From psychophysiology to brain imaging: forty-five years MMN history of investigating acoustic change sensitivity.

Forty-five years have passed since the first publication of the mismatch negativity (MMN) event-related brain potential (ERP) component. The first 10 years of research hardly gained any particular attention of the scientific community interested in acoustic perception. Debates on the nature of sensation versus perception were going on, and the technical possibilities to record ERPs, called in general evoked potentials, were very limited. Subtle changes in pure tone frequency or intensity giving rise to the MMN component were first investigated in humans. The background of the theoretical model developed by Risto Näätänen was the orientation reaction model of E.N. Sokolov published in 1963 so that the MMN was seen first as an electrophysiological correlate of auditory change detection. This fundamental ability of the auditory system seen as crucial for survival led to the development of the first animal model of the MMN (Csépe et al. in Clin Neurophysiol 66: 571-578, 1987). Indeed, it was confirmed that the MMN was the brain correlate of subtle changes detected that might alert to potential threats in the environment and direct the behavioral orientation. The investigations performed after 2000 introduced complex models and more sophisticated methods, both in animal and human studies, so that the MMN method was on the way to become a tool on the first place and not the main goal of research. This approach was further strengthened by the increasing number of studies on different clinical populations aiming at future applications. The aim of our review is to describe and redefine what the MMN may reflect in auditory perception and to show why and how this brain correlate of changes in the auditory scene can be used as a valuable tool in cognitive neuroscience research. We refer to publications selected to underly the argument the MMN cannot be classified anymore as a sign of simple change detection and not all the indicators used to confirm how genuine the MMN elicited by variations of tones are valid for those to  speech contrasts. We provide a fresh view on the broadly used MMN models, provided by some influential publications as well as on the unwritten history of MMN research aiming to give revised picture on what the MMN may truly reflect. We show how the focus and terminology of the MMN research have changed and what kind of misunderstandings and seemingly contradictive results prevent the MMN community to accept a generally usable cognitive model.

Two Prediction Error Systems in the Nonlemniscal Inferior Colliculus: "Spectral" and "Nonspectral".

According to the predictive processing framework, perception emerges from the reciprocal exchange of predictions and prediction errors (PEs) between hierarchically organized neural circuits. The nonlemniscal division of the inferior colliculus (IC) is the earliest source of auditory PE signals, but their neuronal generators, properties, and functional relevance have remained mostly undefined. We recorded single-unit mismatch responses to auditory oddball stimulation at different intensities, together with activity evoked by two sequences of alternating tones to control frequency-specific effects. Our results reveal a differential treatment of the unpredictable "many-standards" control and the predictable "cascade" control by lemniscal and nonlemniscal IC neurons that is not present in the auditory thalamus or cortex. Furthermore, we found that frequency response areas of nonlemniscal IC neurons reflect their role in subcortical predictive processing, distinguishing three hierarchical levels: (1) nonlemniscal neurons with sharply tuned receptive fields exhibit mild repetition suppression without signaling PEs, thereby constituting the input level of the local predictive processing circuitry. (2) Neurons with broadly tuned receptive fields form the main, "spectral" PE signaling system, which provides dynamic gain compensation to near-threshold unexpected sounds. This early enhancement of saliency reliant on spectral features was not observed in the auditory thalamus or cortex. (3) Untuned neurons form an accessory, "nonspectral" PE signaling system, which reports all surprising auditory deviances in a robust and consistent manner, resembling nonlemniscal neurons in the auditory cortex. These nonlemniscal IC neurons show unstructured and unstable receptive fields that could result from inhibitory input controlled by corticofugal projections conveying top-down predictions.

Deviance Detection to Natural Stimuli in Population Responses of the Brainstem of Bats.

