Offset responses in primary auditory cortex are enhanced after notched noise stimulation.

Sensory "aftereffects" are a subgroup of sensory illusions that can be defined as an illusory phenomenon triggered after prolonged exposure to a given sensory inducer. These phenomena are interesting because they can provide insights into the mechanisms of perception. In auditory modality, there is a special interest in the so-called "Zwicker tone" (ZT), an auditory aftereffect triggered after the presentation of a notched noise (NN, broadband noise with a missing frequency band). The ZT has been considered a plausible model of a specific tinnitus subtype since it presents some key characteristics in common with tinnitus. Indeed, both the tinnitus percept and ZT can be triggered by a relative "sensory deprivation," and their pitch corresponds to the frequency region that has been sensory deprived. The effects of a NN presentation on the central auditory system are still barely investigated, and the mechanisms of the ZT are elusive. In this study, we analyzed the laminar structure of the neural activity in the primary cortex of anesthetized and awake guinea pigs during and after white noise (WN) and NN stimulation. We found significantly increased offset responses, in terms of both spiking activity and local field potential amplitude, after NN compared with WN presentation. The offset responses were circumscribed to the granular and upper infragranular layers (input layers) and were maximal when the neuron's best frequency was within or near the missing frequency band. The mechanisms of the offset response and its putative link with the ZT are discussed.NEW & NOTEWORTHY Notched noise (white noise with embedded spectral gap) causes significant excitatory offset responses in the auditory cortex of awake and anesthetized guinea pigs. The largest offset responses were located in the infragranular/granular layers, and current source density analysis revealed that offset responses were associated with an early current sink localized in the upper infragranular layers. We discuss the possibility that the offset responses might be associated with an auditory phantom percept (Zwicker tone).

Evoked Potentials by Tone Burst on the Auditory Cortices in Cats -Comparison of Off Responses in Awake and Anesthetized Conditions.

BACKGROUND: Auditory Brainstem Response (ABR) recording in awake is essential to detect off-responses. This study clarified whether after-termination responses on ABR were offset responses, off-responses or a mixture of the two. METHODS: Evoked potentials in the auditory cortex of cats in response to tone burst stimuli were recorded, and off responses were examined with chronically implanted electrodes. RESULTS: When the fall time at the end of sound stimuli was 5ms or longer, the amplitude of click responses was extremely small. Under this condition, evoked potentials in response to two types of tone bursts (long and short) were recorded.By calculating the differences in evoked potentials between the two-tone bursts, off responses were separated. Off responses were generated during wakefulness by auditory cortex stimulation but were not observed under anesthesia. Pronounced off responses, which were middle latency responses exhibiting bis positive waves, were obtained in response to sound stimuli with a frequency of 2 kHz or higher. Vertex stimulation did not induce off responses either during wakefulness or under anesthesia. CONCLUSION: Off responses are derived from synchronous responses of neurons in the auditory cortex, which are generated when the neurons detect attenuation in the stimulus strength at the end of tone burst stimuli.

Experience-Dependent Coding of Time-Dependent Frequency Trajectories by Off Responses in Secondary Auditory Cortex.

Time-dependent frequency trajectories are an inherent feature of many behaviorally relevant sounds, such as species-specific vocalizations. Dynamic frequency trajectories, even in short sounds, often convey meaningful information, which may be used to differentiate sound categories. However, it is not clear what and where neural responses in the auditory cortical pathway are critical for conveying information about behaviorally relevant frequency trajectories, and how these responses change with experience. Here, we uncover tuning to subtle variations in frequency trajectories in auditory cortex of female mice. We found that auditory cortical responses could be modulated by variations in a pure tone trajectory as small as 1/24th of an octave, comparable to what has been reported in primates. In particular, late spiking after the end of a sound stimulus was more often sensitive to the sound's subtle frequency variation compared with spiking during the sound. Such "Off" responses in the adult A2, but not those in core auditory cortex, were plastic in a way that may enhance the representation of a newly acquired, behaviorally relevant sound category. We illustrate this with the maternal mouse paradigm for natural vocalization learning. By using an ethologically inspired paradigm to drive auditory responses in higher-order neurons, our results demonstrate that mouse auditory cortex can track fine frequency changes, which allows A2 Off responses in particular to better respond to pitch trajectories that distinguish behaviorally relevant, natural sound categories.SIGNIFICANCE STATEMENT A whistle's pitch conveys meaning to its listener, as when dogs learn that distinct pitch trajectories whistled by their owner differentiate specific commands. Many species use pitch trajectories in their own vocalizations to distinguish sound categories, such as in human languages, such as Mandarin. How and where auditory neural activity encodes these pitch trajectories as their meaning is learned but not well understood, especially for short-duration sounds. We studied this in mice, where infants use ultrasonic whistles to communicate to adults. We found that late neural firing after a sound ends can be tuned to how the pitch changes in time, and that this response in a secondary auditory cortical field changes with experience to acquire a pitch change's meaning.

