Sustained neural activity correlates with rapid perceptual learning of auditory patterns.

Repeating structures forming regular patterns are common in sounds. Learning such patterns may enable accurate perceptual organization. In five experiments, we investigated the behavioral and neural signatures of rapid perceptual learning of regular sound patterns. We show that recurring (compared to novel) patterns are detected more quickly and increase sensitivity to pattern deviations and to the temporal order of pattern onset relative to a visual stimulus. Sustained neural activity reflected perceptual learning in two ways. Firstly, sustained activity increased earlier for recurring than novel patterns when participants attended to sounds, but not when they ignored them; this earlier increase mirrored the rapid perceptual learning we observed behaviorally. Secondly, the magnitude of sustained activity was generally lower for recurring than novel patterns, but only for trials later in the experiment, and independent of whether participants attended to or ignored sounds. The late manifestation of sustained activity reduction suggests that it is not directly related to rapid perceptual learning, but to a mechanism that does not require attention to sound. In sum, we demonstrate that the latency of sustained activity reflects rapid perceptual learning of auditory patterns, while the magnitude may reflect a result of learning, such as better prediction of learned auditory patterns.

HIRUDOTHERAPY IN PRESBYACUZIS PRAECOX IN CLEAN-UP WORKERS AFTER THE CHORNOBYL ACCIDENT DURING THE POST-CATASTROPHE YEARS. / GIRUDOTERAPIIa PRY PRESBYACUZIS PRAECOX V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChORNOBYL'S'KIY̆ ATOMNIY̆ ELEKTROSTANTsIÏ U PISLIaAVARIY̆NYKh ROKAKh.

OBJECTIVE: to study the hirudotherapy efficacy in presbyacuzis praecox in clean-up workers (CUWs) of the Chornobyl disaster (ChD) during the post-accident years. MATERIALS AND METHODS: From archive data of previously examined 8,136 males' CUWs we selected among them 129 persons with the determined presbyacuzis praecox during the post-accident years. According to the physical dosime- try data the individual radiation of received by CUWs during the work on a rotational scheme in the Chornobyl exclu- sion zone from the end of 1986 to 1992-1994 amounted to 0.21-0.50 Gy. The examinations were carried out using a modern standard set of audiometric, vestibulometric and electrophysiological methods. Two forms of sensory and neural hearing loss in the elderly were distinguished, namely the presbyacuzis and presbyacuzis praecox. Prior to work in the exclusion zone, patients' auditory and vestibular functions were within normal range. Among 129 patients, 68 ones with presbyacuzis praecox were included in two main age groups (aged 40-49 and 50-59 yrs) and were treated using hirudotherapy, taking into consideration their coagulation hemostasis. Other 61 patients of analogical age groups were treated by allopathotherapy. For the analysis of results obtained, techniques of variational statistics were used. RESULTS: Direct correlation (r = 0.71) between inhibitory processes in central areas of the auditory analyzer in pres- byacuzis praecox in CUWs was established by electrophysiology and by speech audiometry data obtained before the treatment. Hyperacusis signs were detected in CUWs of two main and two control groups. Following the use of two treatment schemas, a significant improving of auditory functions was found (p < 0.05) according to tone and speech audiometries. The positive hirudotherapy effect concerning hearing functions was registered in 88% cases (in 59 CUWs among 68 ones); if allopathotherapy had been used, such effect was found in 65% cases (in 45 control patients among 61 ones of control group). The duration of allopathotherapy effect reached 6-9 months comparing to 12-18 months of hiruditherapy one, being twice longer. Improving the patients' coagulation hemostasis, hirudotherapy activated cardiovascular activity favoring the increase of social adequacy in CUWs with presbyacuzis praecox. CONCLUSIONS: It has been shown that hirudotherapy as a kind of naturopathy has significant advantages over alopa- totherapy by the absence of side effects, 23.0% higher and twice as long as improvement of auditory functions. Hirudotherapy, as an effective therapeutic and recreational measures, should be more widely implemented in clini- cal practice in order to minimize the development and progression of diseases in the special population of people who have been exposed to ionizing radiation due to the Chornobyl catastrophe to continue their vitality.

Task-uninformative visual stimuli improve auditory spatial discrimination in humans but not the ideal observer.

