Learning-induced neural plasticity of speech processing before birth.

Learning, the foundation of adaptive and intelligent behavior, is based on plastic changes in neural assemblies, reflected by the modulation of electric brain responses. In infancy, auditory learning implicates the formation and strengthening of neural long-term memory traces, improving discrimination skills, in particular those forming the prerequisites for speech perception and understanding. Although previous behavioral observations show that newborns react differentially to unfamiliar sounds vs. familiar sound material that they were exposed to as fetuses, the neural basis of fetal learning has not thus far been investigated. Here we demonstrate direct neural correlates of human fetal learning of speech-like auditory stimuli. We presented variants of words to fetuses; unlike infants with no exposure to these stimuli, the exposed fetuses showed enhanced brain activity (mismatch responses) in response to pitch changes for the trained variants after birth. Furthermore, a significant correlation existed between the amount of prenatal exposure and brain activity, with greater activity being associated with a higher amount of prenatal speech exposure. Moreover, the learning effect was generalized to other types of similar speech sounds not included in the training material. Consequently, our results indicate neural commitment specifically tuned to the speech features heard before birth and their memory representations.

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.

The mismatch negativity: an index of cognitive decline in neuropsychiatric and neurological diseases and in ageing.

Cognitive impairment is a core element shared by a large number of different neurological and neuropsychiatric diseases. Irrespective of their different aetiologies and symptomatologies, most appear to converge at the functional deficiency of the auditory-frontal cortex network of auditory discrimination, which indexes cognitive impairment shared by these abnormalities. This auditory-frontal cortical deficiency, and hence cognitive decline, can now be objectively measured with the mismatch negativity and its magnetic equivalent. The auditory-frontal cortical network involved seems, therefore, to play a pivotal, unifying role in the different abnormalities. It is, however, more likely that the dysfunction that can be detected with the mismatch negativity and its magnetoencephalographic equivalent manifests a more widespread brain disorder, namely, a deficient N-methyl-D-aspartate receptor function, shared by these abnormalities and accounting for most of the cognitive decline.

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.

A longitudinal twin study of effects of adolescent alcohol abuse on the neurophysiology of attention and orienting.

BACKGROUND: Long-term functional brain effects of adolescent alcohol abuse remain uncertain, partially because of difficulties in distinguishing inherited deficits from neuronal effects of ethanol and by confounds associated with alcohol abuse, especially nicotine exposure. We conducted a longitudinal twin study to determine neurocognitive effects of adolescent alcohol abuse, as measured with the auditory event-related potential (ERP) component P3, a putative marker of genetic vulnerability to alcoholism. METHODS: Twin pairs (N=177; 150 selected for intrapair concordance/discordance for alcohol-related problems at age 18½) were recruited from ongoing studies of twins born 1975-1979 in Finland. Alcohol and tobacco use were assessed with questionnaires at ages 16, 17, 18½, and ~25, and by a structured psychiatric interview concurrent with the ERP testing at mean age 25.8. During ERP recordings, subjects were instructed to detect target tones within a train of frequent "standards" and to ignore occasional "novel" sounds. To distinguish familial factors from ethanol effects, ERP and self-reported alcohol use measures were incorporated into hierarchical multiple regression (HMR) analysis, and intrapair differences in ERP were associated with intra-pair differences in alcohol variables. RESULTS: Novel-sound P3 amplitude correlated negatively with self-reported alcohol use in both between- and within-family analyses. No similar effect was observed for target-tone P3. HMR results suggest that twins' similarity for novel-sound P3 amplitude is modulated by their alcohol use, and this effect of alcohol use is influenced by genetic factors. CONCLUSIONS: Our results, from a large sample of twins selected from a population-based registry for pairwise concordance/discordance for alcohol problems at 18½, demonstrate that adolescent alcohol abuse is associated with subtle neurophysiological changes in attention and orienting. The changes are reflected in decreased novel-sound P3 amplitude and may be modified by genetic factors.

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.

Training the brain to weight speech cues differently: a study of Finnish second-language users of English.

