Association of lifetime major depressive disorder with enhanced attentional sensitivity measured with P3 response in young adult twins.

Major depression is associated with alterations in the auditory P3 event-related potential (ERP). However, the persistence of these abnormalities after recovery from depressive episodes, especially in young adults, is not well known. Furthermore, the potential influence of substance use on this association is poorly understood. Young adult twin pairs (N = 177) from the longitudinal FinnTwin16 study were studied with a psychiatric interview, and P3a and P3b ERPs elicited by task-irrelevant novel sounds and targets, respectively. Dyadic linear mixed-effect models were used to distinguish the effects of lifetime major depressive disorder from familial factors and effects of alcohol problem drinking and tobacco smoking. P3a amplitude was significantly increased and P3b latency decreased, in individuals with a history of lifetime major depression, when controlling the fixed effects of alcohol abuse, tobacco, gender, twins' birth order, and zygosity. These results suggest that past lifetime major depressive disorder may be associated with enhanced attentional sensitivity.

Aging and non-native speech perception: A phonetic training study.

Cognitive decline is evident in the elderly and it affects speech perception and foreign language learning. A listen-and-repeat training with a challenging speech sound contrast was earlier found to be effective in young monolingual adults and even in advanced L2 university students at the attentive and pre-attentive levels. This study investigates foreign language speech perception in the elderly with the same protocol used with the young adults. Training effects were measured with attentive behavioural measures (N = 9) and with electroencephalography measuring the pre-attentive mismatch negativity (MMN) response (N = 10). Training was effective in identification, but not in discrimination and there were no changes in the MMN. The most attention demanding perceptual functions which benefit from experience-based linguistic knowledge were facilitated through training, whereas pre-attentive processing was unaffected. The elderly would probably benefit from different training types compared to younger adults.

The MMN as a viable and objective marker of auditory development in CI users.

In the present article, we review the studies on the use of the mismatch negativity (MMN) as a tool for an objective assessment of cochlear-implant (CI) functioning after its implantation and as a function of time of CI use. The MMN indexes discrimination of different sound stimuli with a precision matching with that of behavioral discrimination and can therefore be used as its objective index. Importantly, these measurements can be reliably carried out even in the absence of attention and behavioral responses and therefore they can be extended to populations that are not capable of behaviorally reporting their perception such as infants and different clinical patient groups. In infants and small children with CI, the MMN provides the only means for assessing the adequacy of the CI functioning, its improvement as a function of time of CI use, and the efficiency of different rehabilitation procedures. Therefore, the MMN can also be used as a tool in developing and testing different novel rehabilitation procedures. Importantly, the recently developed multi-feature MMN paradigms permit the objective assessment of discrimination accuracy for all the different auditory dimensions (such as frequency, intensity, and duration) in a short recording time of about 30 min. Most recently, such stimulus paradigms have been successfully developed for an objective assessment of music perception, too.

Passive exposure to speech sounds induces long-term memory representations in the auditory cortex of adult rats.

Experience-induced changes in the functioning of the auditory cortex are prominent in early life, especially during a critical period. Although auditory perceptual learning takes place automatically during this critical period, it is thought to require active training in later life. Previous studies demonstrated rapid changes in single-cell responses of anesthetized adult animals while exposed to sounds presented in a statistical learning paradigm. However, whether passive exposure to sounds can form long-term memory representations remains to be demonstrated. To investigate this issue, we first exposed adult rats to human speech sounds for 3 consecutive days, 12 h/d. Two groups of rats exposed to either spectrotemporal or tonal changes in speech sounds served as controls for each other. Then, electrophysiological brain responses from the auditory cortex were recorded to the same stimuli. In both the exposure and test phase statistical learning paradigm, was applied. The exposure effect was found for the spectrotemporal sounds, but not for the tonal sounds. Only the animals exposed to spectrotemporal sounds differentiated subtle changes in these stimuli as indexed by the mismatch negativity response. The results point to the occurrence of long-term memory traces for the speech sounds due to passive exposure in adult animals.

