Brain Metabolism during Hallucination-Like Auditory Stimulation in Schizophrenia

Auditory verbal hallucinations (AVH) in schizophrenia are typically characterized by rich emotional content. Despite the prominent role of emotion in regulating normal perception, the neural interface between emotion-processing regions such as the amygdala and auditory regions involved in perception remains relatively unexplored in AVH. Here, we studied brain metabolism using FDG-PET in 9 remitted patients with schizophrenia that previously reported severe AVH during an acute psychotic episode and 8 matched healthy controls. Participants were scanned twice: (1) at rest and (2) during the perception of aversive auditory stimuli mimicking the content of AVH. Compared to controls, remitted patients showed an exaggerated response to the AVH-like stimuli in limbic and paralimbic regions, including the left amygdala. Furthermore, patients displayed abnormally strong connections between the amygdala and auditory regions of the cortex and thalamus, along with abnormally weak connections between the amygdala and medial prefrontal cortex. These results suggest that abnormal modulation of the auditory cortex by limbic-thalamic structures might be involved in the pathophysiology of AVH and may potentially account for the emotional features that characterize hallucinatory percepts in schizophrenia.     

Smell-induced gamma oscillations in human olfactory cortex are required for accurate perception of odor identity

Studies of neuronal oscillations have contributed substantial insight into the mechanisms of visual, auditory, and somatosensory perception. However, progress in such research in the human olfactory system has lagged behind. As a result, the electrophysiological properties of the human olfactory system are poorly understood, and, in particular, whether stimulus-driven high-frequency oscillations play a role in odor processing is unknown. Here, we used direct intracranial recordings from human piriform cortex during an odor identification task to show that 3 key oscillatory rhythms are an integral part of the human olfactory cortical response to smell: Odor induces theta, beta, and gamma rhythms in human piriform cortex. We further show that these rhythms have distinct relationships with perceptual behavior. Odor-elicited gamma oscillations occur only during trials in which the odor is accurately perceived, and features of gamma oscillations predict odor identification accuracy, suggesting that they are critical for odor identity perception in humans. We also found that the amplitude of high-frequency oscillations is organized by the phase of low-frequency signals shortly following sniff onset, only when odor is present. Our findings reinforce previous work on theta oscillations, suggest that gamma oscillations in human piriform cortex are important for perception of odor identity, and constitute a robust identification of the characteristic electrophysiological response to smell in the human brain. Future work will determine whether the distinct oscillations we identified reflect distinct perceptual features of odor stimuli.

Intracranial recordings from human olfactory cortex reveal a characteristic spectrotemporal response to odors, including theta, beta and gamma oscillations, and show that high-frequency responses are critical for accurate perception of odors.     

Tuning to natural stimulus dynamics in primary auditory cortex

The amplitude and pitch fluctuations of natural soundscapes often exhibit "1/f spectra", which means that large, abrupt changes in pitch or loudness occur proportionally less frequently in nature than gentle, gradual fluctuations. Furthermore, human listeners reportedly prefer 1/f distributed random melodies to melodies with faster (1/f0) or slower (1/f2) dynamics. One might therefore suspect that neurons in the central auditory system may be tuned to 1/f dynamics, particularly given that recent reports provide evidence for tuning to 1/f dynamics in primary visual cortex. To test whether neurons in primary auditory cortex (A1) are tuned to 1/f dynamics, we recorded responses to random tone complexes in which the fundamental frequency and the envelope were determined by statistically independent "1/f(gamma) random walks," with gamma set to values between 0.5 and 4. Many A1 neurons showed clear evidence of tuning and responded with higher firing rates to stimuli with gamma between 1 and 1.5. Response patterns elicited by 1/f(gamma) stimuli were more reproducible for values of gamma close to 1. These findings indicate that auditory cortex is indeed tuned to the 1/f dynamics commonly found in the statistical distributions of natural soundscapes.     

