Stimulus-specific Adaptation Research Articles

Stimulus-Specific Adaptation Decreases the Coupling of Spikes to LFP Phase.

Stimulus repetition suppresses the neural activity in different sensory areas of the brain. This mechanism of so-called stimulus-specific adaptation (SSA) has been observed in both spiking activity and local field potential (LFP) responses. However, much remains to be known about the effect of SSA on the spike–LFP relation. In this study, we approached this issue by investigating the spike-phase coupling (SPC) in control and adapting paradigms. For the control paradigm, pure tones were presented in a random unbiased sequence. In the adapting paradigm, the same stimuli were presented in a random pattern but it was biased to an adapter stimulus. In fact, the adapter occupied 80% of the adapting sequence. During the tasks, LFP and multi-unit activity were recorded simultaneously from the primary auditory cortex of 15 anesthetized rats. To clarify the effect of adaptation on the relation between spike and LFP responses, the SPC of the adapter stimulus in these two paradigms was evaluated. Here, we employed phase locking value method for calculating the SPC. Our data show a strong coupling of spikes to LFP phase most prominently in beta band. This coupling was observed to decrease in the adapting condition compared to the control one. Importantly, we found that adaptation reduces spikes dominantly from the preferred phase of LFP in which spikes are more likely to be present there. As a result, the preferred phase of LFP may play a key role in coordinating neuronal spiking activity in neural adaptation mechanism. This finding is important for interpretation of the underlying neural mechanism of adaptation and also can be used in the context of the network and related connectivity models.

Evoked Response Strength in Primary Auditory Cortex Predicts Performance in a Spectro-Spatial Discrimination Task in Rats.

The extent to which the primary auditory cortex (A1) participates in instructing animal behavior remains debated. Although multiple studies have shown A1 activity to correlate with animals' perceptual judgments (Jaramillo and Zador, 2011; Bizley et al., 2013; Rodgers and DeWeese, 2014), others have found no relationship between A1 responses and reported auditory percepts (Lemus et al., 2009; Dong et al., 2011). To address this ambiguity, we performed chronic recordings of evoked local field potentials (eLFPs) in A1 of head-fixed female rats performing a two-alternative forced-choice auditory discrimination task. Rats were presented with two interleaved sequences of pure tones from opposite sides and had to indicate the side from which the higher-frequency target stimulus was played. Animal performance closely correlated (rrm = 0.68) with the difference between the target and distractor eLFP responses: the more the target response exceeded the distractor response, the better the animals were at identifying the side of the target frequency. Reducing the evoked response of either frequency through stimulus-specific adaptation affected performance in the expected way: target localization accuracy was degraded when the target frequency was adapted and improved when the distractor frequency was adapted. Target frequency eLFPs were stronger on hit trials than on error trials. Our results suggest that the degree to which one stimulus stands out over others within A1 activity may determine its perceptual saliency for the animals and accordingly bias their behavioral choices.SIGNIFICANCE STATEMENT The brain must continuously calibrate the saliency of sensory percepts against their relevance to the current behavioral goal. The inability to ignore irrelevant distractors characterizes a spectrum of human attentional disorders. Meanwhile, the connection between the neural underpinnings of stimulus saliency and sensory decisions remains elusive. Here, we record local field potentials in the primary auditory cortex of rats engaged in auditory discrimination to investigate how the cortical representation of target and distractor stimuli impacts behavior. We find that the amplitude difference between target- and distractor-evoked activity predicts discrimination performance (rrm = 0.68). Specific adaptation of target or distractor shifts performance either below or above chance, respectively. It appears that recent auditory history profoundly influences stimulus saliency, biasing animals toward diametrically-opposed decisions.

Neuronal Encoding in a High-Level Auditory Area: From Sequential Order of Elements to Grammatical Structure.

