A subcortical pathway to the right amygdala mediating "unseen" fear

Neuroimaging studies have shown differential amygdala responses to masked ("unseen") emotional stimuli. How visual signals related to such unseen stimuli access the amygdala is unknown. A possible pathway, involving the superior colliculus and pulvinar, is suggested by observations of patients with striate cortex lesions who show preserved abilities to localize and discriminate visual stimuli that are not consciously perceived ("blindsight"). We used measures of right amygdala neural activity acquired from volunteer subjects viewing masked fear-conditioned faces to determine whether a colliculo-pulvinar pathway was engaged during processing of these unseen target stimuli. Increased connectivity between right amygdala, pulvinar, and superior colliculus was evident when fear-conditioned faces were unseen rather than seen. Right amygdala connectivity with fusiform and orbitofrontal cortices decreased in the same condition. By contrast, the left amygdala, whose activity did not discriminate seen and unseen fear-conditioned targets, showed no masking-dependent changes in connectivity with superior colliculus or pulvinar. These results suggest that a subcortical pathway to the right amygdala, via midbrain and thalamus, provides a route for processing behaviorally relevant unseen visual events in parallel to a cortical route necessary for conscious identification.     

The time course of auditory perceptual learning: neurophysiological changes during speech-sound training

Here we report that training-associated changes in neural activity can precede behavioral learning. This finding suggests that speech-sound learning occurs at a pre-attentive level which can be measured neurophysiologically (in the absence of a behavioral response) to assess the efficacy of training. Children with biologically based perceptual learning deficits as well as people who wear cochlear implants or hearing aids undergo various forms of auditory training. The effectiveness of auditory training can be difficult to assess using behavioral methods because these populations are communicatively impaired and may have attention and/or cognitive deficits. Based on our findings, if neurophysiological changes are seen during auditory training, then the training method is effectively altering the neural representation of the speech/sounds and changes in behavior are likely to follow.     

Large-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems

Large-scale functional connectivity in associative learning: interrelations of the rat auditory, visual, and limbic systems. J. Neurophysiol. 80: 3148-3162, 1998. Functional relations between specialized parts of the brain may be important determinants of learned behaviors. To study this, we examined the interrelations of the auditory system with several extraauditory structures in two groups of rats having different behavioral histories. Both groups were trained to associate a tone conditional stimulus (CS) with an aversive unconditional stimulus (US). For one group, a light presented with the tone predicted the absence of the US (group TL-). In the other group, the light was a neutral stimulus (group TL0). Fluorodeoxyglucose (FDG) incorporation was measured in the presence of the tone-light compound. Because the tone-light compound was physically identical for both groups, neural differences between groups reflected differences in the learned associative properties of the stimuli. Covariances of FDG uptake in the auditory system and extraauditory structures were examined using partial least squares. Three strong covariance or functional connectivity patterns were identified. The first pattern mainly reflected similarities between groups, with strong interrelations between the subcortical auditory system and the thalamocortical visual system, cerebellum, deep cerebellar nuclei, and midline thalamus. This pattern of interactions may represent part of a common circuit for relaying the associative value of the tone CS to the cerebellum and the midline thalamus. The external nucleus of the inferior colliculus and medial division of the medial geniculate nucleus were associated more strongly with this pattern for group TL-, which was interpreted as representing the change of the associative value of the tone by the light, mediated through extraauditory influences on these two regions. A second pattern involved midbrain auditory regions, superior colliculus, zona incerta, and subiculum and was stronger for group TL0. The relations between midbrain structures may represent the excitatory conditioned response (CR) evoked by the tone in this group. The final pattern was strongest in group TL- and involved interrelations of the thalamocortical auditory system with hippocampus, basolateral amygdala, and hypothalamus. This pattern may represent the learned inhibition of the CR to the tone in the presence of the light. These findings are consistent with behavioral studies suggesting that at least two types of associations are formed during associative learning. One is the sensory relation of the stimuli and another is the relation between the CS and the affective components of the US. These behavioral associations are mapped to the patterns of functional connectivity between auditory and extraauditory regions.     

