A Beamformer Analysis of MEG Data Reveals Frontal Generators of the Musically Elicited Mismatch Negativity

To localize the neural generators of the musically elicited mismatch negativity with high temporal resolution we conducted a beamformer analysis (Synthetic Aperture Magnetometry, SAM) on magnetoencephalography (MEG) data from a previous musical mismatch study. The stimuli consisted of a six-tone melodic sequence comprising broken chords in C- and G-major. The musical sequence was presented within an oddball paradigm in which the last tone was lowered occasionally (20%) by a minor third. The beamforming analysis revealed significant right hemispheric neural activation in the superior temporal (STC), inferior frontal (IFC), superior frontal (SFC) and orbitofrontal (OFC) cortices within a time window of 100–200 ms after the occurrence of a deviant tone. IFC and SFC activation was also observed in the left hemisphere. The pronounced early right inferior frontal activation of the auditory mismatch negativity has not been shown in MEG studies so far. The activation in STC and IFC is consistent with earlier electroencephalography (EEG), optical imaging and functional magnetic resonance imaging (fMRI) studies that reveal the auditory and inferior frontal cortices as main generators of the auditory MMN. The observed right hemispheric IFC is also in line with some previous music studies showing similar activation patterns after harmonic syntactic violations. The results demonstrate that a deviant tone within a musical sequence recruits immediately a distributed neural network in frontal and prefrontal areas suggesting that top-down processes are involved when expectation violation occurs within well-known stimuli.     

Mismatch negativity (MMN) for sequences of auditory and visual stimuli: evidence for a mechanism specific to the auditory modality

ERPs to sequences of standard and deviant sinusoidal 100 msec tone pips, high-contrast sinusoidal gratings and to their simultaneously presented combinations were recorded. Mismatch negativity (MMN), an ERP component elicited by deviant stimuli, was estimated for the different stimulus sequences in order to find out whether it reflects modality-specific processes or non-specific attentive phenomena. In addition to the auditory modality, we studied whether the mismatch response could be evoked by a deviant visual stimulus in a visual sequence or by a deviant stimulus in either modality. The results show that only auditory stimuli produced the mismatch response, suggesting that MMN is not a manifestation of a general attentional mechanism but is probably specific to the auditory modality.     

Impaired mismatch negativity (MMN) generation in schizophrenia as a function of stimulus deviance,probability, and interstimulus/interdeviant interval

Schizophrenia is a severe mental disorder associated with disturbances in perception and cognition. Event-related potentials (ERP) provide a mechanism for evaluating potential mechanisms underlying neurophysiological dysfunction in schizophrenia. Mismatch negativity (MMN) is a short-duration auditory cognitive ERP component that indexes operation of the auditory sensory (`echoic') memory system. Prior studies have demonstrated impaired MMN generation in schizophrenia along with deficits in auditory sensory memory performance. MMN is elicited in an auditory oddball paradigm in which a sequence of repetitive standard tones is interrupted infrequently by a physically deviant (`oddball') stimulus. The present study evaluates MMN generation as a function of deviant stimulus probability, interstimulus interval, interdeviant interval and the degree of pitch separation between the standard and deviant stimuli. The major findings of the present study are first, that MMN amplitude is decreased in schizophrenia across a broad range of stimulus conditions, and second, that the degree of deficit in schizophrenia is largest under conditions when MMN is normally largest. The pattern of deficit observed in schizophrenia differs from the pattern observed in other conditions associated with MMN dysfunction, including Alzheimer's disease, stroke, and alcohol intoxication.     