Deviance detection describes an increase of neural response strength caused by a stimulus with a low probability of occurrence. This ubiquitous phenomenon has been reported for humans and multiple other species, from subthalamic areas to the auditory cortex. Cortical deviance detection has been well characterized by a range of studies using a variety of different stimuli, from artificial to natural, with and without a behavioral relevance. This allowed the identification of a broad variety of regularity deviations that are detected by the cortex. Moreover, subcortical deviance detection has been studied with simple stimuli that are not meaningful to the subject. Here, we aim to bridge this gap by using noninvasively recorded auditory brainstem responses (ABRs) to investigate deviance detection at population level in the lower stations of the auditory system of a highly vocal species: the bat Carollia perspicillata (of either sex). Our present approach uses behaviorally relevant vocalization stimuli that are similar to the animals' natural soundscape. We show that deviance detection in ABRs is significantly stronger for echolocation pulses than for social communication calls or artificial sounds, indicating that subthalamic deviance detection depends on the behavioral meaning of a stimulus. Additionally, complex physical sound features like frequency- and amplitude modulation affected the strength of deviance detection in the ABR. In summary, our results suggest that the brain can detect different types of deviants already in the brainstem, showing that subthalamic brain structures exhibit more advanced forms of deviance detection than previously known.

Effect of presentation rate on auditory processing in Rett syndrome: event-related potential study.

BACKGROUND: Rett syndrome (RS) is a rare neurodevelopmental disorder characterized by mutations in the MECP2 gene. Patients with RS have severe motor abnormalities and are often unable to walk, use hands and speak. The preservation of perceptual and cognitive functions is hard to assess, while clinicians and care-givers point out that these patients need more time to process information than typically developing peers. Neurophysiological correlates of auditory processing have been also found to be distorted in RS, but sound presentation rates were relatively quick in these studies (stimulus onset asynchrony, SOA < 1000 ms). As auditory event-related potential (ERP) is typically increased with prolongation of SOA we aim to study if SOA prolongation might compensate for observed abnormalities. METHODS: We presented a repetitive stimulus (1000 Hz) at three different SOAs of 900 ms, 1800 ms, and 3600 ms in children with RS (N = 24, Mean age = 9.0 ± 3.1) and their typical development (TD) peers (N = 27, Mean age = 9.7 ± 3.4) while recording 28-channels electroencephalogram, EEG. Some RS participants (n = 10) did not show clear ERP and were excluded from the analysis. RESULTS: Major ERP components (here assessed as N1P1 and P2N1 peak-to-peak values) were smaller at SOA 900 than at longer SOAs in both groups, pointing out that the basic mechanism of adaptation in the auditory system is preserved in at least in RS patients with evident ERPs. At the same time the latencies of these components were significantly delayed in the RS than in TD. Moreover, late components (P2N1 and N2P2) were drastically reduced in Rett syndrome irrespective of the SOA, suggesting a largely affected mechanism of integration of upcoming sensory input with memory. Moreover, developmental stagnation of auditory ERP characterized patients with RS: absence of typical P2N1 enlargement and P1 and N1 shortening with age at least for shortest SOA. LIMITATIONS: We could not figure out the cause for the high percentage of no-evident ERP RS participants and our final sample of the RS group was rather small. Also, our study did not include a control clinical group. CONCLUSIONS: Thus, auditory ERPs inform us about abnormalities within auditory processing that cannot be fully overcomed by slowing presentation rate.

Extensive representation of sensory deviance in the responses to auditory gaps in unanesthetized rats.

Unexpected changes in incoming sensory streams are associated with large errors in predicting the deviant stimulus relative to a memory trace of past stimuli. Mismatch negativity (MMN) in human studies and the release from stimulus-specific adaptation (SSA) in animal models correlate with prediction errors and deviance detection.1 In human studies, violation of expectations elicited by an unexpected stimulus omission resulted in an omission MMN.2,3,4,5 These responses are evoked after the expected occurrence time of the omitted stimulus, implying that they reflect the violation of a temporal expectancy.6 Because they are often time locked to the end of the omitted stimulus,4,6,7 they resemble off responses. Indeed, suppression of cortical activity after the termination of the gap disrupts gap detection, suggesting an essential role for offset responses.8 Here, we demonstrate that brief gaps in short noise bursts in the auditory cortex of unanesthetized rats frequently evoke offset responses. Importantly, we show that omission responses are elicited when these gaps are expected but are omitted. These omission responses, together with the release from SSA of both onset and offset responses to rare gaps, form a rich and varied representation of prediction-related signals in the auditory cortex of unanesthetized rats, extending substantially and refining the representations described previously in anesthetized rats.

