Impact of reduction of tinnitus intensity on patients' quality of life.

OBJECTIVE: Assess the impact of a reduction of tinnitus intensity achieved through sound stimulation during sleep on the improvement in the patients' quality of life. DESIGN: Acoustic stimuli consisted of a highly customized sound that reproduced the spectral and intensity characteristics of the tinnitus in each patient. This stimulus was uploaded into a portable electronic device and delivered through customized ear buds during sleep, every night for three months. STUDY SAMPLE: Twelve patients with subjective idiopathic chronic tinnitus were studied. RESULTS: Results were assessed through: (1) the measurement in dB SPL of tinnitus intensity reduction over time; (2) the results of three psychometric tests: Tinnitus handicap inventory (THI), Tinnitus reaction questionnaire (TRQ), Tinnitus functional index (TFI); and (3) a Visual analog scale (VAS) for tinnitus annoyance. After three months of treatment, we observed an average decrease in tinnitus intensity of 14.1 dB SPL (p < 0.001), implying a 62% reduction of the perceived sound. This improvement was followed by a statistically significant decrease of TRQ (78%), THI (65%), and TFI (77%). CONCLUSIONS: These results suggested that the intensity reduction achieved through the protocol used in this study had a direct impact on the improvement in the patients' quality of life.

Past, present, and future of sleep medicine research in Latin America.

NONE: Sleep medicine is a relatively young field with exponential growth in development and research in the last decades. Parallel to the advances in the United States, Latin America also had its beginnings in sleep medicine housed in neuroscience laboratories. Since the very first Latin American meeting in 1985, and the first sleep society in 1993, sleep research has undergone significant development in subsequent years. From contributions in animal research that allowed understanding of the activity of the brain during sleep to the studies that improved our knowledge of sleep disorders in humans, Latin America has become a scientific hub for expansion of sleep research. In this article, we present a historical account of the development of sleep medicine in Latin America, the current state of education and the achievements in research throughout history, and the latest advances in the trending areas of sleep science and medicine. These findings were presented during World Sleep Society meeting in Vancouver in 2019 and complement the work on sleep societies and training published by Vizcarra-Escobar et al in their article "Sleep societies and sleep training programs in Latin America" (J Clin Sleep Med. 2020;16(6):983-988).

Auditory input modulates sleep: an intra-cochlear-implanted human model.

To properly demonstrate the effect of auditory input on sleep of intra-cochlear-implanted patients, the following approach was developed. Four implanted deaf patients were recorded during four nights: two nights with the implant OFF, with no auditory input, and two nights with the implant ON, that is, with normal auditory input, being only the common night sounds present, without any additional auditory stimuli delivered. The sleep patterns of another five deaf people were used as controls, exhibiting normal sleep organization. Moreover, the four experimental patients with intra-cochlear devices and the implant OFF also showed normal sleep patterns. On comparison of the night recordings with the implant ON and OFF, a new sleep organization was observed for the recordings with the implant ON, suggesting that brain plasticity may produce changes in the sleep stage percentages while maintaining the ultradian rhythm. During sleep with the implant ON, the analysis of the electroencephalographic delta, theta and alpha bands in the frequency domain, using the Fast Fourier Transform, revealed a diversity of changes in the power originated in the contralateral cortical temporal region. Different power shifts were observed, perhaps related to the exact position of the implant inside the cochlea and the scalp electrode location. In conclusion, this pilot study shows that the auditory input in humans can introduce changes in central nervous system activity leading to shifts in sleep characteristics, as previously demonstrated in guinea pigs. We are postulating that an intra-cochlear-implanted deaf patient may have a better recovery if the implant is maintained ON during the night, that is, during sleep.

Novelty-induced correlation between visual neurons and the hippocampal theta rhythm in sleep and wakefulness.

