Mitophagy Decreases in the Peripheral Vestibular System of Aged C57BL/6J Mice.

BACKGROUND/AIM: Mitophagy is a cardinal process for maintaining healthy and functional mitochondria. A decline in mitophagy has been associated with age-related pathologies. We aimed to investigate mitophagy changes in age-related balance problems using an animal model. MATERIALS AND METHODS: C57BL/6J mice were divided into young (1 month old) and aged (12 months old) groups. Balance performance, mitochondrial DNA integrity, ATP content, mitophagic process, and mitophagy-related genes and proteins were investigated in both groups. RESULTS: Balance and motor performance were reduced in the aged group. Mitochondrial DNA integrity and ATP content, and mRNA levels of PINK1, Parkin, BNIP3, AMBRA1, MUL1, NIX, Bcl2-L-13, Atg3, Atg5, Atg12, and Atg13 in the vestibule were significantly lower in aged mice compared with those in young mice. The protein levels of PINK1, Parkin, BNIP3, LC3B, and OXPHOS subunits were significantly decreased in the aged vestibule. Mitophagosome and mitophagolysosome counts and the immunohistochemical expression of Parkin and BNIP3 were also decreased in the saccule, utricle, and crista ampullaris in the aged group. CONCLUSION: A general decrease in mitophagy with aging might be attributed to a decrease in cellular function in the aged vestibule during the development of age-related balance problems.

Frequency-Dependent Reduction of Cybersickness in Virtual Reality by Transcranial Oscillatory Stimulation of the Vestibular Cortex.

Virtual reality (VR) applications are pervasive of everyday life, as in working, medical, and entertainment scenarios. There is yet no solution to cybersickness (CS), a disabling vestibular syndrome with nausea, dizziness, and general discomfort that most of VR users undergo, which results from an integration mismatch among visual, proprioceptive, and vestibular information. In a double-blind, controlled trial, we propose an innovative treatment for CS, consisting of online oscillatory imperceptible neuromodulation with transcranial alternating current stimulation (tACS) at 10 Hz, biophysically modelled to reach the vestibular cortex bilaterally. tACS significantly reduced CS nausea in 37 healthy subjects during a VR rollercoaster experience. The effect was frequency-dependent and placebo-insensitive. Subjective benefits were paralleled by galvanic skin response modulation in 25 subjects, addressing neurovegetative activity. Besides confirming the role of transcranially delivered oscillations in physiologically tuning the vestibular system function (and dysfunction), results open a new way to facilitate the use of VR in different scenarios and possibly to help treating also other vestibular dysfunctions.

Vestibular modulation of the tail of the rat striatum.

Fragmented and piecemeal evidence from animal and human studies suggests that vestibular information is transmitted to the striatum, a part of the basal ganglia that degenerates in Parkinson's Disease. Nonetheless, surprisingly little is known about the precise effects of activation of the vestibular system on the striatum. Electrophysiological studies have yielded inconsistent results, with many studies reporting only sparse responses to vestibular stimulation in the dorsomedial striatum. In this study, we sought to elucidate the effects of electrical stimulation of the peripheral vestibular system on electrophysiological responses in the tail of the rat striatum, a newly discovered region for sensory input. Rats were anaesthetised with urethane and a bipolar stimulating electrode was placed in the round window in order to activate the peripheral vestibular system. A recording electrode was positioned in the tail of the striatum. Local field potentials (LFPs) were recorded ipsilaterally and contralaterally to the stimulation using a range of current parameters. In order to confirm that the vestibular system was activated, video-oculography was used to monitor vestibular nystagmus. At current amplitudes that evoked vestibular nystagmus, clear triphasic LFPs were evoked in the bilateral tail of the striatum, with the first phase of the waveform exhibiting latencies of less than 22 ms. The LFP amplitude increased with increasing current amplitude (P ≤ 0.0001). In order to exclude the possibility that the LFPs were evoked by the activation of the auditory system, the cochlea was surgically lesioned in some animals. In these animals the LFPs persisted despite the cochlear lesions, which were verified histologically. Overall, the results obtained suggest that there are vestibular projections to the tail of the striatum, which could possibly arise from projections via the vestibular nucleus or cerebellum and the parafasicular nucleus of the thalamus.

