ABSTRACT
Recently developed optogenetic technology, which allows high-fidelity control of neuronal activity, has been applied to investigate the neural circuits underlying sensory processing and behavior. The nasal cavity is innervated by the olfactory nerve and trigeminal nerve, which are closely related to common symptoms of rhinitis, such as impairment of smell, itching, and sneezing. The olfactory system has an amazing ability to distinguish thousands of odorant molecules at trace levels. However, there are many issues in olfactory sensing mechanisms that need to be addressed. Optogenetics offers a novel technical approach to solve this dilemma. Therefore, we review the recent advances in olfactory optogenetics to clarify the mechanisms of chemical sensing, which may help identify the mechanism of dysfunction and suggest possible treatments for impaired smell. Additionally, in rhinitis patients, alterations in the other nerve (trigeminal nerve) that innervates the nasal cavity can lead to hyperresponsiveness to various nociceptive stimuli and central sensitization, causing frequent and persistent itching and sneezing. In the last several years, the application of optogenetics in regulating nociceptive receptors, which are distributed in sensory nerve endings, and amino acid receptors, which are distributed in vital brain regions, to alleviate overreaction to nociceptive stimuli, has gained significant attention. Therefore, we focus on the progress in optogenetics and its application in neuromodulation of nociceptive stimuli and discuss the potential clinical translation for treating rhinitis in the future.
Subject(s)
Optogenetics , Optogenetics/methods , Humans , Animals , Smell/physiology , Nose/physiology , Trigeminal Nerve/physiology , Trigeminal Nerve/physiopathology , Rhinitis/therapy , Rhinitis/physiopathology , Olfactory Nerve/physiology , Nasal Cavity/physiologyABSTRACT
INTRODUCTION: The olfactory and trigeminal system are closely interlinked. Existing literature has primarily focused on characterizing trigeminal stimulation through mechanical and chemical stimulation, neglecting thermal stimulation thus far. The present study aimed to characterize the intranasal sensitivity to heat and the expression of trigeminal receptors (transient receptor potential channels, TRP). METHODS: A total of 20 healthy participants (aged 21-27 years, 11 women) were screened for olfactory function and trigeminal sensitivity using several tests. Under endoscopic control, a thermal stimulator was placed in 7 intranasal locations: anterior septum, lateral vestibulum, interior nose tip, lower turbinate, middle septum, middle turbinate, and olfactory cleft to determine the thermal threshold. Nasal swabs were obtained in 3 different locations (anterior septum, middle turbinate, olfactory cleft) to analyze the expression of trigeminal receptors TRP: TRPV1, TRPV3, TRPA1, TRPM8. RESULTS: The thermal threshold differed between locations (p = 0.018), with a trend for a higher threshold at the anterior septum (p = 0.092). There were no differences in quantitative receptor expression (p = 0.46) at the different sites. The highest overall receptor RNA expression was detected for TRPV1 over all sites (p<0.001). The expression of TRPV3 was highest at the anterior septum compared to the middle turbinate or the olfactory cleft. The thermal sensitivity correlated with olfactory sensitivity and results from tests were related to trigeminal function like intensity ratings of ammonium, a questionnaire regarding trigeminal function, nasal patency, and CO2 thresholds. However, no correlation was found between receptor expression and psychophysical measures of trigeminal function. DISCUSSION: This study provided the first insights about intranasal thermal sensitivity and suggested the presence of topographical differences in thermal thresholds. There was no correlation between thermal sensitivity and trigeminal mRNA receptor expression. However, thermal sensitivity was found to be associated with psychophysical measures of trigeminal and olfactory function.
Subject(s)
Nasal Mucosa , TRPV Cation Channels , Humans , Female , Adult , Male , Nasal Mucosa/metabolism , Young Adult , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Hot Temperature , Trigeminal Nerve/physiology , Trigeminal Nerve/metabolism , Sensory Thresholds/physiology , Transient Receptor Potential Channels/metabolism , Transient Receptor Potential Channels/genetics , TRPM Cation Channels/metabolism , TRPM Cation Channels/genetics , Thermosensing/physiology , TRPA1 Cation Channel/metabolism , TRPA1 Cation Channel/geneticsABSTRACT
BACKGROUND: Assessment of taste and somatosensory perception in clinical practice lacks fast tests that are validated and reliable. Recently, a 12-item identification test for taste and oral trigeminal perception, and its shorter version, the Seven-iTT, was developed. The objectives of this study were to evaluate its test-retest reliability and establish normative data. NEW METHOD: Two-hundred participants (120 women, 80 men) with a good sense of taste performed a whole-mouth identification test using 12 filter-paper strips impregnated with low and high concentrations of sweet, sour, salty, bitter, astringency, and spiciness. Fifty of them repeated the task, with a median interval of 122 days from the first visit. Test-retest reliability was determined using Spearman correlation and the Bland-Altman plot method. RESULTS: There was a significant correlation in identification score between the first and the second session for both versions of the test (r ≥ 0.28; p ≤ 0.048). The Bland-Altman plot reflected a good congruence between the results of the two sessions. Additionally, frequencies of correct identification were consistent between sessions, with women outperforming men (p = 0.005). Hypogeusia was established at Seven-iTT score of 3 of less. COMPARISON WITH EXISTING METHODS: The identification test combines taste and somatosensory perception, thus creating a more detailed diagnosis tool. Scores were correlated with self-rated taste perception. CONCLUSION: The present results confirmed the applicability of Seven-iTT for a reliable, fast evaluation of taste and somatosensory perception in the general population, that can be extended to clinical practice.