Various rhythms have been shown to affect sensory processing such as the waking-sleep cycle and the hippocampal theta waves. Changes in the firing of visual lateral geniculate nucleus neurons have been reported to be dependent on the animal's behavioral state. The lateral geniculate extracellular neuronal firing and hippocampal field activity were recorded in chronically implanted animals to analyze the relationship during quiet wakefulness and sleep associated with stimulation shifts that may introduce novelty. During wakefulness, a change in light flash stimulation pattern (stimuli frequency shift, stimuli on and off) caused an increment in the theta band power in 100% of the cases and a phase-locking of the spikes in 53% of the recorded neurons. During slow wave sleep, there were no consistent changes in the theta power notwithstanding 13% of the neurons exhibited phase-locking, i.e., novelty may induce changes in the temporal correlation of visual neuronal activity with the hippocampal theta rhythm in sleep. The present results suggest that visual processing in slow wave sleep exists, while auditory information and learning were reported during slow wave sleep in animals and newborn humans. The changes in the theta power as well as in the neuronal phase-locking amount indicate that in slow wave sleep, the ability of the hippocampus to detect/process novelty, although present, may be decreased. This is consistent with the noticeable decrease in awareness of the environment during sleep.

Electroencephalographic frequencies associated with heart changes in RR interval variability during paradoxical sleep.

Brain stem autonomic oscillators, hypothalamic and cortico-frontal centre, entrained by baroreceptor input, have been proposed as the control system of the heart rhythm. Recent reported results in animals suggested that the hippocampal theta waves might also participate as a heart rate modulator. A temporal correlation among the firing of neurons in the medulla, the R-wave of the electrocardiogram, hippocampal units, and theta rhythm was reported in guinea pigs. Our present aim is the analysis of the human electroencephalogram (EEG) frequencies power associated with changes in RR interval variability epochs during paradoxical sleep. We hypothesized that the differences in the human balance of the autonomic centres in sleep would be represented in the central nervous system by changes in the low-frequency EEG bands power. The heart rate analysis included 4 s windows, i.e., not considering the lowest component. The result was a consistent increment in the power of the paradoxical sleep delta and theta EEG bands during physiologic high heart RR interval variability epochs; no changes in the EEG bands power were found in the previous windows. The temporal correlation of heart RR interval variability and delta-theta EEG bands increases is proposed to represent a functional interaction when the control of specific centres fails or decreases during paradoxical sleep, a period mainly operating in an "open-loop" fashion.

Hippocampal theta rhythm synchronizes visual neurons in sleep and waking.

The hippocampal theta rhythm (theta) was reported to be associated with movements, attention, auditory processing, autonomic functions, learning and memory and postulated as an associator of discontiguous events. Since visual information includes temporal cues, our study was centered on the correlation between hippocampal theta rhythm and lateral geniculate activity. Phase relationships between hippocampal theta and unit firing were found with both spontaneous and light evoked activity during wakefulness, slow wave and paradoxical sleep. This temporal correlation was dynamic, exhibiting changes related to the sleep-waking cycle and perhaps to attention shifts. Hippocampal theta rhythm may supply a low frequency temporal dimension to the processing of visual information.

Cochlear microphonic changes after noise exposure and gentamicin administration during sleep and waking.

These experiments were designed to investigate the effect of noise, sleep, and gentamicin on the cochlear microphonic (CM) of the guinea pigs. Are the changes observed due to intrinsic cochlear phenomena or to efferent system actions? To answer this question, noise exposure together with efferent system blockade by gentamicin administration was performed. In the normal (non-treated) animal, noise exposure decreased both variability and amplitude of the tone evoked CM in about the first 10 min while the physiological modulation of slow wave sleep increasing the CM is not present. Following administration of gentamicin, noise no longer affect the CM in about the first 10 min, although it produces amplitude and variability increments. The influence of slow wave sleep on the CM is not altered. Thus, gentamicin does not block the CM sleep/wakefulness related shifts. The data were discussed in terms of the influence of gentamicin on the olivo-cochlear bundle. It was hypothesized that the effects of noise on the CM is a result of both peripheral and central influences.

Effects of excitatory amino acid antagonists on the activity of inferior colliculus neurons during sleep and wakefulness.

