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.

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.

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.

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.

Odor-induced sound localization bias under unilateral intranasal trigeminal stimulation.

As a stereo odor cue, internostril odor influx could help us in many spatial tasks, including localization and navigation. Studies have also revealed that this benefit could be modulated by the asymmetric concentrations of both influxes (left nose vs right nose). The interaction between olfaction and vision, such as in object recognition and visual direction judgment, has been documented; however, little has been revealed about the impact of odor cues on sound localization. Here we adopted the ventriloquist paradigm in auditory-odor interactions and investigated sound localization with the concurrent unilateral odor influx. Specifically, we teased apart both the "nature" of the odors (pure olfactory stimulus vs. mixed olfactory/trigeminal stimulus) and the location of influx (left nose vs. right nose) and examined sound localization with the method of constant stimuli. Forty-one participants, who passed the Chinese Smell Identification Test, perceived sounds with different azimuths (0°, 5°, 10°, and 20° unilaterally deflected from the sagittal plane by head-related transfer function) and performed sound localization (leftward or rightward) tasks under concurrent, different unilateral odor influxes (10% v/v phenylethyl alcohol, PEA, as pure olfactory stimulus, 1% m/v menthol as mixed olfactory/trigeminal stimulus, and propylene glycol as the control). Meanwhile, they reported confidence levels of the judgments. Results suggested that unilateral PEA influx did not affect human sound localization judgments. However, unilateral menthol influx systematically biased the perceived sound localization, shifting toward the odor source. Our study provides evidence that unilateral odor influx could bias perceived sound localization only when the odor activates the trigeminal nerves.

Ontogeny of the trigeminal system and associated structures in Alligator mississippiensis.

From the appearance of the vertebrate head, the trigeminal system has played a role in behavioral and ecological adaptation. The trigeminal nerve is the primary cranial somatosensory nerve, also innervating the jaw muscles. In crocodylians, the trigeminal nerve plays a role in modulating the high bite force and unique integumentary sensation. In association with these behaviors, crocodylians are known for large trigeminal nerves, a high volume of trigeminal-innervated musculature, and densely packed, specialized sensory receptors. These innovations also occurred in concert with a restructuring of the lateral braincase wall. These morphologies have previously been investigated in phylogenetic and evolutionary contexts, but an ontogenetic, whole-system investigation of trigeminal tissue and associated musculature, cartilage, and bone is lacking, as is an understanding of developmental timing of morphologies significant to hypotheses of homology. Here, we use contrast-enhanced computed tomography imaging to provide description and analysis of the trigeminal system in an ontogenetic series of Alligator mississippiensis from embryonic to adult form. We explore growth rates and allometric relationships of structures and discuss the significance to hypotheses of homology. We find a high growth rate and allometric trajectory of the trigeminal nerve in comparison to other cranial nerves, likely associated with the large volume of trigeminal musculature and high densities of sensory receptors. We identify a similar trend in the pterygoideus dorsalis muscle, the highest contributor to bite force. We narrow ontogenetic timing of features related to the trigeminal topological paradigm and the undeveloped epipterygoid. Overall, we provide a basis for understanding trigeminal development in crocodylians, which upon comparison across reptiles will reveal ontogenetic origins of morphological variation.

Electrical stimulation of the trigeminal nerve improves olfaction in healthy individuals: A randomized, double-blind, sham-controlled trial.

BACKGROUND: Both activated by environmental odorants, there is a clear role for the intranasal trigeminal and olfactory nerves in smell function. Unfortunately, our ability to perceive odorants decreases with age or with injury, and limited interventions are available to treat smell loss. OBJECTIVE: We investigated whether electrical stimulation of the trigeminal nerve via trigeminal nerve stimulation (TNS) or transcranial direct current stimulation (tDCS) modulates odor sensitivity in healthy individuals. METHODS: We recruited 20 healthy adults (12 Female, mean age = 27) to participate in this three-visit, randomized, double-blind, sham-controlled trial. Participants were randomized to receive one of three stimulation modalities (TNS, tDCS, or sham) during each of their visits. Odor detection thresholds were obtained at baseline, immediately post-intervention, and 30-min post-intervention. Furthermore, participants were asked to complete a sustained attention task and mood assessments before odor detection testing. RESULTS: Findings reveal a timeXcondition interaction for guaiacol (GUA) odorant detection thresholds (F (3.188, 60.57) = 3.833, P = 0.0125), but not phenyl ethyl alcohol (PEA) odorant thresholds. At 30-min post-stimulation, both active TNS and active tDCS showed significantly increased sensitivity to GUA compared to sham TNS (Sham TNS = -8.30% vs. Active TNS = 9.11%, mean difference 17.43%, 95% CI 5.674 to 29.18, p = 0.0044; Sham TNS = -8.30% vs. Active tDCS = 13.58%, mean difference 21.89%, 95% CI 10.47 to 33.32, p = 0.0004). CONCLUSION: TNS is a safe, simple, noninvasive method for boosting olfaction. Future studies should investigate the use of TNS on smell function across different stimulation parameters, odorants, and patient populations.