Detección de novedad y codificación predictiva en el sistema auditivo: Impacto clínico en disfunciones auditivas y vestibulares. Revisión de la literatura / Deviance detection and predictive coding in the auditory system: Clinical impact in auditory and vestibular dysfunctions

Una propiedad fundamental de los sistemas sensoriales es su capacidad para detectar estímulos novedosos en el entorno. El sistema nervioso posee neuronas que disminuyen su respuesta a los estímulos sonoros que se repiten a lo largo del tiempo y otras neuronas que aumentan su frecuencia de disparo ante estímulos novedosos, siendo la diferencia entre ambas respuestas conocida como adaptación-específica a estímulos. En las últimas décadas, se ha propuesto que el cerebro establece, continuamente, predicciones de los estímulos novedosos y del entorno basándose en sus experiencias previas y en modelos de representación internos, teoría denominada codificación predictiva. En esta revisión, abordaremos algunos conceptos de la adaptación-específica a estímulos y codificación predictiva, centrándonos principalmente en el sistema auditivo. Por último, propondremos una explicación teórica basada en el marco de la codificación predictiva para algunas disfunciones neuropsiquiátricas, auditivas y vestibulares.

A fundamental property of sensory systems is their ability to detect novel stimuli in the environment. The nervous system possesses neurons that decrease their response to sound stimuli that are repeated over time and other neurons that increase their firing rate to novel stimuli, the difference between the two responses being known as stimulus-specific adaptation. In recent decades, it has been proposed that the brain continuously makes predictions of novel stimuli and the environment based on its previous experiences and internal representational models, a theory called predictive coding. In this review, we will address some concepts of stimulus-specific adaptation and predictive coding, focusing mainly on the auditory system. Finally, we will propose a theoretical explanation based on the predictive coding framework for some neuropsychiatric, auditory, and vestibular dysfunctions.

Deviance Distraction and Stimulus-Specific Adaptation in the Somatosensory Cortex Reduce with Experience.

Automatic detection of a surprising change in the sensory input is a central element of exogenous attentional control. Stimulus-specific adaptation (SSA) is a potential neuronal mechanism detecting such changes and has been robustly described across sensory modalities and different instances of the ascending sensory pathways. However, little is known about the relationship of SSA to perception. To assess how deviating stimuli influence target signal detection, we used a behavioral cross-modal paradigm in mice and combined it with extracellular recordings from the primary somatosensory whisker cortex. In this paradigm, male mice performed a visual detection task while task-irrelevant whisker stimuli were either presented as repetitive "standard" or as rare deviant stimuli. We found a deviance distraction effect on the animals' performance: Faster reaction times but worsened target detection was observed in the presence of a deviant stimulus. Multiunit activity and local field potentials exhibited enhanced neuronal responses to deviant compared with standard whisker stimuli across all cortical layers, as a result of SSA. The deviant-triggered behavioral distraction correlated with these enhanced neuronal deviant responses only in the deeper cortical layers. However, the layer-specific effect of SSA on perception reduced with increasing task experience as a result of statistical distractor learning. These results demonstrate a layer-specific involvement of SSA on perception that is susceptible to modulation over time.SIGNIFICANCE STATEMENT Detecting sudden changes in our immediate environment is behaviorally relevant and important for efficient perceptual processing. However, the connection between the underpinnings of cortical deviance detection and perception remains unknown. Here, we investigate how the cortical representation of deviant whisker stimuli impacts visual target detection by recording local field potential and multiunit activity in the primary somatosensory cortex of mice engaged in a cross-modal visual detection task. We find that deviant whisker stimuli distract animals in their task performance, which correlates with enhanced neuronal responses for deviants in a layer-specific manner. Interestingly, this effect reduces with the increased experience of the animal as a result of distractor learning on statistical regularities.