Sensitivity to the sequential structure of communication sounds is fundamental not only for language comprehension in humans but also for song recognition in songbirds. By quantifying single-unit responses, we first assessed whether the sequential order of song elements, called syllables, in conspecific songs is encoded in a secondary auditory cortex-like region of the zebra finch brain. Based on a habituation/dishabituation paradigm, we show that, after multiple repetitions of the same conspecific song, rearranging syllable order reinstated strong responses. A large proportion of neurons showed sensitivity to song context in which syllables occurred providing support for the nonlinear processing of syllable sequences. Sensitivity to the temporal order of items within a sequence should enable learning its underlying structure, an ability considered a core mechanism of the human language faculty. We show that repetitions of songs that were ordered according to a specific grammatical structure (i.e., ABAB or AABB structures; A and B denoting song syllables) led to different responses in both anesthetized and awake birds. Once responses were decreased due to song repetitions, the transition from one structure to the other could affect the firing rates and/or the spike patterns. Our results suggest that detection was based on local differences rather than encoding of the global song structure as a whole. Our study demonstrates that a high-level auditory region provides neuronal mechanisms to help discriminate stimuli that differ in their sequential structure.SIGNIFICANCE STATEMENT Sequence processing has been proposed as a potential precursor of language syntax. As a sequencing operation, the encoding of the temporal order of items within a sequence may help in recognition of relationships between adjacent items and in learning the underlying structure. Taking advantage of the stimulus-specific adaptation phenomenon observed in a high-level auditory region of the zebra finch brain, we addressed this question at the neuronal level. Reordering elements within conspecific songs reinstated robust responses. Neurons also detected changes in the structure of artificial songs, and this detection depended on local transitions between adjacent or nonadjacent syllables. These findings establish the songbird as a model system for deciphering the mechanisms underlying sequence processing at the single-cell level.

Integrative stimulus-specific adaptation of the natural sounds in the auditory cortex of the awake rat.

Using oddball stimulus with pure tones, researchers have extensively investigated stimulus-specific adaptation (SSA), which has been regarded as a method of novelty detection, from the inferior colliculus (IC) to the auditory cortex (AC). However, until now, it is not clear whether SSA is preserved for natural sounds or whether it exists for spatial cues in the AC. Moreover, it is also unclear whether SSA integrates different types of cues within a single modality such as sound location and sound identity. Here, we addressed these issues using two natural sounds presented at two different locations while simultaneously performing extracellular recordings in the AC of awake rats. Our data showed that SSA was present in the AC for the natural sounds, the pure tones, and the spatial locations in the neuronal population. We also found that the AC response to a double deviant stimulus (a deviant sound at a deviant location) was stronger than that to a single (either a deviant sound or the same sound at a deviant location); this finding suggests that detecting unexpected events benefits from the integration of different cues within the same modality.

Early postnatal noise exposure degrades the stimulus-specific adaptation of neurons in the rat auditory cortex in adulthood

Many auditory cortical neurons exhibit stimulus-specific adaptation (SSA), i.e., they respond weakly to frequently occurring stimuli but strongly to the same stimuli when presented rarely. SSA has been proposed to be a potential mechanism to engage deviance detection or novelty detection. Previous studies on SSA were investigated in animals reared in normal environment. It has been shown that early postnatal noise exposure impairs the development of cortical processing of sound information. However, it is not understood whether postnatal middle-level noise exposure affects the SSA in the primary auditory cortex (AI), and if yes, whether the impacts of noise exposure on SSA varied with noise exposure periods. Here we used a frequency oddball paradigm to determine the SSA of AI neurons in three groups of rats: the control rats were reared in normal environment without noise exposure, the young noise-exposed rats received a 70 dB SPL white noise exposure from P10 to P56, and the adult noise-exposed rats received the same noise exposure from P57 to P103. We found that early postnatal noise exposure reduced the proportion of SSA neurons in AI and decreased the strength of SSA of AI neurons in the young noise-exposed rats in adulthood. In contrast, the same noise exposure to adult rats had no significant impacts on the SSA of AI neurons in adult noise-exposed rats. The results suggest that environmental noise might be a risk factor for abnormal postnatal development of cortical processing of frequency deviance in a sound sequence.

Temporal expectations modulate face image repetition suppression of early stimulus evoked event-related potentials