Visual mismatch negativity (vMMN): A review and meta-analysis of studies in psychiatric and neurological disorders.

The visual mismatch negativity (vMMN) response is an event-related potential (ERP) component, which is automatically elicited by events that violate predictions based on prior events. VMMN experiments use visual stimulus repetition to induce predictions, and vMMN is obtained by subtracting the response to rare unpredicted stimuli from those to frequent stimuli. One increasingly popular interpretation of the mismatch response postulates that vMMN, similar to its auditory counterpart (aMMN), represents a prediction error response generated by cortical mechanisms forming probabilistic representations of sensory signals. Here we discuss the physiological and theoretical basis of vMMN and review thirty-three studies from the emerging field of its clinical applications, presenting a meta-analysis of findings in schizophrenia, mood disorders, substance abuse, neurodegenerative disorders, developmental disorders, deafness, panic disorder and hypertension. Furthermore, we include reports on aging and maturation as they bear upon many clinically relevant conditions. Surveying the literature we found that vMMN is altered in several clinical populations which is in line with aMMN findings. An important potential advantage of vMMN however is that it allows the investigation of deficits in predictive processing in cognitive domains which rely primarily on visual information; a principal sensory modality and thus of vital importance in environmental information processing and response, and a modality which arguably may be more sensitive to some pathological changes. However, due to the relative infancy of research in vMMN compared to aMMN in clinical populations its potential for clinical application is not yet fully appreciated. The aim of this review and meta-analysis therefore is to present, in a detailed systematic manner, the findings from clinically-based vMMN studies, to discuss their potential impact and application, to raise awareness of this measure and to improve our understanding of disease upon fundamental aspects of visual information processing.

Electrophysiological Indicators of the Age-Related Deterioration in the Sensitivity to Auditory Duration Deviance.

The present study investigates age-related changes in duration discrimination in millisecond time domain. We tested young (N = 20, mean age = 24.5, SD = 2.97) and elderly (N = 20, mean age = 65.2, SD = 2.94) subjects using the mismatch negativity (MMN) paradigm. White-noise bursts of two different durations (50 and 10 ms) were presented in two oddball blocks. In one block (Increment Condition), the repetitive sequence of 10 ms standards was interspersed by occasional 50 ms deviants. In the Decrement Condition, the roles of the two stimuli were reversed. We analyzed the P1-N1 complex, MMN and P3a and found the effect of age for all these components. Moreover, the impact of stimulus presentation condition (increment/decrement) was observed for MMN and P3a. Our results confirmed the previous evidence for deteriorated duration discrimination in elderly people. Additionally, we found that this effect may be influenced by procedural factors.

Comprehensive auditory discrimination profiles recorded with a fast parametric musical multi-feature mismatch negativity paradigm.

OBJECTIVE: Mismatch negativity (MMN), a component of the auditory event-related potential (ERP) in response to auditory-expectancy violation, is sensitive to central auditory processing deficits associated with several clinical conditions and to auditory skills deriving from musical expertise. This sensitivity is more evident for stimuli integrated in complex sound contexts. This study tested whether increasing magnitudes of deviation (levels) entail increasing MMN amplitude (or decreasing latency), aiming to create a balanced version of the musical multi-feature paradigm towards measurement of extensive auditory discrimination profiles in auditory expertise or deficits. METHODS: Using electroencephalography, we measured MMNs in healthy young adults to six types of sound feature change (pitch, timbre, location, intensity, slide and rhythm) at three different magnitudes of deviation, embedded in a music-sounding context. We also behaviourally assessed the individual musical aptitude using the Musical Ear Test (MET). RESULTS: 16 of 18 sound feature changes elicited significant MMNs. For pitch, intensity, location, and slide, the MMN amplitude increased with increasing magnitude of feature change. We observed a ceiling effect for rhythm, and a floor effect for timbre. The slide MMN amplitude correlated positively with MET melody score and negatively with MET rhythm score. CONCLUSIONS: This novel paradigm provides an extensive, objective measure of auditory discrimination profile for different sound features embedded in a complex sound context. SIGNIFICANCE: The paradigm can be adopted to study the neurophysiology of individuals with music processing difficulties or with special musical skills, and may be a useful tool for investigating development, plasticity, and deficits of auditory processing.

