Xihong Wu

Top-down modulation of prepulse inhibition of the startle reflex in humans and rats

Prepulse inhibition (PPI) is the attenuation of the startle reflex when the sudden intense startling stimulus is shortly preceded by a weaker, non-startling sensory stimulus (prepulse). PPI reflects a protective function of reducing disruptive influences to the processing of prepulse signals and is recognized as a model of sensorimotor gating. In humans, PPI is modulated by both attentional and emotional responses to prepulse, indicating that this early-stage gating is top-down modulated by higher-order cognitive processes. Recent studies have confirmed top-down modulation of PPI in animals, because PPI in rats is enhanced by auditory fear conditioning and perceived separation between fear-conditioned prepulse and masker. This review summarizes recent studies of top-down modulation of PPI conducted in humans and those in rats. Since both baseline PPI and attentional modulation of PPI in patients with schizophrenia are impaired, and both baseline PPI and conditional modulation of PPI in rats with isolation rearing are impaired, this review emphasizes that investigation of top-down modulation of PPI is critical for establishing new animal models for studying both cognitive features and neural bases of schizophrenia. Deficits in either baseline PPI or attentional modulation of PPI in either patients with attention-deficit/hyperactivity disorder (ADHD) or ADHD-modeling rats are also discussed.

Constructing long short-term memory based deep recurrent neural networks for large vocabulary speech recognition

Long short-term memory (LSTM) based acoustic modeling methods have recently been shown to give state-of-the-art performance on some speech recognition tasks. To achieve a further performance improvement, in this research, deep extensions on LSTM are investigated considering that deep hierarchical model has turned out to be more efficient than a shallow one. Motivated by previous research on constructing deep recurrent neural networks (RNNs), alternative deep LSTM architectures are proposed and empirically evaluated on a large vocabulary conversational telephone speech recognition task. Meanwhile, regarding to multi-GPU devices, the training process for LSTM networks is introduced and discussed. Experimental results demonstrate that the deep LSTM networks benefit from the depth and yield the state-of-the-art performance on this task.

Distance-Dependent Head-Related Transfer Functions Measured With High Spatial Resolution Using a Spark Gap

A measurement of head-related transfer functions (HRTFs) with high spatial resolution was carried out in this study. HRTF measurement is difficult in the proximal region because of the lack of an appropriate acoustic point source. In this paper, a modified spark gap was used as the acoustic sound source. Our evaluation experiments showed that the spark gap was more like an acoustic point source than others previously used from the viewpoints of frequency response, directivity, power attenuation, and stability. Using this spark gap, high spatial resolution HRTFs were measured at 6344 spatial points, with distances from 20 to 160 cm, elevations from -40deg to 90deg, and azimuths from 0deg to 360deg. Based on these measurements, an HRTF database was obtained and its reliability was confirmed by both objective and subjective evaluations.

Perceptual integration between target speech and target-speech reflection reduces masking for target-speech recognition in younger adults and older adults

This study evaluated unmasking functions of perceptual integration of target speech and simulated target-speech reflection, which were presented by two spatially separated loudspeakers. In both younger-adult listeners with normal hearing and older-adult listeners in the early stages of presbycusis, reducing the time interval between target speech and target-reflection simulation (inter-target interval, ITI) from 64 to 0ms not only progressively enhanced perceptual integration of target-speech signals, but also progressively released target speech from either speech masking or noise masking. When the signal-to-noise ratio was low, the release from speech masking was significantly larger than the release from noise masking in both younger listeners and older listeners, but the longest ITI at which a significant release from speech masking occurred was significantly shorter in older listeners than in younger listeners. These results suggest that in reverberant environments with multi-talker speech, perceptual integration between the direct sound wave and correlated reflections, which facilitates perceptual segregation of various sources, is critical for unmasking attended speech. The age-related reduction of the ITI range for releasing speech from speech masking may be one of the causes for the speech-recognition difficulties experienced by older listeners in such adverse environments.

Differentially Organized Top-Down Modulation of Prepulse Inhibition of Startle

Prepulse inhibition (PPI) of startle is the suppression of the startle reflex when a weaker sensory stimulus (the prepulse) shortly precedes the startling stimulus. PPI can be attentionally enhanced in both humans and laboratory animals. This study investigated whether the following three forebrain structures, which are critical for initial cortical processing of auditory signals, auditory fear conditioning/memories, and spatial attention, respectively, play a role in the top-down modulation of PPI in rats: the primary auditory cortex (A1), lateral nucleus of the amygdala (LA), and posterior parietal cortex (PPC). The results show that, under the noise-masking condition, PPI was enhanced by fear conditioning of the prepulse in a prepulse-specific manner, and the conditioning-induced PPI enhancement was further increased by perceptual separation between the conditioned prepulse and the noise masker. Reversibly blocking glutamate receptors in the A1 with 2 mm kynurenic acid eliminated both the conditioning-induced and perceptual separation-induced PPI enhancements. Blocking the LA eliminated the conditioning-induced but not the perceptual separation-induced PPI enhancement, and blocking the PPC specifically eliminated the perceptual separation-induced PPI enhancement. The two types of PPI enhancements were also eliminated by the extinction manipulation. Thus, the top-down modulation of PPI is differentially organized and depends on operations of various forebrain structures. Due to the fine-tuned modulation by higher-order cognitive processes, functions of PPI can be more flexible to complex environments. The top-down enhancements of PPI in rats are also useful for modeling some mental disorders, such as schizophrenia, attention deficit/hyperactivity disorder, and posttraumatic stress disorder.