The Effectiveness of Trigeminal Nerve Stimulation on Traumatic Brain Injury.

OBJECTIVES: Trigeminal nerve stimulation (TNS) is a promising strategy in treating diseases of the nervous system. In this study, the effects of TNS on traumatic brain injury (TBI) were investigated in a mouse model. MATERIALS AND METHODS: TBI was induced using a weight-drop device, and TNS treatment was delivered in the first hour after the TBI. Twenty-four hours later, the mice's behavior, brain edema, and expression of inflammatory factors were tested. Functional magnetic resonance imaging also was used to explore the possible effects of TNS on brain activity. RESULTS: TNS alleviates TBI-induced neurological dysfunction in animal behavior tests, besides protecting the blood-brain barrier and reducing the level of brain edema. TNS also effectively reduces the level of tumor necrosis factor-α and interleukin 6 and downregulates the cleaved caspase-3 signaling pathway. A series of brain areas was found to be possibly regulated by TNS, thus affecting the neural functions of animals. CONCLUSION: This study elucidates the role of TNS as an effective treatment for TBI by inhibiting the occurrence of a secondary brain injury.

Intraoperative Sneezing Secondary to Indirect Olfactory Nerve Stimulation.

Sneezing is a poorly understood, protective reflex response. It's characterized by the following sequence: eye closure, inspiration, glottic closure, forced expiration with sudden glottic opening, and release of an elevated intrathoracic pressure creating a flow of explosive air through the nose.1 Studies have indicated an anatomic sneezing area of the brainstem corresponding to the central recipient zone of the nasal sensory neurons in the lateral medulla.2 The traditional pathophysiology of the sneeze is thought to begin by stimulation of the distal branches of the trigeminal nerve within the nasal mucosa. Afferent neural stimuli are transmitted to the trigeminal ganglion and then the lateral medulla. The efferent phase then begins, giving rise to the sneezing sequence described earlier.1 In addition to direct nasal irritation, sneezing has been shown to be triggered by several other causes (Table 1). This suggests that alternative mechanisms of sneeze induction other than direct nasal stimulation exist. We report a case of a 34-year-old man undergoing an awake craniotomy for a recurrent World Health Organization grade 2 oligodendroglioma (IDH-mutant, 1p19q-codeleted, ATRX preserved). During the operation we elicited a sneeze response on 3 occasions on stimulation of the olfactory nerve (Video 1). Although we cannot completely exclude costimulation of the sensory trigeminal terminations in the anterior fossa floor, the actual sneezing occurred during tumor peeling away from the arachnoid surface overlaying the olfactory nerve. This suggests a potential accessory route of sneeze stimulation involving the olfactory nerve distinct from the previously described trigemino-related, autonomic (sympathetic and parasympathetic systems) and psychogenic etiologies.

Topography and lateralization of long-latency trigeminal somatosensory evoked potentials.

OBJECTIVE: Long-latency trigeminal somatosensory evoked potentials (SSEPs) have not been sufficiently studied regarding their topography and lateralization. SSEPs are hypothesized to contribute to the evoked potentials after transcranial magnetic stimulation (TMS). This study focused on trigeminal SSEPs with latencies > 100 ms, potentially overlapping with TMS-evoked N100. METHODS: In 14 healthy subjects, the trigeminus was electrically stimulated on the left and right forehead, and time-course, topography, and lateralization of trigeminal SSEPs were examined in 64-channel electroencephalogram (EEG). SSEPs were then compared to TMS-evoked potentials when TMS was applied to the left and right dorsolateral prefrontal cortex. RESULTS: Trigeminal stimulation produced a somatosensory N140 with topographic maximum over centroparietal electrodes with larger amplitudes contra- than ipsilaterally to the stimulation. Contralateral potentials after TMS were partly comparable in their topography but differed in latencies. CONCLUSIONS: SSEPs generated by electrical stimulation of the trigeminus occurred over somatosensory areas with a contralateral lateralization. Therefore, contralateral potentials after TMS should be interpreted with caution, as they may include somatosensory components. SIGNIFICANCE: The topography and lateralization of long-latency trigeminal SSEPs should be considered in future TMS-EEG designs.