Frequency Change Detection in Human Auditory Cortex

We offer a model of how human cortex detects changes in the auditory environment. Auditory change detection has recently been the object of intense investigation via the mismatch negativity (MMN). MMN is a preattentive response to sudden changes in stimulation, measured noninvasively in the electroencephalogram (EEG) and the magnetoencephalogram (MEG). It is elicited in the oddball paradigm, where infrequent deviant tones intersperse a series of repetitive standard tones. However, little apart from the participation of tonotopically organized auditory cortex is known about the neural mechanisms underlying change detection and the MMN. In the present study, we investigate how poststimulus inhibition might account for MMN and compare the effects of adaptation with those of lateral inhibition in a model describing tonotopically organized cortex. To test the predictions of our model, we performed MEG and EEG measurements on human subjects and used both small- (<1/3 octave) and large- (>5 octaves) frequency differences between the standard and deviant tones. The experimental results bear out the prediction that MMN is due to both adaptation and lateral inhibition. Finally, we suggest that MMN might serve as a probe of what stimulus features are mapped by human auditory cortex.     

Mismatch negativity in the auditory event-related potentials in response to abrupt and smooth displacements of virtual sound source

The work investigated event-related potentials, mismatch negativity (MMN), and P3a component under dichotic stimulation with deviant stimuli simulating abrupt or smooth displacement of auditory images to the left or to the right from the head midline by means of interaural time delay introduced into the deviant stimuli. Repetitive standard stimuli were localized near the head midline. All deviant stimuli elicited mismatch negativity and P3a component. It was shown the MMN for smooth deviant motion was lower than that for the abrupt deviant displacement. MMN amplitude for both deviant types obviously depended on interaural time delay, which confirms that MMN might be considered as a measure of the auditory system spatial discriminative ability. The P3a component demonstrated the same amplitude dependences as the MMN. The results obtained are discussed in respect to manifestation of the processes underlying the auditory motion detection in the event-related potentials.     

Fast detection of unexpected sound intensity decrements as revealed by human evoked potentials

The detection of deviant sounds is a crucial function of the auditory system and is reflected by the automatically elicited mismatch negativity (MMN), an auditory evoked potential at 100 to 250 ms from stimulus onset. It has recently been shown that rarely occurring frequency and location deviants in an oddball paradigm trigger a more negative response than standard sounds at very early latencies in the middle latency response of the human auditory evoked potential. This fast and early ability of the auditory system is corroborated by the finding of neurons in the animal auditory cortex and subcortical structures, which restore their adapted responsiveness to standard sounds, when a rare change in a sound feature occurs. In this study, we investigated whether the detection of intensity deviants is also reflected at shorter latencies than those of the MMN. Auditory evoked potentials in response to click sounds were analyzed regarding the auditory brain stem response, the middle latency response (MLR) and the MMN. Rare stimuli with a lower intensity level than standard stimuli elicited (in addition to an MMN) a more negative potential in the MLR at the transition from the Na to the Pa component at circa 24 ms from stimulus onset. This finding, together with the studies about frequency and location changes, suggests that the early automatic detection of deviant sounds in an oddball paradigm is a general property of the auditory system.     

Automatic and effortful processes in auditory memory reflected by event-related potentials. Age-related findings

Mismatch negativity (MMN) and N2b were elicited during a selective dichotic-listening task in 16 young (Y), 16 middle-aged (M) and 19 elderly (E) subjects to evaluate automatic and effortful memory comparison of auditory stimuli. Sequences of standard (80%) and deviant (20%) tones were dichotically presented to subjects in two runs. In each run, subjects were instructed to give a button-press response to the deviant (target) tones in the ear designated as attended and to ignore the input to the other ear.Peak latencies, peak amplitudes and mean amplitudes were calculated for MMN and N2b components in each subject. MMN latency and amplitude were quite stable regardless of age, while N2b latency was significantly longer in M and E subjects than in Y subjects. These results are interpreted as reflecting that automatic processes of comparison in auditory memory of stimuli presented at short interstimulus intervals remain quite stable from 23 to 77 years of age; however, those requiring attentional effort decline with age.     

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. Bioelectromagnetics 30:241–248, 2009. © 2009 Wiley‐Liss, Inc.     