Metabotropic glutamate subtype 5 receptors modulate fear-conditioning induced enhancement of prepulse inhibition in rats

Non-startling acoustic events presented shortly before an intense startling sound can inhibit the acoustic startle reflex. This phenomenon is called prepulse inhibition (PPI), and is widely used as a model of sensorimotor gating. The present study investigated whether PPI can be modulated by fear conditioning, whose acquisition can be blocked by the specific antagonist of metabotropic glutamate receptors subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)-pyridine (MPEP). The results show that a gap embedded in otherwise continuous noise sounds, which were delivered by two spatially separated loudspeakers, could inhibit the startle reflex induced by an intense sound that was presented 50 ms after the gap. The inhibitory effect depended on the duration of the gap, and was enhanced by fear conditioning that was introduced by temporally pairing the gap with footshock. Intraperitoneal injection of MPEP (0.5 or 5mg/kg) 30 min before fear conditioning blocked the enhancing effect of fear conditioning on PPI, but did not affect either the baseline startle magnitude or PPI if no fear conditioning was introduced. These results indicate that PPI is enhanced when the prepulse signifies an aversive event after fear conditioning. Also, mGlu5Rs play a role in preserving the fear-conditioning-induced enhancement of PPI.

Human Auditory Cortex Activity Shows Additive Effects of Spectral and Spatial Cues during Speech Segregation

In noisy social gatherings, listeners perceptually integrate sounds originating from one persons voice (e.g., fundamental frequency (f(0)) and harmonics) at a particular location and segregate these from concurrent sounds of other talkers. Though increasing the spectral or the spatial distance between talkers promotes speech segregation, synergetic effects of spatial and spectral distances are less well understood. We studied how spectral and/or spatial distances between 2 simultaneously presented steady-state vowels contribute to perception and activation in auditory cortex using magnetoencephalography. Participants were more accurate in identifying both vowels when they differed in f(0) and location than when they differed in a single cue only or when they shared the same f(0) and location. The combined effect of f(0) and location differences closely matched the sum of single effects. The improvement in concurrent vowel identification coincided with an object-related negativity that peaked at about 140 ms after vowel onset. The combined effect of f(0) and location closely matched the sum of the single effects even though vowels with different f(0), location, or both generated different time courses of neuromagnetic activity. We propose that during auditory scene analysis, acoustic differences among the various sources are combined linearly to increase the perceptual distance between the co-occurring sound objects.

Auditory Fear Conditioning Modulates Prepulse Inhibition in Socially Reared Rats and Isolation-Reared Rats

Prepulse inhibition (PPI) is the reduction of the startle reflex when the startling stimulus is shortly preceded by a non-startling stimulus. Previous studies have shown that PPI in rats can be enhanced by auditory fear conditioning (AFC) but weakened by isolation rearing. This study investigated whether isolation rearing affects the effect of AFC on PPI. The results show that PPI was lower in isolation-reared rats than that in socially reared rats, and it was markedly enhanced by AFC in socially reared rats. However, the AFC-induced PPI enhancement in isolation-reared rats was much lower than that in socially reared rats. Moreover, the AFC-induced PPI enhancement was blocked by intraperitoneal injection (1 mg/kg) of the selective antagonist of metabotropic glutamate receptor subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)-pyridine (MPEP), 30 minutes before AFC. The baseline startle was also enhanced by isolation rearing. Thus, isolation rearing impairs not only PPI but also the AFC-induced PPI enhancement, which depends on mGluR5 activity. This study advances the animal model for investigating both neural bases and cognitive features of schizophrenia.

The Effect of Voice Cuing on Releasing Speech From Informational Masking Disappears in Older Adults

Objective: To investigate whether older adults can use voice information to unmask speech. Design: Under a voice-priming condition, before a target-speech sentence was presented with a noise or speech masker, one or two voice-priming sentences were recited with the same voice reciting the target sentence. Eighteen younger adults and 12 older adults with clinically normal hearing were instructed to loudly repeat the target sentence. Results: Presenting the voice-priming sentence(s) improved target-speech identification only when the masker was speech in younger adults but not older adults. Conclusion: For older adults, the inability to use voice information to reduce informational masking contributes to their speech-recognition difficulties in “cocktail-party” environments.

Transient Auditory Storage of Acoustic Details Is Associated with Release of Speech from Informational Masking in Reverberant Conditions.

Perceptual integration of the sound directly emanating from the source with reflections needs both temporal storage and correlation computation of acoustic details. We examined whether the temporal storage is frequency dependent and associated with speech unmasking. In Experiment 1, a break in correlation (BIC) between interaurally correlated wideband or narrowband noises was detectable even when an interaural interval (IAI) was introduced. The longest IAI, which varied markedly across participants, could be up to about 20 ms for wideband noise and decreased as the center frequency was increased for narrowband noises. In Experiment 2, when the interval between target speech and its single-reflection simulation (intertarget interval [ITI]) was reduced from 64 to 0 ms, intelligibility of target speech was markedly improved under speech-masking but not noise-masking conditions. The longest effective ITI correlated with the longest IAI for detecting the BIC only in the low-frequency (<or=400 Hz) narrowband noise. Thus the ability to temporally store fine details contributes to perceptual integration of correlated leading and lagging sounds, which in turn, contributes to releasing speech from informational masking in noisy, reverberant environments.