Mismatch negativity (MMN) as biomarker predicting psychosis in clinically at-risk individuals.

The early detection of young people at-risk of developing a severe mental illness like schizophrenia offers the opportunity of introducing treatment earlier than currently possible. There is some evidence that early intervention improves prognosis and functional outcome, or even prevents the full clinical manifestation of the condition in some individuals. A key prerequisite to facilitate early intervention would be a biomarker that can reliably predict a transition to schizophrenia. A smaller event-related mismatch negativity (MMN) potential has emerged as one of the most robust psychophysiological finding in schizophrenia akin of a biomarker of the condition. More recent research further demonstrates that MMN, but also P3a amplitudes, are already reduced in the prodromal phase of illness. Several lines of pre-clinical and clinical research support this notion and are reviewed in this article together with current obstacles, which are still limiting the translation of MMN as a biomarker into clinical practice.

Criteria for determining whether mismatch responses exist in animal models: Focus on rodents.

The mismatch negativity (MMN) component of the auditory event-related potential, elicited in response to unexpected stimuli in the auditory environment, has great value for cognitive neuroscience research. It is changed in several neuropsychiatric disorders such as schizophrenia. The ability to measure and manipulate MMN-like responses in animal models, particularly rodents, would provide an enormous opportunity to learn more about the neurobiology underlying MMN. However, the MMN in humans is a very specific phenomenon: how do we decide which features we should focus on emulating in an animal model to achieve the highest level of translational validity? Here we discuss some of the key features of MMN in humans and summarise the success with which they have been translated into rodent models. Many studies from several different labs have successfully shown that the rat brain is capable of generating deviance detection responses that satisfy of the criteria for the human MMN.

The mismatch negativity as a measure of auditory stream segregation in a simulated "cocktail-party" scenario: effect of age.

With age the ability to understand speech in multitalker environments usually deteriorates. The central auditory system has to perceptually segregate and group the acoustic input into sequences of distinct auditory objects. The present study used electrophysiological measures to study effects of age on auditory stream segregation in a multitalker scenario. Younger and older adults were presented with streams of short speech stimuli. When a single target stream was presented, the occurrence of a rare (deviant) syllable among a frequent (standard) syllable elicited the mismatch negativity (MMN), an electrophysiological correlate of automatic deviance detection. The presence of a second, concurrent stream consisting of the deviant syllable of the target stream reduced the MMN amplitude, especially when located nearby the target stream. The decrease in MMN amplitude indicates that the rare syllable of the target stream was less perceived as deviant, suggesting reduced stream segregation with decreasing stream distance. Moreover, the presence of a concurrent stream increased the MMN peak latency of the older group but not that of the younger group. The results provide neurophysiological evidence for the effects of concurrent speech on auditory processing in older adults, suggesting that older adults need more time for stream segregation in the presence of concurrent speech.

Phonetic training and non-native speech perception--New memory traces evolve in just three days as indexed by the mismatch negativity (MMN) and behavioural measures.

Language-specific, automatically responding memory traces form the basis for speech sound perception and new neural representations can also evolve for non-native speech categories. The aim of this study was to find out how a three-day phonetic listen-and-repeat training affects speech perception, and whether it generates new memory traces. We used behavioural identification, goodness rating, discrimination, and reaction time tasks together with mismatch negativity (MMN) brain response registrations to determine the training effects on native Finnish speakers. We trained the subjects the voicing contrast in fricative sounds. Fricatives are not differentiated by voicing in Finnish, i.e., voiced fricatives do not belong to the Finnish phonological system. Therefore, they are extremely hard for Finns to learn. However, only after three days of training, the native Finnish subjects had learned to perceive the distinction. The results show striking changes in the MMN response; it was significantly larger on the second day after two training sessions. Also, the majority of the behavioural indicators showed improvement during training. Identification altered after four sessions of training and discrimination and reaction times improved throughout training. These results suggest remarkable language-learning effects both at the perceptual and pre-attentive neural level as a result of brief listen-and-repeat training in adult participants.