Foreign-language learning is a prime example of a task that entails perceptual learning. The correct comprehension of foreign-language speech requires the correct recognition of speech sounds. The most difficult speech-sound contrasts for foreign-language learners often are the ones that have multiple phonetic cues, especially if the cues are weighted differently in the foreign and native languages. The present study aimed to determine whether non-native-like cue weighting could be changed by using phonetic training. Before the training, we compared the use of spectral and duration cues of English /i/ and /I/ vowels (e.g., beat vs. bit) between native Finnish and English speakers. In Finnish, duration is used phonologically to separate short and long phonemes, and therefore Finns were expected to weight duration cues more than native English speakers. The cross-linguistic differences and training effects were investigated with behavioral and electrophysiological methods, in particular by measuring the MMN brain response that has been used to probe long-term memory representations for speech sounds. The behavioral results suggested that before the training, the Finns indeed relied more on duration in vowel recognition than the native English speakers did. After the training, however, the Finns were able to use the spectral cues of the vowels more reliably than before. Accordingly, the MMN brain responses revealed that the training had enhanced the Finns' ability to preattentively process the spectral cues of the English vowels. This suggests that as a result of training, plastic changes had occurred in the weighting of phonetic cues at early processing stages in the cortex.

No effects of mobile phone use on cortical auditory change-detection in children: an ERP study.

We investigated the effect of mobile phone use on the auditory sensory memory in children. Auditory event-related potentials (ERPs), P1, N2, mismatch negativity (MMN), and P3a, were recorded from 17 children, aged 11-12 years, in the recently developed multi-feature paradigm. This paradigm allows one to determine the neural change-detection profile consisting of several different types of acoustic changes. During the recording, an ordinary GSM (Global System for Mobile Communications) mobile phone emitting 902 MHz (pulsed at 217 Hz) electromagnetic field (EMF) was placed on the ear, over the left or right temporal area (SAR(1g) = 1.14 W/kg, SAR(10g) = 0.82 W/kg, peak value = 1.21 W/kg). The EMF was either on or off in a single-blind manner. We found that a short exposure (two 6 min blocks for each side) to mobile phone EMF has no statistically significant effects on the neural change-detection profile measured with the MMN. Furthermore, the multi-feature paradigm was shown to be well suited for studies of perception accuracy and sensory memory in children. However, it should be noted that the present study only had sufficient statistical power to detect a large effect size.

Numerical discrimination in newborn infants as revealed by event-related potentials to tone sequences.

Humans are able to attentively discriminate number from 6 months of age. However, the age of the emergence of this ability at the pre-attentive stage of processing remains unclear. Event-related potentials (ERPs) were recorded in newborn human infants aged from 3 to 5 days. At 500-ms intervals, the infants were passively exposed to 200-ms sequences of four tones. Each tone could be either 1000 or 1500 Hz in frequency. In most sequences (standards), the ratio of the tones of one frequency to those of the other frequency in a sequence was 2 : 2. In the remaining sequences (deviants, P = 0.1), this ratio was either 3 : 1 or 4 : 0. The mismatch response of ERPs could not be found for 3 : 1 deviants, but it was a robust finding for 4 : 0 deviants, showing the neurophysiological ability of the infants to register the larger deviant-standard difference. The findings suggest very early sensitivity to auditory numerical information in infancy.

Statistical language learning in neonates revealed by event-related brain potentials.

BACKGROUND: Statistical learning is a candidate for one of the basic prerequisites underlying the expeditious acquisition of spoken language. Infants from 8 months of age exhibit this form of learning to segment fluent speech into distinct words. To test the statistical learning skills at birth, we recorded event-related brain responses of sleeping neonates while they were listening to a stream of syllables containing statistical cues to word boundaries. RESULTS: We found evidence that sleeping neonates are able to automatically extract statistical properties of the speech input and thus detect the word boundaries in a continuous stream of syllables containing no morphological cues. Syllable-specific event-related brain responses found in two separate studies demonstrated that the neonatal brain treated the syllables differently according to their position within pseudowords. CONCLUSION: These results demonstrate that neonates can efficiently learn transitional probabilities or frequencies of co-occurrence between different syllables, enabling them to detect word boundaries and in this way isolate single words out of fluent natural speech. The ability to adopt statistical structures from speech may play a fundamental role as one of the earliest prerequisites of language acquisition.

Efficiency of working memory encoding in twins discordant for schizophrenia.