Stimulus-specific adaptation (SSA) in the auditory system: Functional relevance and underlying mechanisms.

Rapid detection of novel stimuli that appear suddenly in the surrounding environment is crucial for an animal's survival. Stimulus-specific adaptation (SSA) may be an important mechanism underlying novelty detection. In this review, we discuss the latest advances in SSA research by addressing four main aspects: 1) the frequency dependence of SSA and the origin of SSA in the auditory cortex: 2) spatial SSA and its comparison with frequency SSA: 3) feature integration in SSA and its implications in novelty detection: 4) functional significance and the physiological mechanism of SSA. Although SSA has been extensively investigated, the cognitive insights from SSA studies are extremely limited. Future work should aim to bridge these gaps.

Alzheimer's Disease, Hearing Loss, and Deviance Detection.

Age-related hearing loss is a widespread condition among the elderly, affecting communication and social participation. Given its high incidence, it is not unusual that individuals suffering from age-related hearing loss also suffer from other age-related neurodegenerative diseases, a scenario which severely impacts their quality of life. Furthermore, recent studies have identified hearing loss as a relevant risk factor for the development of dementia due to Alzheimer's disease, although the underlying associations are still unclear. In order to cope with the continuous flow of auditory information, the brain needs to separate repetitive sounds from rare, unexpected sounds, which may be relevant. This process, known as deviance detection, is a key component of the sensory perception theory of predictive coding. According to this framework, the brain would use the available incoming information to make predictions about the environment and signal the unexpected stimuli that break those predictions. Such a system can be easily impaired by the distortion of auditory information processing that accompanies hearing loss. Changes in cholinergic neuromodulation have been found to alter auditory deviance detection both in humans and animal models. Interestingly, some theories propose a role for acetylcholine in the development of Alzheimer's disease, the most common type of dementia. Acetylcholine is involved in multiple neurobiological processes such as attention, learning, memory, arousal, sleep and/or cognitive reinforcement, and has direct influence on the auditory system at the levels of the inferior colliculus and auditory cortex. Here we comment on the possible links between acetylcholine, hearing loss, and Alzheimer's disease, and association that is worth further investigation.

Cross-Modal Interaction and Integration Through Stimulus-Specific Adaptation in the Thalamic Reticular Nucleus of Rats.

Stimulus-specific adaptation (SSA), defined as a decrease in responses to a common stimulus that only partially generalizes to other rare stimuli, is a widespread phenomenon in the brain that is believed to be related to novelty detection. Although cross-modal sensory processing is also a widespread phenomenon, the interaction between the two phenomena is not well understood. In this study, the thalamic reticular nucleus (TRN), which is regarded as a hub of the attentional system that contains multi-modal neurons, was investigated. The results showed that SSA existed in an interactive oddball stimulation, which mimics stimulation changes from one modality to another. In the bimodal integration, SSA to bimodal stimulation was stronger than to visual stimulation alone but similar to auditory stimulation alone, which indicated a limited integrative effect. Collectively, the present results provide evidence for independent cross-modal processing in bimodal TRN neurons.

No evidence for auditory N1 dishabituation in healthy adults after presentation of rare novel distractors.

Previous studies were not able to show that presentation of change stimuli leads to dishabituation of the auditory evoked potential (AEP) component N1 for repeated stimuli. However, these change stimuli were usually themselves repeatedly presented. Here, we tested whether the presentation of non-repeating distractor stimuli ('novels') would lead to N1 dishabituation. The study sample consisted of 18 healthy participants who had to identify auditory target stimuli (´targets´) among repeated standard stimuli and rare novels. AEPs to standards were separately averaged, depending on the preceding stimulus (standards after standards, standards after targets, and standards after novels) and were compared by F statistics and Bayesian t-test. Moreover, N1 repetition effects within recording blocks were analyzed in single trial analyses. The analyses showed that targets elicited significantly larger N1 amplitudes than standards and standards elicited larger N1 amplitudes than novels. In contrast, the N1 amplitude to standards did not vary with the preceding stimulus. The single trial analyses revealed significant, but similar N1 amplitude decreases within the recording blocks for all standards. The current study revealed no evidence for N1 dishabituation, as the N1 amplitude for standards after novels was not increased as compared to the N1 for standards after standards. Thus, stimulus variation had no impact on the N1 of repeated standards, as also suggested by the single trial analyses. The lack of N1 dishabituation is at odds with the assumption that the N1 amplitude decrease after repeated stimulation results from habituation.

