Diagnostic subgroups of developmental dyslexia have different deficits in neural processing of tones and phonemes.

The present study addressed auditory processing in 8-11-year-old children with developmental dyslexia by means of event-related brain potentials (ERP). Cortical sound reception was evaluated by recording N250 responses to syllables and tones and cortical sound discrimination by analyzing the mismatch negativity (MMN) to syllable and tone changes. We found that both cortical sound reception and sound discrimination were impaired in dyslexic children. The analysis of the data obtained from two dyslexic subgroups, Dyslexics-1 being impaired in non-word reading (or both non-word and frequent word reading) and Dyslexics-2 in frequent word reading but not in non-word reading, revealed that the MMN was specifically diminished in the latter group whereas it was normal-like in Dyslexics-1. However, no differences were found between these subgroups in sound reception as indicated by the responses elicited by the standard stimuli. These results show that different diagnostic subgroups of dyslexics have different patterns of auditory processing deficits as suggested by similarly impaired sound reception in both dyslexic groups and the sound-discrimination impairment specific to one of the groups.     

Mismatch negativity in children and adults, and effects of an attended task

Attention has been shown to modulate the amplitude of the mismatch negativity (MMN) elicited by a small deviation in auditory stimuli in adults. The present study examined the effects of attention and deviant size on MMN amplitude in children. Children and adults were presented with sequences of tones containing standards (1000 Hz) and three deviants varying in degree of deviance from the standard (1050, 1200, and 1500 Hz). Tones were presented in three conditions: (1) while participants ignored them; (2) while participants listened to them and responded to all three deviants; and (3) while participants again ignored them. We found that the MMNs elicited by the hard deviant (1050 Hz) were larger when the children were actively discriminating the stimuli than when they were ignoring them. However, the MMNs elicited by the easy and medium deviants (1500 and 1200 Hz, respectively) in the children and by all three deviants in the adults were not affected by attention.     

Tonotopic auditory cortex and the magnetoencephalographic (MEG) equivalent of the mismatch negativity

Two tone stimuli, one frequent (standard) and the other infrequent (a slightly higher, deviant tone), were presented in random order and at short intervals to subjects reading texts they had selected. In different blocks, standards were either 250, 1,000, or 4,000 Hz, with the deviants always being 10% higher in frequency than the standards of the same blocks. Magnetic responses elicited by the standard and deviant tones included N1m, the magnetoencephalographic equivalent of the electrical N1 (its supratemporal component). In addition, deviant stimuli elicited MMNm, the magnetic equivalent of the electrical mismatch negativity, MMN. The equivalent dipole sources of the two responses were located in supratemporal auditory cortex, with the MMNm source being anterior to that of N1m. The dipole orientations of both sources in the sagittal plane depended on stimulus frequency, suggesting that the responses are generated by tonotopically organized neuronal populations. The tonotopy reflected by the frequency dependence of the MMNm source might be that of the neural trace system underlying frequency representation of auditory stimuli in sensory memory.     

Neuroimaging Evidence for Top-Down Maturation of Selective Auditory Attention

This study investigated maturational differences of selective auditory attention effects on transient evoked responses and 40-Hz auditory steady-state responses between children and adults. Magnetoencephalography (MEG) was recorded from children and adults performing a task where they attended to 40-Hz amplitude-modulated (AM) tones of 1,200?Hz while ignoring 40-Hz AM tones of 800?Hz. By using standard dipole-modeling procedures, the N1m of the transient evoked fields and the 40-Hz ASSRs were localized to secondary and primary auditory cortices, respectively. Source waveforms for the transient evoked fields and ASSRs were reconstructed at these locations and compared between attended and unattended tones. Source waveforms revealed attention enhances the sustained negativity of the transient evoked responses in both adults and children around 250 and 400?ms. ASSRs were also found to be enhanced within this time range but only for adults. The results provide evidence for a limited role of attention modification of the 40-Hz ASSRs in children around the age of 12?years old. Because ASSRs are generated in a lower auditory processing stage as compared to the transient auditory evoked responses, findings from the present study could indicate that the maturation of attention progresses in top-to-bottom manner. These findings fit with the notion that as a person gains sensory experience selective gating of relevant from irrelevant information likely occurs at earlier and earlier processing levels in order to become more automatic and efficient.     

