Order effects in task-free learning: Tuning to information-carrying sound features.

Event-related potentials (ERPs) acquired during task-free passive listening can be used to study how sensitivity to common pattern repetitions and rare deviations changes over time. These changes are purported to represent the formation and accumulation of precision in internal models that anticipate future states based on probabilistic and/or statistical learning. This study features an unexpected finding; a strong order-dependence in the speed with which deviant responses are elicited that anchors to first learning. Participants heard four repetitions of a sequence in which an equal number of short (30 msec) and long (60 msec) pure tones were arranged into four blocks in which one was common (the standard, p = .875) and the other rare (the deviant, p = .125) with probabilities alternating across blocks. Some participants always heard the sequences commencing with the 30 msec deviant block, and others always with the 60 msec deviant block first. A deviance-detection component known as mismatch negativity (MMN) was extracted from responses and the point in time at which MMN reached maximum amplitude was used as the dependent variable. The results show that if participants heard sequences commencing with the 60 msec deviant block first, the MMN to the 60 msec and 30 msec deviant peaked at an equivalent latency. However, if participants heard sequences commencing with the 30 msec deviant first, the MMN peaked earlier to the 60 msec deviant. Furthermore, while the 30 msec MMN latency did not differ as a function of sequence composition, the 60 msec MMN latency did and was earlier when the sequences began with a 30 msec deviant first. By examining MMN latency effects as a function of age and hearing level it was apparent that the differentiation in 30 msec and 60 msec MMN latency expands with older age and raised hearing threshold due to prolongation of the time taken for the 30 msec MMN to peak. The observations are discussed with reference to how the initial sound composition may tune the auditory system to be more sensitive to different cues (i.e., offset responses vs perceived loudness). The order-effect demonstrates a remarkably powerful anchoring to first learning that might reflect initial tuning to the most valuable discriminating feature within a given listening environment, an effect that defies explanation based on statistical information alone.

The impact of spatial variance on precision estimates in an auditory oddball paradigm.

Predictive processing theories suggest that a principal function of the brain is to reduce the surprise of incoming sensory information by creating accurate and precise models of the environment. These models are commonly explored by looking at the prediction errors elicited when experience departs from predictions. One such prediction error is the mismatch negativity (MMN). Using this component, it is possible to examine the effect of external noise on the precision of the developed model. Recent studies have shown that the brain may not update its model every time there is a change in the environment, rather it will only update it when doing so will increase precision and or accuracy of the model. The current study examined this process using oddball sound sequences with high and low spatial variability and examining how this affected the elicited MMN to a duration deviant sound. The results showed a strong null effect of spatial variance both at a local and sequence levels. These results indicate that variability in the sound sequence will not invariably affect model precision estimates and thus the amplitude of the MMN component.

Computational Modeling of Oddball Sequence Processing Exposes Common and Differential Auditory Network Changes in First-Episode Schizophrenia-Spectrum Disorders and Schizophrenia.

BACKGROUND AND HYPOTHESIS: Differences in sound relevance filtering in schizophrenia are proposed to represent a key index of biological changes in brain function in the illness. This study featured a computational modeling approach to test the hypothesis that processing differences might already be evident in first-episode, becoming more pronounced in the established illness. STUDY DESIGN: Auditory event-related potentials to a typical oddball sequence (rare pitch deviations amongst regular sounds) were recorded from 90 persons with schizophrenia-spectrum disorders (40 first-episode schizophrenia-spectrum, 50 established illness) and age-matched healthy controls. The data were analyzed using dynamic causal modeling to identify the changes in effective connectivity that best explained group differences. STUDY RESULTS: Group differences were linked to intrinsic (within brain region) connectivity changes. In activity-dependent measures these were restricted to the left auditory cortex in first-episode schizophrenia-spectrum but were more widespread in the established illness. Modeling suggested that both established illness and first-episode schizophrenia-spectrum groups expressed significantly lower inhibition of inhibitory interneuron activity and altered gain on superficial pyramidal cells with the data indicative of differences in both putative N-methyl-d-aspartate glutamate receptor activity-dependent plasticity and classic neuromodulation. CONCLUSIONS: The study provides further support for the notion that examining the ability to alter responsiveness to structured sound sequences in schizophrenia and first-episode schizophrenia-spectrum could be informative to uncovering the nature and progression of changes in brain function during the illness. Furthermore, modeling suggested that limited differences present at first-episode schizophrenia-spectrum may become more expansive with illness progression.

