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Abstract Background One year after persistent peripheral facial paresis (PFP), prescriptions of conventional rehabilitation are often downgraded into maintenance rehabilitation or discontinued, the patient entering what is seen as a chronic stage. This therapeutic choice is not consistent with current knowledge about behavior-induced plasticity, which is available all life long and may allow intense sensorimotor rehabilitation to remain effective. This prospective, randomized, multicenter single-blind study in subjects with chronic unilateral PFP evaluates changes in facial motor function with a Guided Self-rehabilitation Contract (GSC) vs. conventional therapy alone, carried out for six months. Methods Eighty-two adult subjects with chronic unilateral PFP (> 1 year since facial nerve injury) will be included in four tertiary, maxillofacial surgery (2), otolaryngology (1) and rehabilitation (1) centers to be randomized into two rehabilitation groups. In the experimental group, the PM&R specialist will implement the GSC method, which for PFP involves intensive series of motor strengthening performed daily on three facial key muscle groups, i.e. Frontalis, Orbicularis oculi and Zygomatici. The GSC strategy involves: i) prescription of a daily self-rehabilitation program, ii) teaching of the techniques involved in the program, iii) encouragement and guidance of the patient over time, in particular by requesting a quantified diary of the work achieved to be returned by the patient at each visit. In the control group, participants will benefit from community-based conventional therapy only, according to their physician’s prescription. The primary outcome measure is the composite score of Sunnybrook Facial Grading System. Secondary outcome measures include clinical and biomechanical facial motor function quantifications (Créteil Scale and 3D facial motion analysis through the Cara system), quality of life (Facial Clinimetric Evaluation and Short-Form 12), aesthetic considerations (FACE-Q scale) and mood representations (Hospital Anxiety and Depression scale). Participants will be evaluated every three months by a blinded investigator, in addition to four phone calls (D30/D60/D120/D150) to monitor compliance and tolerance to treatment. Discussion This study will increase the level of knowledge on the effects of intense facial motor streng- Facial paralysisthening prescribed through a GSC in patients with chronic peripheral facial paresis. Trial registration ClinicalTrials.gov, NCT04074018 . Registered 29 August 2019. Protocol version Version N°4.0—04/02/2021.

Introduction Several studies have shown that efferent pathways of the auditory system improve perception of speech-in-noise. But, the majority of investigations assessing the role of efferent pathways on speech perception have used contralateral suppression of otoacoustic emissions as a measure of efferent activity. By studying the effect of efferent activity on the speech-evoked auditory brainstem response (ABR), some more light could be shed on the effect of efferent pathways on the encoding of speech in the auditory pathway. Objectives To investigate the relationship between contralateral suppression of transient evoked otoacoustic emission (CSTEOAE) and unmasking of speech ABR. Methods A total of 23 young adults participated in the study. The CSTEOAE was measured using linear clicks at 60 dB peSPL and white noise at 60 dB sound pressure level (SPL). The speech ABR was recorded using the syllable /da/ at 80 dB SPL in quiet, ipsilateral noise, and binaural noise conditions. In the ipsilateral noise condition, white noise was presented to the test ear at 60 dB SPL, and, in the binaural noise condition, two separate white noises were presented to both ears. Results The F0 amplitude of speech ABR was higher in quiet condition; however, the mean amplitude of F0 was not significantly different across conditions. Correlation analysis showed a significant positive correlation between the CSTEOAE and the magnitude of unmasking of F0 amplitude of speech ABR. Conclusions The findings of the present study suggests that the efferent pathways are involved in speech-in-noise processing.