Level of interest in video clips modulates event-related potentials to auditory probes.

This study examined whether a participant's level of interest in visual materials could be assessed by event-related potentials to auditory probe stimuli. Twelve young adults performed an auditory target detection task while viewing either interesting or less interesting (neutral) silent video clips. The auditory probe stimuli consisted of target (2000 Hz, p=0.15), standard (1800 Hz, p=0.70), and nontarget deviant (500 Hz, p=0.15) tones. Button press responses to target tones were required. Both target and deviant tones elicited a large P3 wave, the amplitude of which was smaller while participants were viewing interesting video clips than neutral video clips or simple still images (control condition). The amplitude reduction of the P3 to deviant tones was more prominent than that of the P3 to target tones. The difference between the neutral and control conditions was significant only for the deviant P3. The three-tone probe task using perceptually deviant, nontarget stimuli may be a useful objective method to assess how strongly a visual material attracts the viewer's attention.     

Common N1 and mismatch negativity neural evoked components are revealed by independent component model‐based clustering analysis

Mismatch negativity (MMN) is an event‐related brain potential that appears when an auditory regularity is violated. Two main hypotheses have been proposed to explain it: the adaptation hypothesis and the memory‐based hypothesis. Critically, they differ in whether the MMN can be distinguished from the N1. In this study, we assessed the differential contribution of the N1 and the MMN using independent component analysis (ICA) combined with model‐based clustering. Our results show that the neural responses associated with the standard and deviant tones are explained by three clusters of reliable ICs with frontocentral scalp distribution. Two of these clusters exhibited a common N1 for both the standard and deviant tones and one cluster showed an enhancement of the anterior N1 at the MMN time range. These results support the adaptation hypothesis, which proposes that MMN is generated by neural mechanisms similar to those associated with auditory N1.     

Augmentation of auditory N1 in children with fragile X syndrome

We compared the N1 responses of the auditory event-related brain potentials (ERPs) in school-aged children with fragile X syndrome to age-matched controls in order to assess auditory processing. Event-related potentials to non-attended standard and deviant tone stimuli were recorded with EEG electrodes and here the standard tones were analysed. The amplitude of the N1 component to standard tones was significantly larger in children with fragile X syndrome than in control children. In addition, the global field power maximum of ERP corresponding to the N2 component was significantly (p<0.05) larger in fragile X children than in controls. The N2 scalp distribution in children with fragile X syndrome appeared more frontal than that in controls. Furthermore, the fragile X children exhibited no habituation of N1 and an absence of N2 sensitization for repeated tones. Increased responsiveness observed in the N1 evoked potential together with abnormal habituation of auditory responses in childhood may indicate increased sensory sensitivity for auditory stimuli in fragile X syndrome. The data, though very limited, suggest that stimulus processing in the auditory afferent pathways and/or in the corresponding cortical receiving areas is abnormal in children with fragile X syndrome.     

Effect of deviance direction and calculation method on duration and frequency mismatch negativity (MMN)

The mismatch negativity (MMN) component of the auditory event-related potential (ERP) reflects the process of change detection in the auditory system. The present study investigated the effect of deviance direction (increment vs. decrement) and calculation method (traditional vs. same-stimulus) on the amplitude of MMN. MMN was recorded for increments and decrements in frequency and duration in 20 adults. The stimuli (standard/deviant) were 250 Hz/350 Hz (frequency MMN) and 200 ms/300 ms (duration MMN) for increment MMN and vice versa for decrement MMN. Amplitude of MMN was calculated in two ways: the traditional method (subtracting ERP to the standard from the deviant presented in the same block) and the same-stimulus method (subtracting ERP to identical stimuli presented as standard in one block and deviant in another block). We found that increments in frequency produced higher MMN amplitudes compared to decrements for both methods of calculation. For duration deviance, the decrement MMN was absent in the traditional method, while the decrement and increment MMN did not differ for the same-stimulus method. These findings suggest that the brain processes frequency increments and decrements in different ways. The results also suggest the use of same-stimulus method for the calculation of duration MMN when long duration stimuli are used.     