Mismatch negativity to changes in a continuous tone with regularly varying frequencies

By using the mismatch negativity (MMN) component of the event-related potential, it was demonstrated that changes within a repetitively presented tone pattern can be automatically (i.e., involuntarily and attention-independently) detected by the human brain. Patterns consisting of 5 tones, immediately succeeding one another and differing in frequency, were delivered to subjects reading a self-selected book. There was a frequent , “standard” (P = 0.90) and an infrequent, “deviant” (P = 0.10) pattern presented in random order. The deviant pattern elicited the MMN even when the auditory stimulation was continuous, that is, no empty between-pattern interval indicated the beginning of a tone pattern. It may be concluded that the MMN mechanism is not necessarily timed by an “external” reference but is able to use “internal” units extracted from the repetitive structure inherent in the incessant flow of acoustic signals. The MMN paradigm seems to provide a tool to illuminate the organization of acoustic signals into auditory units.     

Allocentric or craniocentric representation of acoustic space: an electrotomography study using mismatch negativity

The world around us appears stable in spite of our constantly moving head, eyes, and body. How this is achieved by our brain is hardly understood and even less so in the auditory domain. Using electroencephalography and the so-called mismatch negativity, we investigated whether auditory space is encoded in an allocentric (referenced to the environment) or craniocentric representation (referenced to the head). Fourteen subjects were presented with noise bursts from loudspeakers in an anechoic environment. Occasionally, subjects were cued to rotate their heads and a deviant sound burst occurred, that deviated from the preceding standard stimulus either in terms of an allocentric or craniocentric frame of reference. We observed a significant mismatch negativity, i.e., a more negative response to deviants with reference to standard stimuli from about 136 to 188 ms after stimulus onset in the craniocentric deviant condition only. Distributed source modeling with sLORETA revealed an involvement of lateral superior temporal gyrus and inferior parietal lobule in the underlying neural processes. These findings suggested a craniocentric, rather than allocentric, representation of auditory space at the level of the mismatch negativity.     

Mismatch negativity of ERP in cross-modal attention

Event-related potentials were measured in 12 healthy youth subjects aged 19-22 using the paradigm "cross-modal and delayed response" which is able to improve unattended purity and to avoid the effect of task target on the deviant components of ERP. The experiment included two conditions: (i) Attend visual modality, ignore auditory modality; (ii) attend auditory modality, ignore visual modality. The stimuli under the two conditions were the same. The difference wave was obtained by subtracting ERPs of the standard stimuli from that of the deviant stim-uli. The present results showed that mismatch negativity (MMN), N2b and P3 components can be produced in the auditory and visual modalities under attention condition. However, only MMN was observed in the two modalities un-der inattention condition. Auditory and visual MMN have some features in common: their largest MMN wave peaks were distributed respectively over their primary sensory projection areas of the scalp under attention condition, but over front     

Fractionating the musical mind: insights from congenital amusia

Music, like language, is acquired effortlessly in early life and fulfils a multitude of social, cultural and emotional functions. However, those with a disorder recently termed 'congenital amusia' (CA) fail to recognise common tunes from their culture, do not hear when notes are 'out of tune' and sometimes report that music sounds like a 'din' or 'banging'. The core deficit appears to be a problem in discriminating pitch direction, a building block for the representation of melodic contour. Familial studies suggest the disorder is heritable and associated with structural differences in temporal and frontal cortices. The disorder provides a window onto the neuro-cognitive architecture of musical processing, and the possible etiologies of disordered development.     

Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families

Tourette disorder (TD) is a neuropsychiatric disorder with a complex mode of inheritance and is characterized by multiple waxing and waning motor and phonic tics. This article reports the results of the largest genetic linkage study yet undertaken for TD. The sample analyzed includes 238 nuclear families yielding 304 "independent" sibling pairs and 18 separate multigenerational families, for a total of 2,040 individuals. A whole-genome screen with the use of 390 microsatellite markers was completed. Analyses were completed using two diagnostic classifications: (1) only individuals with TD were included as affected and (2) individuals with either TD or chronic-tic (CT) disorder were included as affected. Strong evidence of linkage was observed for a region on chromosome 2p (-log P = 4.42, P = 3.8 x 10(-5) in the analyses that included individuals with TD or CT disorder as affected. Results in several other regions also provide moderate evidence (-log P >2.0) of additional susceptibility loci for TD.     