Repeated exposure to a stimulus leads to reduced responses of stimulus-selective sensory neurons, an effect known as repetition suppression or stimulus-specific adaptation. Several influential models have been proposed to explain repetition suppression within hierarchically-organised sensory systems, with each specifying different mechanisms underlying repetition effects. We manipulated temporal expectations within a face repetition experiment to test a critical prediction of the predictive coding model of repetition suppression: that repetition effects will be larger following stimuli that appear at expected times compared to stimuli that appear at unexpected times. We recorded event-related potentials from 18 participants and mapped the spatiotemporal progression of repetition effects using mass univariate analyses. We then assessed whether the magnitudes of observed face image repetition effects were influenced by temporal expectations. In each trial participants saw an adapter face, followed by a 500 ms or 1000 ms interstimulus interval (ISI), and then a test face, which was the same or a different face identity to the adapter. Participants’ expectations for whether the test face would appear after a 500 ms ISI were cued by the sex of the adapter face. Our analyses revealed multiple repetition effects with distinct scalp topographies, extending until at least 800 ms from stimulus onset. An early (158–203 ms) repetition effect was larger for stimuli following surprising, rather than expected, 500 ms ISI durations, contrary to the model predictions of the predictive coding model of repetition suppression. During this time window temporal expectation effects were larger for alternating, compared to repeated, test stimuli. Statistically significant temporal expectation by stimulus repetition interactions were not found for later (230–609 ms) time windows. Our results provide further evidence that repetition suppression can reduce neural effects of expectation and surprise, indicating that there are multiple interactive mechanisms supporting sensory predictions within the visual hierarchy.

Pattern-sensitive neurons reveal encoding of complex auditory regularities in the rat inferior colliculus

A ‘pattern alternation paradigm’ has been previously used in human ERP recordings to investigate the brain encoding of complex auditory regularities, but prior studies on regularity encoding in animal models to examine mechanisms of adaptation of auditory neuronal responses have used primarily oddball stimulus sequences to study stimulus-specific adaptation alone. In order to examine the sensitivity of neuronal adaptation to expected and unexpected events embedded in a complex sound sequence, we used a similar patterned sequence of sounds. We recorded single unit activity and compared neuronal responses in the rat inferior colliculus (IC) to sound stimuli conforming to pattern alternation regularity with those to stimuli in which occasional sound repetitions violated that alternation.Results show that some neurons in the rat inferior colliculus are sensitive to the history of patterned stimulation and to violations of patterned regularity, demonstrating that there is a population of subcortical neurons, located as early as the level of the midbrain, that can detect more complex stimulus regularities than previously supposed and that are as sensitive to complex statistics as some neurons in primary auditory cortex.Our findings indicate that these pattern-sensitive neurons can extract temporal and spectral regularities between successive acoustic stimuli. This is important because the extraction of regularities from the sound sequences will result in the development of expectancies for future sounds and hence, the present results are compatible with predictive coding models. Our results demonstrate that some collicular neurons, located as early as in the midbrain level, are involved in the generation and shaping of prediction errors in ways not previously considered and thus, the present findings challenge the prevailing view that perceptual organization of sound only emerges at the auditory cortex level.

Frequency-Dependent Stimulus-Specific Adaptation and Regularity Sensitivity in the Rat Auditory Thalamus

Recent electrophysiological studies in animals using oddball stimuli have demonstrated that neurons along the auditory pathway from the inferior colliculus to the auditory cortex (AC) have a strong response to rarely presented stimuli. This phenomenon is termed stimulus-specific adaptation (SSA), which is regarded as novelty detection. However, in the medial geniculate body (MGB), it is not clear whether SSA is frequency dependent or if neurons in the MGB are sensitive to the regularity of the stimuli. In this present study, we analyzed the relationship between stimulus frequency and SSA, as well as explored regularity sensitivity using extracellular recordings in the MGBs of rats with regular and irregular oddball stimuli. It was found MGB neurons exhibited strong SSA when the pure-tone stimulus of the oddball stimulus deviated far from the characteristic frequency, even in the ventral region of the MGB, suggesting that the MGB may contribute to SSA in the primary AC. Moreover, we found the neuronal population in the MGB was sensitive to high-order sound structure, where deviant responses were smaller and standard responses were stronger for irregular oddball stimuli. We conclude that regularity detection occurs in the MGB, but in a manner distinct from the AC.

Modeling Neural Adaptation in Auditory Cortex

Neural responses recorded from auditory cortex exhibit adaptation, a stimulus-specific decrease that occurs when the same sound is presented repeatedly. Stimulus-specific adaptation is thought to facilitate perception in noisy environments. Although adaptation is assumed to arise independently from cortex, this has been difficult to validate directly in vivo. In this study, we used a neural network model of auditory cortex with multicompartmental cell modeling to investigate cortical adaptation. We found that repetitive, non-adapted inputs to layer IV neurons in the model elicited frequency-specific decreases in simulated single neuron, population-level and local field potential (LFP) activity, consistent with stimulus-specific cortical adaptation. Simulated recordings of LFPs, generated solely by excitatory post-synaptic inputs and recorded from layers II/III in the model, showed similar waveform morphologies and stimulus probability effects as auditory evoked responses recorded from human cortex. We tested two proposed mechanisms of cortical adaptation, neural fatigue and neural sharpening, by varying the strength and type of inter- and intra-layer synaptic connections (excitatory, inhibitory). Model simulations showed that synaptic depression modeled in excitatory (AMPA) synapses was sufficient to elicit a reduction in neural firing rate, consistent with neural fatigue. However, introduction of lateral inhibition from local layer II/III interneurons resulted in a reduction in the number of responding neurons, but not their firing rates, consistent with neural sharpening. These modeling results demonstrate that adaptation can arise from multiple neural mechanisms in auditory cortex.