In vivo investigation of mitochondria in lateral line afferent neurons and hair cells.

To process sensory stimuli, intense energy demands are placed on hair cells and primary afferents. Hair cells must both mechanotransduce and maintain pools of synaptic vesicles for neurotransmission. Furthermore, both hair cells and afferent neurons must continually maintain a polarized membrane to propagate sensory information. These processes are energy demanding and therefore both cell types are critically reliant on mitochondrial health and function for their activity and maintenance. Based on these demands, it is not surprising that deficits in mitochondrial health can negatively impact the auditory and vestibular systems. In this review, we reflect on how mitochondrial function and dysfunction are implicated in hair cell-mediated sensory system biology. Specifically, we focus on live imaging approaches that have been applied to study mitochondria using the zebrafish lateral-line system. We highlight the fluorescent dyes and genetically encoded biosensors that have been used to study mitochondria in lateral-line hair cells and afferent neurons. We then describe the impact this in vivo work has had on the field of mitochondrial biology as well as the relationship between mitochondria and sensory system development, function, and survival. Finally, we delineate the areas in need of further exploration. This includes in vivo analyses of mitochondrial dynamics and biogenesis, which will round out our understanding of mitochondrial biology in this sensitive sensory system.

Novel ways to modulate the vestibular system: Magnetic vestibular stimulation, deep brain stimulation and transcranial magnetic stimulation / transcranial direct current stimulation.

BACKGROUND: Advances in neurotechnologies are revolutionizing our understanding of complex neural circuits and enabling new treatments for disorders of the human brain. In the vestibular system, electromagnetic stimuli can now modulate vestibular reflexes and sensations of self-motion by artificially stimulating the labyrinth, cerebellum, cerebral cortex, and their connections. OBJECTIVE: In this narrative review, we describe evolving neuromodulatory techniques including magnetic vestibular stimulation (MVS), deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), and transcranial direct-current stimulation (tDCS) and discuss current and potential future application in the field of neuro-otology. RESULTS: MVS triggers both vestibular nystagmic (persistent) and perceptual (lasting ∼1 min) responses that may serve as a model to study central adaptational mechanisms and pathomechanisms of hemispatial neglect. By systematically mapping DBS electrodes, targeted stimulation of central vestibular pathways allowed modulating eye movements, vestibular heading perception, spatial attention and graviception, resulting in reduced anti-saccade error rates and hypometria, improved heading discrimination, shifts in verticality perception and transiently decreased spatial attention. For TMS/tDCS treatment trials have demonstrated amelioration of vestibular symptoms in various neuro-otological conditions, including chronic vestibular insufficiency, Mal-de-Debarquement and cerebellar ataxia. CONCLUSION: Neuromodulation has a bright future as a potential treatment of vestibular dysfunction. MVS, DBS and TMS may provide new and sophisticated, customizable, and specific treatment options of vestibular symptoms in humans. While promising treatment responses have been reported for TMS/tDCS, treatment trials for vestibular disorders using MVS or DBS have yet to be defined and performed.

Pharmacological characterization and differential expression of NMDA receptor subunits in the chicken vestibular system during development.

Previous studies demonstrated that in vitro preparations of the isolated vestibular system of diverse animal species still exhibit stable resting electrical activity and mechanically evoked synaptic transmission between hair cells and primary afferent endings. However, there are no reports related to their neurodevelopment. Therefore, this research aimed to examine whether NMDA receptors mediate these electrical signals in an isolated preparation of the chicken vestibular system at three developmental stages, E15, E18, and E21. We found that the spontaneous and mechanically evoked discharges from primary afferents of the posterior semicircular canal were modulated by agonists NMDA and glycine, but not by the agonist d-serine applied near the synapses. Moreover, the individually applied by bath perfusion of three NMDA receptor antagonists (MK-801, ifenprodil, and 2-naphthoic acid) or high Mg2+ decreased the resting discharge rate, the NMDA response, and the discharge rate of mechanically evoked activity from these primary afferents. Furthermore, we found that the vestibular ganglion shows a stage-dependent increase in the expression of NMDA receptor subunits GluN1, GluN2 (A-C), and GluN3 (A-B), being greater at E21, except for GluN2D, which was inversely related to the developmental stage. However, in the crista ampullaris, the expression pattern remained constant throughout development. This could suggest the possible existence of presynaptic NMDA receptors. Our results highlight that although the NMDA receptors are functionally active at the early embryonic stages of the vestibular system, NMDA and glycine reach their mature functionality to increase NMDA responses close to hatching (E21).