It has been proposed that patients with schizophrenia and some of their relatives suffer from reduced neurocognitive efficiency, increasing their sensitivity to experimental task demands. The present study evaluated such a possibility during performance of a working memory task by schizophrenia patients and their co-twins along with a healthy control sample. Electrophysiological data were obtained from sets of nine twin pairs (monozygotic and dizygotic pairs collapsed) discordant for a diagnosis of schizophrenia and from nine matched healthy control twin pairs, during administration of a variable-load spatial working memory task. Event-related potentials (ERPs) were measured immediately after memory set onset and during a delay period. For correctly performed trials, slow-wave ERP activity measured during the late stimulus encoding and delay periods exhibited a significant Diagnostic Group-by-Memory Load interaction, with schizophrenia patients showing a differentially strong load effect. Patients' co-twins displayed an intermediate level of load sensitivity while healthy controls showed no significant load effect. These results support an inefficiency model of neurocognitive dysfunction in schizophrenia, a pattern that appears to be related to the pathogenesis and inheritance of the disorder. Furthermore, this inefficiency appeared during the late stimulus encoding stage of working memory functioning, possibly reflecting disruptions in stimulus representation consolidation.

Preattentive auditory information processing under exposure to the 902 MHz GSM mobile phone electromagnetic field: a mismatch negativity (MMN) study.

Previous studies on the effects of the mobile phone electromagnetic field (EMF) on various event-related potential (ERP) components have yielded inconsistent and even contradictory results, and often failed in replication. The mismatch negativity (MMN) is an auditory ERP component elicited by infrequent (deviant) stimuli differing in some physical features from the repetitive frequent (standard) stimuli in a sound sequence. The MMN provides a sensitive measure for cortical auditory stimulus feature discrimination, regardless of attention and other contaminating factors. In this study, MMN responses to duration, intensity, frequency, and gap changes were recorded in healthy young adults (n = 17), using a multifeature paradigm including several types of auditory change in the same stimulus sequence, while a GSM mobile phone was placed on either ear with the EMF (902 MHz pulsed at 217 Hz; SAR(1g) = 1.14 W/kg, SAR(10g) = 0.82 W/kg, peak value = 1.21 W/kg, measured with an SAM phantom) on or off. An MMN was elicited by all deviant types, while its amplitude and latency showed no significant differences due to EMF exposure for any deviant types. In the present study, we found no conclusive evidence that acute exposure to GSM mobile phone EMF affects cortical auditory change detection processing reflected by the MMN.

Abnormally high EEG alpha synchrony during working memory maintenance in twins discordant for schizophrenia.

BACKGROUND: The present analyses aimed to test the prediction that schizophrenia patients and their non-schizophrenic co-twins would display reduced efficiency of the neurocognitive mechanisms subserving active maintenance of spatial information in working memory. METHODS: Upper alpha frequency band EEG event-related desynchronization and synchronization (ERD/ERS) were calculated as percent changes in power relative to an inter-trial baseline across 4 memory loads in a spatial delayed-response task. RESULTS: During the delay, the diagnostic groups showed equivalent ERD/ERS activity over posterior scalp regions at the lowest memory load; however, as memory load increased, patients, and to an intermediate degree, their non-schizophrenic co-twins (monozygotic and dizygotic pairs collapsed together), showed significantly greater increases in ERD/ERS amplitude as compared with controls. CONCLUSIONS: These findings demonstrate abnormally increased ERD/ERS amplitudes with increasing memory load in patients with schizophrenia and their co-twins, consistent with inefficiency of the neurocognitive mechanisms supporting active maintenance of information across a delay.

Effects of an NMDA-receptor antagonist MK-801 on an MMN-like response recorded in anesthetized rats.

In the human brain, auditory sensory memory has been extensively studied using a well-defined component of event-related potential named the mismatch negativity (MMN). The MMN is generated in the auditory and frontal cortices in response to deviant stimuli. In monkeys, cortical N-methyl-d-aspartate (NMDA) receptors have a central role in the generation of the MMN. MMN-like responses have also been recorded in other animals, including rats. The present study aimed at determining whether the MMN-like response in rats depends on an intact NMDA-receptor system. We recorded auditory evoked responses during an oddball paradigm epidurally in anesthetized rats that had received intraperitoneal injections of saline or an NMDA-receptor antagonist MK-801. An MMN-like response was recorded in the oddball paradigm in saline-treated rats. Further, this response was dose-dependently blocked by MK-801. These results suggest that the MMN-like response in rats depends on an intact NMDA-receptor system.

Parameter-specific modulation of the mismatch negativity to duration decrement and increment: evidence for asymmetric processes.