Differential effects of acetylcholine in the chicken auditory neostriatum and hyperstriatum ventrale — studies in vivo and in vitro

1. The effect of acetylcholine (ACh) on the response properties of single units in the caudal auditory telencephalon was studied both in awake chickens and in an in vitro slice preparation. 2. Two types of electrophysiological behavior in response to ACh were observed: an inhibition of cell firing typical for the majority of neurons in the auditory hyperstriatum ventrale and a facilitation of neuronal responses seen predominantly in neostriatal auditory units. 3. The facilitatory effect of ACh is also present in hyperstriatal cells, but is usually dominated by an indirect inhibition. 4. ACh-induced facilitation on single unit responses could be mimicked in awake birds by applying potentially arousing sensory stimuli. 5. The effects of ACh are antagonized by the muscarinic receptor blocker scopolamine. 6. Inhibitory responses can also be antagonized by the GABA-antagonist bicuculline and thus can be attributed to an ACh-induced activation of GABAergic inhibitory interneurons. Evidence is given that the facilitatory responses result from a closure of voltage-dependent potassium channels. 7. The results are discussed with respect to a possible role of cholinergic afferents in telencephalic processing of auditory information and in comparison with the cholinergic influences in the mammalian neocortex.     

Continuity of Visual and Auditory Rhythms Influences Sensorimotor Coordination

People often coordinate their movement with visual and auditory environmental rhythms. Previous research showed better performances when coordinating with auditory compared to visual stimuli, and with bimodal compared to unimodal stimuli. However, these results have been demonstrated with discrete rhythms and it is possible that such effects depend on the continuity of the stimulus rhythms (i.e., whether they are discrete or continuous). The aim of the current study was to investigate the influence of the continuity of visual and auditory rhythms on sensorimotor coordination. We examined the dynamics of synchronized oscillations of a wrist pendulum with auditory and visual rhythms at different frequencies, which were either unimodal or bimodal and discrete or continuous. Specifically, the stimuli used were a light flash, a fading light, a short tone and a frequency-modulated tone. The results demonstrate that the continuity of the stimulus rhythms strongly influences visual and auditory motor coordination. Participants'' movement led continuous stimuli and followed discrete stimuli. Asymmetries between the half-cycles of the movement in term of duration and nonlinearity of the trajectory occurred with slower discrete rhythms. Furthermore, the results show that the differences of performance between visual and auditory modalities depend on the continuity of the stimulus rhythms as indicated by movements closer to the instructed coordination for the auditory modality when coordinating with discrete stimuli. The results also indicate that visual and auditory rhythms are integrated together in order to better coordinate irrespective of their continuity, as indicated by less variable coordination closer to the instructed pattern. Generally, the findings have important implications for understanding how we coordinate our movements with visual and auditory environmental rhythms in everyday life.     

Auditory steady-state responses to multiple simultaneous stimuli

Steady-state responses can follow multiple simultaneous auditory stimuli. If the stimuli are modulated at different rates, responses specific to each stimulus can be assessed by measuring in the frequency domain response the spectral component corresponding to the rate of modulation. When each stimulus has a different carrier frequency or different ear of presentation, the responses when 8 stimuli are presented simultaneously are not significantly different than when each stimulus is presented alone. Since significant responses can be recognized down to intensities that average 14 dB above behavioral threshold, this technique may be useful in objective audiometry. It is also possible to record steady-state responses to multiple modulations of the same carrier frequency. In this case, the amplitude of the responses when the stimuli are combined is smaller than when the stimuli are presented alone. The decrease in amplitude depends upon the number of concomitant stimuli and their relative intensities. These effects are probably due to the compressive rectification occurring during cochlear transduction, and the data may be used to model cochlear processing of auditory stimuli.     

Auditory Cortical Areas Activated by Slow Frequency-Modulated Sounds in Mice

Species-specific vocalizations in mice have frequency-modulated (FM) components slower than the lower limit of FM direction selectivity in the core region of the mouse auditory cortex. To identify cortical areas selective to slow frequency modulation, we investigated tonal responses in the mouse auditory cortex using transcranial flavoprotein fluorescence imaging. For differentiating responses to frequency modulation from those to stimuli at constant frequencies, we focused on transient fluorescence changes after direction reversal of temporally repeated and superimposed FM sweeps. We found that the ultrasonic field (UF) in the belt cortical region selectively responded to the direction reversal. The dorsoposterior field (DP) also responded weakly to the reversal. Regarding the responses in UF, no apparent tonotopic map was found, and the right UF responses were significantly larger in amplitude than the left UF responses. The half-max latency in responses to FM sweeps was shorter in UF compared with that in the primary auditory cortex (A1) or anterior auditory field (AAF). Tracer injection experiments in the functionally identified UF and DP confirmed that these two areas receive afferent inputs from the dorsal part of the medial geniculate nucleus (MG). Calcium imaging of UF neurons stained with fura-2 were performed using a two-photon microscope, and the presence of UF neurons that were selective to both direction and direction reversal of slow frequency modulation was demonstrated. These results strongly suggest a role for UF, and possibly DP, as cortical areas specialized for processing slow frequency modulation in mice.     