The effect of schizophrenia risk factors on mismatch responses in a rat model.

Reduced mismatch negativity (MMN), a robust finding in schizophrenia, has prompted interest in MMN as a preclinical biomarker of schizophrenia. The rat brain can generate human-like mismatch responses (MMRs) which therefore enables the exploration of the neurobiology of reduced MMRs. Given epidemiological evidence that two developmental factors, maternal infection and adolescent cannabis use, increase the risk of schizophrenia, we determined the effect of these two developmental risk factors on rat MMR amplitude in different auditory contexts. MMRs were assessed in awake adult male and female Wistar rats that were offspring of pregnant dams treated with either a viral infection mimetic (poly I:C) inducing maternal immune activation (MIA) or saline control. In adolescence, subgroups of the prenatal treatment groups were exposed to either a synthetic cannabinoid (adolescent cannabinoid exposure: ACE) or vehicle. The context under which MMRs were obtained was manipulated by employing two different oddball paradigms, one that manipulated the physical difference between rare and common auditory stimuli, and another that manipulated the probability of the rare stimulus. The design of the multiple stimulus sequences across the two paradigms also allowed an investigation of context on MMRs to two identical stimulus sequences. Male offspring exposed to each of the risk factors for schizophrenia (MIA, ACE or both) showed a reduction in MMR, which was evident only in the probability paradigm, with no effects seen in the physical difference. Our findings highlight the importance of contextual factors induced by paradigm manipulations and sex for modeling schizophrenia-like MMN impairments in rats.

Why mismatch negativity continues to hold potential in probing altered brain function in schizophrenia.

The brain potential known as mismatch negativity (MMN) is one of the most studied indices of altered brain function in schizophrenia. This review looks at what has been learned about MMN in schizophrenia over the last three decades and why the level of interest and activity in this field of research remains strong. A diligent consideration of available evidence suggests that MMN can serve as a biomarker in schizophrenia, but perhaps not the kind of biomarker that early research supposed. This review concludes that MMN measurement is likely to be most useful as a monitoring and response biomarker enabling tracking of an underlying pathology and efficacy of interventions, respectively. The role of, and challenges presented by, pre-clinical models is discussed as well as the merits of different methodologies that can be brought to bear in pursuing a deeper understanding of pathophysiology that might explain smaller MMN in schizophrenia.

Modeling Distraction: How Stimulus-driven Attention Capture Influences Goal-directed Behavior.

The importance of paying attention to a task at hand is emphasized from an early age and extends throughout life. The costs of attentional focus, however, include the potential to miss important changes in the environment, so some process for monitoring nontask information is essential. In this study, a model of latent cognitive variables was applied to data obtained from a two-alternative forced-choice task where participants identified the longer of two sounds. Using an adaptive procedure task, accuracy was maintained at a higher or lower level creating two difficulties, and the sounds were heard either where frequency changes in the sound were rare or common (oddball and multistandard conditions, respectively). Frequency changes created stimulus-driven "distraction" effects in the oddball sequence only, and cognitive modeling (using the linear ballistic accumulator) attributed these effects to slowed accumulation of evidence about tone length on these trials. Concurrent recording of auditory ERPs revealed these delays in evidence accumulation to be related to the amplitude of N2 or mismatch negativity period and P300 response components. In contrast, the response time on trials after a rare frequency change was associated with increased caution in decision-making. Results support the utility of mapping behavioral and ERP measures of performance to latent cognitive processes that contribute to performance and are consistent with a momentary diversion of resources to evaluate the deviant sound feature and remodel predictions about sound.