Stimulus-specific adaptation in the anesthetized mouse revealed by brainstem auditory evoked potentials

Neural responses to sensory inputs in a complex and natural environment must be weighted according to their relevance. To do so, the brain needs to be able to deal with sudden stimulus fluctuations in an ever-changing acoustic environment. Stimulus-specific adaptation (SSA) is a phenomenon of some neurons along the auditory pathway that show a reduced response to repetitive sounds while responsive to those that occur rarely. SSA has been shown from the inferior colliculus to auditory cortex, but has not been detected in the cochlear nucleus. To discover where SSA is first generated along the auditory pathway, auditory brainstem responses (ABRs) to pure tones were evaluated in anesthetized mice using an oddball paradigm. Using a typical narrow band-pass filter, changes in the ABRs suggest unspecific short-term adaptation may occur as early as the auditory nerve fibers. Furthermore, after applying a wide band-pass filter –allowing the visualization of a late slow wave in the ABR– we found a reduction of the amplitude of the response to repetitive sounds, compared to rare ones, in the slow wave component P0 that follow the fast wave V. Previous studies have shown the P0 shows temporal correlation with the sustained responses of inferior colliculus, thus we suggest that this nucleus is the first to show stimulus specific adaptation in the auditory pathway.

Deviance sensitivity in the auditory cortex of freely moving rats.

Deviance sensitivity is the specific response to a surprising stimulus, one that violates expectations set by the past stimulation stream. In audition, deviance sensitivity is often conflated with stimulus-specific adaptation (SSA), the decrease in responses to a common stimulus that only partially generalizes to other, rare stimuli. SSA is usually measured using oddball sequences, where a common (standard) tone and a rare (deviant) tone are randomly intermixed. However, the larger responses to a tone when deviant does not necessarily represent deviance sensitivity. Deviance sensitivity is commonly tested using a control sequence in which many different tones serve as the standard, eliminating the expectations set by the standard ('deviant among many standards'). When the response to a tone when deviant (against a single standard) is larger than the responses to the same tone in the control sequence, it is concluded that true deviance sensitivity occurs. In primary auditory cortex of anesthetized rats, responses to deviants and to the same tones in the control condition are comparable in size. We recorded local field potentials and multiunit activity from the auditory cortex of awake, freely moving rats, implanted with 32-channel drivable microelectrode arrays and using telemetry. We observed highly significant SSA in the awake state. Moreover, the responses to a tone when deviant were significantly larger than the responses to the same tone in the control condition. These results establish the presence of true deviance sensitivity in primary auditory cortex in awake rats.

Hierarchical stimulus processing in rodent primary and lateral visual cortex as assessed through neuronal selectivity and repetition suppression

Similar to primates, visual cortex in rodents appears to be organized in two distinct hierarchical streams. However, there is still little known about how visual information is processed along those streams in rodents. In this study, we examined how repetition suppression and position and clutter tolerance of the neuronal representations evolve along the putative ventral visual stream in rats. To address this question, we recorded multiunit spiking activity in primary visual cortex (V1) and the more downstream visual laterointermediate (LI) area of head-restrained Long-Evans rats. We employed a paradigm reminiscent of the continuous carry-over design used in human neuroimaging. In both areas, stimulus repetition attenuated the early phase of the neuronal response to the repeated stimulus, with this response suppression being greater in area LI. Furthermore, stimulus preferences were more similar across positions (position tolerance) in area LI than in V1, even though the absolute responses in both areas were very sensitive to changes in position. In contrast, the neuronal representations in both areas were equally good at tolerating the presence of limited visual clutter, as modeled by the presentation of a single flank stimulus. When probing tolerance of the neuronal representations with stimulus-specific adaptation, we detected no position tolerance in either examined brain area, whereas, on the contrary, we revealed clutter tolerance in both areas. Overall, our data demonstrate similarities and discrepancies in processing of visual information along the ventral visual stream of rodents and primates. Moreover, our results stress caution in using neuronal adaptation to probe tolerance of the neuronal representations. NEW & NOTEWORTHY Rodents are emerging as a popular animal model that complement primates for studying higher level visual functions. Similar to findings in primates, we demonstrate a greater repetition suppression and position tolerance of the neuronal representations in the downstream laterointermediate area of Long-Evans rats compared with primary visual cortex. However, we report no difference in the degree of clutter tolerance between the areas. These findings provide additional evidence for hierarchical processing of visual stimuli in rodents.