记忆水平依赖的海马-前额叶神经节律交互

海马(HPC)和前额叶皮层(PFC)的协同作用是记忆加工过程的关键,其相互作用对学习和记忆功能至关重要.大量证据表明,情景记忆的形成、巩固与检索依赖于特征神经节律在PFC和HPC脑区间的同步作用,这些节律包括theta节律、gamma节律和sharp wave ripples (SWRs)节律等,在精神类疾病中患者往往...     

Topography of alpha and theta oscillatory responses upon auditory and visual stimuli in humans

Brain resonance phenomena and induced rhythms in the brain recently gained importance in electroencephalographic, magnetoencephalographic and cellular studies (Ba\c sar and Bullock 1992). It was hypothesized that evoked potentials are superpositions of induced rhythms caused by resonance phenomena in neural populations (Ba\c sar et al. 1992). According to Ba\c sar (1972), such resonance phenomena are reflected in the main peaks of the amplitude frequency characteristics computed from EEG responses. The present study is based on a frequency domain approach for the evaluation of topography- and modality-dependent properties of oscillatory brain responses. EEG and evoked potentials were recorded from vertex, parietal and occipital scalp locations in 24 volunteers. Two combined methods were applied: (1) amplitude frequency characteristics were computed from the transient evoked responses, and (2) frequency components of the transient responses were obtained by adaptive digital filtering. Our main goal was to investigate theta (4--7 Hz) and alpha (8--15 Hz) response components. (1) Amplitude frequency characteristics. Auditory stimuli elicited theta-alpha compound responses in the 4--11 Hz frequency band (e.g. typical peaking frequency around 7 Hz for vertex recordings). Visual stimuli elicited alpha responses (e.g. typical peaking frequency for vertex recordings around 9--12 Hz). Frequency maxima for visual stimuli thus had main peaks at higher frequency values than frequency maxima for auditory stimuli. (2) Digital filtering confirmed these results: for vertex recordings, theta vs. alpha response amplitudes were 9 vs 6 for auditory stimuli and 5 vs 5 for visual stimuli, thus confirming a shift towards higher frequencies, i.e. a more prominent contribution of the alpha range, in the case of visual stimulation. We hypothesize that these properties might reflect site- and modality-specific features of stimulus encoding in the brain in which resonance properties of neuron populations are involved. Furthermore we emphasize the utility of the systems theory approach for a better understanding of brain function by means of EPs. Received: 25 February 1994 / Accepted in revised form: 5 August 1994     

Cortical signatures of auditory object binding in children with autism spectrum disorder are anomalous in concordance with behavior and diagnosis

Organizing sensory information into coherent perceptual objects is fundamental to everyday perception and communication. In the visual domain, indirect evidence from cortical responses suggests that children with autism spectrum disorder (ASD) have anomalous figure–ground segregation. While auditory processing abnormalities are common in ASD, especially in environments with multiple sound sources, to date, the question of scene segregation in ASD has not been directly investigated in audition. Using magnetoencephalography, we measured cortical responses to unattended (passively experienced) auditory stimuli while parametrically manipulating the degree of temporal coherence that facilitates auditory figure–ground segregation. Results from 21 children with ASD (aged 7–17 years) and 26 age- and IQ-matched typically developing children provide evidence that children with ASD show anomalous growth of cortical neural responses with increasing temporal coherence of the auditory figure. The documented neurophysiological abnormalities did not depend on age, and were reflected both in the response evoked by changes in temporal coherence of the auditory scene and in the associated induced gamma rhythms. Furthermore, the individual neural measures were predictive of diagnosis (83% accuracy) and also correlated with behavioral measures of ASD severity and auditory processing abnormalities. These findings offer new insight into the neural mechanisms underlying auditory perceptual deficits and sensory overload in ASD, and suggest that temporal-coherence-based auditory scene analysis and suprathreshold processing of coherent auditory objects may be atypical in ASD.