Age and inter-stimulus interval effects on event-related potentials to frequent and infrequent auditory stimuli.

The aim of this study was to investigate aging effects on non-attended changes of auditory stimulation, by using psychophysiological methods. Event-related potentials (ERPs) were recorded to frequent (standard; 950 Hz, p = 0.9) and infrequent (deviant; 1045 Hz, p = 0.1) auditory stimuli in older (mean age = 60.8 years) and younger (mean age = 21.3 years) subjects. In various blocks the inter-stimulus interval (ISI) was either 800, 2400 or 7200 ms. During the experimental sessions the subjects read books, and ignored the auditory stimuli. As a function of ISI, the amplitude of the N1 and the amplitude and latency of the P2 increased. The P2 amplitude was larger in the younger group. In the 120-180 ms latency range the deviant stimuli elicited more negative ERPs (mismatch negativity, MMN) than the standard stimuli. The amplitude of the MMN did not change as a function of ISI. MMN was larger in the younger group. Thus the younger subjects were more sensitive to the deviant stimuli. In the younger group, at the two shorter ISIs, the MMN was followed by a positive wave (P3a). The emergence of this component is an indication of the increased activity of the orienting system in the younger subjects, in comparison to the older age group.     

Auditory streaming affects the processing of successive deviant and standard sounds

This study investigated the temporal relation between two early mechanisms of auditory information processing: the segregation of the auditory input into streams and the automatic deviance detection indicated by the mismatch negativity (MMN). To address this question the processing of successive deviant and standard tones within streaming and nonstreaming conditions was analyzed. In the streaming condition the amplitude reduction of MMN elicited by the second of two successive deviants was found to be smaller for successive deviants presented in different than in same streams. No corresponding MMN differences were obtained in a nonstreaming condition. These results demonstrate that stream segregation precedes deviance detection. Moreover, modulations of the N1 amplitudes elicited by successive standard tones in the streaming condition demonstrate that not only deviance-related processing but even initial sound processing is affected by streaming.     

Abnormal frequency discrimination in children with SLI as indexed by mismatch negativity (MMN)

For several decades, the aetiology of specific language impairment (SLI) has been associated with a central auditory processing deficit disrupting the normal language development of affected children. One important aspect for language acquisition is the discrimination of different acoustic features, such as frequency information. Concerning SLI, studies to date that examined frequency discrimination abilities have been contradictory. We hypothesized that an auditory processing deficit in children with SLI depends on the frequency range and the difference between the tones used. Using a passive mismatch negativity (MMN)-design, 13 boys with SLI and 13 age- and IQ-matched controls (7-11 years) were tested with two sine tones of different frequency (700Hz versus 750Hz). Reversed hemispheric activity between groups indicated abnormal processing in SLI. In a second time window, MMN2 was absent for the children with SLI. It can therefore be assumed that a frequency discrimination deficit in children with SLI becomes particularly apparent for tones below 750Hz and for a frequency difference of 50Hz. This finding may have important implications for future research and integration of various research approaches.     

Visual emotional context modulates brain potentials elicited by unattended tones.

To examine whether brain electrical responses to environmental stimuli were influenced by emotional contexts, event-related potentials (ERPs) elicited by nonstartle probe tones were recorded from 13 student volunteers while they were viewing emotionally positive, neutral, and negative slides of the International Affective Picture System. The auditory stimuli consisted of high-deviant (2000 Hz, p=.08), low-deviant (1050 Hz, p=.08), and standard (1000 Hz, p=.84) tones with a mean onset-to-onset interval of 600 ms. Participants were told to ignore the tones. High-deviant tones elicited a larger N1 (peaking around 100 ms) when participants were viewing negative slides than when viewing positive slides. The amplitude of the P2 elicited by standard tones (peaking around 170 ms) was smaller when participants were viewing positive slides than when viewing negative and neutral slides. The amplitude of the mismatch negativity (150-200 ms) tended to reduce during positive slide presentation, but this difference appeared to be due to reduction of the P2 elicited by standard tones. These findings suggest that visually induced emotional states have a sequential effect on auditory information processing, in that the influence of negative emotion appears at an earlier stage than that of positive emotion.     