The influence of vestibular system and fetal presentation on handedness, cognitive and motor development: A comparison between cephalic and breech presentation.

Genetics are undoubtedly implicated in the ontogenesis of laterality. Nonetheless, environmental factors, such as the intrauterine environment, may also play a role in the development of functional and behavioral lateralization. The aim of this study was to test the Left-Otolithic Dominance Theory (LODT; Previc, 1991) by investigating a hypothetical developmental pattern where it is assumed that a breech presentation, which is putatively associated with a dysfunctional and weakly lateralized vestibular system, can lead to weak handedness and atypical development associated with language and motor difficulties. We used the ALSPAC cohort of children from 7 to 10 years of age to conduct our investigation. Our results failed to show an association between the vestibular system and fetal presentation, nor any influence of the latter on hand preference, hand performance, or language and motor development. Bayesian statistical analyses supported these findings. Contrary to our LODT-derived hypotheses, this study offers evidence that fetal presentation does not influence the vestibular system's lateralization and seems to be a poor indicator for handedness. Nonetheless, we found that another non-genetic factor, prematurity, could lead to atypical development of handedness.

Recent advancements in bioelectronic devices to interface with the peripheral vestibular system.

Balance disorders affect approximately 30% of the population throughout their lives and result in debilitating symptoms, such as spontaneous vertigo, nystagmus, and oscillopsia. The main cause of balance disorders is peripheral vestibular dysfunction, which may occur as a result of hair cell loss, neural dysfunction, or mechanical (and morphological) abnormality. The most common cause of vestibular dysfunction is arguably vestibular hair cell damage, which can result from an array of factors, such as ototoxicity, trauma, genetics, and ageing. One promising therapy is the vestibular prosthesis, which leverages the success of the cochlear implant, and endeavours to electrically integrate the primary vestibular afferents with the vestibular scene. Other translational approaches of interest include stem cell regeneration and gene therapies, which aim to restore or modify inner ear receptor function. However, both of these techniques are in their infancy and are currently undergoing further characterization and development in the laboratory, using animal models. Another promising translational avenue to treating vestibular hair cell dysfunction is the potential development of artificial biocompatible hair cell sensors, aiming to replicate functional hair cells and generate synthetic 'receptor potentials' for sensory coding of vestibular stimuli to the brain. Recently, artificial hair cell sensors have demonstrated significant promise, with improvements in their output, such as sensitivity and frequency selectivity. This article reviews the history and current state of bioelectronic devices to interface with the labyrinth, spanning the vestibular implant and artificial hair cell sensors.

Purinergic signaling in the peripheral vestibular system.

The inner ear comprises the cochlea and vestibular system, which detect sound and acceleration stimulation, respectively. The function of the inner ear is regulated by ion transport activity among sensory epithelial cells, neuronal cells, non-sensory epithelial cells, and luminal fluid with a unique ionic composition of high [K+] and low [Na+], which enables normal hearing and balance maintenance. One of the important mechanisms regulating ion transport in the inner ear is purinergic signaling. Various purinergic receptors are distributed throughout inner ear epithelial cells and neuronal cells. To date, most studies have focused on the role of purinergic receptors in the cochlea, and few studies have examined these receptors in the vestibular system. As purinergic receptors play an important role in the cochlea, they would likely do the same in the vestibular system, which is fairly similar to the cochlea in cellular structure and function. Based on available studies performed to date, purinergic signaling is postulated to be involved in the regulation of ion homeostasis, protection of hair cells, otoconia formation, and regulation of electrical signaling from the sensory epithelium to vestibular neurons. In this review, the distribution and roles of purinergic receptors in the peripheral vestibular system are summarized and discussed.

Pulsed infrared stimulation evoked electrical potential in mouse vestibular system.