In order to survive and function in the world, we must understand the content of our environment. This requires us to gather and parse complex, sometimes conflicting, information. Yet, the brain is capable of translating sensory stimuli from disparate modalities into a cohesive and accurate percept with little conscious effort. Previous studies of multisensory integration have suggested that the brain's integration of cues is well-approximated by an ideal observer implementing Bayesian causal inference. However, behavioral data from tasks that include only one stimulus in each modality fail to capture what is in nature a complex process. Here we employed an auditory spatial discrimination task in which listeners were asked to determine on which side they heard one of two concurrently presented sounds. We compared two visual conditions in which task-uninformative shapes were presented in the center of the screen, or spatially aligned with the auditory stimuli. We found that performance on the auditory task improved when the visual stimuli were spatially aligned with the auditory stimuli-even though the shapes provided no information about which side the auditory target was on. We also demonstrate that a model of a Bayesian ideal observer performing causal inference cannot explain this improvement, demonstrating that humans deviate systematically from the ideal observer model.

A Gestalt inference model for auditory scene segregation.

Our current understanding of how the brain segregates auditory scenes into meaningful objects is in line with a Gestaltism framework. These Gestalt principles suggest a theory of how different attributes of the soundscape are extracted then bound together into separate groups that reflect different objects or streams present in the scene. These cues are thought to reflect the underlying statistical structure of natural sounds in a similar way that statistics of natural images are closely linked to the principles that guide figure-ground segregation and object segmentation in vision. In the present study, we leverage inference in stochastic neural networks to learn emergent grouping cues directly from natural soundscapes including speech, music and sounds in nature. The model learns a hierarchy of local and global spectro-temporal attributes reminiscent of simultaneous and sequential Gestalt cues that underlie the organization of auditory scenes. These mappings operate at multiple time scales to analyze an incoming complex scene and are then fused using a Hebbian network that binds together coherent features into perceptually-segregated auditory objects. The proposed architecture successfully emulates a wide range of well established auditory scene segregation phenomena and quantifies the complimentary role of segregation and binding cues in driving auditory scene segregation.

Shared understanding of narratives is correlated with shared neural responses.

Humans have a striking ability to infer meaning from even the sparsest and most abstract forms of narratives. At the same time, flexibility in the form of a narrative is matched by inherent ambiguity in its interpretation. How does the brain represent subtle, idiosyncratic differences in the interpretation of abstract and ambiguous narratives? In this fMRI study, subjects were scanned either watching a novel 7-min animation depicting a complex narrative through the movement of geometric shapes, or listening to a narration of the animation's social story. Using an intersubject representational similarity analysis that compared interpretation similarity and neural similarity across subjects, we found that the more similar two people's interpretations of the abstract shapes animation were, the more similar were their neural responses in regions of the default mode network (DMN) and fronto-parietal network. Moreover, these shared responses were modality invariant: the shapes movie and the verbal interpretation of the movie elicited shared responses in linguistic areas and a subset of the DMN when subjects shared interpretations. Together, these results suggest a network of high-level regions that are not only sensitive to subtle individual differences in narrative interpretation during naturalistic conditions, but also resilient to large differences in the modality of the narrative.

Hearing emotional sounds: category representation in the human amygdala.

Previous studies have shown that the amygdala is more involved in processing animate categories, such as humans and animals, than inanimate objects, but little is known regarding whether this animate advantage applies to auditory stimuli. To address this issue, we performed a functional Magnetic Resonance Imaging (fMRI) study with emotion and category as factors, in which subjects heard sounds from different categories (i.e., humans, animals, and objects) in negative and neutral dimensions. Emotional levels and semantic familiarity were matched across categories. The results showed that the amygdala responded more to human vocalization than to animal vocalization and sounds of inanimate objects in both negative and neutral valences, and more to animal sounds than to objects in neural condition. In addition, the amygdala, together with the insula and the right superior temporal sulcus, further distinguished human voices from animal sounds. These data indicated that the amygdala is prepared to respond to animate sources, especially human vocalizations in auditory modality.

Effects of global and local contexts on chord processing: An ERP study.

In real life, the processing of an incoming event is continuously influenced by prior information at multiple timescales. The present study investigated how harmonic contexts at both local and global levels influence the processing of an incoming chord in an event-related potentials experiment. Chord sequences containing two phrases were presented to musically trained listeners, with the last critical chord either harmonically related or less related to its preceding context at local and/or global levels. ERPs data showed an ERAN-like effect for local context in early time window and a N5-like component for later interaction between the local context and global context. These results suggest that both the local and global contexts influence the processing of an incoming music event, and the local effect happens earlier than the global. Moreover, the interaction between the local context and global context in N5 may suggest that music syntactic integration at local level takes place prior to the integration at global level.