Fundamental studies in neuroimmunophysiology are the keystone for development of new therapeutic approaches to the treatment of infectious, allergic, oncologic and autoimmune diseases. The achievements in this field allowed approving new treatment methods based on irritation of afferent and efferent fibers of autonomic nerves. That became possible due to numerous studies of pathways between the immune and nervous systems performed over last two decades. The milestones in the history of neuroimmune communication research are represented here. The immune system organs – bone marrow, thymus and spleen are coupled to central nervous system (CNS) via sympathetic nerves. Information about LPS and bacteria emergence in peritoneum, intestine and parenchymal organs reaches the brain via parasympathetic pathways. After vagotomy, the brain neurons do not respond to this kind of antigens. The pattern of brain responses to different applied antigens (the EEG changes and the quantity of c-Fos-positive neurons) is specific for definite antigen, like as algorithms of electroneurogram after exposure to different cytokines. Activation of parasympathetic nerves causes the inhibition of inflammation. The entry of any antigens into the body initiates production of cytokines (IL-1, TNFα, IL-6, IFNγ etc.), via specific receptors which are present on peripheral neurons and terminals of vagus nerve, i.e. the vagal afferent terminals and neurons respond to cytokine action, and these signals are transmitted to CNS neurons. The afferent vagal fibers end on the dorsal vagal complex neurons in the caudal part of medulla oblongata. The information about bacterial antigens, LPS and inflammation is transmitted to the brain via afferent autonomic neural pathways. The speed of this process is high and significantly depends on the rates of cytokine production that are transmitters of signals upon the antigen exposure. It is important to emphasize that this events occur within minutes, and the response to the received information proceeds by reflex mechanisms, i.e., within fraction of a second, as exemplified by inflammation (“inflammation reflex”). This is a fundamentally new and revolutionary discovery in the functional studies of immune system regulation. Clinical efficiency of n. vagus stimulation by pulsed ultrasound was shown, being used for the treatment of inflammatory, allergic and autoimmune diseases, e.g., multiple sclerosis, rheumatoid arthritis, renal inflammatory diseases. Electrical stimulation of the vagus nerve reduces the death of animals in septic shock by 80%. The mentioned data have made a revolution in understanding the functional arrangement of immune system in the body. A hypothesis is represented, which suggests how the information on the antigen exposure is transmitted to the brain.

Discovered in 1865 by Jules Bernard Luys, the subthalamic nucleus is a set of small nuclei located in the diencephalon, inferior to the thalamus and superior to the substantia nigra, that can be visualized in a posterior coronal section. Histologically, it consists of neurons compactly distributed and filled with a large number of blood vessels and sparse myelinated fibers. This review presents an analysis of this anatomical region, considering what is most recent in the literature. Subthalamic neurons are excitatory and use glutamate as the neurotransmitter. In healthy individuals, these neurons are inhibited by nerve cells located in the side globus pallidus. However, if the fibers that make up the afferent circuit are damaged, the neurons become highly excitable, thus causing motor disturbances that can be classified as hyperkinetic, for example ballism and chorea, or hypokinetic, for example Parkinson disease (PD). The advent of deep brain stimulation has given the subthalamic nucleus great visibility. Studies reveal that the stimulation of this nucleus improves the motor symptoms of PD.

Crianças portadoras de Transtorno do Déficit de Atenção/Hiperatividade (TDAH) apresentam como um de seus principais sintomas a dificuldade de atenção. Na audição, a Atenção Seletiva que se caracteriza por ser a capacidade de compreender a fala em ambientes ruidosos, pode ser avaliada de várias formas, salientando-se o funcionamento do Sistema Eferente Olivococlear Medial. Este sistema pode ser avaliado pelo exame de emissões otoacústicas (EOA). OBJETIVO: Este trabalho teve por objetivo verificar a ocorrência do efeito de supressão de EOA, caracterizado pela diminuição da amplitude de resposta das emissões otoacústicas evocadas por estímulo transiente (EOAT) em resposta a apresentação de ruído contralateral, em crianças com TDAH (grupo estudo) e normais (grupo controle). Forma de Estudo: Estudo caso-controle. MATERIAL E MÉTODO: Foi realizado um estudo com 20 crianças alocadas em dois grupos de 10 crianças, pareadas por sexo e idade. Foi realizado o exame de EOAET sem e com ruído em ambos os grupos. RESULTADOS: Não houve diferença nas respostas das EOAET sem e com ruído, entre os grupos estudados. CONCLUSÕES: Pôde-se concluir que não há diferenças no funcionamento do Sistema Eferente Olivococlear Medial nas crianças com transtorno do déficit de atenção/hiperatividade em relação às crianças normais.Attention deficit hyperactivity disorder (ADHD) patients show, as one of the main symptoms, an attentional impairment. Selective attention in the hearing process is the ability to understand speech in a noisy environment, which can be evaluated by several methods. One of the main approaches is the functioning of the Medial Olivocochlear Efferent System, which can be accessed by Transient-Evoked Otoacoustic Emissions (TOAE). OBJECTIVE:This study aimed at evaluating the suppression effect of contralateral noise on TOAE in ADHD (study group) and normal subjects (control group). Study Design: Case-control study. MATERIAL AND METHODS: A study with 20 children distributed in two, age- and gender-matched groups. RESULTS: No differences were found in TOAE responses between the two groups, with and without noise. CONCLUSIONS: We conclude that there were no functional differences in the Medial Olivocochlear Efferent System in the two groups analyzed.