The contribution of N-methyl-D-aspartate to the response to sound of guinea pig inferior colliculus neurons was analyzed by recording single-unit activity before and after iontophoretic injection of a receptor specific antagonist, 2-amino-5-phosphonovaleric acid (AP5), during the sleep-waking cycle. The AP5 produced a significant firing decrease in most of the units recorded, while some neurons exhibited a particular decrease in the later part of the response. A latency reduction in one out of three units in paradoxical sleep was observed. A low proportion of them exhibited a significant firing increase. These actions were observed in wakefulness (W) as well as during sleep phases. We compared the action of kynurenic acid (Kyn) and the electrical stimulation of the auditory cortex on the same inferior colliculus neuron in anesthetized animals and during W. Both Kyn iontophoresis and cortical stimulation evoked similar changes, decreased firing rate in most inferior colliculus units, whereas a low proportion of them increased their discharge, in anesthetized guinea pigs and in W. Ascending as well as descending - efferent - glutamatergic fibers impinging on inferior colliculus neurons contribute to sound-evoked responses. The enhanced unitary activity observed in some neurons with after glutamatergic receptor blocking may indicate that polysynaptic pathways involving inhibitory neurons decreased their activity. These effects were observed in anesthetized and in behaving animals.

Temporal correlations between heart rate, medullary units and hippocampal theta rhythm in anesthetized, sleeping and awake guinea pigs.

The aim of the present report was to determine whether or not the heart rate could show any relation to a central electrographic rhythm such as hippocampus theta. Our experimental design included anesthetized as well as chronically implanted guinea pigs. The cross-correlation, spike trigger averaging, between the medullary neurons firing, or the R-wave of the electrocardiogram, or hippocampal units, and theta rhythm revealed phase-locking during epochs of wakefulness, slow wave sleep and paradoxical sleep, and under anesthesia. A special case was paradoxical sleep, an epoch known to lack autonomic function control (open-loop), in which a great majority of the recorded units (83%) exhibited theta phase-locking. The experimental control was a flat cross-correlation after unit firing shuffling. A brain-stem autonomic oscillator, together with a hypothalamic and a cortico-frontal centers entrained by baroreceptor input, have been proposed as the heart rhythm control system. The present report suggests that hippocampal theta waves may participate, in coordination with the hypothalamic center, as a heart rate modulator.

The Impact of Sound on Electroencephalographic Waves during Sleep in Patients Suffering from Tinnitus.

Based on the knowledge that sensory processing continues during sleep and that a relationship exists between sleep and learning, a new strategy for treatment of idiopathic subjective tinnitus, consisted of customized sound stimulation presented during sleep, was tested. It has been previously shown that this treatment induces a sustained decrease in tinnitus intensity; however, its effect on brain activity has not yet been studied. In this work, we compared the impact of sound stimulation in tinnitus patients in the different sleep stages. Ten patients with idiopathic tinnitus were treated with sound stimulation mimicking tinnitus during sleep. Power spectra and intra- and inter-hemispheric coherence of electroencephalographic waves from frontal and temporal electrodes were measured with and without sound stimulation for each sleep stage (stages N2 with sleep spindles; N3 with slow wave sleep and REM sleep with Rapid Eye Movements). The main results found were that the largest number of changes, considering both the power spectrum and wave׳s coherence, occurred in stages N2 and N3. The delta and theta bands were the most changed, with important changes also in coherence of spindles during N2. All changes were more frequent in temporal areas. The differences between the two hemispheres do not depend, at least exclusively, on the side where the tinnitus is perceived and, hence, of the stimulated side. These results demonstrate that sound stimulation during sleep in tinnitus patients׳ influences brain activity and open an avenue for investigating the mechanism underlying tinnitus and its treatment.

Temporal correlation between auditory neurons and the hippocampal theta rhythm induced by novel stimulations in awake guinea pigs.