Age-related alteration in processing of temporal sound features in the auditory midbrain of the CBA mouse

The perception of complex sounds, such as speech and animal vocalizations, requires the central auditory system to analyze rapid, ongoing fluctuations in sound frequency and intensity. A decline in temporal acuity has been identified as one component of age-related hearing loss. The detection of short, silent gaps is thought to reflect an important fundamental dimension of temporal resolution. In this study we compared the neural response elicited by silent gaps imbedded in noise of single neurons in the inferior colliculus (IC) of young and old CBA mice. IC neurons were classified by their temporal discharge patterns. Phasic units, which accounted for the majority of response types encountered, tended to have the shortest minimal gap thresholds (MGTs), regardless of age. We report three age-related changes in neural processing of silent gaps. First, although the shortest MGTs (1-2 msec) were observed in phasic units from both young and old animals, the number of neurons exhibiting the shortest MGTs was much lower in old mice, regardless of the presentation level. Second, in the majority of phasic units, recovery of response to the stimulus after the silent gap was of a lower magnitude and much slower in units from old mice. Finally, the neuronal map representing response latency versus best frequency was found to be altered in the old IC. These results demonstrate a central auditory system correlate for age-related decline in temporal processing at the level of the auditory midbrain.     

Soldiers, surgeons and the campaigns to combat sexually transmitted diseases in colonial India, 1805-1860

Here, we examine the connectivity of two previously identified telencephalic stations of the auditory system of adult zebra finches, the neostriatal "shelf" that underlies the high vocal center (HVC) and the archistriatal "cup" adjacent to the robust nucleus of the archistriatum (RA). We used different kinds of neuroanatomical tracers to visualize the projections from the shelf to the HVC. In addition, we show that the shelf projects to the cup and that the cup projects to thalamic, midbrain, and pontine nuclei of the ascending auditory pathway. Our observations extend to songbirds anatomical features that are found in the auditory pathways of a nonoscine bird, the pigeon (Wild et al. [1993] J. Comp. Neurol. 337:32-62), and we suggest that the descending auditory projections found in mammals may also be a general property of the avian brain. Finally, we show that the oscine song control system is closely apposed to auditory pathways at many levels. Our observations may help in understanding the evolution and organization of networks for vocal communication and vocal learning in songbirds.     

Effect of environmental sound familiarity on dynamic neural activation/inhibition patterns: an ERD mapping study

The aim of this study was to analyze the timing and topography of brain activity in relation to the cognitive processing of different types of auditory information. We specifically investigated the effects of familiarity on environmental sound identification, an issue which has been little studied with respect to cognitive processes, neural substrates, and time course of brain activity. To address this issue, we implemented and applied an electroencephalographic mapping method named event-related desynchronization, which allows one to assess the dynamics of neuronal activity with high temporal resolution (here, 125 ms); we used 19 recording electrodes with standard positioning. We designed an activation paradigm in which healthy subjects were asked to discriminate binaurally heard sounds belonging to one of two distinct categories, "familiar" (i.e., natural environmental sounds) or "unfamiliar" (i.e., altered environmental sounds). The sounds were selected according to strict preexperimental tests so that the former should engage greater semantic, and the latter greater structural, analysis, which we predicted to preferentially implicate left posterior and right brain regions, respectively. During the stimulations, significant desynchronizations (thought to reflect neuronal activations) were recorded over left hemisphere regions for familiar sounds and right temporofrontal regions for unfamiliar sounds, but with only few significant differences between the two sound categories and a common bilateral activation in the frontal regions. However, strongly significant differences between familiar and unfamiliar sounds occurred near the end of and following the stimulations, due to synchronizations (though to reflect deactivations) which appeared over the left posterior regions, as well as the vertex and bilateral frontal cortex, only after unfamiliar sounds. These unexpected synchronizations after the unfamiliar stimuli may reflect an awareness of the unfamiliarity of such sounds, which may have induced an inhibition of semantic and episodic representations because the latter could not be associated with meaningless sounds.     

Exploring auditory saltation using the "reduced-rabbit" paradigm.

Sensory saltation is a spatiotemporal illusion in which the judged positions of stimuli are shifted toward subsequent stimuli that follow closely in time. So far, studies on saltation in the auditory domain have usually employed subjective rating techniques, making it difficult to exactly quantify the extent of saltation. In this study, temporal and spatial properties of auditory saltation were investigated using the "reduced-rabbit" paradigm and a direct-location method. In 3 experiments, listeners judged the position of the 2nd sound within sequences of 3 short sounds by using a hand pointer. When the delay between the 2nd and 3rd sound was short, the target sound was shifted toward the subsequent sound. The magnitude of displacement increased when the temporal and spatial distance between the sounds was reduced. In a 4th experiment, a modified reduced-rabbit paradigm was used to test the hypothesis that auditory saltation is associated with an impairment of target sound localization. The findings are discussed with regard to a spatiotemporal integration approach in which the processing of auditory information is combined with information from subsequent stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMR spectroscopy and brain diseases. Clinical applications