A associação entre zumbido e hiperacusia é frequente na literatura. OBJETIVOS: Verificar a ocorrência e o efeito de supressão das emissões otoacústicas transientes (EOATs), a existência de associação entre graus de zumbido e de hiperacusia, entre efeito supressor das EOATs e lateralidade, graus de zumbido e de hiperacusia, em adultos normo-ouvintes com queixas de zumbido e hiperacusia. MATERIAIS E MÉTODOS: Foram incluídos, nesta forma de estudo transversal, 25 indivíduos normo-ouvintes com queixas de zumbido e hiperacusia. Utilizou-se o Tinnitus Handicap Inventory (THI) para classificação do grau do zumbido e o Loudness Discomfort Level (LDL) para o da hiperacusia. RESULTADOS: A ocorrência das EOATs variou de 33% a 88%. Houve 63,7% de presença de efeito de supressão na orelha direita e 81,7% na orelha esquerda. Não ocorreu correlação significativa entre os graus de zumbido e os graus de hiperacusia em ambas as orelhas e não houve associação significativa entre efeito de supressão das EOATs e lateralidade, grau de zumbido e de hiperacusia. CONCLUSÃO: A ocorrência de EOATs foi inferior à encontrada em adultos normo-ouvintes. Obteve-se maior percentual de presença do efeito de supressão das EOATs em ambas as orelhas. Não houve associação entre as variáveis analisadas.The association between tinnitus and hyperacusis is common according to the literature. AIM: To verify the occurrence and the suppression effect of transient otoacoustic emissions (TEOAE), the existence of association between tinnitus degrees and hyperacusis degrees, and between the suppressive effect of TEOAE and laterality, tinnitus and hyperacusis degrees in normal hearing adults with complaints of tinnitus and hyperacusis. MATERIALS AND METHODS: 25 normal hearing subjects with complaints of hyperacusis and tinnitus were studied in this cross-sectional study. The Tinnitus Handicap Inventory (THI) was used for the classification of tinnitus degrees, and the Loudness Discomfort Level (LDL) for the hyperacusis classification. RESULTS: The occurrence of TEOAE ranged from 33 to 88%. We observed the presence of TEOAE suppression effect on 63.7% in the right ear and 81.7% in the left ear. There was no significant correlation between the degrees of tinnitus and hyperacusis in both ears. No statistically significant associations between the TEOAE suppression effect and laterality, tinnitus degrees and hyperacusis degrees were found. CONCLUSION: The occurrence of TEOAE was lower than that found in normal hearing adults. A higher percentage of the presence of TEOAE suppression effect has been found in both ears. No association between the variables was observed.

Funções da via auditiva eferente incluem a modulação das células ciliadas externas, proteção contra ruído e melhora na detecção da fonte sonora em ambientes ruidosos. Genotoxicidade são danos ao DNA. OBJETIVOS: Analisar associação entre funções da via auditiva eferente com marcadores genotóxicos. Adicionalmente, considerou-se tabagismo e gênero como principais variáveis intervenientes. MATERIAL E MÉTODO: Estudo prospectivo-clínico, quantitativo, transversal, contemporâneo. Foi realizada uma análise da função da via auditiva eferente e indicadores de genotoxicidade em 60 voluntários adultos jovens. RESULTADOS: Idade média dos voluntários foi de 24,86±3,68 anos; 30 do gênero masculino e 30 do gênero feminino, 15 de cada gênero tabagistas e 15 não tabagistas; indivíduos do gênero masculino tabagistas apresentaram maior ocorrência de efeito de supressão das EOAEPDs nas frequências de 2000 e 6000Hz na orelha do lado esquerdo; mulheres tabagistas apresentaram maior prevalência de queixa de dificuldade de ouvir em ambiente ruidoso; indivíduos tabagistas e mulheres apresentaram maiores danos ao DNA; indivíduos com queixas de dificuldade auditiva e zumbido apresentaram maiores índices de genotoxicidade. CONCLUSÕES: Em adultos jovens normo-ouvintes que referem queixas relacionadas às funções da via auditiva eferente, como zumbido e dificuldade auditiva, já é possível observar associação com genotoxicidade considerando interações entre gênero e tabagismo.Efferent auditory pathways modulate outer hair cells of the cochlea, protect against noise, and improve the detection of sound sources in noisy environments. Genotoxicity is DNA damage. AIM: To study the association between auditory pathway efferent functions with genotoxic markers. The study also considered smoking and gender as two main variables. METHODS: A prospective-clinical, quantitative, cross-sectional, contemporary study. The function of efferent auditory pathways and genotoxicity tests in 60 healthy young subjects were assessed. RESULTS: The mean age of subjects was 24.86 years +/- 3.68 years; there were 30 males and 30 females, 15 of each gender smokers and 15 non-smokers. Male smokers had a higher incidence of DPOEA suppression effect at 2000 and 6000 Hz in the left ear; female smokers had a higher prevalence of complaints of difficulty to hear in noisy environments; smokers and women had a higher mean DNA damage; subjects with complaints of hearing loss and tinnitus had higher genotoxicity. CONCLUSIONS: In young normal-hearing adults that complain about efferent auditory pathways functions, such as tinnitus and hearing impairment, there are possible associations with genotoxicity; interactions between gender and smoking are considered.

