The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional informat...The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional information from echoes. Here we investigated how neurons in the inferior colliculus respond to the paired sounds that produce precedence-effect illusions, and whether their firing behavior can be modulated through inhibition with gamma-aminobutyric acid （GABA）. We recorded extracellularly from 36 neurons in rat inferior colliculus under three conditions： no injection, injection with saline, and injection with gamma-aminobutyric acid. The paired sounds that produced precedence effects were two identical 4-ms noise bursts, which were delivered contralaterally or ipsilaterally to the recording site. The normalized neural responses were measured as a function of different inter-stimulus delays and half-maximal interstimulus delays were acquired. Neuronal responses to the lagging sounds were weak when the inter-stimulus delay was short, but increased gradually as the delay was lengthened. Saline injection produced no changes in neural responses, but after local gamma-arninobutyric acid application, responses to the lagging stimulus were suppressed. Application of gamma-aminobutyric acid affected the normalized response to lagging sounds, independently of whether they or the paired sounds were contralateral or ipsilateral to the recording site. These observations suggest that local inhibition by gamma-aminobutyric acid in the rat inferior colliculus shapes the neural responses to lagging sounds, and modulates the precedence effect.展开更多
In this invited review I provide a selective overview of recent research on brain mechanisms and cognitive processes involved in auditory hallucinations. The review is focused on research carried out in the "VOIC...In this invited review I provide a selective overview of recent research on brain mechanisms and cognitive processes involved in auditory hallucinations. The review is focused on research carried out in the "VOICE" ERC Advanced Grant Project, funded by the European Research Council, but I also review and discuss the literature in general. Auditory hallucinations are suggested to be perceptual phenomena, with a neuronal origin in the speech perception areas in the temporal lobe. The phenomenology of auditory hallucinations is conceptualized along three domains, or dimensions; a perceptual dimension, experienced as someone speaking to the patient; a cognitive dimension, experienced as an inability to inhibit, or ignore the voices, and an emotional dimension, experienced as the "voices" having primarily a negative, or sinister, emotional tone. I will review cognitive, imaging, and neurochemistry data related to these dimensions, primarily the first two. The reviewed data are summarized in a model that sees auditory hallucinations as initiated from temporal lobe neuronal hyper-activation that draws attentional focus inward, and which is not inhibited due to frontal lobe hypo-activation. It is further suggested that this is maintained through abnormal glutamate and possibly gamma-amino-butyric-acid transmitter mediation, which could point towards new pathways for pharmacological treatment. A final section discusses new methods of acquiring quantitative data on the phenomenology and subjective experience of auditory hallucination that goes beyond standard interview questionnaires, by suggesting an iP hone/iP od app.展开更多
Anxiety and stress disorders are a major public health issue. However, their pathophysiology is still unclear. The gamma amino acid butyric acid(GABA) neurochemical system has been strongly implicated in their pathoge...Anxiety and stress disorders are a major public health issue. However, their pathophysiology is still unclear. The gamma amino acid butyric acid(GABA) neurochemical system has been strongly implicated in their pathogenesis and treatment by numerous preclinical and clinical studies, the most recent of which have been highlighted and critical review in this paper. Changes in cortical GABA appear related to normal personality styles and responses to stress. While there is accumulating animal and human neuroimaging evidence of cortical and subcortical GABA deficits across a number of anxiety conditions, a clear pattern of findings in specific brain regions for a given disorder is yet to emerge. Neuropsychiatric conditions with anxiety as a clinical feature may have GABA deficits as an underlying feature. Different classes of anxiolytic therapies support GABA function, and this may be an area in which newer GABA neuroimaging techniques could soon offer more personalized therapy. Novel GABAergic pharmacotherapies in development offer potential improvements over current therapies in reducing sedative and physiologic dependency effects, while offering rapid anxiolysis.展开更多
基金supported by the National Natural Science Foundation of China,No.81271090 and the Beijing Natural Science Foundation,No.7112055
文摘The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional information from echoes. Here we investigated how neurons in the inferior colliculus respond to the paired sounds that produce precedence-effect illusions, and whether their firing behavior can be modulated through inhibition with gamma-aminobutyric acid （GABA）. We recorded extracellularly from 36 neurons in rat inferior colliculus under three conditions： no injection, injection with saline, and injection with gamma-aminobutyric acid. The paired sounds that produced precedence effects were two identical 4-ms noise bursts, which were delivered contralaterally or ipsilaterally to the recording site. The normalized neural responses were measured as a function of different inter-stimulus delays and half-maximal interstimulus delays were acquired. Neuronal responses to the lagging sounds were weak when the inter-stimulus delay was short, but increased gradually as the delay was lengthened. Saline injection produced no changes in neural responses, but after local gamma-arninobutyric acid application, responses to the lagging stimulus were suppressed. Application of gamma-aminobutyric acid affected the normalized response to lagging sounds, independently of whether they or the paired sounds were contralateral or ipsilateral to the recording site. These observations suggest that local inhibition by gamma-aminobutyric acid in the rat inferior colliculus shapes the neural responses to lagging sounds, and modulates the precedence effect.
基金Supported by European Research Council Advanced Grant,No.#249516Research Council of Norway FRIBIOMED Grant,No.807696SFF Grant,No.222373
文摘In this invited review I provide a selective overview of recent research on brain mechanisms and cognitive processes involved in auditory hallucinations. The review is focused on research carried out in the "VOICE" ERC Advanced Grant Project, funded by the European Research Council, but I also review and discuss the literature in general. Auditory hallucinations are suggested to be perceptual phenomena, with a neuronal origin in the speech perception areas in the temporal lobe. The phenomenology of auditory hallucinations is conceptualized along three domains, or dimensions; a perceptual dimension, experienced as someone speaking to the patient; a cognitive dimension, experienced as an inability to inhibit, or ignore the voices, and an emotional dimension, experienced as the "voices" having primarily a negative, or sinister, emotional tone. I will review cognitive, imaging, and neurochemistry data related to these dimensions, primarily the first two. The reviewed data are summarized in a model that sees auditory hallucinations as initiated from temporal lobe neuronal hyper-activation that draws attentional focus inward, and which is not inhibited due to frontal lobe hypo-activation. It is further suggested that this is maintained through abnormal glutamate and possibly gamma-amino-butyric-acid transmitter mediation, which could point towards new pathways for pharmacological treatment. A final section discusses new methods of acquiring quantitative data on the phenomenology and subjective experience of auditory hallucination that goes beyond standard interview questionnaires, by suggesting an iP hone/iP od app.
文摘Anxiety and stress disorders are a major public health issue. However, their pathophysiology is still unclear. The gamma amino acid butyric acid(GABA) neurochemical system has been strongly implicated in their pathogenesis and treatment by numerous preclinical and clinical studies, the most recent of which have been highlighted and critical review in this paper. Changes in cortical GABA appear related to normal personality styles and responses to stress. While there is accumulating animal and human neuroimaging evidence of cortical and subcortical GABA deficits across a number of anxiety conditions, a clear pattern of findings in specific brain regions for a given disorder is yet to emerge. Neuropsychiatric conditions with anxiety as a clinical feature may have GABA deficits as an underlying feature. Different classes of anxiolytic therapies support GABA function, and this may be an area in which newer GABA neuroimaging techniques could soon offer more personalized therapy. Novel GABAergic pharmacotherapies in development offer potential improvements over current therapies in reducing sedative and physiologic dependency effects, while offering rapid anxiolysis.
