Repetitive auditory stimulation at a critical prenatal period modulates the postnatal functional development of the auditory as well as visual system in chicks (Gallus domesticus)

The extrinsic sensory stimulation plays a crucial role in the formation and integration of sensory modalities during development. Postnatal behavior is thereby influenced by the type and timing of presentation of prenatal sensory stimuli. In this study, fertilized eggs of white Leghorn chickens during incubation were exposed to either species‐specific calls or no sound. To find the prenatal critical period when auditory stimulation can modulate visual system development, the former group was divided into three subgroups: in subgroup A (SGA), the stimulus was provided during embryonic day (E)10 to E16, in SGB E17‐ hatching, and in SGC E10‐hatching. The auditory and visual perceptual learning was recorded at posthatch day (PH) 1–3, whereas synaptic plasticity (evident from synaptophysin and PSD‐95 expression), was observed at E19, E20, and PH 1–3. An increased number of responders were observed in both auditory and visual preference tests at PH 1 following stimulation. Although a decrease in latency of entry and an increase in total time spent were observed in all stimulated groups, it was most significant in SGC in auditory preference and in SGB and SGC in visual preference test. The auditory cortex of SGC and visual Wulst of SGB and SGC revealed higher expression of synaptic proteins, compared to control and SGA. A significant inter‐hemispheric and gender‐based difference in expression was also found in all groups. These results indicate facilitation of postnatal behaviour and synaptogenesis in both auditory and visual systems following prenatal repetitive auditory stimulation, only when given during prenatal critical period of development. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 688–701, 2013     

Precognitive and cognitive elements in sound localization

Sound localization behavior is of great importance for an animal's survival. To localize a sound, animals have to detect a sound source and assign a location to it. In this review we discuss recent results on the underlying mechanisms and on modulatory influences in the barn owl, an auditory specialist with very well developed capabilities to localize sound. Information processing in the barn owl auditory pathway underlying the computations of detection and localization is well understood. This analysis of the sensory information primarily determines the following orienting behavior towards the sound source. However, orienting behavior may be modulated by cognitive (top-down) influences such as attention. We show how advanced stimulation techniques can be used to determine the importance of different cues for sound localization in quasi-realistic stimulation situations, how attentional influences can improve the response to behaviorally relevant stimuli, and how attention can modulate related neural responses. Taken together, these data indicate how sound localization might function in the usually complex natural environment.     

节律性听觉刺激下的神经振荡同步化及其应用

大脑的感觉、情绪、认知等功能与其神经振荡模式有密切的联系。通过施加节律性刺激可以调控大脑的神经振荡模式,进而影响个体感受、情绪状态和认知功能等。与近年来常见的非侵入性电刺激和磁刺激相比,同样依赖于外部刺激输入的节律性感觉刺激具有成本低、易操作等优点,被认为是一种极具潜力的神经调控手段。本文以节律性听觉刺激为例,系统综述了不同类型的节律性听觉刺激如何影响大脑的神经振荡模式,进而影响相关状态和功能;并通过总结外部节律性听觉刺激对个体感知觉、情绪与认知功能的影响,讨论其生理机制和应用前景。     

Integration of touch and sound in auditory cortex

To form a coherent percept of the environment, our brain combines information from different senses. Such multisensory integration occurs in higher association cortices; but supposedly, it also occurs in early sensory areas. Confirming the latter hypothesis, we unequivocally demonstrate supra-additive integration of touch and sound stimulation at the second stage of the auditory cortex. Using high-resolution fMRI of the macaque monkey, we quantified the integration of auditory broad-band noise and tactile stimulation of hand and foot in anaesthetized animals. Integration was found posterior to and along the lateral side of the primary auditory cortex in the caudal auditory belt. Integration was stronger for temporally coincident stimuli and obeyed the principle of inverse effectiveness: greater enhancement for less effective stimuli. These findings demonstrates that multisensory integration occurs early and close to primary sensory areas and--because it occurs in anaesthetized animals--suggests that this integration is mediated by preattentive bottom-up mechanisms.     