Primacy biases endure the addition of frequency variability.

The primacy bias (PB) is a phenomenon that indicates the brain does not always process sensory information as an 'ideal Bayesian observer', but rather is disproportionately influenced by first impressions. This study was designed to establish whether a PB observed in auditory event-related potentials (ERPs) to a sequence of sound remained evident in the presence of increased levels of tone frequency variation. Two groups of participants were presented with a novel oddball paradigm, while simultaneously having cortical activity recorded with an EEG. In the control group, participants heard a two-tone sequence where the probability of the two tones of different duration switched after 480 sounds/2.4 min block, so that the tone initially encountered as rare became common and vice versa. The key manipulation introduced in the test group was a change of frequency in each block, removing a key element of regularity. The additional frequency variation resulted in no significant difference in the PB between the groups. The data suggest powerful first learning effects are not disrupted by frequency changes, indicating the robustness of learning heuristics.

Reduced Primacy Bias in Autism during Early Sensory Processing.

Recent theories of autism propose that a core deficit in autism would be a less context-sensitive weighting of prediction errors. There is also first support for this hypothesis on an early sensory level. However, an open question is whether this decreased context sensitivity is caused by faster updating of one's model of the world (i.e., higher weighting of new information), proposed by predictive coding theories, or slower model updating. Here, we differentiated between these two hypotheses by investigating how first impressions shape the mismatch negativity (MMN), reflecting early sensory prediction error processing. An autism and matched control group of human adults (both n = 27, 8 female) were compared on the multi-timescale MMN paradigm, in which tones were presented that were either standard (frequently occurring) or deviant (rare), and these roles reversed every block. A well-replicated observation is that the initial model (i.e., the standard and deviant sound in the first block) influences MMN amplitudes in later blocks. If autism is characterized by faster model updating, and thus a smaller primacy bias, we hypothesized (and demonstrate using a simple reinforcement learning model) that their MMN amplitudes should be less influenced by the initial context. In line with this hypothesis, we found that MMN responses in the autism group did not differ between the initial deviant and initial standard sounds as they did in the control group. These findings are consistent with the idea that autism is characterized by faster model updating during early sensory processing, as proposed by predictive coding accounts of autism.SIGNIFICANCE STATEMENT Recent theories of autism propose that a core deficit in autism is that they are faster to update their models of the world based on new sensory information. Here, we tested this hypothesis by investigating how first impressions shape brain responses during early sensory processing, and hypothesized that individuals with autism would be less influenced by these first impressions. In line with earlier studies, our results show that early sensory processing was influenced by first impressions in a control group. However, this was not the case in an autism group. This suggests that individuals with autism are faster to abandon their initial model, and is consistent with the proposal that they are faster to update their models of the world.

Relevance to the higher order structure may govern auditory statistical learning in neonates.

Hearing is one of the earliest senses to develop and is quite mature by birth. Contemporary theories assume that regularities in sound are exploited by the brain to create internal models of the environment. Through statistical learning, internal models extrapolate from patterns to predictions about subsequent experience. In adults, altered brain responses to sound enable us to infer the existence and properties of these models. In this study, brain potentials were used to determine whether newborns exhibit context-dependent modulations of a brain response that can be used to infer the existence and properties of internal models. Results are indicative of significant context-dependence in the responsivity to sound in newborns. When common and rare sounds continue in stable probabilities over a very long period, neonates respond to all sounds equivalently (no differentiation). However, when the same common and rare sounds at the same probabilities alternate over time, the neonate responses show clear differentiations. The context-dependence is consistent with the possibility that the neonate brain produces more precise internal models that discriminate between contexts when there is an emergent structure to be discovered but appears to adopt broader models when discrimination delivers little or no additional information about the environment.