Subject(s)
Taste Perception , Humans , Female , Male , Adult , Reproducibility of Results , Young Adult , Middle Aged , Taste Perception/physiology , Trigeminal Nerve/physiology , Reference Values , Taste/physiology , Aged , AdolescentABSTRACT
Humans naturally integrate signals from the olfactory and intranasal trigeminal systems. A tight interplay has been demonstrated between these two systems, and yet the neural circuitry mediating olfactory-trigeminal (OT) integration remains poorly understood. Using functional magnetic resonance imaging (fMRI), combined with psychophysics, this study investigated the neural mechanisms underlying OT integration. Fifteen participants with normal olfactory function performed a localization task with air-puff stimuli, phenylethyl alcohol (PEA; rose odor), or a combination thereof while being scanned. The ability to localize PEA to either nostril was at chance. Yet, its presence significantly improved the localization accuracy of weak, but not strong, air-puffs, when both stimuli were delivered concurrently to the same nostril, but not when different nostrils received the two stimuli. This enhancement in localization accuracy, exemplifying the principles of spatial coincidence and inverse effectiveness in multisensory integration, was associated with multisensory integrative activity in the primary olfactory (POC), orbitofrontal (OFC), superior temporal (STC), inferior parietal (IPC) and cingulate cortices, and in the cerebellum. Multisensory enhancement in most of these regions correlated with behavioral multisensory enhancement, as did increases in connectivity between some of these regions. We interpret these findings as indicating that the POC is part of a distributed brain network mediating integration between the olfactory and trigeminal systems. PRACTITIONER POINTS: Psychophysical and neuroimaging study of olfactory-trigeminal (OT) integration. Behavior, cortical activity, and network connectivity show OT integration. OT integration obeys principles of inverse effectiveness and spatial coincidence. Behavioral and neural measures of OT integration are correlated.
Subject(s)
Brain Mapping , Magnetic Resonance Imaging , Olfactory Cortex , Humans , Male , Female , Adult , Olfactory Cortex/physiology , Olfactory Cortex/diagnostic imaging , Young Adult , Olfactory Perception/physiology , Phenylethyl Alcohol , Psychophysics , Trigeminal Nerve/physiology , Trigeminal Nerve/diagnostic imaging , OdorantsABSTRACT
INTRODUCTION: Chemosensory function in pregnant women is far from being fully understood due to the lack of data and inconsistencies between the results of self-reports and objective studies. METHODS: In the present study in pregnant and non-pregnant women (npregnant = 14, nnon-pregnant = 13), we measured EEG-derived electrophysiological response measures supported by psychophysical olfactory and trigeminal tests. RESULTS: Results indicate that the olfactory event-related potential amplitudes or latencies of the P1, N1, and P2 components remain unchanged in pregnant women. In accordance with these findings, no difference was observed between pregnant and non-pregnant women in psychophysical olfactory tests. However, pregnant women displayed a lower degree of sensitivity to trigeminal stimuli compared to non-pregnant controls, which was also reflected in the electrophysiological responses to trigeminal stimuli. CONCLUSION: Counterintuitive as they may seem, our findings demonstrate a "flattening" of chemosomatosensory responses. Psychological processes occurring during pregnancy, such as changes in socioemotional perception of odors resulting from the diminished stress response, may provide a background to these results. Overall, the present results indicate the absence of major differences between non-pregnant and pregnant women in terms of measured olfactory function though chemosomatosensory function of the pregnant women appears to be decreased.