F153. NEUROMAGNETIC MISMATCH NEGATIVITY IN CLINICAL HIGH RISK AND FIRST-EPISODE PSYCHOSIS INDIVIDUALS

BackgroundAuditory mismatch negativity (MMN) and its magnetic counterpart (MMNm) are event-related potentials/fields elicited by violations of previously established auditory regularities (Näätänen et al. 2007). Reduced MMN amplitude is a robust finding in both medicated and unmedicated schizophrenia (ScZ) patients (for a review, see Umbricht & Krljes, 2005), potentially indicating impaired predictive processes (Sauer et al. 2017). Furthermore, several studies have examined MMN responses in individuals at clinical high risk for psychosis (CHR) and have found MMN deficits to be present already in this population, indicating that MMN is compromised before psychosis onset and could represent a marker of risk for psychosis development. However, not all studies have reported significant differences in MMN amplitude between clinical high risk and healthy individuals and there is evidence to suggest that MMN deficits are primarily observed in CHR individuals who transition to psychosis (Bodatsch et al., 2015).MethodsThe purpose of the present study is to investigate MEG recorded MMNm amplitude responses to both duration deviants and sound omissions in n = 90 CHR-individuals who were screened with the Schizophrenia Proneness Instrument and the Comprehensive Assessment of At Risk Mental States. N = 50 healthy controls served as a comparison group. We employed an auditory oddball paradigm in which three different sequences of auditory stimuli were presented binaurally at ~ 70 dB (150 ms SOA, 700 – 100 ms ISI). The standard sequence contained five identical tones (80 ms) and the deviant sequence contained four identical tones and one duration deviant tone (40 ms). In addition, an omission sequence which contained only four identical tones was included to examine auditory predictions. Participants were instructed to focus their attention away from the sounds and to perform a simple visual detection task. We analyzed MMNm responses to unpredictable deviant and omitted sounds in bsensor and source space. The linearly constrained minimum variance (LCMV) beamformer was used to identify the generators of the MMNm responses and to compute artefact-free source-level time-courses.ResultsConsistent with previous studies revealing MMN sources in auditory cortical areas, bilateral MMNm sources were localized in auditory cortices for both duration deviants and sound omissions. Our data show attenuated MMNm responses elicited by duration deviant sounds in CHR individuals compared to healthy controls.DiscussionTaken together, the study findings suggest that reduced MMNm amplitude is present before psychosis onset and reflects aberrant predictive processing rather than deficient stimulus-specific adaptation. Clinical follow-up measurements will be obtained to determine whether MMNm amplitudes are a potential biomarker for predicting onset of psychosis.

Stimulus specific adaptation in the auditory system of insects: Can a single neuron learn?

Stimulus-specific adaptation (SSA) is the suppression of a neuron's activity to repetitive stimuli while maintaining responsiveness to infrequent signals. In Neoconocephalus katydids, one auditory interneuron (TN-1) shows strong SSA in oddball paradigms, when standard and oddball pulses differ in carrier frequency. SSA occurred for pulse rates from >140 Hz down to 1 Hz. At fast repetition rates (>100 Hz), responses to the common pulses ceased, while oddballs elicit single spikes. At slower rates (<50 Hz), both standard and oddball pulses elicited spiking, with responses to oddballs being significantly larger, comparable to SSA described in vertebrate hearing systems. At slow rates, SSA also occurred when the shape of standard and oddball pulses differed, while having identical spectral properties. We identified at least two dendritic mechanisms that contribute to SSA at fast pulse rates (>100 Hz). The mechanisms underlying SSA at slow pulse rates are less well understood; likely, dendritic Ca2 + -gated currents contribute to SSA at slow pulse rates. At slow rates, response reduction to repeated pulses resembles habituation as oddball pulses cause dishabituation, i.e., the response to the following standard pulse is larger than that to the preceding one. Whether this habituation is generated within TN-1 or by its synaptic inputs remains an open question.