The hippocampal theta rhythm is associated with the processing of sensory systems such as touch, smell, vision and hearing, as well as with motor activity, the modulation of autonomic processes such as cardiac rhythm, and learning and memory processes. The discovery of temporal correlation (phase locking) between the theta rhythm and both visual and auditory neuronal activity has led us to postulate the participation of such rhythm in the temporal processing of sensory information. In addition, changes in attention can modify both the theta rhythm and the auditory and visual sensory activity. The present report tested the hypothesis that the temporal correlation between auditory neuronal discharges in the inferior colliculus central nucleus (ICc) and the hippocampal theta rhythm could be enhanced by changes in sensory stimulation. We presented chronically implanted guinea pigs with auditory stimuli that varied over time, and recorded the auditory response during wakefulness. It was observed that the stimulation shifts were capable of producing the temporal phase correlations between the theta rhythm and the ICc unit firing, and they differed depending on the stimulus change performed. Such correlations disappeared approximately 6 s after the change presentation. Furthermore, the power of the hippocampal theta rhythm increased in half of the cases presented with a stimulation change. Based on these data, we propose that the degree of correlation between the unitary activity and the hippocampal theta rhythm varies with--and therefore may signal--stimulus novelty.

In vivo approach to the cellular mechanisms for sensory processing in sleep and wakefulness.

1. The present review analyzes sensory processing during sleep and wakefulness from a single neuronal viewpoint. Our premises are that processing changes throughout the sleep-wakefulness cycle may be at least partially evidenced in single neurons by (a) changes in the phase locking of the response to the hippocampal theta rhythm, (b) changes in the discharge rate and firing pattern of the response to sound, and (c) changes in the effects of the neurotransmitters involved in the afferent and efferent pathways. 2. The first part of our report is based on the hypothesis that the encoding of sensory information needs a timer in order to be processed and stored, and that the hippocampal theta rhythm could contribute to the temporal organization. We have demonstrated that the guinea pig's auditory and visual neuronal discharge exhibits a temporal relationship (phase locking) to the hippocampal theta waves during wakefulness and sleep phases. 3. The concept that the neural network organization during sleep versus wakefulness is different and can be modulated by sensory signals and vice versa, and that the sensory input may be influenced by the CNS state, i.e., asleep or awake, is introduced. During sleep the evoked firing of auditory units increases, decreases, or remains similar to that observed during quiet wakefulness. However, there has been no auditory unit yet that stops firing as the guinea pig enters sleep. Approximately half of the cortical neurons studied did not change firing rate when passing into sleep while others increased or decreased. Thus, the system is continuously aware of the environment. We postulate that those neurons that changed their evoked firing during sleep are also related to still unknown sleep processes. 4. Excitatory amino acid neurotransmitters participate in the synaptic transmission of the afferent and efferent pathways in the auditory system. In the inferior colliculus, however, the effects of glutamate's mediating the response to sound and the efferent excitation evoked by cortical stimulation failed to show differences in sleep and wakefulness. 5. Considering that neonates and also infants spend most of the time asleep, the continuous arrival of sensory information to the brain during both sleep phases may serve to "sculpt" the brain by activity-dependent mechanisms of neural development, as has been postulated for wakefulness.

A search for a mesencephalic periaqueductal gray-cochlear nucleus connection

Peroxidasa del rábano (HRP), introducida en la substancia grisperiacueductal mesencefálica (PAG) y en la region del complejo olivar superior lateral, demostró la existencia de vías indirectas desde estas zonas hacia el núcleo coclear (NC). No habiéndose demostrado vías directas, hemos propuesto conexiones indirectas a través del ya conocido sistema auditivo eferente. Los resultados obtenidos sugieren tres posibilidades: 1) La PAG está conectada al complejo olivar superior lateral donde existen neuronas cuyas fibras eferentes llegan hasta el NC; 2) Neuronas localizadas en la PAG dorsal demonstraron estar conectadas con el colículo inferior (IC). Se postula la posibilidad que estas fibras PAG-IC hagan sinapsis con neuronas conocidas cuyos axones van desde el IC hasta el NC; 3) Neuronas del cuerpo trapezoide, que comunican con el NC, están también conectadas hacia y desde la PAG. Un estudio electrofisiológico previo (1) ha demostrado cambios en la frecuencia y en la probabilidad de descarga de las neuronas de NC como consecuencia de la estimulación de la PAG. Se postuló además una acción, a través de encefalinas, de la PAG sobre el NC. Los resultados actuales apoyan, anatómicamente, las acciones funcionales de la PAG sobre el NC descritas