Accumulation of cardiolipin and lysocardiolipin in fibroblasts from Tangier disease subjects

Tangier disease (TD) is an inherited disorder of lipid metabolism characterized by very low high density lipoprotein (HDL) plasma levels, cellular cholesteryl ester accumulation and reduced cholesterol excretion in response to HDL apolipoproteins. Molecular defects in the ATP binding cassette transporter 1 (ABCA1) have recently been identified as the cause of TD. ABCA1 plays a key role in the translocation of cholesterol across the plasma membrane, and defective ABCA1 causes cholesterol storage in TD cells. Not only cholesterol efflux, but also phospholipid efflux was shown to be impaired in TD cells. By use of thin layer chromatography, high performance liquid chromatography and time-of-flight secondary ion mass spectrometry, we characterized the cellular phospholipid content in fibroblasts from three homozygous TD patients. The cellular content of the major phospholipids was not found to be significantly altered in TD fibroblasts. However, the two phospholipids cardiolipin and lysocardiolipin, which make up minute amounts in normal cells, were at least 3–5-fold enriched in fibroblasts from TD subjects. A structurally closely related phospholipid (lysobisphosphatidic acid) has recently been shown to be enriched in Niemann–Pick type C, another lipid storage disorder. Altogether these data may indicate that the role of these phospholipids is a regulatory one rather than that of a bulk mediator of cholesterol solubilization in sterol trafficking and efflux.     

The mismatch negativity for duration decrement of auditory stimuli in healthy subjects

The amplitude and latency of the mismatch negativity (MMN) elicited by occasional shorter-duration tones (25 and 50 ms) in a sequence of 75 ms standard tones were studied in 40 healthy subjects (9–84 years). The replicability and age dependence of the MMN-responses were determined. The 25 ms deviant tone evoked a clear response in 39 of the subjects, while the 50 ms deviant tone evoked an observable MMN only in 32 of the subjects. The MMN peak amplitude for the 25 ms deviants was significantly larger than for the 50 ms deviants. There was no significant difference in the peak latencies (measured from stimulus offset). For the 25 ms deviant, the amplitude diminished with increasing age. The MMN curves for the 25 ms deviant, measured on separate days in 14 subjects, looked very replicable. As a result of noise and filtering effect, the product-moment correlations were poor. The results indicate that the signal-to-noise ratio for the MMN to 25 ms deviants, obtained even in a 25 min recording session, is large enough for clinical use and individual diagnostics when undetectable (or very low amplitude) MMN is used as a sign of pathology. However, judged from the low correlation coefficients, despite the good replicability in visual evaluation, better methods for MMN quantification have to be used for clinical follow-up.     

A mismatch negativity elicited with stationary and moving auditory images of different azimuth positions

Characteristics of mismatch negativity elicited by dichotic stimulation were examined using deviant stimuli simulating movement of fused auditory images towards the standard stimuli or in the reverse direction. The effect of stationary deviants localized at 90 degrees in respect to standards was also measured. The standard stimuli were localized near either of ears or along the head midline. The spatial locations were produced by introducing interaural time differences into the click trains. All deviant stimuli evoked the mismatch negativity. The deviants moving from standards seem to evoke the lowest mismatch negativity with the longest latency at all azimuthal locations of standard stimuli. Besides, the deviant shift from standards proved to be the only direction at which the characteristics of mismatch negativity depended upon the standard's azimuth. It is seems that the discrimination of interaural time delay is essentially dependent on the pattern of interaural delay changes at the moment when the deviant occurs.     