Psychosocial stress attenuates general sound processing and duration change detection

An EEG-compatible adaptation of the Trier Social Stress Test was developed to induce psychosocial stress in healthy subjects while investigating their auditory processing of unattended sounds and salivary levels of the stress hormone cortisol. The mismatch negativity (MMN) and N1/P2 were assessed using a multifeature paradigm, while subjects were attending to visual tasks with high or low attentional workload. Only the responses to duration change were affected by the stress manipulation. Cortisol levels during stress were inversely related to the MMN amplitudes of duration deviants. During anticipatory stress, responses to the standard tones (general sound processing) increased, but their amplitude was not correlated with cortisol levels. We found that psychosocial stressor anticipation attenuates both general and deviance-specific sound processing, suggesting that cortisol interferes with cortical memory-trace formation.     

Processing of auditory stimuli during auditory and visual attention as revealed by event-related potentials

Auditory event-related brain potentials (ERPs) were recorded during auditory and visual selective attention tasks. Auditory stimuli consisted of frequent standard tones (1000 Hz) and infrequent deviant tones (1050 Hz and 1300 Hz) delivered randomly to the left and right ears. Visual stimuli were vertical line gratings randomly presented on a video monitor at mean intervals of 6 s. During auditory attention, the subject attended to the stimuli in a designated ear and responded to the 1300-Hz deviants occurring among the attended tones. During visual attention, the subject responded to the occasional visual stimuli. ERPs for tones delivered to the attended ear were negatively displaced relative to ERPs elicited by tones delivered to the unattended ear and to ERPs elicited by auditory stimuli during visual attention. This attention effect consisted of negative difference waves with early and late components. Mismatch negativities (MMNs) were elicited by 1300-Hz and 1050-Hz deviants irrespective of whether they occurred among attended or unattended tones. MMN amplitudes were unaffected by attention, supporting the proposal that the MMN is generated by an automatic cerebral discrimination process.     

The auditory evoked magnetic fields to very high frequency tones

We studied the auditory evoked magnetic fields (AEFs) in response to pure tones especially at very high frequencies (from 4000 Hz to 40,000 Hz). This is the first systematic study of AEFs using tones above 5000 Hz, the upper audible range of humans, and ultrasound. We performed two experiments. In the first, AEFs were recorded in 12 subjects from both hemispheres under binaural listening conditions. Six types of auditory stimulus (pure tones of five different frequencies: 4000 Hz, 8000 Hz, 10,000 Hz, 12,000 Hz, 14,000 Hz, and a click sound as the target stimulus) were used. In the second experiment, we used 1000 Hz, 15,000 Hz, and two ultrasounds with frequencies of 20,000 Hz and 40,000 Hz. The subjects could detect all stimuli in the first experiment but not the ultrasounds in the second experiment.We analyzed N1m, the main response with approximately 100 ms in peak latency, and made the following findings. (1) N1m responses to the tones up to 12,000 Hz were clearly recorded from at least one hemisphere in all 12 subjects. N1m for 14,000 Hz was identified in at least one hemisphere in 10 subjects, and in both hemispheres in six subjects. No significant response could be identified to ultrasounds over 20,000 Hz. (2) The amplitude of the N1m to the tones above 8000 Hz was significantly smaller than that to 4000 Hz in both hemispheres. There was a tendency for the peak latency of the N1m to be longer for the tones with higher frequencies, but no significant change was found. (3) The equivalent current dipole (ECD) of the N1m was located in the auditory cortex. There was a tendency for the ECD for the tones with higher frequencies to lie in more medial and posterior areas, but no significant change was found. (4) As for the interhemispheric difference, the N1m amplitude for all frequency tones was significantly larger and the ECDs were estimated to be located more anterior and medial in the right hemisphere than the left. The priority of the right hemisphere, that is the larger amplitude, for very high frequency tones was confirmed. (5) The orientation of the ECD in the left hemisphere became significantly more vertical the higher the tones. This result was consistent with previous studies which revealed the sensitivity of the frequency difference in the left hemisphere.From these findings we suggest that tonotopy in the auditory cortex exists up to the upper limit of audible range within the small area, where the directly air-conducted ultrasounds are not reflected.     