Subject(s)
Electroencephalography , Trigeminal Nerve , Humans , Female , Pregnancy , Adult , Trigeminal Nerve/physiology , Electroencephalography/methods , Evoked Potentials/physiology , Young Adult , Olfactory Perception/physiology , Smell/physiology , OdorantsABSTRACT
Background/aim: In this study, we investigated the blink reflex (BR) after simultaneous and asynchronous stimulation of two trigeminal nerve branches. The objective was to characterize the physiology of trigeminal and facial circuits. Materials and methods: We performed three sets of experiments: recording BR response i. after supraorbital nerve stimulation (SON), after mental nerve stimulation (MN), and after simultaneous SON and MN stimulation (SON+MN) in 18 healthy individuals; ii. after MN (at an intensity eliciting BR response) preceding SON at various interstimulus intervals (ISIs) in seven healthy subjects; iii after MN (at sensory threshold) preceding SON at various ISIs. We compared the magnitudes of early and late responses. Results: The R1 amplitude after simultaneous SON+MN stimulation was greater than responses after single stimulation of the same branches. After simultaneous stimulations, the R2 and R2c areas under the curve (AUC) were smaller than the arithmetic sums of R2 and R2c AUC obtained after single stimulations. The second experiment provided a recovery excitability curve. In the third step, we obtained facilitation of R1 and inhibition of late responses. Conclusion: The SON+MN stimulation caused an increased R1 circuit excitability compared to the arithmetic sum of the single stimulations; however, magnitudes of late responses did not potentiate. Thus, we have provided evidence for R1 circuit enhancement by simultaneous stimulation in humans, whereas modulation of late responses exhibited a recovery curve similar to that shown for paired SON stimulation.
Subject(s)
Blinking , Electric Stimulation , Healthy Volunteers , Humans , Blinking/physiology , Adult , Male , Female , Electric Stimulation/methods , Trigeminal Nerve/physiology , Young Adult , ElectromyographyABSTRACT
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.
Subject(s)
Hippocampus , Trigeminal Nerve , Animals , Hippocampus/physiology , Rats , Male , Trigeminal Nerve/physiology , Rats, Sprague-Dawley , Transcranial Direct Current Stimulation/methods , Locus Coeruleus/physiologySubject(s)
Locus Coeruleus , Pupil , Trigeminal Nerve , Humans , Trigeminal Nerve/physiology , Locus Coeruleus/physiology , Pupil/physiology , Male , Adult , Female , Electric Stimulation/methods , Healthy Volunteers , Young AdultABSTRACT
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.
Subject(s)
Horse Diseases , Neural Conduction , Animals , Horses , Horse Diseases/diagnosis , Female , Male , Neural Conduction/physiology , Head , Prospective Studies , Trigeminal Nerve/physiologyABSTRACT
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.
Subject(s)
Dry Eye Syndromes , Humans , Dry Eye Syndromes/physiopathology , Dry Eye Syndromes/therapy , Trigeminal Nerve/physiology , Parasympathetic Nervous System/physiology , Parasympathetic Nervous System/physiopathology , Electric Stimulation Therapy/methods , Tears/physiology , Tears/metabolism , Treatment OutcomeABSTRACT
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.
Subject(s)
Brain , Cranial Nerves , Humans , Cranial Nerves/physiology , Vagus Nerve/physiology , Facial Nerve/physiology , Skull , Trigeminal Nerve/physiology , Hypoglossal Nerve , Glossopharyngeal Nerve/physiology , Oculomotor Nerve , Abducens NerveABSTRACT
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.
Subject(s)
Anesthesia, General , Feasibility Studies , Humans , Female , Anesthesia, General/methods , Male , Adult , Middle Aged , Prospective Studies , Aged , Intraoperative Neurophysiological Monitoring/methods , Electric Stimulation/methods , Reflex, Trigeminocardiac/physiology , Trigeminal Nerve/physiology , Young Adult , Reflex/physiologyABSTRACT
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.
Subject(s)
Neurosurgery , Reflex, Trigeminocardiac , History, 19th Century , Neurosurgery/history , Humans , History, 20th Century , Reflex, Trigeminocardiac/physiology , Italy , Trigeminal Nerve/surgery , Trigeminal Nerve/physiologyABSTRACT
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.
Subject(s)
Blinking , Trigeminal Nerve , Humans , Blinking/physiology , Trigeminal Nerve/physiology , Male , Adult , Female , Young Adult , Physical Stimulation , ElectromyographyABSTRACT
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.
Subject(s)
Reflex , Trigeminal Nerve , Humans , Trigeminal Nerve/physiology , Reflex/physiology , Electric Stimulation/methods , Neck Muscles/physiology , ElectromyographyABSTRACT
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.
Subject(s)
Trigeminal Nerve , Humans , Trigeminal Nerve/physiology , Pain Threshold/physiology , Nasal Cavity/innervationABSTRACT
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.
Subject(s)
Auditory Perception , Consciousness , Humans , Reproducibility of Results , Electric Stimulation , Auditory Perception/physiology , Acoustic Stimulation/methods , Acoustics , Trigeminal Nerve/physiologyABSTRACT
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.
Subject(s)
Blepharoptosis , Masseter Muscle , Rats , Animals , Rats, Gunn , Neurons, Afferent , Motor Neurons , Eyelids , Tegmentum Mesencephali , Trigeminal Nuclei , Trigeminal Nerve/physiologyABSTRACT
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.
Subject(s)
Trigeminal Neuralgia , Humans , Trigeminal Neuralgia/diagnosis , Trigeminal Nerve/physiology , Blinking , Evoked Potentials, Somatosensory , PainABSTRACT
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.