State-Dependent Changes in Auditory Sensory Gating in Different Cortical Areas in Rats

Sensory gating is a process in which the brain’s response to a repetitive stimulus is attenuated; it is thought to contribute to information processing by enabling organisms to filter extraneous sensory inputs from the environment. To date, sensory gating has typically been used to determine whether brain function is impaired, such as in individuals with schizophrenia or addiction. In healthy subjects, sensory gating is sensitive to a subject’s behavioral state, such as acute stress and attention. The cortical response to sensory stimulation significantly decreases during sleep; however, information processing continues throughout sleep, and an auditory evoked potential (AEP) can be elicited by sound. It is not known whether sensory gating changes during sleep. Sleep is a non-uniform process in the whole brain with regional differences in neural activities. Thus, another question arises concerning whether sensory gating changes are uniform in different brain areas from waking to sleep. To address these questions, we used the sound stimuli of a Conditioning-testing paradigm to examine sensory gating during waking, rapid eye movement (REM) sleep and Non-REM (NREM) sleep in different cortical areas in rats. We demonstrated the following: 1. Auditory sensory gating was affected by vigilant states in the frontal and parietal areas but not in the occipital areas. 2. Auditory sensory gating decreased in NREM sleep but not REM sleep from waking in the frontal and parietal areas. 3. The decreased sensory gating in the frontal and parietal areas during NREM sleep was the result of a significant increase in the test sound amplitude.     

Auditory processing across the sleep-wake cycle: simultaneous EEG and fMRI monitoring in humans

We combined fMRI and EEG recording to study the neurophysiological responses associated with auditory stimulation across the sleep-wake cycle. We found that presentation of auditory stimuli produces bilateral activation in auditory cortex, thalamus, and caudate during both wakefulness and nonrapid eye movement (NREM) sleep. However, the left parietal and, bilaterally, the prefrontal and cingulate cortices and the thalamus were less activated during NREM sleep compared to wakefulness. These areas may play a role in the further processing of sensory information required to achieve conscious perception during wakefulness. Finally, during NREM sleep, the left amygdala and the left prefrontal cortex were more activated by stimuli having special affective significance than by neutral stimuli. These data suggests that the sleeping brain can process auditory stimuli and detect meaningful events.     

前额叶皮层在社交行为中的作用

社交行为对于个体身心健康和社会发展都极其重要。社交行为障碍已成为多种精神类疾病的典型临床表征,对个体的发展有严重不良影响。前额叶皮层作为调节社交行为的关键脑区之一,参与了社交、情绪、决策等高级功能,其内部神经元、神经胶质细胞的活动变化及相互作用对调节社交行为有着重要影响,而且前额叶皮层与其他脑区之间的协作也会影响不同的社会行为。本文回顾了前额叶皮层中神经元、神经胶质细胞以及脑区投射与社交行为关系的最新研究,系统综述了前额叶皮层在社交行为调节中的作用,以期为社交障碍的神经机制和有效诊疗提供参考。     

Activity in a Premotor Cortical Nucleus of Zebra Finches Is Locally Organized and Exhibits Auditory Selectivity in Neurons but Not in Glia

Motor functions are often guided by sensory experience, most convincingly illustrated by complex learned behaviors. Key to sensory guidance in motor areas may be the structural and functional organization of sensory inputs and their evoked responses. We study sensory responses in large populations of neurons and neuron-assistive cells in the songbird motor area HVC, an auditory-vocal brain area involved in sensory learning and in adult song production. HVC spike responses to auditory stimulation display remarkable preference for the bird''s own song (BOS) compared to other stimuli. Using two-photon calcium imaging in anesthetized zebra finches we measure the spatio-temporal structure of baseline activity and of auditory evoked responses in identified populations of HVC cells. We find strong correlations between calcium signal fluctuations in nearby cells of a given type, both in identified neurons and in astroglia. In identified HVC neurons only, auditory stimulation decorrelates ongoing calcium signals, less for BOS than for other sound stimuli. Overall, calcium transients show strong preference for BOS in identified HVC neurons but not in astroglia, showing diversity in local functional organization among identified neuron and astroglia populations.     

Representation of Early Sensory Experience in the Adult Auditory Midbrain: Implications for Vocal Learning

Vocal learning in songbirds and humans occurs by imitation of adult vocalizations. In both groups, vocal learning includes a perceptual phase during which juveniles birds and infants memorize adult vocalizations. Despite intensive research, the neural mechanisms supporting this auditory memory are still poorly understood. The present functional MRI study demonstrates that in adult zebra finches, the right auditory midbrain nucleus responds selectively to the copied vocalizations. The selective signal is distinct from selectivity for the bird''s own song and does not simply reflect acoustic differences between the stimuli. Furthermore, the amplitude of the selective signal is positively correlated with the strength of vocal learning, measured by the amount of song that experimental birds copied from the adult model. These results indicate that early sensory experience can generate a long-lasting memory trace in the auditory midbrain of songbirds that may support song learning.     