Listeners' processing of a given reduced word pronunciation variant directly reflects their exposure to this variant: Evidence from native listeners and learners of French.

In casual conversations, words often lack segments. This study investigates whether listeners rely on their experience with reduced word pronunciation variants during the processing of single segment reduction. We tested three groups of listeners in a lexical decision experiment with French words produced either with or without word-medial schwa (e.g., /ʀvy/ and /ʀvy/ for revue). Participants also rated the relative frequencies of the two pronunciation variants of the words. If the recognition accuracy and reaction times (RTs) for a given listener group correlate best with the frequencies of occurrence holding for that given listener group, recognition is influenced by listeners' exposure to these variants. Native listeners' relative frequency ratings correlated well with their accuracy scores and RTs. Dutch advanced learners' accuracy scores and RTs were best predicted by their own ratings. In contrast, the accuracy and RTs from Dutch beginner learners of French could not be predicted by any relative frequency rating; the rating task was probably too difficult for them. The participant groups showed behaviour reflecting their difference in experience with the pronunciation variants. Our results strongly suggest that listeners store the frequencies of occurrence of pronunciation variants, and consequently the variants themselves.

Dynamic cortical representations of perceptual filling-in for missing acoustic rhythm.

In the phenomenon of perceptual filling-in, missing sensory information can be reconstructed via interpolation or extrapolation from adjacent contextual cues by what is necessarily an endogenous, not yet well understood, neural process. In this investigation, sound stimuli were chosen to allow observation of fixed cortical oscillations driven by contextual (but missing) sensory input, thus entirely reflecting endogenous neural activity. The stimulus employed was a 5 Hz frequency-modulated tone, with brief masker probes (noise bursts) occasionally added. For half the probes, the rhythmic frequency modulation was moreover removed. Listeners reported whether the tone masked by each probe was perceived as being rhythmic or not. Time-frequency analysis of neural responses obtained by magnetoencephalography (MEG) shows that for maskers without the underlying acoustic rhythm, trials where rhythm was nonetheless perceived show higher evoked sustained rhythmic power than trials for which no rhythm was reported. The results support a model in which perceptual filling-in is aided by differential co-modulations of cortical activity at rates directly relevant to human speech communication. We propose that the presence of rhythmically-modulated neural dynamics predicts the subjective experience of a rhythmically modulated sound in real time, even when the perceptual experience is not supported by corresponding sensory data.

Subplate neurons are the first cortical neurons to respond to sensory stimuli.

In utero experience, such as maternal speech in humans, can shape later perception, although the underlying cortical substrate is unknown. In adult mammals, ascending thalamocortical projections target layer 4, and the onset of sensory responses in the cortex is thought to be dependent on the onset of thalamocortical transmission to layer 4 as well as the ear and eye opening. In developing animals, thalamic fibers do not target layer 4 but instead target subplate neurons deep in the developing white matter. We investigated if subplate neurons respond to sensory stimuli. Using electrophysiological recordings in young ferrets, we show that auditory cortex neurons respond to sound at very young ages, even before the opening of the ears. Single unit recordings showed that auditory responses emerged first in cortical subplate neurons. Subsequently, responses appeared in the future thalamocortical input layer 4, and sound-evoked spike latencies were longer in layer 4 than in subplate, consistent with the known relay of thalamic information to layer 4 by subplate neurons. Electrode array recordings show that early auditory responses demonstrate a nascent topographic organization, suggesting that topographic maps emerge before the onset of spiking responses in layer 4. Together our results show that sound-evoked activity and topographic organization of the cortex emerge earlier and in a different layer than previously thought. Thus, early sound experience can activate and potentially sculpt subplate circuits before permanent thalamocortical circuits to layer 4 are present, and disruption of this early sensory activity could be utilized for early diagnosis of developmental disorders.

Extensive Tonotopic Mapping across Auditory Cortex Is Recapitulated by Spectrally Directed Attention and Systematically Related to Cortical Myeloarchitecture.