Early cortical processing of pitch height and the role of adaptation and musicality.

Pitch is an important perceptual feature; however, it is poorly understood how its cortical correlates are shaped by absolute vs relative fundamental frequency (f0), and by neural adaptation. In this study, we assessed transient and sustained auditory evoked fields (AEFs) at the onset, progression, and offset of short pitch height sequences, taking into account the listener's musicality. We show that neuromagnetic activity reflects absolute f0 at pitch onset and offset, and relative f0 at transitions within pitch sequences; further, sequences with fixed f0 lead to larger response suppression than sequences with variable f0 contour, and to enhanced offset activity. Musical listeners exhibit stronger f0-related AEFs and larger differences between their responses to fixed vs variable sequences, both within sequences and at pitch offset. The results resemble prominent psychoacoustic phenomena in the perception of pitch contours; moreover, they suggest a strong influence of adaptive mechanisms on cortical pitch processing which, in turn, might be modulated by a listener's musical expertise.

Sensitivity to the temporal structure of rapid sound sequences - An MEG study.

To probe sensitivity to the time structure of ongoing sound sequences, we measured MEG responses, in human listeners, to the offset of long tone-pip sequences containing various forms of temporal regularity. If listeners learn sequence temporal properties and form expectancies about the arrival time of an upcoming tone, sequence offset should be detectable as soon as an expected tone fails to arrive. Therefore, latencies of offset responses are indicative of the extent to which the temporal pattern has been acquired. In Exp1, sequences were isochronous with tone inter-onset-interval (IOI) set to 75, 125 or 225ms. Exp2 comprised of non-isochronous, temporally regular sequences, comprised of the IOIs above. Exp3 used the same sequences as Exp2 but listeners were required to monitor them for occasional frequency deviants. Analysis of the latency of offset responses revealed that the temporal structure of (even rather simple) regular sequences is not learnt precisely when the sequences are ignored. Pattern coding, supported by a network of temporal, parietal and frontal sources, improved considerably when the signals were made behaviourally pertinent. Thus, contrary to what might be expected in the context of an 'early warning system' framework, learning of temporal structure is not automatic, but affected by the signal's behavioural relevance.

Effects of Ketamine Administration on Auditory Information Processing in the Neocortex of Nonhuman Primates.

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts broad effects on consciousness and perception. Since NMDA receptor antagonists induce cognitive impairments, ketamine has been used for translational research on several psychiatric diseases, such as schizophrenia. Whereas the effects of ketamine on cognitive functions have been extensively studied, studies on the effects of ketamine on simple sensory information processing remain limited. In this study, we investigated the cortex-wide effects of ketamine administration on auditory information processing in nonhuman primates using whole-cortical electrocorticography (ECoG). We first recorded ECoG from awake monkeys on presenting auditory stimuli of different frequencies or different durations. We observed auditory evoked responses (AERs) across the cortex, including in frontal, parietal, and temporal areas, while feature-specific responses were obtained around the temporal sulcus. Next, we examined the effects of ketamine on cortical auditory information processing. We conducted ECoG recordings from monkeys that had been administered anesthetic doses of ketamine from 10 to 180 min following administration. We observed significant changes in stimulus feature-specific responses. Electrodes showing a frequency preference or offset responses were altered following ketamine administration, while those of the AERs were not strongly influenced. However, the frequency preference of a selected electrode was not significantly altered by ketamine administration over time following administration, while the imbalances in the onset and offset persisted over the course of 150 min following ketamine administration in all three monkeys. These results suggest that ketamine affects the ability to distinguish between sound frequency and duration in different ways. In conclusion, future research on the NMDA sensitivity of cortical wide sensory information processing may provide a new perspective into the development of nonhuman primate models of psychiatric disorders.