To improve accuracy of VsEP and avoid the inherent limitation of mechanical vibration, we designed an infrared optical stimulation approach to stimulate mouse vestibular system and measured the evoked potential. IR pulses (1871 nm, 30 pps and 100 µs pulse width) were delivered to mice with different vestibular dysfunction levels and the evoked potential was recorded. The result suggests that the amplitude and latency of the IR-evoked potential (IR-VsEP) were significantly associated with vestibular function integrity. Immunofluorescence staining confirmed that magnitude of IR-VsEP decreased was consistent with the loss of HCs. Micro-CT imaging revealed that the optical fiber was orientating towards the vestibular system. Taken together, we found that: 1) IR stimulation can generate VsEP evoked potential in vestibular system (IR-VsEP), which can be potentially used for vestibular function evaluation; 2) intact HCs and fully functional synaptic transmission are crucial for efficient IR-induced vestibular system stimulation.

Neurotransmitter and neurotransmitter receptor expression in the saccule of the human vestibular system.

The saccule is one of the vestibular sensory organs of the inner ear. It detects head movements and provides information to maintain balance and orient in space. Despite its critical role, very little is known about its neurotransmission and regulation. Multiple disease entities and medications affect balance, which is why information on neurotransmission in the vestibular end organs including the saccule could have important pharmacological implications. To the best of our knowledge, this is the first paper to describe immunohistochemical expression of a large panel of neurotransmitters and receptors in the human saccule. Saccular tissue was sampled freshly during surgery. Based partly on previous findings in non-humans and partly on potential biological relevance, the neurotransmitters cholecystokinin, dopamine, GABA, glutamate, histamine and serotonin as well as receptors for these were selected for the tested panel. The neuroepithelium expressed glutamate receptor 1 (GluR1), metabotropic glutamate receptor (mGluR), GABA A receptor α (GABAARα), GABA B receptor 2 and cholecystokinin receptor B (CCKBR), whereas l-glutamate, GluR1, CCKBR, GABAARα, dopamine and serotonin receptor 1D were expressed in the subepithelial stroma. The non-sensory epithelium expressed GluR1, mGluR, histamine receptor 3, CCKAR and dopamine transporter. These findings provide a basis for pharmacological research and potential drug development.

Effects of primary Sjögren's syndrome on hearing and vestibular systems.

OBJECTIVE: This study aimed to evaluate primary Sjögren's syndrome patients in terms of hearing and vestibular functions. METHODS: The patient group consisted of 35 individuals diagnosed with primary Sjögren's syndrome and a control group of 35 healthy individuals similar in terms of age and gender. RESULTS: The rate of hearing loss in the patient group was significantly higher than in the control group (p = 0.021). The N1 latency value for the ocular vestibular-evoked myogenic potentials test was significantly longer in the patient group than in the control group (p = 0.037). Additionally, the posterior semicircular canal and lateral semicircular canal vestibulo-ocular reflex gain values were significantly lower than in the control group (p = 0.022 and p < 0.001, respectively). CONCLUSION: These results indicate subclinical vestibular involvement and hearing loss in primary Sjögren's syndrome patients. Vestibular-evoked myogenic potentials and video head impulse tests can be used to detect vestibular involvement in primary Sjögren's syndrome patients.

Kinematic Analysis of 360° Turning in Stroke Survivors Using Wearable Motion Sensors.

BACKGROUND: A stroke often bequeaths surviving patients with impaired neuromusculoskeletal systems subjecting them to increased risk of injury (e.g., due to falls) even during activities of daily living. The risk of injuries to such individuals can be related to alterations in their movement. Using inertial sensors to record the digital biomarkers during turning could reveal the relevant turning alterations. OBJECTIVES: In this study, movement alterations in stroke survivors (SS) were studied and compared to healthy individuals (HI) in the entire turning task due to its requirement of synergistic application of multiple bodily systems. METHODS: The motion of 28 participants (14 SS, 14 HI) during turning was captured using a set of four Inertial Measurement Units, placed on their sternum, sacrum, and both shanks. The motion signals were segmented using the temporal and spatial segmentation of the data from the leading and trailing shanks. Several kinematic parameters, including the range of motion and angular velocity of the four body segments, turning time, the number of cycles involved in the turning task, and portion of the stance phase while turning, were extracted for each participant. RESULTS: The results of temporal processing of the data and comparison between the SS and HI showed that SS had more cycles involved in turning, turn duration, stance phase, range of motion in flexion-extension, and lateral bending for sternum and sacrum (p-value < 0.035). However, HI exhibited larger angular velocity in flexion-extension for all four segments. The results of the spatial processing, in agreement with the prior method, showed no difference between the range of motion in flexion-extension of both shanks (p-value > 0.08). However, it revealed that the angular velocity of the shanks of leading and trailing legs in the direction of turn was more extensive in the HI (p-value < 0.01). CONCLUSIONS: The changes in upper/lower body segments of SS could be adequately identified and quantified by IMU sensors. The identified kinematic changes in SS, such as the lower flexion-extension angular velocity of the four body segments and larger lateral bending range of motion in sternum and sacrum compared to HI in turning, could be due to the lack of proper core stability and effect of turning on vestibular system of the participants. This research could facilitate the development of a targeted and efficient rehabilitation program focusing on the affected aspects of turning movement for the stroke community.