Pessoas com dificuldade para compreensão de fala com som competitivo podem apresentar ausência do efeito de supressão das emissões otoacústicas e do reflexo acústico. OBJETIVO: Estudar o desempenho do sistema auditivo eferente em indivíduos normo-ouvintes com queixa de reconhecer a fala na presença de ruído. MATERIAL E MÉTODO: Estudo prospectivo, com amostra composta por 50 voluntários, com idades entre 19 e 32 anos, normo-ouvintes, que referiram (com queixa-CQ) ou não (sem queixa-SQ) dificuldade de compreender a fala no ruído. As emissões otoacústicas evocadas produto de distorção (EOAEPDs) foram testadas nas frequências de 1500 a 6000Hz. O reflexo acústico contralateral (RAC) foi pesquisado nas frequências de 500 a 4000Hz. RESULTADOS: Os grupos diferiram estatisticamente quanto à ocorrência de RAC nas orelhas do lado esquerdo na frequência de 4000Hz. Na frequência de 1500 Hz nas orelhas do lado direito constatou-se predomínio estatisticamente significante da ausência do efeito de supressão das EOAEPDs no grupo CQ. Nas orelhas do lado esquerdo, a ausência do efeito de supressão das EOAEPDs foi maior no grupo CQ em 1500Hz e 2000Hz. CONCLUSÃO: Em normo-ouvintes com autorrelato de dificuldade de reconhecer a fala na presença de ruído verificou-se: ausência de supressão das EOAEPDs nas frequências médias em ambas as orelhas e ausência de reflexo acústico contralateral em 4000Hz na orelha esquerda.Subjects presenting difficulties in understanding speech with competing sounds may have absence of otoacoustic emission suppression and the acoustic reflex. AIM: To study the performance of the efferent auditory system in normal hearing subjects complaining of difficulties to understand speech in noise. MATERIAL AND METHODS: A prospective study comprising 50 normal-hearing subjects aged from 19 to 32 years, reporting difficulties with speech recognition in noise (with complaints - WC) or not (with no complaints - WNC). Distortion product evoked otoacoustic emissions (DPOAEs) were tested at frequencies from 1500 to 6000 Hz.The contralateral acoustic reflex (CAR) was investigated from 500 to 4000 Hz. RESULTS: Groups differed statistically as to the occurrence of CAR in the left ear at 4000 Hz. At 1500 Hz, there was a statistically significant effect - absence of DPOAEs in the WC group in the right ear. In left ears, absence of DPOAE suppression was higher in the WC at 1500 Hz and 2000 Hz. CONCLUSION: An association between self-reported difficulties in discriminating speech in noise and the absence of contralateral acoustic reflex at 4000 Hz in the left ear was observed; there was also absence of the suppression effect of DPOAEs, especially at middle frequencies in both ears.