Repeated Stimulus Exposure Alters the Way Sound Is Encoded in the Human Brain

Auditory training programs are being developed to remediate various types of communication disorders. Biological changes have been shown to coincide with improved perception following auditory training so there is interest in determining if these changes represent biologic markers of auditory learning. Here we examine the role of stimulus exposure and listening tasks, in the absence of training, on the modulation of evoked brain activity. Twenty adults were divided into two groups and exposed to two similar sounding speech syllables during four electrophysiological recording sessions (24 hours, one week, and up to one year later). In between each session, members of one group were asked to identify each stimulus. Both groups showed enhanced neural activity from session-to-session, in the same P2 latency range previously identified as being responsive to auditory training. The enhancement effect was most pronounced over temporal-occipital scalp regions and largest for the group who participated in the identification task. The effects were rapid and long-lasting with enhanced synchronous activity persisting months after the last auditory experience. Physiological changes did not coincide with perceptual changes so results are interpreted to mean stimulus exposure, with and without being paired with an identification task, alters the way sound is processed in the brain. The cumulative effect likely involves auditory memory; however, in the absence of training, the observed physiological changes are insufficient to result in changes in learned behavior.     

非侵入性脑刺激应用于创伤后应激障碍和物质滥用障碍的记忆干预

记忆是进行思维、想象等高级心理活动的基础，是累积经验、促进个体生存的重要功能。然而，创伤后应激障碍和物质滥用障碍具有某种非适应性记忆过强的特征，不利于个体生存。因此，以病理性改变的记忆为靶点，通过削弱或更新非适应性记忆，可以达到缓解症状甚至治愈的目的。记忆并非是对经验的刻板记录，而是对经验不断更新整合的过程，因此记忆有被干预的可能。记忆的再次激活可能会诱发记忆消退和再巩固，这为记忆相关精神疾病的干预提供了思路和启发。非侵入性脑刺激（noninvasive brain stimulation,NIBS）技术作为一种时间、空间分辨率较高的无创神经调控技术，近年来开始被结合运用到记忆干预研究中。不同刺激参数的NIBS （如频率、极性，以及受刺激区域的初始神经激活状态）应用于特定大脑皮质区域，可以调节神经可塑性，增强或降低靶点脑区的兴奋性，从而削弱或增强行为表现，实现记忆消退增强或在再巩固时间窗内干预记忆。本文首先介绍了记忆相关的脑功能基础研究与局部脑区干预方案的理论联系，继而回顾了近年来NIBS与记忆干预相结合应用于创伤或物质滥用相关障碍的临床干预研究，为精神疾病临床诊疗提供理论依据和启发。     

Prenatal Loud Music and Noise: Differential Impact on Physiological Arousal,Hippocampal Synaptogenesis and Spatial Behavior in One Day-Old Chicks

Prenatal auditory stimulation in chicks with species-specific sound and music at 65 dB facilitates spatial orientation and learning and is associated with significant morphological and biochemical changes in the hippocampus and brainstem auditory nuclei. Increased noradrenaline level due to physiological arousal is suggested as a possible mediator for the observed beneficial effects following patterned and rhythmic sound exposure. However, studies regarding the effects of prenatal high decibel sound (110 dB; music and noise) exposure on the plasma noradrenaline level, synaptic protein expression in the hippocampus and spatial behavior of neonatal chicks remained unexplored. Here, we report that high decibel music stimulation moderately increases plasma noradrenaline level and positively modulates spatial orientation, learning and memory of one day-old chicks. In contrast, noise at the same sound pressure level results in excessive increase of plasma noradrenaline level and impairs the spatial behavior. Further, to assess the changes at the molecular level, we have quantified the expression of functional synapse markers: synaptophysin and PSD-95 in the hippocampus. Compared to the controls, both proteins show significantly increased expressions in the music stimulated group but decrease in expressions in the noise group. We propose that the differential increase of plasma noradrenaline level and altered expression of synaptic proteins in the hippocampus are responsible for the observed behavioral consequences following prenatal 110 dB music and noise stimulation.     

Faster Sound Stream Segmentation in Musicians than in Nonmusicians

The musician''s brain is considered as a good model of brain plasticity as musical training is known to modify auditory perception and related cortical organization. Here, we show that music-related modifications can also extend beyond motor and auditory processing and generalize (transfer) to speech processing. Previous studies have shown that adults and newborns can segment a continuous stream of linguistic and non-linguistic stimuli based only on probabilities of occurrence between adjacent syllables, tones or timbres. The paradigm classically used in these studies consists of a passive exposure phase followed by a testing phase. By using both behavioural and electrophysiological measures, we recently showed that adult musicians and musically trained children outperform nonmusicians in the test following brief exposure to an artificial sung language. However, the behavioural test does not allow for studying the learning process per se but rather the result of the learning. In the present study, we analyze the electrophysiological learning curves that are the ongoing brain dynamics recorded as the learning is taking place. While musicians show an inverted U shaped learning curve, nonmusicians show a linear learning curve. Analyses of Event-Related Potentials (ERPs) allow for a greater understanding of how and when musical training can improve speech segmentation. These results bring evidence of enhanced neural sensitivity to statistical regularities in musicians and support the hypothesis of positive transfer of training effect from music to sound stream segmentation in general.     