Resting-state glutamatergic neurotransmission is related to the peak latency of the auditory mismatch negativity (MMN) for duration deviants: An (1)H-MRS-EEG study.

Mismatch negativity (MMN), an ERP elicited by a deviant stimulus in a train of standard stimuli, has been suggested to be associated to glutamatergic neurotransmission, mediated by glutamatergic NMDA receptors. In this study, we examined the relationship between interindividual variation of (1)H-MRS-measured glutamate+glutamine (Glx) in the superior temporal gyrus and MMN for duration and frequency deviants in 19 healthy young adults (9 male). We found a significant relationship between the peak latency of the duration-MMN peak and creatine-scaled Glx (p = .0003, η(2) = .43), with increased Glx level being associated to earlier peak of the duration-MMN (r = -.63). In contrast, the amplitude of the duration-MMN was not related to Glx. There was no significant relationship between Glx and the frequency-MMN. The present study is the first to demonstrate that interindividual variation in the glutamatergic neurotransmission affects the MMN response in healthy individuals.

Mismatch negativity (MMN) deficiency: a break-through biomarker in predicting psychosis onset.

Currently, the mismatch negativity (MMN) deficit is one of the most robust and replicable findings in schizophrenia, reflecting cognitive and functional decline, psychosocial and socio-occupational impairment, and executive dysfunction in these patients. An important break-through has very recently taken place here in the prediction of conversion to psychosis when the MMN in particular to change in tone duration was recorded in clinically at risk-mental state (ARMS) individuals. Attenuations in the MMN in these patients may be very useful in helping clinicians determine who are most likely to develop a psychotic disorder, as we will review in the present article.

Early visual evoked potentials and mismatch negativity in Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Cortical visual association areas are highly vulnerable to Alzheimer's disease (AD) microscopic pathology. Visual evoked potentials (VEPs) provide the tools to examine the functional integrity of these areas and may provide useful indicators of early disease progression. OBJECTIVE: To assess the functional integrity of visual association area processing in AD and amnestic mild cognitive impairment (aMCI) using VEPs. METHODS: We investigated the visual processing of healthy older adults (n = 26), AD (n = 20), and aMCI (n = 25) patients in a visual oddball paradigm designed to elicit the visual P1, N1, and visual mismatch negativity (vMMN). RESULTS: AD patients showed a significant reduction of P1 and N1 VEP amplitudes and aMCI patients showed a reduction in N1 amplitude compared to healthy older adults. P1 amplitude in response to deviant stimuli and vMMN amplitude were found to be associated with the degree of cognitive impairment as measured by the Mini-Mental State Examination. CONCLUSIONS: Changes in VEPs in AD may be a consequence of the microscopic AD pathology typically found in the extrastriate cortex. Neural measures of visual processing may help to better characterize subgroups of aMCI patients likely to develop AD. Additionally, VEPs and vMMN may provide objective markers of cognitive decline.

Electrophysiological evidence for change detection in speech sound patterns by anesthetized rats.