The workings of the auditory pathway of patients with tinnitus and normal hearing can be associated with an auditory efferent pathway dysfunction at the level of the superior olivary complex. Otoacoustic emission suppression with contralateral noise can represent an alternative to its evaluation. AIM:to investigate Transient Otoacoustic Emission suppression in normal hearing adults with and without tinnitus and to compare the two groups. Study design: cross-sectional contemporary cohort. MATERIALS AND METHODS: we assessed 40 female individuals between 18 and 59 years of age, 20 without tinnitus and 20 with it. We studied the TOAE suppression with a contralateral white noise at 50 dBSPL. RESULTS: TOAE amplitude was lower in the group with tinnitus. There was no difference between the groups with and without tinnitus in terms of TOAE suppression, except in the frequency of 1000 Hz in the left ear in the tinnitus group. CONCLUSION: the afferent system assessment may contribute to the topographic diagnosis of tinnitus; however, we still need further studies to establish the proper methodology and normative values to carry out these tests.O funcionamento da via auditiva de pacientes com queixa de zumbido e audição normal pode estar relacionado a uma disfunção da via eferente auditiva, no nível do complexo olivar superior. A supressão das emissões otoacústicas com ruído contralateral pode representar uma alternativa para sua avaliação. OBJETIVO: Investigar a supressão das emissões otoacústicas por estímulo transiente (EOAT) em indivíduos adultos, ouvintes normais com e sem queixa de zumbido e comparar os dois grupos. Forma de estudo: Coorte contemporânea com corte transversal. MATERIAL E MÉTODO: Foram avaliados 40 sujeitos, do gênero feminino, entre 18 e 59 anos de idade, sendo 20 sem queixa de zumbido e 20 com queixa de zumbido. Foi realizada a pesquisa da supressão das EOAT com ruído branco contralateral a 50 dBNPS contralateralmente. RESULTADOS: A amplitude das EOAT foi inferior no grupo com zumbido. Não houve diferença entre o grupo com e sem zumbido com relação à supressão das EOAT, exceto na frequência de 1000 Hz na orelha esquerda no grupo com zumbido. CONCLUSÃO: A avaliação do sistema eferente pode contribuir para o diagnóstico topográfico do zumbido, porém são necessários mais estudos que possam estabelecer o método adequado e valores normativos para a realização dos testes.

The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent

Glucose sensing within autonomic neurocircuits is critical for the effective integration and regulation of a variety of physiological homeostatic functions including the co-ordination of vagally-mediated reflexes regulating gastrointestinal functions. Glucose regulates gastrointestinal functions via actions at multiple sites of action, from modulating the activity of enteric neurons, endocrine cells and glucose transporters within the intestine, to regulating the activity and responsiveness of the peripheral terminals, cell bodies and central terminals of vagal sensory neurons, to modifying both the activity and synaptic responsiveness of central brainstem neurons. Unsurprisingly, significant impairment in gastrointestinal functions results occurs in pathophysiological states where glucose levels are dysregulated, such as diabetes. A substantial obstacle to the development of new therapies to modify the disease, rather than treat the symptoms, are the gaps in our understanding of the mechanisms by which glucose modulates gastrointestinal functions, particularly vagally-mediated responses and a more complete understanding of disease-related plasticity within these neurocircuits may open new avenues and targets for research.

Corticotropin releasing factor (CRF) is a primary mediator of endocrine, autonomic and behavioral stress responses. Studies in both humans and animal models have implicated CRF in a wide-variety of psychiatric conditions including anxiety disorders such as post-traumatic stress disorder (PTSD), depression, sleep disorders and addiction among others. The central nucleus of the amygdala (CeA), a key limbic structure with one of the highest concentrations of CRF-producing cells outside of the hypothalamus, has been implicated in anxiety-like behavior and a number of stress-induced disorders. This study investigated the specific role of CRF in the CeA on both endocrine and behavioral responses to stress. We used RNA Interference (RNAi) techniques to locally and specifically knockdown CRF expression in CeA. Behavior was assessed using the elevated plus maze (EPM) and open field test (OF). Knocking down CRF expression in the CeA had no significant effect on measures of anxiety-like behavior in these tests. However, it did have an effect on grooming behavior, a CRF-induced behavior. Prior exposure to a stressor sensitized an amygdalar CRF effect on stress-induced HPA activation. In these stress-challenged animals silencing CRF in the CeA significantly attenuated corticosterone responses to a subsequent behavioral stressor. Thus, it appears that while CRF projecting from the CeA does not play a significant role in the expression stress-induced anxiety-like behaviors on the EPM and OF it does play a critical role in stress-induced HPA activation.