OBJECTIVE: The mismatch negativity (MMN) component of event-related potentials (ERPs) reflects a change-detection process in the brain. The present study investigated whether stimulus parameters (sound type and duration) exert a differential influence on the MMN for a duration decrement and increment of an equal magnitude. Some asymmetries were reported in the previous studies; yet no systematical study has been conducted. METHODS: ERPs were recorded from 16 healthy adults presented with repetitive standard sounds interspersed with duration changes (deviant sounds). In separate sequences, stimuli were vowels, music chord, sinusoid, or band-pass filtered white noise. The stimulus durations (standard/deviant) were either 200/120 ms or 400/240 ms for decrements, and vice versa for increments. RESULTS: The MMN for the increments was abolished in the 400/240 ms condition, whereas the MMN for decrements was significant irrespective of the sound duration. The amplitude of the increment MMN paralleled with the spectral complexity of the stimulus sound, whereas that of the decrement MMN was larger for natural sounds than artificial sounds. CONCLUSIONS: The observed interactions demonstrated asymmetries in the MMN for duration increment and decrement. SIGNIFICANCE: The present findings suggest that the effects of stimulus parameters should be taken into account when comparing different studies, especially where clinical populations are involved, with one another.

Mismatch negativity reflects numbers of tones of specific frequencies in humans.

The human brain can automatically quantify objects and events. The mismatch negativity (MMN) of the event-related potential (ERP) was recently found to reflect one such ability in the auditory modality. The present study aimed to further validate the finding. ERPs were recorded in adult humans who passively listened to a series of 300-ms sequences of tones. The sequences occurred at 300-ms silent intervals. They comprised a total of six tones that each was either 440 or 660 Hz in frequency. MMN was found for a rare 4:2 ratio interspersed with a frequent 3:3 ratio between the tones of the different frequencies in a sequence, suggesting the ability of the human brain to preattentively discriminate numbers of sounds of specific frequencies at least at a 3:2 ratio.

Preperceptual human number sense for sequential sounds, as revealed by mismatch negativity brain response?

Humans and some other species can nonlinguistically operate on the quantities of things or events, including sounds. Whether this ability is restricted to conscious percepts of sounds developing in approximately 200 ms is, however, unclear. To this end, we recorded the mismatch negativity (MMN) brain response, an index of preperceptual auditory change detection, of adult humans who passively listened to rare sequences of four 50-ms tones ("deviants") interspersed among frequently repeated tones ("standards"). Each tone was either 1000 or 1500 Hz in frequency. Deviants differed from standards in a ratio of the tones of the 2 frequencies. MMN was found for deviants by 160 ms from the onset of their largest ratio difference from standards (2:2 vs. 4:0), suggesting some ability of the human brain to operate on the number of sequential sounds of specific frequencies at a preperceptual time scale.

Mismatch negativity (MMN) as an index of central auditory system plasticity.

The mismatch negativity (MMN) is an electric brain response which is automatically elicited by any discriminable change in a repetitive sound or sound pattern. When this change is made smaller in magnitude, the MMN is attenuated in amplitude, eventually vanishing at around the discrimination threshold. Therefore the MMN provides a unique objective index for a subject or patient's discrimination accuracy. Furthermore, with the MMN, these discrimination thresholds can be separately determined for all the different auditory attributes. Moreover, the individual's ability to discriminate complex sound stimuli and patterns such as different phonemes can also be measured by using the MMN.

Neonatal frequency discrimination in 250-4000-Hz range: electrophysiological evidence.

OBJECTIVE: The precision of sound frequency discrimination in newborn infants in the 250-4000-Hz frequency range was determined using the neonatal electrophysiological mismatch response (MMR), the infant equivalent of adult mismatch negativity (MMN). METHODS: The electroencephalogram (EEG) was recorded in 11 full-term sleeping newborn infants mostly in active sleep (67% of the time). Pure tones were presented through loudspeakers in an oddball paradigm with a 800-ms stimulus onset asynchrony (SOA). Each stimulus block contained a standard (p=0.76) of 250, 1000, or 4000Hz in frequency (in separate blocks) and deviants with a frequency change of either 5% or 20% of the standard (p=0.12 of each). RESULTS: A positive ERP deflection was found at 200-300ms from stimulus onset in response to the 20% deviation from the 250, 1000, and 4000Hz standard frequencies. The amplitude of the response in the 200-300ms time window was significantly larger for the 20% than 5% deviation. CONCLUSIONS: We observed in newborn infants automatic frequency discrimination as reflected by a positive MMR. The newborns were able to discriminate frequency change of 20% in the 250-4000-Hz frequency range, whereas the discrimination of the 5% frequency change was not statistically confirmed. SIGNIFICANCE: The present data hence suggest that the neonatal frequency discrimination has lower resolution than that in adult and older children data.