Neural Substrates and Models of Omission Responses and Predictive Processes.

Predictive coding theories argue that deviance detection phenomena, such as mismatch responses and omission responses, are generated by predictive processes with possibly overlapping neural substrates. Molecular imaging and electrophysiology studies of mismatch responses and corollary discharge in the rodent model allowed the development of mechanistic and computational models of these phenomena. These models enable translation between human and non-human animal research and help to uncover fundamental features of change-processing microcircuitry in the neocortex. This microcircuitry is characterized by stimulus-specific adaptation and feedforward inhibition of stimulus-selective populations of pyramidal neurons and interneurons, with specific contributions from different interneuron types. The overlap of the substrates of different types of responses to deviant stimuli remains to be understood. Omission responses, which are observed both in corollary discharge and mismatch response protocols in humans, are underutilized in animal research and may be pivotal in uncovering the substrates of predictive processes. Omission studies comprise a range of methods centered on the withholding of an expected stimulus. This review aims to provide an overview of omission protocols and showcase their potential to integrate and complement the different models and procedures employed to study prediction and deviance detection.This approach may reveal the biological foundations of core concepts of predictive coding, and allow an empirical test of the framework's promise to unify theoretical models of attention and perception.

Cross-Modal Interaction and Integration Through Stimulus-Specific Adaptation in the Thalamic Reticular Nucleus of Rats / 神经科学通报·英文版

Stimulus-specific adaptation (SSA), defined as a decrease in responses to a common stimulus that only partially generalizes to other rare stimuli, is a widespread phenomenon in the brain that is believed to be related to novelty detection. Although cross-modal sensory processing is also a widespread phenomenon, the interaction between the two phenomena is not well understood. In this study, the thalamic reticular nucleus (TRN), which is regarded as a hub of the attentional system that contains multi-modal neurons, was investigated. The results showed that SSA existed in an interactive oddball stimulation, which mimics stimulation changes from one modality to another. In the bimodal integration, SSA to bimodal stimulation was stronger than to visual stimulation alone but similar to auditory stimulation alone, which indicated a limited integrative effect. Collectively, the present results provide evidence for independent cross-modal processing in bimodal TRN neurons.

The posterior auditory field is the chief generator of prediction error signals in the auditory cortex.

The auditory cortex (AC) encompasses distinct fields subserving partly different aspects of sound processing. One essential function of the AC is the detection of unpredicted sounds, as revealed by differential neural activity to predictable and unpredictable sounds. According to the predictive coding framework, this effect can be explained by repetition suppression and/or prediction error signaling. The present study investigates functional specialization of the rat AC fields in repetition suppression and prediction error by combining a tone frequency oddball paradigm (involving high-probable standard and low-probable deviant tones) with two different control sequences (many-standards and cascade). Tones in the control sequences were comparable to deviant events with respect to neural adaptation but were not violating a regularity. Therefore, a difference in the neural activity between deviant and control tones indicates a prediction error effect, whereas a difference between control and standard tones indicates a repetition suppression effect. Single-unit recordings revealed by far the largest prediction error effects for the posterior auditory field, while the primary auditory cortex, the anterior auditory field, the ventral auditory field, and the suprarhinal auditory field were dominated by repetition suppression effects. Statistically significant repetition suppression effects occurred in all AC fields, whereas prediction error effects were less robust in the primary auditory cortex and the anterior auditory field. Results indicate that the non-lemniscal, posterior auditory field is more engaged in context-dependent processing underlying deviance-detection than the other AC fields, which are more sensitive to stimulus-dependent effects underlying differential degrees of neural adaptation.