Pigeon as a model to study peripheral projections from the horizontal semicircular canal vestibular apparatus to a brainstem target immunoreactive for AMPA.

PURPOSE: To evaluate whether the pigeon (Columba livia) is a good model for evaluating the vestibular system involved with postural maintenance during movement. METHODS: This study maps the brainstem targets of the horizontal ampullary inputs from the vestibular periphery of the pigeon. We used biotin dextran amine (BDA) injection in horizontal semicircular canal (HSCC), immunohistochemistry for GluR2/3 and GluR4 AMPA and computerized histomorphology reconstruction. RESULTS: Our results show the same distribution pattern with ipsilateral projections to vestibular nuclear complex (VNC) from the HSCC, with the majority of labeled fibers being, long, thin, with few varicosities and many ramifications. Horizontal semicircular canal projections achieve neurons belonging to all nuclei of the VNC with exception of dorsal portion of lateral vestibular nucleus and this area express GluR2/3 and GluR4 AMPA receptors reinforcing the idea of glutamate participation in these connections. CONCLUSIONS: Pigeon is an appropriated experimental model to study of projections of HSCC and reinforcing the information that the vestibular system has strong relation with the fast responses necessary for postural control. Moreover, its phylogenetic organization apparently conservation, also seems to be a fundamental characteristic for vertebrates.

Ontogenetic variation in the crocodylian vestibular system.

Crocodylians today live in tropical to subtropical environments, occupying mostly shallow waters. Their body size changes drastically during ontogeny, as do their skull dimensions and bite forces, which are associated with changes in prey preferences. Endocranial neurosensory structures have also shown to change ontogenetically, but less is known about the vestibular system of the inner ear. Here we use 30 high-resolution computed tomography (CT) scans and three-dimensional geometric morphometrics to investigate the size and shape changes of crocodylian endosseous labyrinths throughout ontogeny, across four stages (hatchling, juvenile, subadult and adult). We find two major patterns of ontogenetic change. First, the labyrinth increases in size during ontogeny, with negative allometry in relation to skull size. Second, labyrinth shape changes significantly, with hatchlings having shorter semicircular canal radii, with thicker diameters and an overall dorsoventrally shorter labyrinth than those of more mature individuals. We argue that the modification of the labyrinth during crocodylian ontogeny is related to constraints imposed by skull growth, due to fundamental changes in the crocodylian braincase during ontogeny (e.g. verticalisation of the basicranium), rather than changes in locomotion, diet, or other biological functions or behaviours.

Health Care Resource Utilization and Costs for Adults With Mild Traumatic Brain Injury With Chronic Vestibular Impairment.