Effects of auditory response patterns on stimulus-specific adaptation of inferior colliculus neurons in awake mice

To explore whether the pattern of neuron's auditory response to a sound stimulus affects the characteristics of stimulus-specific adaptation (SSA) in awake mice. The auditory responses of the neurons in the inferior colliculus to sound stimuli were recorded using microelectrodes in awake mice. The sequence of sound stimuli consisted of random combinations of pure tones of two different frequencies (f1 and f2) with different repetition rates. The auditory responses of the neurons to standard and deviant stimuli were calculated, namely s(f2)/s(f2) and d(f1)/d(f2), respectively. Three indexes of the responses were also calculated, including the firing difference index (FDI), frequency-specific index (SI), and common SSA index(CSI). The CSI of neurons with a greater FDI was significantly higher than that of neurons with a smaller FDI (P < 0.05). The primary-like neurons showed different characteristics of SSAs in different time periods; SSA was significantly increased in the phase of sustained response compared with that at the onset of response (P < 0.05). The auditory response pattern to sound stimuli is also an important factor that affect SSA of inferior colliculus neurons in awake mice.

The Neuronal Basis of Predictive Coding Along the Auditory Pathway: From the Subcortical Roots to Cortical Deviance Detection.

In this review, we attempt to integrate the empirical evidence regarding stimulus-specific adaptation (SSA) and mismatch negativity (MMN) under a predictive coding perspective (also known as Bayesian or hierarchical-inference model). We propose a renewed methodology for SSA study, which enables a further decomposition of deviance detection into repetition suppression and prediction error, thanks to the use of two controls previously introduced in MMN research: the many-standards and the cascade sequences. Focusing on data obtained with cellular recordings, we explain how deviance detection and prediction error are generated throughout hierarchical levels of processing, following two vectors of increasing computational complexity and abstraction along the auditory neuraxis: from subcortical toward cortical stations and from lemniscal toward nonlemniscal divisions. Then, we delve into the particular characteristics and contributions of subcortical and cortical structures to this generative mechanism of hierarchical inference, analyzing what is known about the role of neuromodulation and local microcircuitry in the emergence of mismatch signals. Finally, we describe how SSA and MMN are occurring at similar time frame and cortical locations, and both are affected by the manipulation of N-methyl-D-aspartate receptors. We conclude that there is enough empirical evidence to consider SSA and MMN, respectively, as the microscopic and macroscopic manifestations of the same physiological mechanism of deviance detection in the auditory cortex. Hence, the development of a common theoretical framework for SSA and MMN is all the more recommendable for future studies. In this regard, we suggest a shared nomenclature based on the predictive coding interpretation of deviance detection.

Evidence for spatiotemporally distinct effects of image repetition and perceptual expectations as measured by event-related potentials

Repeated stimulus presentation leads to reductions in responses of cortical neurons, known as repetition suppression or stimulus-specific adaptation. Circuit-based models of repetition suppression provide a framework for investigating patterns of repetition effects that propagate through cortical hierarchies. To further develop such models it is critical to determine whether (and if so, when) repetition effects are modulated by factors such as expectation and attention. We investigated whether repetition effects are influenced by perceptual expectations, and whether the time courses of each effect are similar or distinct, by presenting pairs of repeated and alternating face images and orthogonally manipulating expectations regarding the likelihood of stimulus repetition. Event-related potentials (ERPs) were recorded from n = 39 healthy adults, to map the spatiotemporal progression of stimulus repetition and stimulus expectation effects, and interactions between these, using mass univariate analyses. We also tested for another expectation effect that may contribute to repetition effects in many previous experiments: that repeated stimulus identities are predictable after seeing the first stimulus in a trial, but unrepeated stimulus identities cannot be predicted. Separate blocks were presented with predictable and unpredictable alternating face identities. Multiple repetition and expectation effects were identified between 99 and 800ms from stimulus onset, which did not statistically interact at any point and exhibited distinct spatiotemporal patterns of effects. Repetition effects in blocks with predictable alternating faces were smaller than in unpredictable alternating face blocks between 117-179 ms and 506–652ms, and larger between 246 and 428ms. The distinct spatiotemporal patterns of repetition and expectation effects support separable mechanisms underlying these phenomena. However, previous studies of repetition effects, in which the repeated (but not unrepeated) stimulus was predictable, are likely to have conflated repetition and stimulus predictability effects.