Emergence of abstract sound representations in the ascending auditory system.

Auditory processing begins by decomposing sounds into their frequency components, raising the question of where the representation of sounds as wholes emerges in the auditory system. To address this question, we used stimulus-specific adaptation (SSA), the reduction in the responses of a neuron to a common sound (standard) which does not generalize to another, rare sound (deviant). SSA to tone frequency has been demonstrated in multiple stations of the auditory pathway, including the inferior colliculus (IC), medial geniculate body (MGB) and auditory cortex. We designed wideband stimuli (tone clouds) that have identical frequency components but are nevertheless distinct. Tone clouds evoked early and substantial SSA in primary auditory cortex (A1) but only late and minor SSA in IC and MGB. These results imply that while in IC and MGB sounds are largely represented in terms of their frequency components, in A1 they are represented as abstract entities.

Stimulus-Specific Adaptation in Auditory Thalamus Is Modulated by the Thalamic Reticular Nucleus.

A striking property of the auditory system is its capacity for the stimulus-specific adaptation (SSA), which is the reduction of neural response to repeated stimuli but a recuperative response to novel stimuli. SSA is found in both the medial geniculate body (MGB) and thalamic reticular nucleus (TRN). However, it remains unknown whether the SSA of MGB neurons is modulated by inhibitory inputs from the TRN, as it is difficult to investigate using the extracellular recording method. In the present study, we performed intracellular recordings in the MGB of anesthetized guinea pigs and examined whether and how the TRN modulates the SSA of MGB neurons with inhibitory inputs. This was accomplished by using microinjection of lidocaine to inactivate the neural activity of the TRN. We found that (1) MGB neurons with hyperpolarized membrane potentials exhibited SSA at both the spiking and subthreshold levels; (2) SSA of MGB neurons depends on the interstimulus interval (ISI), where a shorter ISI results in stronger SSA; and (3) the long-lasting hyperpolarization of MGB neurons decreased after the burst firing of the TRN was inactivated. As a result, SSA of these MGB neurons was diminished after inactivation of the TRN. Taken together, our results revealed that the SSA of the MGB is strongly modulated by the neural activity of the TRN, which suggests an alternative circuit mechanism underlying the SSA of the auditory thalamus.

The reduced auditory evoked potential component N1 after repeated stimulation: Refractoriness hypothesis vs. habituation account.

Similar to other event-related potential (ERP) components, the amplitude of the auditory evoked N1 depends on the interstimulus interval (ISI). At ISIs > 0.4 s, the amplitude of the N1 increases with longer ISIs, until it saturates at ISIs around 10 s. This amplitude increase with increasing ISI has been conceptualized as a function of N1 recovery or N1 refractoriness. Habituation (as a simple form of learning) represents an elaborated, opposing account for such stimulus repetition effects. For passive oddball experiments (stimulation protocols with frequent standards and rare deviants), the two accounts make different predictions. According to the habituation account, the presentation of small deviants should lead to an increased N1 for subsequent standards (= dishabituation); according to the N1 refractoriness account, there should be no or just minor effects on the N1. In the current study, we tested these predictions and compared the ERPs to standards after small deviants and to standards preceded by other standards. We observed that the ERPs to standards after small deviants were characterized by a small mismatch negativity with an onset latency > 150 ms, but the N1 to standards after deviants did not differ from the N1 to standards preceded by other standards. This negative finding is in line with other previous studies that were also not able to reveal evidence for N1 dishabituation. Aside from this repeated lack of evidence for dishabituation, the N1 habituation account is challenged by the finding that the N1 decrease is stronger for more intense stimuli. Overall, the current and previous findings are more compatible with the N1 refractoriness account, although the mechanisms underlying N1 refractoriness remain to be elucidated. Knowledge about these mechanisms would also help to understand why N1 deficits in schizophrenia are more pronounced at longer ISIs.

In vivo whole-cell recordings of stimulus-specific adaptation in the inferior colliculus.