We studied the relationship between auditory activity in the midbrain and selective phonotaxis in females of the treefrog, Pseudacris crucifer. Gravid females were tested in two-stimulus playback tests using synthetic advertisement calls of different frequencies (2600 versus 2875 Hz; 2800 versus 3500 Hz; 2600 versus 3500 Hz). Tests were conducted with and without a background of synthesized noise, which was filtered to resemble the spectrum of a chorus of spring peepers. There were no significant preferences for calls of any frequency in the absence of background noise. With background noise, females preferred calls of 3500 Hz to those of 2600 Hz. Multi-unit recordings of neural responses to synthetic sounds were made from the torus semicircularis of the same females following the tests of phonotaxis. We measured auditory threshold at 25 frequencies (1800-4200 Hz) as well as the magnitude of the neural response when stimulus amplitude was held constant and frequency was varied. This procedure yielded isointensity response contours, which we obtained at six amplitudes in the absence of noise and at the stimulus amplitude used during the phonotaxis tests with background noise. Individual differences in audiograms and isointensity responses were poorly correlated with behavioural data except for the test of 2600 Hz versus 3500 Hz calls in noise. The shape of the neural response contours changed with stimulus amplitude and in the presence of the simulated frog chorus. At 85 dB sound pressure level (SPL), the level at which females were tested, the contours of females were quite flat. The contours were more peaked at lower SPLs as well as during the broadcast of chorus noise and white noise at an equivalent spectrum level (45-46 dB/Hz). Peaks in the isointensity response plots of most females occurred at stimulus frequencies ranging from 3200 to 3400 Hz, frequencies close to the median best excitatory frequency (BEF) of 3357 Hz but higher than the mean of the mid-frequency of the male advertisement call (3011 Hz). Addition of background noise may cause a shift in the neural response-intensity level functions. Our results highlight the well-known nonlinearity of the auditory system and the danger inherent in focusing solely on threshold measures of auditory sensitivity when studying the proximate basis of female choice. The results also show an unexpected effect of the natural and noisy acoustic environment on behaviour and responses of the auditory system. Copyright 1998 The Association for the Study of Animal Behaviour.     

Cortical Responses in Rats Predict Perceptual Sensitivities to Complex Sounds.

The common assumption that perceptual sensitivities are related to neural representations of sensory stimuli has seldom been directly demonstrated. The authors analyzed the similarity of spike trains evoked by complex sounds in the rat auditory cortex and related cortical responses to performance in an auditory task. Rats initially learned to identify 2 highly different periodic, frequency-modulated sounds and then were tested with increasingly similar sounds. Rats correctly classified most novel sounds; their accuracy was negatively correlated with acoustic similarity. Rats discriminated novel sounds with slower modulation more accurately than sounds with faster modulation. This asymmetry was consistent with similarities in cortical representations of the sounds, demonstrating that perceptual sensitivities to complex sounds can be predicted from the cortical responses they evoke. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional neuroanatomy of auditory pathways in the sound-producing fish Pollimyrus

We have described the acoustic pathway from the ear to the diencephalon in a sound-producing fish (Pollimyrus) based on simultaneous neurophysiological recordings from single neurons and injections of biotin pathway tracers at the recording sites. Fundamental transformations of auditory information from highly phase-locked and entrained responses in primary eighth nerve afferents and first-order medullary neurons to more weakly phase-locked responses in the auditory midbrain were revealed by physiological recordings. Anatomical pathway tracing uncovered a bilateral array of both first- and second-order medullary nuclei and a perilemniscal nucleus. Interconnections within the medullary auditory areas were extensive. Medullary nuclei projected to the auditory midbrain by means of the lateral lemniscus. Midbrain auditory areas projected to both ipsilateral and contralateral optic tecta and to an array of three nuclei in the auditory thalamus. The significance of these findings to the elucidation of mechanisms for the analysis of communication sounds and spatial hearing in this vertebrate animal is discussed.     

Neuronal mechanisms of auditory backward recognition masking in macaque auditory cortex

The sensation of a single sound event can be altered by subsequent sounds. This study searched for neural mechanisms of such retroactive effects in macaque auditory cortex by comparing neural responses to single tones with responses to two consecutive tones. Retroactive influences were found to affect late parts of the response to a tone, which comprised 53/134 of the recordings of action potentials and 88/131 of the recordings of field potentials performed in primary, caudal, and medial auditory fields. If before or during the occurrence of the late response to the first tone a second tone was presented the late response was suppressed. Suppression of late cortical responses parallels perceptual phenomena like backward recognition masking, suggesting that suppression of late responses provides a neural correlate of auditory backward effects.     