Exploring Memory Representations with Activity-Based Genetics

The brain is thought to represent specific memories through the activity of sparse and distributed neural ensembles. In this review, we examine the use of immediate early genes (IEGs), genes that are induced by neural activity, to specifically identify and genetically modify neurons activated naturally by environmental experience. Recent studies using this approach have identified cellular and molecular changes specific to neurons activated during learning relative to their inactive neighbors. By using opto- and chemogenetic regulators of neural activity, the neurons naturally recruited during learning can be artificially reactivated to directly test their role in coding external information. In contextual fear conditioning, artificial reactivation of learning-induced neural ensembles in the hippocampus or neocortex can substitute for the context itself. That is, artificial stimulation of these neurons can apparently cause the animals to “think” they are in the context. This represents a powerful approach to testing the principles by which the brain codes for the external world and how these circuits are modified with learning.A central feature of nervous systems is that, to function properly, specific neurons must become active in response to specific stimuli. The nature of this selective activation and its modification with experience is the focus of much neuroscience research, ranging from studies of sensory processing in experimental animals to disorders of thought such as schizophrenia in humans. The central dogma of neuroscience is that perceptions, memories, thoughts, and higher mental functions arise from the pattern and timing of the activity in neural ensembles in specific parts of the brain at specific points in time. Until quite recently, the investigation of these “circuit”-based questions has primarily been limited to observational techniques, such as single unit recording, functional magnetic resonance imagery (fMRI), and calcium imaging, to document the patterns of neural activity evoked by sensory experience or even complex psychological contingencies in human fMRI studies. These techniques have been enormously successful and created a framework for understanding information processing in the brain. For example, recordings in the visual system have indicated that, in the primary visual cortex, neurons are tuned to the orientation of linear stimuli (Hubel and Wiesel 1962). In contrast, neurons in higher brain areas can respond to discrete items. The most striking example of this specificity comes from in vivo recording in the human medial temporal lobe in which single units have been identified that respond to photos of the actress Halle Berry as well as her written name (Quiroga et al. 2005). This highly selective tuning of neural activity is suggestive of function, but how can this be directly tested? What would be the effect of stimulating just this rare population of neurons, a memory of the actress, a sensory illusion of her image? How does this type of specific firing arise? Do these neurons differ from their nonresponsive neighbors in terms of biochemistry, cell biology, or connectivity? Do they undergo molecular alterations when new information is learned about this individual and are these changes required for the learning? These types of questions have recently become accessible to study in mice through the use of activity-based genetic manipulation, in which neurons that are activated by a specific sensory stimulus can be altered to express any gene of experimental interest. These studies and approaches will be the focus of this work.     

Network Evolution Induced by Asynchronous Stimuli through Spike-Timing-Dependent Plasticity

In sensory neural system, external asynchronous stimuli play an important role in perceptual learning, associative memory and map development. However, the organization of structure and dynamics of neural networks induced by external asynchronous stimuli are not well understood. Spike-timing-dependent plasticity (STDP) is a typical synaptic plasticity that has been extensively found in the sensory systems and that has received much theoretical attention. This synaptic plasticity is highly sensitive to correlations between pre- and postsynaptic firings. Thus, STDP is expected to play an important role in response to external asynchronous stimuli, which can induce segregative pre- and postsynaptic firings. In this paper, we study the impact of external asynchronous stimuli on the organization of structure and dynamics of neural networks through STDP. We construct a two-dimensional spatial neural network model with local connectivity and sparseness, and use external currents to stimulate alternately on different spatial layers. The adopted external currents imposed alternately on spatial layers can be here regarded as external asynchronous stimuli. Through extensive numerical simulations, we focus on the effects of stimulus number and inter-stimulus timing on synaptic connecting weights and the property of propagation dynamics in the resulting network structure. Interestingly, the resulting feedforward structure induced by stimulus-dependent asynchronous firings and its propagation dynamics reflect both the underlying property of STDP. The results imply a possible important role of STDP in generating feedforward structure and collective propagation activity required for experience-dependent map plasticity in developing in vivo sensory pathways and cortices. The relevance of the results to cue-triggered recall of learned temporal sequences, an important cognitive function, is briefly discussed as well. Furthermore, this finding suggests a potential application for examining STDP by measuring neural population activity in a cultured neural network.     