Auditory selective attention is vital in natural soundscapes. But it is unclear how attentional focus on the primary dimension of auditory representation-acoustic frequency-might modulate basic auditory functional topography during active listening. In contrast to visual selective attention, which is supported by motor-mediated optimization of input across saccades and pupil dilation, the primate auditory system has fewer means of differentially sampling the world. This makes spectrally-directed endogenous attention a particularly crucial aspect of auditory attention. Using a novel functional paradigm combined with quantitative MRI, we establish in male and female listeners that human frequency-band-selective attention drives activation in both myeloarchitectonically estimated auditory core, and across the majority of tonotopically mapped nonprimary auditory cortex. The attentionally driven best-frequency maps show strong concordance with sensory-driven maps in the same subjects across much of the temporal plane, with poor concordance in areas outside traditional auditory cortex. There is significantly greater activation across most of auditory cortex when best frequency is attended, versus ignored; the same regions do not show this enhancement when attending to the least-preferred frequency band. Finally, the results demonstrate that there is spatial correspondence between the degree of myelination and the strength of the tonotopic signal across a number of regions in auditory cortex. Strong frequency preferences across tonotopically mapped auditory cortex spatially correlate with R1-estimated myeloarchitecture, indicating shared functional and anatomical organization that may underlie intrinsic auditory regionalization.SIGNIFICANCE STATEMENT Perception is an active process, especially sensitive to attentional state. Listeners direct auditory attention to track a violin's melody within an ensemble performance, or to follow a voice in a crowded cafe. Although diverse pathologies reduce quality of life by impacting such spectrally directed auditory attention, its neurobiological bases are unclear. We demonstrate that human primary and nonprimary auditory cortical activation is modulated by spectrally directed attention in a manner that recapitulates its tonotopic sensory organization. Further, the graded activation profiles evoked by single-frequency bands are correlated with attentionally driven activation when these bands are presented in complex soundscapes. Finally, we observe a strong concordance in the degree of cortical myelination and the strength of tonotopic activation across several auditory cortical regions.

Music viewed by its entropy content: A novel window for comparative analysis.

Polyphonic music files were analyzed using the set of symbols that produced the Minimal Entropy Description, which we call the Fundamental Scale. This allowed us to create a novel space to represent music pieces by developing: (a) a method to adjust a textual description from its original scale of observation to an arbitrarily selected scale, (b) a method to model the structure of any textual description based on the shape of the symbol frequency profiles, and (c) the concept of higher order entropy as the entropy associated with the deviations of a frequency-ranked symbol profile from a perfect Zipfian profile. We call this diversity index the '2nd Order Entropy'. Applying these methods to a variety of musical pieces showed how the space of 'symbolic specific diversity-entropy' and that of '2nd order entropy' captures characteristics that are unique to each music type, style, composer and genre. Some clustering of these properties around each musical category is shown. These methods allow us to visualize a historic trajectory of academic music across this space, from medieval to contemporary academic music. We show that the description of musical structures using entropy, symbol frequency profiles and specific symbolic diversity allows us to characterize traditional and popular expressions of music. These classification techniques promise to be useful in other disciplines for pattern recognition and machine learning.

Statistical Learning of Melodic Patterns Influences the Brain's Response to Wrong Notes.

The theory of statistical learning has been influential in providing a framework for how humans learn to segment patterns of regularities from continuous sensory inputs, such as speech and music. This form of learning is based on statistical cues and is thought to underlie the ability to learn to segment patterns of regularities from continuous sensory inputs, such as the transition probabilities in speech and music. However, the connection between statistical learning and brain measurements is not well understood. Here we focus on ERPs in the context of tone sequences that contain statistically cohesive melodic patterns. We hypothesized that implicit learning of statistical regularities would influence what was held in auditory working memory. We predicted that a wrong note occurring within a cohesive pattern (within-pattern deviant) would lead to a significantly larger brain signal than a wrong note occurring between cohesive patterns (between-pattern deviant), even though both deviant types were equally likely to occur with respect to the global tone sequence. We discuss this prediction within a simple Markov model framework that learns the transition probability regularities within the tone sequence. Results show that signal strength was stronger when cohesive patterns were violated and demonstrate that the transitional probability of the sequence influences the memory basis for melodic patterns. Our results thus characterize how informational units are stored in auditory memory trace for deviance detection and provide new evidence about how the brain organizes sequential sound input that is useful for perception.

Auditory object perception: A neurobiological model and prospective review.