To navigate everyday environments, the auditory system must analyze the temporal coherence of sound elements scattered across different frequencies to organize them into discrete perceptual objects. This neuroimaging study reveals that this process is altered in autism, potentially explaining the often-experienced sensory overload.     

Interactions between distinct GABA(A) circuits in hippocampus

Synchronous activity among synaptically connected interneurons is thought to organize temporal patterns such as gamma and theta rhythms in cortical circuits. Interactions between distinct interneuron circuits may underlie more complex patterns, such as nested rhythms. Here, we demonstrate such an interaction between two groups of CA1 interneurons, GABA(A,slow) and GABA(A,fast) cells, that may contribute to theta and gamma rhythms, respectively. Stratum lacunosum-moleculare (SL-M) stimuli that activate GABA(A,slow) inhibitory postsynaptic currents (IPSCs) in pyramidal cells simultaneously depress the rate and amplitude of spontaneous GABA(A,fast) IPSCs for several hundred milliseconds. This suppression has a similar pharmacological profile to GABA(A,slow) IPSCs, and SL-M stimuli elicit GABA(A,slow) IPSCs in interneurons. We conclude that GABA(A,slow) cells inhibit both pyramidal cells and GABA(A,fast) interneurons and postulate that this interaction contributes to nested theta/gamma rhythms in hippocampus.     

Sensory-Motor Interactions for Vocal Pitch Monitoring in Non-Primary Human Auditory Cortex

The neural mechanisms underlying processing of auditory feedback during self-vocalization are poorly understood. One technique used to study the role of auditory feedback involves shifting the pitch of the feedback that a speaker receives, known as pitch-shifted feedback. We utilized a pitch shift self-vocalization and playback paradigm to investigate the underlying neural mechanisms of audio-vocal interaction. High-resolution electrocorticography (ECoG) signals were recorded directly from auditory cortex of 10 human subjects while they vocalized and received brief downward (−100 cents) pitch perturbations in their voice auditory feedback (speaking task). ECoG was also recorded when subjects passively listened to playback of their own pitch-shifted vocalizations. Feedback pitch perturbations elicited average evoked potential (AEP) and event-related band power (ERBP) responses, primarily in the high gamma (70–150 Hz) range, in focal areas of non-primary auditory cortex on superior temporal gyrus (STG). The AEPs and high gamma responses were both modulated by speaking compared with playback in a subset of STG contacts. From these contacts, a majority showed significant enhancement of high gamma power and AEP responses during speaking while the remaining contacts showed attenuated response amplitudes. The speaking-induced enhancement effect suggests that engaging the vocal motor system can modulate auditory cortical processing of self-produced sounds in such a way as to increase neural sensitivity for feedback pitch error detection. It is likely that mechanisms such as efference copies may be involved in this process, and modulation of AEP and high gamma responses imply that such modulatory effects may affect different cortical generators within distinctive functional networks that drive voice production and control.     

Background gamma activity in the rabbit electroencephalogram as an index of the level of sustained (tonic) attention in the active oddball paradigm in rabbits

Tonic brain activity substantially affects the character of subjects' responsiveness to sensory stimuli. The dynamics of background gamma-band activity in rabbit electroencephalogram was investigated in the active oddball paradigm modified for animal studies. It was shown that increase in the power and coherence of gamma activity reflects the target stimulus expectancy. Correct responses to stimuli occur at a particular level of background gamma activity, which is likely to correspond to the optimal level of sustained (tonic) attention. Decrease in the level of background gamma activity leads to omissions of responses to target stimuli, while it's excessive level results in erroneous responses to nontarget stimuli (false alarms). The observed dynamics of tonic gamma activity can be interpreted as the result of variations in the level of tonic cholinergic activation of the brain cortex.     