Cross-Modal Multivariate Pattern Analysis

Multivariate pattern analysis (MVPA) is an increasingly popular method of analyzing functional magnetic resonance imaging (fMRI) data^1-4. Typically, the method is used to identify a subject''s perceptual experience from neural activity in certain regions of the brain. For instance, it has been employed to predict the orientation of visual gratings a subject perceives from activity in early visual cortices⁵ or, analogously, the content of speech from activity in early auditory cortices⁶.Here, we present an extension of the classical MVPA paradigm, according to which perceptual stimuli are not predicted within, but across sensory systems. Specifically, the method we describe addresses the question of whether stimuli that evoke memory associations in modalities other than the one through which they are presented induce content-specific activity patterns in the sensory cortices of those other modalities. For instance, seeing a muted video clip of a glass vase shattering on the ground automatically triggers in most observers an auditory image of the associated sound; is the experience of this image in the "mind''s ear" correlated with a specific neural activity pattern in early auditory cortices? Furthermore, is this activity pattern distinct from the pattern that could be observed if the subject were, instead, watching a video clip of a howling dog?In two previous studies^7,8, we were able to predict sound- and touch-implying video clips based on neural activity in early auditory and somatosensory cortices, respectively. Our results are in line with a neuroarchitectural framework proposed by Damasio^9,10, according to which the experience of mental images that are based on memories - such as hearing the shattering sound of a vase in the "mind''s ear" upon seeing the corresponding video clip - is supported by the re-construction of content-specific neural activity patterns in early sensory cortices.     

Serotonin and Prefrontal Cortex Function: Neurons,Networks, and Circuits

Higher-order executive tasks such as learning, working memory, and behavioral flexibility depend on the prefrontal cortex (PFC), the brain region most elaborated in primates. The prominent innervation by serotonin neurons and the dense expression of serotonergic receptors in the PFC suggest that serotonin is a major modulator of its function. The most abundant serotonin receptors in the PFC, 5-HT1A, 5-HT2A and 5-HT3A receptors, are selectively expressed in distinct populations of pyramidal neurons and inhibitory interneurons, and play a critical role in modulating cortical activity and neural oscillations (brain waves). Serotonergic signaling is altered in many psychiatric disorders such as schizophrenia and depression, where parallel changes in receptor expression and brain waves have been observed. Furthermore, many psychiatric drug treatments target serotonergic receptors in the PFC. Thus, understanding the role of serotonergic neurotransmission in PFC function is of major clinical importance. Here, we review recent findings concerning the powerful influences of serotonin on single neurons, neural networks, and cortical circuits in the PFC of the rat, where the effects of serotonin have been most thoroughly studied.     

Perturbateurs endocriniens et troubles du comportement

Prenatal environmental events that disturb neurodevelopment are suspected to increase the risk of psychiatric disorders. Estrogenic hormones such as diethylstilbestrol (DES) and environmental monomers like Bisphenol A (BPA) have the potential to disturb the development of the foetus and especially its brain. We reviewed the epidemiological studies investigating a possible association between prenatal DES or BPA exposure and risk of psychiatric disorders and discussed the hypothetical biological mechanisms linking this prenatal exposure with psychiatric disorders. The principal methodological issues that could represent confounding factors and may explain conflicting results are discussed. Interestingly, prenatal exposure to DES and BPA has been linked to epigenetic alterations associated with urogenital lesions observed in the exposed offspring, supporting the hypothesis that this environmental factor can indeed alter epigenetic regulations. Following the same line of thinking, these endocrine disruptors may modify the epigenetic mechanisms involved in neurodevelopment and, in turn, increase the occurrence of psychiatric disorders.     

The mismatch negativity as an index of the perception of speech sounds by the human brain

The present article outlines the contribution of the mismatch negativity (MMN), and its magnetic equivalent MMNm, to our understanding of the perception of speech sounds in the human brain. MMN data indicate that each sound, both speech and non-speech, develops its neural representation corresponding to the percept of this sound in the neurophysiological substrate of auditory sensory memory. The accuracy of this representation, determining the accuracy of the discrimination between different sounds, can be probed with MMN separately for any auditory feature or stimulus type such as phonemes. Furthermore, MMN data show that the perception of phonemes, and probably also of larger linguistic units (syllables and words), is based on language-specific phonetic traces developed in the posterior part of the left-hemisphere auditory cortex. These traces serve as recognition models for the corresponding speech sounds in listening to speech.