The inferior colliculus is an auditory structure where inputs from multiple lower centers converge, allowing the emergence of complex coding properties of auditory information such as stimulus-specific adaptation. Stimulus-specific adaptation is the adaptation of neuronal responses to a specific repeated stimulus, which does not entirely generalize to other new stimuli. This phenomenon provides a mechanism to emphasize saliency and potentially informative sensory inputs. Stimulus-specific adaptation has been traditionally studied analyzing the somatic spiking output. However, studies that correlate within the same inferior colliculus neurons their intrinsic properties, subthreshold responses and the level of acoustic stimulus-specific adaptation are still pending. For this, we recorded in vivo whole-cell patch-clamp neurons in the mouse inferior colliculus while stimulating with current injections or the classic auditory oddball paradigm. Our data based on cases of ten neuron, suggest that although passive properties were similar, intrinsic properties differed between adapting and non-adapting neurons. Non-adapting neurons showed a sustained-regular firing pattern that corresponded to central nucleus neurons and adapting neurons at the inferior colliculus cortices showed variable firing patterns. Our current results suggest that synaptic stimulus-specific adaptation was variable and could not be used to predict the presence of spiking stimulus-specific adaptation. We also observed a small trend towards hyperpolarized membrane potentials in adapting neurons and increased synaptic inhibition with consecutive stimulus repetitions in all neurons. This finding indicates a more simple type of adaptation, potentially related to potassium conductances. Hence, these data represent a modest first step in the intracellular study of stimulus-specific adaptation in inferior colliculus neurons in vivo that will need to be expanded with pharmacological manipulations to disentangle specific ionic channels participation.

Deviance detection in physiologically identified cell types in the rat auditory cortex.

Auditory deviance detection is a function of the auditory system that allows reduction of the processing demand for repetitive stimuli while stressing unpredictable ones, which are potentially more informative. Deviance detection has been extensively studied in humans using the oddball paradigm, which evokes an event-related potential known as mismatch negativity (MMN). The same stimulation paradigms are used in animal studies that aim to elucidate the neuronal mechanisms underlying deviance detection. In order to understand the circuitry responsible for deviance detection in the auditory cortex (AC), it is necessary to determine the properties of excitatory and inhibitory neurons separately. Measuring the spike widths of neurons recorded extracellularly from the anaesthetized rat AC, we classified them as fast spiking or regular spiking units. These two neuron types are generally considered as putative inhibitory or excitatory, respectively. In response to an oddball paradigm, we found that both types of units showed similar amounts of deviance detection overall. When considering each AC field separately, we found that only in A1 fast spiking neurons showed higher deviance detection levels than regular spiking neurons, while in the rest of the fields there was no such distinction. Interpreting these responses in the context of the predictive coding framework, we found that the responses of both types of units reflect mainly prediction error signaling (i.e., genuine deviance detection) rather than repetition suppression.

The release from refractoriness hypothesis of N1 of event-related potentials needs reassessment.

N1 of event-related potentials (ERPs) is augmented in amplitude in ∼50-150 ms by occasional changes (deviants) in the physical features of a sound repeated at intervals of from ∼400 ms to seconds (standard). The release-from-refractoriness hypothesis links the N1 augmentation to a deviant-feature-specific neural population that is fresh to fully respond as opposed to a standard-feature-specific neural population that is unresponsive due to its post-response refractoriness. The present work explored this hypothesis in the context of ERP studies, behavioral habituation studies and studies on stimulus-specific adaptation (SSA). The idea of hundreds of milliseconds neural population-level refractoriness was observed to be founded upon negative N1 evidence (no observable effect of dishabituating stimuli on N1 to standards - the null hypothesis retained) and merely supported by positive N1 evidence (null hypotheses rejected). This idea was also found to be directly challenged by positive N1 evidence. No conclusive network- or single-neuron-level evidence was found for the refractoriness. Therefore, the validity of the release-from-refractoriness hypothesis of N1 to guide psychophysiological research needs reassessment.