An audio-vocal interface in echolocating horseshoe bats

The control of vocalization depends significantly on auditory feedback in any species of mammals. Echolocating horseshoe bats, however, provide an excellent model system to study audio-vocal (AV) interactions. These bats can precisely control the frequency of their echolocation calls by monitoring the characteristics of the returning echo; they compensate for flight-induced Doppler shifts in the echo frequency by lowering the frequency of the subsequent vocalization cells (Schnitzler, 1968; Schuller et al., 1974, 1975). It was the aim of this study to investigate the neuronal mechanisms underlying this Doppler-shift compensation (DSC) behavior. For that purpose, the neuronal activity of single units was studied during spontaneous vocalizations of the bats and compared with responses to auditory stimuli such as playback vocalizations and artificially generated acoustic stimuli. The natural echolocation situation was simulated by triggering an acoustic stimulus to the bat's own vocalization and by varying the time delay of this artificial "echo" relative to the vocalization onset. Single-unit activity was observed before, during, and/or after the bat's vocalization as well as in response to auditory stimuli. However, the activity patterns associated with vocalization differed from those triggered by auditory stimuli even when the auditory stimuli were acoustically identical to the bat's vocalization. These neurons were called AV neurons. Their distribution was restricted to an area in the paralemniscal tegmentum of the midbrain. When the natural echolocation situation was stimulated, the responses of AV neurons depended on the time delay between the onset of vocalization and the beginning of the simulated echo. This delay sensitivity disappeared completely when the act of vocalization was replaced by an auditory stimulus that mimicked acoustic self-stimulation during the emission of an echolocation call. The activity of paralemniscal neurons was correlated with all parameters of echolocation calls and echoes that are relevant in context with DSC. These results suggest a model for the regulation of vocalization frequencies by inhibitory auditory feedback.     

Temporal integration of sequential auditory events: silent period in sound pattern activates human planum temporale

Temporal integration is a fundamental process that the brain carries out to construct coherent percepts from serial sensory events. This process critically depends on the formation of memory traces reconciling past with present events and is particularly important in the auditory domain where sensory information is received both serially and in parallel. It has been suggested that buffers for transient auditory memory traces reside in the auditory cortex. However, previous studies investigating "echoic memory" did not distinguish between brain response to novel auditory stimulus characteristics on the level of basic sound processing and a higher level involving matching of present with stored information. Here we used functional magnetic resonance imaging in combination with a regular pattern of sounds repeated every 100 ms and deviant interspersed stimuli of 100-ms duration, which were either brief presentations of louder sounds or brief periods of silence, to probe the formation of auditory memory traces. To avoid interaction with scanner noise, the auditory stimulation sequence was implemented into the image acquisition scheme. Compared to increased loudness events, silent periods produced specific neural activation in the right planum temporale and temporoparietal junction. Our findings suggest that this area posterior to the auditory cortex plays a critical role in integrating sequential auditory events and is involved in the formation of short-term auditory memory traces. This function of the planum temporale appears to be fundamental in the segregation of simultaneous sound sources.     

Development and differentiation of the anuran auditory brainstem during metamorphosis: an acetylcholinesterase histochemical study

The time course of cell differentiation and the presence of histochemically defined areas in brainstem auditory nuclei were examined in developing bullfrogs, Rana catesbeiana, using cresyl violet staining and acetylcholinesterase (AChE) histochemistry. In the medulla, the dorsolateral nucleus (DLN) can be seen as a distinct structure in its adult location only at Gosner stage 40 and beyond. The majority of cells in the DLN are not fully differentiated until late metamorphic climax (stages 45-46) and early postmetamorphosis. The more ventral vestibular nucleus differentiates earlier (stage 37) than the DLN. Adult-like organization of auditory nuclei in the torus semicircularis (TS) of the midbrain cannot be reliably discerned until metamorphic climax stages. Cellular masses in the brainstem reveal AChE from the earliest stage examined (stage 27) but the intensity of staining differs among cell groups. Staining intensity in the DLN is at a peak in recently metamorphosed froglets. The time course of cell differentiation in the DLN precedes slightly or is coincident with the increased, transient presence of AChE. Staining of the superior olive stabilizes at a moderate level in early postmetamorphic stages. Ventral regions of the principal nucleus in the TS stain more intensely than dorsal regions beginning at stage 40. This dorsal-ventral gradient in staining persists in adult stages. There is a transient decline in staining of the laminar nucleus in metamorphic climax stages. Staining intensity in the magnocellular nucleus peaks during stages 40-46 and in early postmetamorphic froglets and then declines in adults, paralleling the pattern seen in the DLN. These data suggest that metamorphic climax and early froglet periods are an important developmental window for major differentiation and maturational events in the auditory brainstem.     