OBJECTIVE: To quantify the economic burden of all-cause health care resource utilization (HCRU) among adults with and without chronic vestibular impairment (CVI) after a mild traumatic brain injury (mTBI). DESIGN: Retrospective matched cohort study. SETTING: IQVIA Integrated Data Warehouse. PARTICIPANTS: People with mTBI+CVI (n=20,441) matched on baseline age, sex, year of mTBI event, and Charlson Comorbidity Index (CCI) score to people with mTBI only (n=20,441) (N=40,882). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: All-cause health HCRU and costs at 12 and 24 months post mTBI diagnosis. RESULTS: People with mTBI+CVI had significantly higher all-cause HCRU and costs at both time points than those with mTBI only. Multivariable regression analysis showed that, when controlling for baseline variables, costs of care were 1.5 times higher for mTBI+CVI than mTBI only. CONCLUSIONS: People who developed CVI after mTBI had greater overall HCRU and costs for up to 2 years after the injury event compared with people who did not develop CVI after controlling for age, sex, region, and CCI score. Further research on access to follow-up services and effectiveness of interventions to address CVI is warranted.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): genetic and clinical aspects.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) typically presents in middle life with a combination of neuropathy, ataxia and vestibular disease, with patients reporting progressive imbalance, oscillopsia, sensory disturbance and a dry cough. Examination identifies a sensory neuropathy or neuronopathy and bilaterally impaired vestibulo-ocular reflex. The underlying genetic basis is of biallelic AAGGG expansions in the second intron of replication factor complex subunit 1 (RFC1). The frequency and phenotype spectrum of RFC1 disease is expanding, ranging from typical CANVAS to site-restricted variants affecting the sensory nerves, cerebellum and/or the vestibular system. Given the wide phenotype spectrum of RFC1, the differential diagnosis is broad. RFC1 disease due to biallelic AAGGG expansions is probably the most common cause of recessive ataxia. The key to suspecting the disease (and prompt genetic testing) is a thorough clinical examination assessing the three affected systems and noting the presence of chronic cough.

A comprehensive review of the effects of caffeine on the auditory and vestibular systems.

Coffee, of which caffeine is a critical component, is probably the most frequently used psychoactive stimulant in the world. The effects of caffeine on the auditory and vestibular system have been investigated under normal and pathological conditions, such as acoustic trauma, ototoxicity, auditory neuropathy, and vestibular disorders, using various tests. Lower incidences of hearing loss and tinnitus have been reported in coffee consumers. The stimulatory effect of caffeine is represented by either a shorter latency or enhanced amplitude in electrophysiological tests of the auditory system. Furthermore, in the vestibular system, oculomotor testing revealed significant effects of caffeine, while other tests did not reveal any significant caffeine effects. It could be that caffeine improves transmission in the auditory and vestibular systems' central pathways. Importantly, the effects of caffeine seem to be dose-dependent. Also, inconsistent findings have been observed regarding caffeine's effects on the auditory and vestibular systems and related disorders. Overall, these findings suggest that caffeine does not strongly influence the peripheral auditory and vestibular systems. Instead, caffeine's effects seem to occur almost solely at the level of the central nervous system.

Hearing loss versus vestibular loss as contributors to cognitive dysfunction.

In the last 5 years, there has been a surge in evidence that hearing loss (HL) may be a risk factor for cognitive dysfunction, including dementia. At the same time, there has been an increase in the number of studies implicating vestibular loss in cognitive dysfunction. Due to the fact that vestibular disorders often present with HL and other auditory disorders such as tinnitus, it has been suggested that, in many cases, what appears to be vestibular-related cognitive dysfunction may be due to HL (e.g., Dobbels et al. Front Neurol 11:710, 2020). This review analyses the studies of vestibular-related cognitive dysfunction which have controlled HL. It is suggested that despite the fact that many studies in the area have not controlled HL, many other studies have (~ 19/44 studies or 43%). Therefore, although there is certainly a need for further studies controlling HL, there is evidence to suggest that vestibular loss is associated with cognitive dysfunction, especially related to spatial memory. This is consistent with the overwhelming evidence from animal studies that the vestibular system transmits specific types of information about self-motion to structures such as the hippocampus.

Estudo de propriedades psicométricas do M-chat no Brasil / Study of M-chat psychometric proprieties in Brazil / Estudio de las propiedades psicométricas de M-chat en Brasil