Shorter Contextual Timescale Rather Than Memory Deficit in Aging.

Many aspects of cognitive ability and brain function that change as we age look like deficits on account of measurable differences in comparison to younger adult groups. One such difference occurs in auditory sensory responses that index perceptual learning. Meta-analytic findings show reliable age-related differences in auditory responses to repetitive patterns of sound and to rare violations of those patterns, variously attributed to deficits in auditory sensory memory and inhibition. Here, we determine whether proposed deficits would render older adults less prone to primacy effects, robustly observed in young adults, which present as a tendency for first learning to have a disproportionate influence over later perceptual inference. The results confirm this reduced sensitivity to primacy effects but do not support impairment in auditory sensory memory as the origin of this difference. Instead, the aging brain produces data consistent with shorter timescales of contextual reference. In conclusion, age-related differences observed previously for perceptual inference appear highly context-specific necessitating reconsideration of whether and to what function the notion of deficit should be attributed, and even whether the notion of deficit is appropriate at all.

Acute effects of Δ9-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity.

RATIONALE: Mismatch negativity (MMN) is a candidate endophenotype for schizophrenia subserved by N-methyl-D-aspartate receptor (NMDAR) function and there is increasing evidence that prolonged cannabis use adversely affects MMN generation. Few human studies have investigated the acute effects of cannabinoids on brain-based biomarkers of NMDAR function and synaptic plasticity. OBJECTIVES: The current study investigated the acute effects of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone and in combination on the mismatch negativity (MMN). METHODS: In a randomised, double-blind, crossover placebo-controlled study, 18 frequent and 18 less-frequent cannabis users underwent 5 randomised drug sessions administered via vaporiser: (1) placebo; (2) THC 8 mg; (3) CBD 400 mg; (4) THC 8 mg + CBD 4 mg [THC + CBDlow]; (5) THC 12 mg + CBD 400 mg [THC + CBDhigh]. Participants completed a multifeature MMN auditory oddball paradigm with duration, frequency and intensity deviants (6% each). RESULTS: Relative to placebo, both THC and CBD were observed to increase duration and intensity MMN amplitude in less-frequent users, and THC also increased frequency MMN in this group. The addition of low-dose CBD added to THC attenuated the effect of THC on duration and intensity MMN amplitude in less-frequent users. The same pattern of effects was observed following high-dose CBD added to THC on duration and frequency MMN in frequent users. CONCLUSIONS: The pattern of effects following CBD combined with THC on MMN may be subserved by different underlying neurobiological interactions within the endocannabinoid system that vary as a function of prior cannabis exposure. These results highlight the complex interplay between the acute effects of exogenous cannabinoids and NMDAR function. Further research is needed to determine how this process normalises after the acute effects dissipate and following repeated acute exposure.

A cognitive model of response omissions in distraction paradigms.

The effects of distraction on responses manifest in three ways: prolonged reaction times, and increased error and response omission rates. However, the latter effect is often ignored or assumed to be due to a separate cognitive process. We investigated omissions occurring in two paradigms that manipulated distraction. One required simple stimulus detection of younger participants, the second required choice responses and was completed by both younger and older participants. We fit data from these paradigms with a model that identifies three causes of omissions: two are related to the process of accumulating the evidence on which a response is based: intrinsic omissions (due to between-trial variation in accumulation rates making it impossible to ever reach the evidence threshold) and design omissions (due to response windows that cause slow responses not to be recorded; a third, contaminant omissions, allows for a cause unrelated to the response process. In both data sets systematic differences in omission rates across conditions were accounted for by task-related omissions. Intrinsic omissions played a lesser role than design omissions, even though the presence of design omissions was not evident in descriptive analyses of the data. The model provided an accurate account of all aspects of the detection data and the choice-response data, but slightly underestimated overall omissions in the choice paradigm, particularly in older participants, suggesting that further investigation of contaminant omission effects is needed.