The development of sexual behavior in túngara frogs (Physalaemus pustulosus).

We examined the emergence of a critical component of sex, response to sexual signals—phonotaxis—in male and female túngara frogs (Physalaemus pustulosus). We determined the ontogenetic trajectories of phonotactic responses as animals developed from metamorphic froglets to reproductive adults. The results demonstrated that species-typical phonotaxis emerges quite early during postmetamorphic development, well before sexual maturity, suggesting that a developmentally early bias in the auditory system for species-typical signals might be a more general phenomenon than previously thought, and that the neural circuits responsible for processing and responding to conspecific advertisement signals in a species-typical manner might develop long before the coordinated behavior is demanded of the organism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bottom–up and top–down influences on auditory scene analysis: Evidence from event-related brain potentials.

The physiological processes underlying the segregation of concurrent sounds were investigated through the use of event-related brain potentials. The stimuli were complex sounds containing multiple harmonics, one of which could be mistuned so that it was no longer an integer multiple of the fundamental. Perception of concurrent auditory objects increased with degree of mistuning and was accompanied by negative and positive waves that peaked at 180 and 400 ms poststimulus, respectively. The negative wave, referred to as object-related negativity, was present during passive listening, but the positive wave was not. These findings indicate bottom–up and top–down influences during auditory scene analysis. Brain electrical source analyses showed that distinguishing simultaneous auditory objects involved a widely distributed neural network that included auditory cortices, the medial temporal lobe, and posterior association cortices. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurophysiological correlate of the auditory after-image ('Zwicker tone')

The 'Zwicker tone' (ZT) is an auditory after-image that can be evoked most effectively when a band-suppressed noise (relative width of gap 1/3 octave) presented for a certain period of time has been switched off. The sensation of this purely monaural phenomenon is that of a pure tone with a frequency corresponding to the center frequency of the gap and an equivalent level of 10-15 dB above auditory threshold. The sensation decays gradually; it may last as long as 10 s depending on how long the evoking noise was presented. The search for a physiological correlate has been futile so far, probably because the search was confined to more peripheral levels of the auditory system (inferior colliculus). A neuromagnetic study was performed in normal-hearing subjects in order to look for a neurophysiological correlate of the ZT in the auditory cortex. With a stimulation paradigm especially designed for this study, we have been able to isolate poststimulus activity which appears to be related to the ZT and which originates in the supratemporal auditory cortex. It is a sustained neuromagnetic activity that shows a clear-cut dipolar field distribution, and it appears that this activity has certain similarities with the tone-evoked auditory sustained response. The hypothesis is put forward that during the sensation of the ZT a process takes place in the auditory cortex which is similar to that underlying the sustained response, and which gives rise to the sensation of the ZT. In contrast to the sustained response, however, which is due to neural activity evoked by an external acoustic stimulus, the sustained activity associated with the ZT is due to a temporary absolute or relative reduction of neural activity originating from those regions in which the ZT exciting stimulus caused an adaptation. These differences in neural activity cannot be distinguished by the auditory system from a corresponding external acoustic signal. Preliminary studies in patients suffering from tonal tinnitus yielded results which exhibit a certain similarity with those obtained in the ZT experiment.     

Event-related brain activity associated with auditory pattern processing

One of the basic properties of the auditory system is the ability to analyse complex temporal patterns. Here, we investigated the neural activity associated with auditory pattern processing using event-related brain potentials. Participants were presented with a continuously repeating sequence of four tones with rare changes in either the frequency or timing of one of the tones. Both frequency- and time-deviant sounds generated mismatch negativity (MMN) waves that peaked at midline central electrode sites and inverted in polarity at inferior temporal and occipital sites, consistent with generators in the supratemporal plane. The MMN scalp topography was similar for the frequency- and time-deviant stimuli, suggesting that both spectral and temporal relations among elements of an auditory pattern are encoded in a unified memory trace.