O objetivo deste estudo foi avaliar as propriedades psicométricas do Modified Checklist for Autism in Toddlers (M-Chat) em crianças de 24 a 36 meses de idade com (Grupo 1/n = 88) e sem (Grupo 2/n = 1116) o transtorno do espectro do autismo (TEA). Avaliou-se a consistência interna e estimou-se a sensibilidade, especificidade, valor preditivo positivo (VPP), valor preditivo negativo (VPN). Além disso, construiu-se a curva Receiver Operating Characteristic (ROC). Para avaliar a validade discriminante, comparou-se a proporção de falhas entre as crianças com e sem o TEA, utilizando o teste qui-quadrado ou teste Exato de Fisher. Comparou-se ainda o número de falhas segundo sexo, faixa etária e grupo do participante por meio do teste de Mann-Whitney. O M-Chat apresentou consistência interna elevada (0,78 e 0,86), reprodutibilidade satisfatória (Kappa de 0,6 a 0,79 e CCI = 0,87 e 0,89), alta sensibilidade (0,807 e 0,932), especificidade (0,927 e 0,706) e VPN (0,984 e 0,992), porém as estimativas do VPP (0,467 e 0,250) não foram satisfatórias. Quanto à validade discriminante, observou-se que a proporção de falhas foi significativamente maior no grupo de crianças com TEA. Observou-se também que o número de falhas foi maior entre as crianças do sexo masculino, com faixa etária de 25-36 meses e no grupo com TEA. A versão brasileira do M-Chat tem propriedades psicométricas adequadas no que se refere à confiabilidade, sensibilidade, especificidade, VPN e validade discriminante, o que torna recomendável sua aplicação para rastrear crianças com sinais do TEA.(AU)

This study aims to assess the psychometric properties of the instrument Modified Checklist for Autism in Toddlers (M-CHAT) in children from 24 to 36 months old with (Group 1/n = 88) and without (Group 2/n = 1116) Autism Spectrum Disorder (ASD). Internal consistency was evaluated and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated. Also, the Receiver Operating Characteristic (ROC) curve was generated. To evaluate the discriminant validity, the proportion of flaws among children with and without ASD was assessed by applying the Chi-square test or by the Exact Fisher test. The number of flaws based on sex, age group, and participant's group was also compared with the Mann-Whitney Test. The M-CHAT showed high internal consistency (0.78 and 0.86), satisfactory reproductivity (Kappa 0.60 and 0.79 and ICC = 0.87 and 0.89), high sensibility (0.807 and 0.932), specificity (0.927 and 0.706), and NPV (0.984 and 0.992); however, PPV estimates (0.467 and 0.250) were not satisfactory. Regarding the discriminant validity, the proportion of flaws was significantly higher in the group of children with ASD. Moreover, the number of flaws was larger among boys, in the age group 25-36 months, and in the group with ASD. The Brazilian version of M-CHAT has adequate psychometric properties concerning reliability, sensitivity, specificity, NPV and discriminant validity, which makes its application recommendable to track children with ASD signs.(AU)

Ese estudio tuvo como objetivo evaluar las propiedades psicométricas del Modified Checklist for Autism in Toddlers (M-CHAT) en niños de 24 a los 36 meses de edad con (grupo 1/n=88) y sin (grupo 2/n=1116) el trastorno del espectro autista (TEA). Fueron evaluadas la consistencia interna y estimadas la sensibilidad, especificidad, valor predictivo positivo (VPP), valor predictivo negativo (VPN). Además, se construyó la curva Receiver Operating Characteristic (ROC). Para evaluar la validad discriminante se comparó la proporción de los fracasos entre los niños con y sin TEA, utilizando el examen chi-cuadrado o la prueba exacta de Fisher. Se compararon también el número de fracasos según el sexo, edad y grupo de participantes por medio del teste Mann-Whitney. El M-CHAT presentó consistencia interna elevada (0,78 y 0,86), reproductividad satisfactoria (Kappa de 0,60 a 0,79 e CCI = 0,87 e 0,89), alta sensibilidad (0,807 e 0,932), especificidad (0,927 e 0,706) y VPN (0,984 e 0,992), pero las estimativas del VPP (0,467 e 0,250) no fueron satisfactorias. Acerca de la validad discriminante, se observó que la proporción de fallas fue significativamente mayor en el grupo de niños con TEA. El número de fracasos fue mayor entre los niños varones, de 25 a 36 meses de edad y no en el grupo con TEA. La versión brasileña del M-CHAT tiene propiedades psicométricas adecuadas en lo que concierne a la confiabilidad, sensibilidad, especificidad, VPN y validad discriminante, lo que hace que su aplicación sea recomendada para rastrear los niños con señales de TEA.(AU)