Hierarchical Learning of Statistical Regularities over Multiple Timescales of Sound Sequence Processing: A Dynamic Causal Modeling Study.

Our understanding of the sensory environment is contextualized on the basis of prior experience. Measurement of auditory ERPs provides insight into automatic processes that contextualize the relevance of sound as a function of how sequences change over time. However, task-independent exposure to sound has revealed that strong first impressions exert a lasting impact on how the relevance of sound is contextualized. Dynamic causal modeling was applied to auditory ERPs collected during presentation of alternating pattern sequences. A local regularity (a rare p = .125 vs. common p = .875 sound) alternated to create a longer timescale regularity (sound probabilities alternated regularly creating a predictable block length), and the longer timescale regularity changed halfway through the sequence (the regular block length became shorter or longer). Predictions should be revised for local patterns when blocks alternated and for longer patterning when the block length changed. Dynamic causal modeling revealed an overall higher precision for the error signal to the rare sound in the first block type, consistent with the first impression. The connectivity changes in response to errors within the underlying neural network were also different for the two blocks with significantly more revision of predictions in the arrangement that violated the first impression. Furthermore, the effects of block length change suggested errors within the first block type exerted more influence on the updating of longer timescale predictions. These observations support the hypothesis that automatic sequential learning creates a high-precision context (first impression) that impacts learning rates and updates to those learning rates when predictions arising from that context are violated. The results further evidence automatic pattern learning over multiple timescales simultaneously, even during task-independent passive exposure to sound.

The influence of variability on mismatch negativity amplitude.

Mismatch Negativity (MMN) to pattern deviations reveals exquisite pattern detection ability in the brain. MMN amplitude is proposed to be precision-weighted, being inversely proportional to variability within a patterned sound sequence. Two experiments were conducted to determine whether pattern variability, shown to influence MMN to simple pattern deviance, also extends to MMN elicited to abstract pattern deviants. Participants were presented with 3-tone triplet sequences that were defined by regular frequency ascendance with adjacent (A C deviants for adjacent and non-adjacent dependencies, was smaller for the latter, was impervious to variance in tone loudness, but showed prolonged sensitivity to the level of variability at sequence onset.

Acoustics versus linguistics? Context is Part and Parcel to lateralized processing of the parts and parcels of speech.

The purpose of this review is to provide an accessible exploration of key considerations of lateralization in speech and non-speech perception using clear and defined language. From these considerations, the primary arguments for each side of the linguistics versus acoustics debate are outlined and explored in context of emerging integrative theories. This theoretical approach entails a perspective that linguistic and acoustic features differentially contribute to leftward bias, depending on the given context. Such contextual factors include stimulus parameters and variables of stimulus presentation (e.g., noise/silence and monaural/binaural) and variances in individuals (sex, handedness, age, and behavioural ability). Discussion of these factors and their interaction is also aimed towards providing an outline of variables that require consideration when developing and reviewing methodology of acoustic and linguistic processing laterality studies. Thus, there are three primary aims in the present paper: (1) to provide the reader with key theoretical perspectives from the acoustics/linguistics debate and a synthesis of the two viewpoints, (2) to highlight key caveats for generalizing findings regarding predominant models of speech laterality, and (3) to provide a practical guide for methodological control using predominant behavioural measures (i.e., gap detection and dichotic listening tasks) and/or neurophysiological measures (i.e., mismatch negativity) of speech laterality.

Context is everything: How context shapes modulations of responses to unattended sound.