Thalamic activation modulates the responses of neurons in rat primary auditory cortex: an in vivo intracellular recording study

Auditory cortical plasticity can be induced through various approaches. The medial geniculate body (MGB) of the auditory thalamus gates the ascending auditory inputs to the cortex. The thalamocortical system has been proposed to play a critical role in the responses of the auditory cortex (AC). In the present study, we investigated the cellular mechanism of the cortical activity, adopting an in vivo intracellular recording technique, recording from the primary auditory cortex (AI) while presenting an acoustic stimulus to the rat and electrically stimulating its MGB. We found that low-frequency stimuli enhanced the amplitudes of sound-evoked excitatory postsynaptic potentials (EPSPs) in AI neurons, whereas high-frequency stimuli depressed these auditory responses. The degree of this modulation depended on the intensities of the train stimuli as well as the intervals between the electrical stimulations and their paired sound stimulations. These findings may have implications regarding the basic mechanisms of MGB activation of auditory cortical plasticity and cortical signal processing.     

Behavioral and neuronal investigations of hypervigilance in patients with fibromyalgia syndrome

Painful stimuli are of utmost behavioral relevance and thereby affect attentional resources. In health, variable effects of pain on attention have been observed, indicating alerting as well as distracting effects of pain. In the human brain, these effects are closely related to modulations of neuronal gamma oscillations. As hypervigilance as an abnormal increase of attention to external stimuli has been implicated in chronic pain states, we assumed both attentional performance and pain-induced gamma oscillations to be altered in patients with fibromyalgia syndrome (FMS). We recorded electroencephalography from healthy subjects (n = 22) and patients with FMS (n = 19) during an attention demanding visual reaction time task. In 50% of the trials we applied painful laser stimuli. The results of self-assessment questionnaires confirm that patients with FMS consider themselves hypervigilant towards pain as compared to healthy controls. However, the experimental findings indicate that the effects of painful stimuli on attentional performance and neuronal gamma oscillations do not differ between patients and healthy subjects. We further found a significant correlation between the pain-induced modulation of visual gamma oscillations and the pain-induced modulation of reaction times. This relationship did not differ between groups either. These findings confirm a close relationship between gamma oscillations and the variable attentional effects of pain, which appear to be comparable in health and disease. Thus, our results do not provide evidence for a behavioral or neuronal manifestation of hypervigilance in patients with FMS.     

Late-night presentation of an auditory stimulus phase delays human circadian rhythms

Although light is considered the primary entrainer of circadian rhythms in humans, nonphotic stimuli, including exercise and melatonin also phase shift the biological clock. Furthermore, in birds and nonhuman mammals, auditory stimuli are effective zeitgebers. This study investigated whether a nonphotic auditory stimulus phase shifts human circadian rhythms. Ten subjects (5 men and 5 women, ages 18-72, mean age +/- SD, 44.7 +/- 21.4 yr) completed two 4-day laboratory sessions in constant dim light (<20 lux). They received two consecutive presentations of either a 2-h auditory or control stimulus from 0100 to 0300 on the second and third nights (presentation order of the stimulus and control was counterbalanced). Core body temperature (CBT) was collected and stored in 2-min bins throughout the study and salivary melatonin was obtained every 30 min from 1900 to 2330 on the baseline and poststimulus/postcontrol nights. Circadian phase of dim light melatonin onset (DLMO) and of CBT minimum, before and after auditory or control presentation was assessed. The auditory stimulus produced significantly larger phase delays of the circadian melatonin (mean +/- SD, -0.89 +/- 0.40 h vs. -0.27 +/- 0.16 h) and CBT (-1.16 +/- 0.69 h vs. -0.44 +/- 0.27 h) rhythms than the control. Phase changes for the two circadian rhythms also positively correlated, indicating direct effects on the biological clock. In addition, the auditory stimulus significantly decreased fatigue compared with the control. This study is the first demonstration of an auditory stimulus phase-shifting circadian rhythms in humans, with shifts similar in size and direction to those of other nonphotic stimuli presented during the early subjective night. This novel stimulus may be a useful countermeasure to facilitate circadian adaptation after transmeridian travel or shift work.     

Neural Processing of Short-Term Recurrence in Songbird Vocal Communication

Background

Many situations involving animal communication are dominated by recurring, stereotyped signals. How do receivers optimally distinguish between frequently recurring signals and novel ones? Cortical auditory systems are known to be pre-attentively sensitive to short-term delivery statistics of artificial stimuli, but it is unknown if this phenomenon extends to the level of behaviorally relevant delivery patterns, such as those used during communication.