Late fMRI Response Components Are Altered in Autism Spectrum Disorder.

Disrupted cortical neural inhibition has been hypothesized to be a primary contributor to the pathophysiology of autism spectrum disorder (ASD). This hypothesis predicts that ASD will be associated with an increase in neural responses. We tested this prediction by comparing fMRI response magnitudes to simultaneous visual, auditory, and motor stimulation in ASD and neurotypical (NT) individuals. No increases in the initial transient response in any brain region were observed in ASD, suggesting that there is no increase in overall cortical neural excitability. Most notably, there were widespread fMRI magnitude increases in the ASD response following stimulation offset, approximately 6-8 s after the termination of sensory and motor stimulation. In some regions, the higher fMRI offset response in ASD could be attributed to a lack of an "undershoot"-an often observed feature of fMRI responses believed to reflect inhibitory processing. Offset response magnitude was associated with reaction times (RT) in the NT group and may explain an overall reduced RT in the ASD group. Overall, our results suggest that increases in neural responsiveness are present in ASD but are confined to specific components of the neural response, are particularly strong following stimulation offset, and are linked to differences in RT.

Event-related potential arithmetic to analyze offset potentials from conscious mice.

BACKGROUND: This paper presents a method for isolating time-dependent event-related potential (ERP) components which are superimposed on the gross ERP waveform. The experimental data that inspired this approach was recorded from the auditory cortex of conscious laboratory mice in response to presentation of ten different duration pure-tone auditory stimuli. NEW METHOD: The grand-average ERP for each individual stimulus displayed a relatively low amplitude deflection following stimulus offset. In order to isolate this component for analysis, a series of simple arithmetic operations were performed, involving averaging of multiple stimuli ERPs and subtracting this from each individual ERP. RESULTS: Offset potentials were isolated and quantified. Peak latency was determined by auditory stimulus duration; peak amplitude did not reach the threshold for statistical significance, over the range of durations tested. COMPARISON WITH EXISTING METHOD(S): To the best of my knowledge there are no alternative methods for isolating offset potentials from the gross ERP waveform at present. This novel approach may introduce less subjective bias to analyses than manually selecting measurement windows and performing custom baseline corrections. CONCLUSIONS: A similar method may be applied to other human or non-human datasets to identify and characterize time-dependent sensory-cognitive processes obscured by gross waveform morphology.

Modeling Responses in the Superior Paraolivary Nucleus: Implications for Forward Masking in the Inferior Colliculus.

A phenomenological model of the responses of neurons in the superior paraolivary nucleus (SPON) of the rodent is presented in this study. Pure tones at the characteristic frequency (CF) and broadband noise stimuli evoke offset-type responses in these neurons. SPON neurons also phase-lock to the envelope of sinusoidally amplitude-modulated (SAM) stimuli for a range of modulation frequencies. Model SPON neuron received inhibitory input that was relayed by the ipsilateral medial nucleus of the trapezoid body from the contralateral model ventral cochlear nucleus neuron. The SPON model response was simulated by detecting the slope of its inhibitory postsynaptic potential. Responses of the proposed model to pure tones at CF and broadband noise were offset-type independent of the duration of the input stimulus. SPON model responses were also synchronized to the envelope of SAM stimuli with precise timing for a range of modulation frequencies. Modulation transfer functions (MTFs) obtained from the model response to SAM stimuli resemble the physiological MTFs. The output of the proposed SPON model provides an input for models of physiological responses at higher levels of the ascending auditory pathway and can also be utilized to infer possible mechanisms underlying gap detection and duration encoding as well as forward masking at the level of the auditory midbrain.