The concept of perceptual inferences taking place over multiple timescales simultaneously raises questions about how the brain can balance the demands of remaining sensitive to local rarity while utilising more global longer-term predictability to modulate cortical responses. In the present study auditory evoked potentials to four presentations of the same sound sequence containing predictable structure on a local (milliseconds to seconds) and more global (many minutes) timescales were recorded. The results from 33 participants are used to demonstrate that predictions about both local (internal predictive models) and global (meta-models that define expected precisions associated with familiar internal model states) regularities are formed. The study exposes more local context-based modulations of the P1 but more global order-based modulations of the auditory evoked N2 components. The results are discussed in terms of theoretical links advocating that uncertainty at multiple timescales could lead to differential component modulations, and the importance of considering the broader learning context in auditory evoked potential studies.

Do rat auditory event related potentials exhibit human mismatch negativity attributes related to predictive coding?

Rodent models play a significant role in understanding disease mechanisms and the screening of new treatments. With regard to psychiatric disorders such as schizophrenia, however, it is difficult to replicate the human symptoms in rodents because these symptoms are often either 'uniquely human' or are only conveyed via self-report. There is a growing interest in rodent mismatch responses (MMRs) as a translatable 'biomarker' for disorders such as schizophrenia. In this review, we will summarize the attributes of human MMN, and discuss the scope of exploring the attributes of human MMN in rodents. Here, we examine how reliably MMRs that are measured in rats mimic human attributes, and present original data examining whether manipulations of stimulus conditions known to modulate human MMN, do the same for rat MMRs. Using surgically-implanted epidural electroencephalographic electrodes and wireless telemetry in freely-moving rats, we observed human-like modulations of MMRs, namely that larger MMRs were elicited to unexpected (deviant) stimuli that a) had a larger change in pitch compared to the expected (standard) stimulus, b) were less frequently presented (lower probability), and c) had no jitter (stable stimulus onset asynchrony) compared to high jitter. Overall, these findings contribute to the mounting evidence for rat MMRs as a good analogue of human MMN, bolstering the development of a novel approach in future to validate the preclinical models based on a translatable biomarker, MMN.

Making Sense of Mismatch Negativity.

Evoked potentials provide valuable insight into brain processes that are integral to our ability to interact effectively and efficiently in the world. The mismatch negativity (MMN) component of the evoked potential has proven highly informative on the ways in which sensitivity to regularity contributes to perception and cognition. This review offers a compendium of research on MMN with a view to scaffolding an appreciation for its use as a tool to explore the way regularities contribute to predictions about the sensory environment over many timescales. In compiling this work, interest in MMN as an index of sensory encoding and memory are addressed, as well as attention. Perspectives on the possible underlying computational processes are reviewed as well as recent observations that invite consideration of how MMN relates to how we learn, what we learn, and why.

Effect of Immune Activation during Early Gestation or Late Gestation on Inhibitory Markers in Adult Male Rats.

People with schizophrenia exhibit deficits in inhibitory neurons and cognition. The timing of maternal immune activation (MIA) may present distinct schizophrenia-like phenotypes in progeny. We investigated whether early gestation [gestational day (GD) 10] or late gestation (GD19) MIA, via viral mimetic polyI:C, produces deficits in inhibitory neuron indices (GAD1, PVALB, SST, SSTR2 mRNAs) within cortical, striatal, and hippocampal subregions of male adult rat offspring. In situ hybridisation revealed that polyI:C offspring had: (1) SST mRNA reductions in the cingulate cortex and nucleus accumbens shell, regardless of MIA timing; (2) SSTR2 mRNA reductions in the cortex and striatum of GD19, but not GD10, MIA; (3) no alterations in cortical or striatal GAD1 mRNA of polyI:C offspring, but an expected reduction of PVALB mRNA in the infralimbic cortex, and; (4) no alterations in inhibitory markers in hippocampus. Maternal IL-6 response negatively correlated with adult offspring SST mRNA in cortex and striatum, but not hippocampus. These results show lasting inhibitory-related deficits in cortex and striatum in adult offspring from MIA. SST downregulation in specific cortical and striatal subregions, with additional deficits in somatostatin-related signalling through SSTR2, may contribute to some of the adult behavioural changes resulting from MIA and its timing.