Human infants are able to detect changes in grammatical rules in a speech sound stream. Here, we tested whether rats have a comparable ability by using an electrophysiological measure that has been shown to reflect higher order auditory cognition even before it becomes manifested in behavioral level. Urethane-anesthetized rats were presented with a stream of sequences consisting of three pseudowords carried out at a fast pace. Frequently presented "standard" sequences had 16 variants which all had the same structure. They were occasionally replaced by acoustically novel "deviant" sequences of two different types: structurally consistent and inconsistent sequences. Two stimulus conditions were presented for separate animal groups. In one stimulus condition, the standard and the pattern-obeying deviant sequences had an AAB structure, while the pattern-violating deviant sequences had an ABB structure. In the other stimulus condition, these assignments were reversed. During the stimulus presentation, local-field potentials were recorded from the dura, above the auditory cortex. Two temporally separate differential brain responses to the deviant sequences reflected the detection of the deviant speech sound sequences. The first response was elicited by both types of deviant sequences and reflected most probably their acoustical novelty. The second response was elicited specifically by the structurally inconsistent deviant sequences (pattern-violating deviant sequences), suggesting that rats were able to detect changes in the pattern of three-syllabic speech sound sequence (i.e., location of the reduplication of an element in the sequence). Since all the deviant sound sequences were constructed of novel items, our findings indicate that, similarly to the human brain, the rat brain has the ability to automatically generalize extracted structural information to new items.

Rapid categorization of sound objects in anesthetized rats as indexed by the electrophysiological mismatch response.

It is not known whether animals can, similarly to humans, categorize auditory objects based on an abstract rule in combining their physical features. We recorded local-field potentials from the dura above the primary auditory cortex in urethane-anesthetized rats presented with sound series occasionally violating a rule (e.g., "the higher the frequency, the weaker the intensity"). In a separate control condition, the same frequency and intensity levels were applied in the sound objects, but they obeyed no rule. Responses found selectively to the violations of the rule suggest that an abstract rule was represented in the rat brain, enabling auditory categorization.

Mismatch negativity (MMN) as an index of cognitive dysfunction.

Cognition is often affected in a variety of neuropsychiatric, neurological, and neurodevelopmental disorders. The neural discriminative response, reflected in mismatch negativity (MMN) and its magnetoencephalographic equivalent (MMNm), has been used as a tool to study a variety of disorders involving auditory cognition. MMN/MMNm is an involuntary brain response to auditory change or, more generally, to pattern regularity violation. For a number of disorders, MMN/MMNm amplitude to sound deviance has been shown to be attenuated or the peak-latency of the component prolonged compared to controls. This general finding suggests that while not serving as a specific marker to any particular disorder, MMN may be useful for understanding factors of cognition in various disorders, and has potential to serve as an indicator of risk. This review presents a brief history of the MMN, followed by a description of how MMN has been used to index auditory processing capability in a range of neuropsychiatric, neurological, and neurodevelopmental disorders. Finally, we suggest future directions for research to further enhance our understanding of the neural substrate of deviance detection that could lead to improvements in the use of MMN as a clinical tool.

vMMN for schematic faces: automatic detection of change in emotional expression.

Our brain is able to automatically detect changes in sensory stimulation, including in vision. A large variety of changes of features in stimulation elicit a deviance-reflecting event-related potential (ERP) component known as the mismatch negativity (MMN). The present study has three main goals: (1) to register vMMN using a rapidly presented stream of schematic faces (neutral, happy, and angry; adapted from Öhman etal., 2001); (2) to compare elicited vMMNs to angry and happy schematic faces in two different paradigms, in a traditional oddball design with frequent standard and rare target and deviant stimuli (12.5% each) and in an version of an optimal multi-feature paradigm with several deviant stimuli (altogether 37.5%) in the stimulus block; (3) to compare vMMNs to subjective ratings of valence, arousal and attention capture for happy and angry schematic faces, i.e., to estimate the effect of affective value of stimuli on their automatic detection. Eleven observers (19-32 years, six women) took part in both experiments, an oddball and optimum paradigm. Stimuli were rapidly presented schematic faces and an object with face-features that served as the target stimulus to be detected by a button-press. Results show that a vMMN-type response at posterior sites was equally elicited in both experiments. Post-experimental reports confirmed that the angry face attracted more automatic attention than the happy face but the difference did not emerge directly at the ERP level. Thus, when interested in studying change detection in facial expressions we encourage the use of the optimum (multi-feature) design in order to save time and other experimental resources.