Visual mismatch negativity to vanishing parts of objects in younger and older adults.

We investigated visual mismatch negativity (vMMN) to vanishing parts of continuously present objects by comparing the event-related potentials (ERPs) to infrequently (deviant) and frequently (standard) disappearing parts of the objects. This paradigm both excludes low-level stimulus-specific adaptation differences between the responses to deviants and standards, and increases the ecological validity of the stimuli. In comparison to frequently disappearing parts of the stimulus objects, infrequently vanishing parts elicited posterior negative event-related brain activity (vMMN). However, no vMMN emerged to the reappearance of the same parts of the objects. We compared the ERPs of an older and a younger sample of participants. In the 120–180 ms time period vMMN was similar in the two age groups, but in the 180–220 ms time period vMMN emerged only in the younger participants. We consider this difference as an index of more elaborate automatic processing of infrequent stimulus changes in younger adults.

The effect of inhibition on stimulus-specific adaptation in the inferior colliculus.

The inferior colliculus is a center of convergence for inhibitory and excitatory synaptic inputs that may be activated simultaneously by sound stimulation. Stimulus repetition may generate response habituation by changing the efficacy of neuron's synaptic inputs. Specialized IC neurons reduce their response to repetitive tones, but restore their firing when a different and infrequent tone occurs, a phenomenon known as stimulus specific adaptation. Here, using the microiontophoresis technique, we determined the role of GABAA-, GABAB-, and glycinergic receptors in stimulus-specific adaptation (SSA). We found that blockade of postsynaptic GABAB receptors selectively modulated response adaptation to repetitive sounds, whereas blockade of presynaptic GABAB receptors exerted a gain control effect on neuron excitability. Adaptation decreased when postsynaptic GABAB receptors were blocked, but increased if the blockade affected the presynaptic GABAB receptors. A dual, paradoxical effect was elicited by blockade of glycinergic receptors, i.e., both increase and decrease in adaptation. Moreover, simultaneous co-application of GABAA, GABAB, and glycinergic antagonists demonstrated that local GABA- and glycine-mediated inhibition contributes to only about 50% of SSA. Therefore, inhibition via chemical synapses dynamically modulate the strength and dynamics of stimulus-specific adaptation, but does not generate it.

Familiar But Unexpected: Effects of Sound Context Statistics on Auditory Responses in the Songbird Forebrain.

Rapid discrimination of salient acoustic signals in the noisy natural environment may depend, not only on specific stimulus features, but also on previous experience that generates expectations about upcoming events. We studied the neural correlates of expectation in the songbird forebrain by using natural vocalizations as stimuli and manipulating the category and familiarity of context sounds. In our paradigm, we recorded bilaterally from auditory neurons in awake adult male zebra finches with multiple microelectrodes during repeated playback of a conspecific song, followed by further playback of this test song in different interleaved sequences with other conspecific or heterospecific songs. Significant enhancement in the auditory response to the test song was seen when its acoustic features differed from the statistical distribution of context song features, but not when it shared the same distribution. Enhancement was also seen when the time of occurrence of the test song was uncertain. These results show that auditory forebrain responses in awake animals in the passive hearing state are modulated dynamically by previous auditory experience and imply that the auditory system can identify the category of a sound based on the global features of the acoustic context. Furthermore, this probability-dependent enhancement in responses to surprising stimuli is independent of stimulus-specific adaptation, which tracks familiarity, suggesting that the two processes could coexist in auditory processing. These findings establish the songbird as a model system for studying these phenomena and contribute to our understanding of statistical learning and the origin of human ERP phenomena to unexpected stimuli.SIGNIFICANCE STATEMENT Traditional auditory neurophysiology has mapped acoustic features of sounds to the response properties of neurons; however, growing evidence suggests that neurons can also encode the probability of sounds. We recorded responses of songbird auditory neurons in a novel paradigm that presented a familiar test stimulus in a sequence with similar or dissimilar sounds. The responses encode, not only stimulus familiarity, but also the expectation for a class of sounds based on the recent statistics of varying sounds in the acoustic context. Our approach thus provides a model system that uses a controlled stimulus paradigm to understand the mechanisms by which top-down processes (expectation and memory) and bottom-up processes (based on stimulus features) interact in sensory coding.