Methodology/Principal Findings

We recorded and analyzed complete auditory scenes of spontaneously communicating zebra finch (Taeniopygia guttata) pairs over a week-long period, and show that they can produce tens of thousands of short-range contact calls per day. Individual calls recur at time scales (median interval 1.5 s) matching those at which mammalian sensory systems are sensitive to recent stimulus history. Next, we presented to anesthetized birds sequences of frequently recurring calls interspersed with rare ones, and recorded, in parallel, action and local field potential responses in the medio-caudal auditory forebrain at 32 unique sites. Variation in call recurrence rate over natural ranges leads to widespread and significant modulation in strength of neural responses. Such modulation is highly call-specific in secondary auditory areas, but not in the main thalamo-recipient, primary auditory area.

Conclusions/Significance

Our results support the hypothesis that pre-attentive neural sensitivity to short-term stimulus recurrence is involved in the analysis of auditory scenes at the level of delivery patterns of meaningful sounds. This may enable birds to efficiently and automatically distinguish frequently recurring vocalizations from other events in their auditory scene.     

Encoding and decoding amplitude-modulated cochlear implant stimuli—a point process analysis

Cochlear implant speech processors stimulate the auditory nerve by delivering amplitude-modulated electrical pulse trains to intracochlear electrodes. Studying how auditory nerve cells encode modulation information is of fundamental importance, therefore, to understanding cochlear implant function and improving speech perception in cochlear implant users. In this paper, we analyze simulated responses of the auditory nerve to amplitude-modulated cochlear implant stimuli using a point process model. First, we quantify the information encoded in the spike trains by testing an ideal observer’s ability to detect amplitude modulation in a two-alternative forced-choice task. We vary the amount of information available to the observer to probe how spike timing and averaged firing rate encode modulation. Second, we construct a neural decoding method that predicts several qualitative trends observed in psychophysical tests of amplitude modulation detection in cochlear implant listeners. We find that modulation information is primarily available in the sequence of spike times. The performance of an ideal observer, however, is inconsistent with observed trends in psychophysical data. Using a neural decoding method that jitters spike times to degrade its temporal resolution and then computes a common measure of phase locking from spike trains of a heterogeneous population of model nerve cells, we predict the correct qualitative dependence of modulation detection thresholds on modulation frequency and stimulus level. The decoder does not predict the observed loss of modulation sensitivity at high carrier pulse rates, but this framework can be applied to future models that better represent auditory nerve responses to high carrier pulse rate stimuli. The supplemental material of this article contains the article’s data in an active, re-usable format.     

A generalized linear model for estimating spectrotemporal receptive fields from responses to natural sounds

In the auditory system, the stimulus-response properties of single neurons are often described in terms of the spectrotemporal receptive field (STRF), a linear kernel relating the spectrogram of the sound stimulus to the instantaneous firing rate of the neuron. Several algorithms have been used to estimate STRFs from responses to natural stimuli; these algorithms differ in their functional models, cost functions, and regularization methods. Here, we characterize the stimulus-response function of auditory neurons using a generalized linear model (GLM). In this model, each cell's input is described by: 1) a stimulus filter (STRF); and 2) a post-spike filter, which captures dependencies on the neuron's spiking history. The output of the model is given by a series of spike trains rather than instantaneous firing rate, allowing the prediction of spike train responses to novel stimuli. We fit the model by maximum penalized likelihood to the spiking activity of zebra finch auditory midbrain neurons in response to conspecific vocalizations (songs) and modulation limited (ml) noise. We compare this model to normalized reverse correlation (NRC), the traditional method for STRF estimation, in terms of predictive power and the basic tuning properties of the estimated STRFs. We find that a GLM with a sparse prior predicts novel responses to both stimulus classes significantly better than NRC. Importantly, we find that STRFs from the two models derived from the same responses can differ substantially and that GLM STRFs are more consistent between stimulus classes than NRC STRFs. These results suggest that a GLM with a sparse prior provides a more accurate characterization of spectrotemporal tuning than does the NRC method when responses to complex sounds are studied in these neurons.