possible. Nasal trigeminal suprathreshold sensitivity to mechanical stimuli is associated with the perception of nasal patency at the inferior turbinate. This opens a window into the assessment of the perception of nasal airflow in various clinical purposes, especially for patients with sinonasal diseases.

Intraoperative Mapping of the Sensory Root of the Trigeminal Nerve in Patients with Pontocerebellar Angle Pathology.

OBJECTIVE: The aim of the present study was to determine the position of the 3 sensory branches of the trigeminal nerve in the preganglionic tract using intraoperative neurophysiological mapping. METHODS: We included consecutive adult patients who underwent neurosurgical treatment of cerebellopontine angle lesions. The trigeminal nerve was antidromically stimulated at 3 sites along its circumference with different stimulus intensities at a distance of ≤1 cm from the brainstem. The sensory nerve action potentials (SNAPs) were recorded from each main trigeminal branch (V1 [ophthalmic branch], V2 [maxillary branch], and V3 [mandibular branch]). RESULTS: We analyzed 13 patients. The stimulation points at which we obtained the greatest number of congruous and exclusive SNAPs (SNAPs only on the stimulated branch) was the stimulation point for V3 (20.7%). The stimulation intensity at which we obtained the highest number of congruent and exclusive SNAPs with the stimulated branch was 0.5 mA. CONCLUSIONS: Using our recording conditions, trigeminal stimulation is a reliable technique for mapping the V3 and V1 branches using an intensity not exceeding 0.5. However, reliable identification of the fibers of V2 is more difficult. Stimulation of the trigeminal nerve can be a reliable technique to identify the V3 and V1 branches if rhizotomy of these branches is necessary.

Chemosensation in anxiety: the trigeminal system matters.

The presence of a perceptual bias due to anxiety is well demonstrated in cognitive and sensory task for the visual and auditory modality. Event-related potentials, by their specific measurement of neural processes, have strongly contributed to this evidence. There is still no consensus as to whether such a bias exists in the chemical senses; chemosensory event-related potentials (CSERPs) are an excellent tool to clarify the heterogeneous results, especially since the Late Positive Component (LPC) may be an indicator of emotional involvement after chemosensory stimulation. This research examined the association between state and trait anxiety and the amplitude and latency of pure olfactory and mixed olfactory-trigeminal LPC. In this study, 20 healthy participants (11 women) with a mean age of 24.6 years (SD = 2.6) completed a validated questionnaire to measure anxiety (STAI), and CSERP was recorded during 40 pure olfactory stimulations (phenyl ethanol) and 40 mixed olfactory-trigeminal stimulations (eucalyptol). LPC latency and amplitude were measured at Cz (electrode located at midline central) for each participant. We observed a significant negative correlation between LPC latencies and the state anxiety scores for the mixed olfactory-trigeminal condition (r(18) = -0.513; P = 0.021), but not for the pure olfactory condition. We did not observe any effect on LPC amplitudes. This study suggests that a higher level of state anxiety is related to a more rapid perceptual electrophysiological response for mixed olfactory-trigeminal stimuli but not for pure odors.

Impact of trigeminal and/or olfactory nerve stimulation on measures of inspiratory neural drive: Implications for breathlessness.

The perception of breathlessness is mechanistically linked to the awareness of increased inspiratory neural drive (IND). Stimulation of upper airway cold receptors on the trigeminal nerve (TGN) with TGN agonists such as menthol or cool air to the face/nose has been hypothesized to reduce breathlessness by decreasing IND. The aim of this systematic scoping review was to identify and summarize the results of studies in animals and humans reporting on the impact of TGN stimulation or blockade on measures of IND. Thirty-one studies were identified, including 19 in laboratory animals and 12 in human participants. Studies in laboratory animals consistently reported that as TGN activity increased, measures of IND decreased (e.g., phrenic nerve activity). In humans, stimulation of the TGN with a stream of cool air to the face/nose decreased the sensitivity of the ventilatory chemoreflex response to hypercapnia. Otherwise, TGN stimulation with menthol or cool air to the face/note had no effect on measures of IND in humans. This review provides new insight into a potential neural mechanism of breathlessness relief with selected TGN agonists.

Impact of trigeminal nerve and/or olfactory nerve stimulation on activity of human brain regions involved in the perception of breathlessness.

Breathlessness is a centrally processed symptom, as evidenced by activation of distinct brain regions such as the insular cortex and amygdala, during the anticipation and/or perception of breathlessness. Inhaled L-menthol or blowing cool air to the face/nose, both selective trigeminal nerve (TGN) stimulants, relieve breathlessness without concurrent improvements in physiological outcomes (e.g., breathing pattern), suggesting a possible but hitherto unexplored central mechanism of action. Four databases were searched to identify published reports supporting a link between TGN stimulation and activation of brain regions involved in the anticipation and/or perception of breathlessness. The collective results of the 29 studies demonstrated that TGN stimulation activated 12 brain regions widely implicated in the anticipation and/or perception of breathlessness, including the insular cortex and amygdala. Inhaled L-menthol or cool air to the face activated 75% and 33% of these 12 brain regions, respectively. Our findings support the hypothesis that TGN stimulation contributes to breathlessness relief by altering the activity of brain regions involved in its central neural processing.

Trigeminal stimulation is required for neural representations of bimodal odor localization: A time-resolved multivariate EEG and fNIRS study.

Whereas neural representations of spatial information are commonly studied in vision, olfactory stimuli might also be able to create such representations via the trigeminal system. We explored in two independent multi-method electroencephalography-functional near-infrared spectroscopy (EEG+fNIRS) experiments (n1=18, n2=14) if monorhinal odor stimuli can evoke spatial representations in the brain. We tested whether this representation depends on trigeminal properties of the stimulus, and if the retention in short-term memory follows the "sensorimotor recruitment theory", using multivariate representational similarity analysis (RSA). We demonstrate that the delta frequency band up to 5 Hz across the scull entail spatial information of which nostril has been stimulated. Delta frequencies were localized in a network involving primary and secondary olfactory, motor-sensory and occipital regions. RSA on fNIRS data showed that monorhinal stimulations evoke neuronal representations in motor-sensory regions and that this representation is kept stable beyond the time of perception. These effects were no longer valid when the odor stimulus did not sufficiently stimulate the trigeminal nerve as well. Our results are first evidence that the trigeminal system can create spatial representations of bimodal odors in the brain and that these representations follow similar principles as the other sensory systems.

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 20 min 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.