Interaction with the world is a multisensory experience, but most of what is known about the neural correlates of perception comes from studying vision. Auditory inputs enter cortex with its own set of unique qualities, and leads to use in oral communication, speech, music, and the understanding of emotional and intentional states of others, all of which are central to the human experience. To better understand how the auditory system develops, recovers after injury, and how it may have transitioned in its functions over the course of hominin evolution, advances are needed in models of how the human brain is organized to process real-world natural sounds and "auditory objects". This review presents a simple fundamental neurobiological model of hearing perception at a category level that incorporates principles of bottom-up signal processing together with top-down constraints of grounded cognition theories of knowledge representation. Though mostly derived from human neuroimaging literature, this theoretical framework highlights rudimentary principles of real-world sound processing that may apply to most if not all mammalian species with hearing and acoustic communication abilities. The model encompasses three basic categories of sound-source: (1) action sounds (non-vocalizations) produced by 'living things', with human (conspecific) and non-human animal sources representing two subcategories; (2) action sounds produced by 'non-living things', including environmental sources and human-made machinery; and (3) vocalizations ('living things'), with human versus non-human animals as two subcategories therein. The model is presented in the context of cognitive architectures relating to multisensory, sensory-motor, and spoken language organizations. The models' predictive values are further discussed in the context of anthropological theories of oral communication evolution and the neurodevelopment of spoken language proto-networks in infants/toddlers. These phylogenetic and ontogenetic frameworks both entail cortical network maturations that are proposed to at least in part be organized around a number of universal acoustic-semantic signal attributes of natural sounds, which are addressed herein.

Fetal rhythm-based language discrimination: a biomagnetometry study.

Using fetal biomagnetometry, this study measured changes in fetal heart rate to assess discrimination of two rhythmically different languages (English and Japanese). Two-minute passages in English and Japanese were read by the same female bilingual speaker. Twenty-four mother-fetus pairs (mean gestational age=35.5 weeks) participated. Fetal magnetocardiography was recorded while the participants were presented first with passage 1, a passage in English, and then, following an 18 min interval, with passage 2, either a different passage in English (English-English condition: N=12) or in Japanese (English-Japanese condition: N=12). The fetal magnetocardiogram was reconstructed following independent components analysis decomposition. The mean interbeat intervals were calculated for a 30 s baseline interval directly preceding each passage and for the first 30 s of each passage. We then subtracted the mean interbeat interval of the 30 s baseline interval from that of the first 30 s interval, yielding an interbeat interval change value for each passage. A significant interaction between condition and passage indicated that the English-Japanese condition elicited a more robust interbeat interval change for passage 2 (novelty phase) than for passage 1 (familiarity phase), reflecting a faster heart rate during passage 2, whereas the English-English condition did not. This effect indicates that fetuses are sensitive to the change in language from English to Japanese. These findings provide the first evidence for fetal language discrimination as assessed by fetal biomagnetometry and support the hypothesis that rhythm constitutes a prenatally available building block in language acquisition.

Tone identification behavior in Rattus norvegicus: muscarinic receptor blockage lowers responsiveness in nontarget selective neurons, while nicotinic receptor blockage selectively lowers target responses.

Learning to associate a stimulus with reinforcement causes plasticity in primary sensory cortex. Neural activity caused by the associated stimulus is paired with reinforcement, but population analyses have not found a selective increase in response to that stimulus. Responses to other stimuli increase as much as, or more than, responses to the associated stimulus. Here, we applied population analysis at a new time point and additionally evaluated whether cholinergic receptor blockers interacted with the plastic changes in cortex. Three days of tone identification behavior caused responsiveness to increase broadly across primary auditory cortex, and target responses strengthened less than overall responsiveness. In pharmacology studies, behaviorally impairing doses of selective acetylcholine receptor blockers were administered during behavior. Neural responses were evaluated on the following day, while the blockers were absent. The muscarinic group, blocked by scopolamine, showed lower responsiveness and an increased response to the tone identification target that exceeded both the 3-day control group and task-naïve controls. Also, a selective increase in the late phase of the response to the tone identification stimulus emerged. Nicotinic receptor antagonism, with mecamylamine, more modestly lowered responses the following day and lowered target responses more than overall responses. Control acute studies demonstrated the muscarinic block did not acutely alter response rates, but the nicotinic block did. These results lead to the hypothesis that the decrease in the proportion of the population spiking response that is selective for the target may be explained by the balance between effects modulated by muscarinic and nicotinic receptors.

The Importance of Spatiotemporal Information in Biological Motion Perception: White Noise Presented with a Step-like Motion Activates the Biological Motion Area.