Processing of novel sounds and frequency changes in the human auditory cortex: Magnetoencephalographic recordings

Whole-head magnetoencephalographic (MEG) responses to repeating standard tones and to infrequent slightly higher deviant tones and complex novel sounds were recorded together with event-related brain potentials (ERPs). Deviant tones and novel sounds elicited the mismatch negativity (MMN) component of the ERP and its MEG counterpart (MMNm) both when the auditory stimuli were attended to and when they were ignored. MMNm generators were located bilateral to the superior planes of the temporal lobes where preattentive auditory discrimination appears to occur. A subsequent positive P3a component was elicited by deviant tones and with a larger amplitude by novel sounds even when the sounds were to be ignored. Source localization for the MEG counterpart of P3a (P3am) suggested that the auditory cortex in the superior temporal plane is involved in the neural network of involuntary attention switching to changes in the acoustic environment.     

Deficits in automatically detecting changes in conjunction of auditory features in patients with schizophrenia

Disturbances in processing simple acoustic changes in a stream of stimuli have been widely reported in patients with schizophrenia, but little is know about auditory feature conjunction in these individuals. This study was designed to examine the extent to which patients with schizophrenia automatically process changes in conjunction of auditory features by using event-related brain potentials. Seventeen patients and 17 age-matched controls were presented with frequent low pitch tones at 45 degrees to the left of center and frequent high pitch tones at 45 degrees to the right of center while performing a continuous visual serial-choice reaction time task. The sequence of auditory stimuli included rare conjunction-deviants comprised of a different combination of features (e.g., low pitch tone at 45 degrees right) and double-deviant tones that differed from the standard tones in both pitch and location (i.e., middle pitch at 0 degrees azimuth). Conjunction-deviant stimuli elicited an MMN wave that was maximum at frontocentral sites. Compared with controls, the MMN to conjunction-deviant was reduced in patients and was more centrally distributed. Double-deviant sounds generated a biphasic MMN followed by a P3a wave at central sites. Both MMN and P3a were reduced in patients compared with controls. These results show that patients with schizophrenia have difficulty in automatically detecting changes in a combination of auditory features as well as orienting to what "normally" would be considered salient by healthy individuals.     

Does mismatch negativity show differences in reading-disabled children compared to normal children and children with attention deficit?

An auditory event-related potential (ERP) component called mismatch negativity (MMN) was examined in three groups of children (n = 63) aged 8-14 years. A control group comprised healthy children in second or sixth grade of comprehensive school (n = 21). The two clinical groups included children with reading disability (RD) (n = 21) and children with attention deficit (AD) (n = 21). MMN was elicited in a passive oddball paradigm by duration changes in a continuous sound, consisting of two alternating (600 and 800 Hz) 100 msec tones. The deviant tones were either 30 or 50 msec in duration. Both deviants elicited a clear MMN in all groups. Statistical analyses showed no systematic difference in the MMN peak latencies or amplitudes between the groups. A significant difference between the RD group and the control group was observed in the lateralization of the MMN peak amplitudes.     

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.     

The processing of sound duration after left hemisphere stroke: Event-related potential and behavioral evidence

The ability of left-hemisphere stroke patients ( n = 8) and healthy control subjects ( n = 8) to process sounds preattentively and attentively was studied by recording auditory event-related potentials (ERPs) and behavioral responses. For the right-ear stimulation, the mismatch negativity (MMN) was significantly smaller in the patients than control subjects over both hemispheres. For the left-ear stimuli, the MMN was significantly smaller in the patient group than in the control group over the left hemisphere, whereas no group differences were obtained over the right hemisphere. In addition, the N1 amplitude was reduced bilaterally for the right-ear stimulation (with the reduction being larger over the left hemisphere), whereas no significant effects on the N1 amplitude were found for the left-ear stimulation. Behaviorally, the patients detected significantly fewer deviant tones than did the control subjects irrespective of the stimulated ear. The present results thus suggest that the long-latency ERPs can be used to probe such auditory processing deficits that are difficult to define with behavioral measures. Especially by recording MMN to monaural stimuli, the discrimination accuracy can be separately determined for the left and right temporal lobes.