Humans can easily recognize the motion of living creatures using only a handful of point-lights that describe the motion of the main joints (biological motion perception). This special ability to perceive the motion of animate objects signifies the importance of the spatiotemporal information in perceiving biological motion. The posterior STS (pSTS) and posterior middle temporal gyrus (pMTG) region have been established by many functional neuroimaging studies as a locus for biological motion perception. Because listening to a walking human also activates the pSTS/pMTG region, the region has been proposed to be supramodal in nature. In this study, we investigated whether the spatiotemporal information from simple auditory stimuli is sufficient to activate this biological motion area. We compared spatially moving white noise, having a running-like tempo that was consistent with biological motion, with stationary white noise. The moving-minus-stationary contrast showed significant differences in activation of the pSTS/pMTG region. Our results suggest that the spatiotemporal information of the auditory stimuli is sufficient to activate the biological motion area.

Timing predictability enhances regularity encoding in the human subcortical auditory pathway.

The encoding of temporal regularities is a critical property of the auditory system, as short-term neural representations of environmental statistics serve to auditory object formation and detection of potentially relevant novel stimuli. A putative neural mechanism underlying regularity encoding is repetition suppression, the reduction of neural activity to repeated stimulation. Although repetitive stimulation per se has shown to reduce auditory neural activity in animal cortical and subcortical levels and in the human cerebral cortex, other factors such as timing may influence the encoding of statistical regularities. This study was set out to investigate whether temporal predictability in the ongoing auditory input modulates repetition suppression in subcortical stages of the auditory processing hierarchy. Human auditory frequency-following responses (FFR) were recorded to a repeating consonant-vowel stimuli (/wa/) delivered in temporally predictable and unpredictable conditions. FFR amplitude was attenuated by repetition independently of temporal predictability, yet we observed an accentuated suppression when the incoming stimulation was temporally predictable. These findings support the view that regularity encoding spans across the auditory hierarchy and point to temporal predictability as a modulatory factor of regularity encoding in early stages of the auditory pathway.

Scanning the world in three seconds: Mismatch negativity as an indicator of temporal segmentation.

It has been shown recently that a temporal window of approximately 3 s has a modulatory effect on mismatch negativity (MMN). This special temporal window has been interpreted as representing the "subjective present," and reflecting a temporal segmentation in behavioral and cognitive functions. A more detailed look into the temporal structure of the MMN appeared to be reasonable as group data might shadow the underlying mechanisms because of too-high response variance. In this study, we tested one subject on 11 successive days at the same circadian phase using a passive auditory oddball paradigm with interstimulus intervals (ISIs) ranging from 1 s to 6 s. We observed a U-shape function of MMN showing the largest amplitudes to the oddball stimuli with an ISI of 2 s and 3 s being flanked by smaller response amplitudes for shorter and longer ISIs. This result pattern can be explained with an oscillatory neural mechanism underlying the temporal modulation of MMN. Besides confirming and substantiating temporal segmentation in sensory processing, the present study also demonstrates that a single case study can be a useful and complementary tool in cognitive research.

Abnormal Complex Auditory Pattern Analysis in Schizophrenia Reflected in an Absent Missing Stimulus Mismatch Negativity.

The simple mismatch negativity (MMN) to tones deviating physically (in pitch, loudness, duration, etc.) from repeated standard tones is robustly reduced in schizophrenia. Although generally interpreted to reflect memory or cognitive processes, simple MMN likely contains some activity from non-adapted sensory cells, clouding what process is affected in schizophrenia. Research in healthy participants has demonstrated that MMN can be elicited by deviations from abstract auditory patterns and complex rules that do not cause sensory adaptation. Whether persons with schizophrenia show abnormalities in the complex MMN is unknown. Fourteen schizophrenia participants and 16 matched healthy underwent EEG recording while listening to 400 groups of 6 tones 330 ms apart, separated by 800 ms. Occasional deviant groups were missing the 4th or 6th tone (50 groups each). Healthy participants generated a robust response to a missing but expected tone. The schizophrenia group was significantly impaired in activating the missing stimulus MMN, generating no significant activity at all. Schizophrenia affects the ability of "primitive sensory intelligence" and pre-attentive perceptual mechanisms to form implicit groups in the auditory environment. Importantly, this deficit must relate to abnormalities in abstract complex pattern analysis rather than sensory problems in the disorder. The results indicate a deficit in parsing of the complex auditory scene which likely impacts negatively on successful social navigation in schizophrenia. Knowledge of the location and circuit architecture underlying the true novelty-related MMN and its pathophysiology in schizophrenia will help target future interventions.