Auditory event-related potentials to deviant stimuli during drowsiness and stage 2 sleep

Twelve subjects were tested using a 3-tone auditory oddball paradigm consisting of a standard 1000 Hz tone (P = 80%) and two deviants, namely, a 1200 Hz tone and a 2000 Hz tone (both P = 10%). Testing took place in 3 conditions: (1) attend, in which the subject had to count one of the deviant tones; (2) ignore, in which the subject read a book; and (3) sleep, in which the subject was encouraged to go to sleep during presentation of the tones.In the awake conditions stimulus deviance elicited mismatch negativity (MMN) and P3. During drowsiness, no separate mismatch negativity (MMN) could be detected, but the 2000 Hz tone evoked a broad fronto-central early negative deflection, suggesting an overlap of N₁ and MMN. In the same condition, P210, N330 and P430 appeared, all being sensitive to magnitude of deviance. During stage 2, the P210, N330 and P430 amplitudes increased, most notably to the large deviant.These data indicate that differential processing of auditory inputs is maintained during drowsiness and stage 2 sleep, but do not support the notion that MMN or P3 activity comparable to the waking state occurs to oddball stimuli during this stage. It is hypothesised that during light sleep, scanning of the environment is performed by a different system than in the awake state and that during drowsiness a gradual switch between these two systems takes place.     

One Digit Interruption: The Altered Force Patterns during Functionally Cylindrical Grasping Tasks in Patients with Trigger Digits

Most trigger digit (TD) patients complain that they have problems using their hand in daily or occupational tasks due to single or multiple digits being affected. Unfortunately, clinicians do not know much about how this disease affects the subtle force coordination among digits during manipulation. Thus, this study examined the differences in force patterns during cylindrical grasp between TD and healthy subjects. Forty-two TD patients with single digit involvement were included and sorted into four groups based on the involved digits, including thumb, index, middle and ring fingers. Twelve healthy subjects volunteered as healthy controls. Two testing tasks, holding and drinking, were performed by natural grasping with minimal forces. The relations between the force of the thumb and each finger were examined by Pearson correlation coefficients. The force amount and contribution of each digit were compared between healthy controls and each TD group by the independent t test. The results showed all TD groups demonstrated altered correlation patterns of the thumb relative to each finger. Larger forces and higher contributions of the index finger were found during holding by patients with index finger involved, and also during drinking by patients with affected thumb and with affected middle finger. Although no triggering symptom occurred during grasping, the patients showed altered force patterns which may be related to the role of the affected digit in natural grasping function. In conclusion, even if only one digit was affected, the subtle force coordination of all the digits was altered during simple tasks among the TD patients. This study provides the information for the future studies to further comprehend the possible injuries secondary to the altered finger coordination and also to adopt suitable treatment strategies.     

The habituation of event-related potentials to speech sounds and tones

We examined the short- and long-term habituation of auditory event-related potentials (ERPs) elicited by tones, complex tones and digitized speech sounds (vowels and consonant-vowel-consonant syllables). Twelve different stimuli equated in loudness and duration (300 msec) were studied. To examine short-term habituation stimuli were presented in trains of 6 with interstimulus intervals of 0.5 or 1.0 sec. The first 4 stimuli in a train were identical standards. On 50% of the trains the standard in the 5th position was replaced by a deviant probe stimulus, and on 20% of the trains the standard in the 6th position was replaced by a target, a truncated standard that required a speeded button press response.Short-term habituation (STH) was complete by the third stimulus in the train and resulted in amplitude decrements of 50–75% for the N1 component. STH was partially stimulus specific in that amplitudes were larger following deviant stimuli in the 5th position than following standards. STH of the N1 was more marked for speech sounds than for loudness-matched tones or complex tones at short ISI. In addition, standard and deviant stimuli that differed in phonetic structure showed more cross-habituation than did tones or complex tones that differed in frequency. This pattern of results suggests that STH is a function of the acoustic resemblance of successive stimuli.The long-term habituation (LTH) of the ERP was studied by comparing amplitudes across balanced 5.25 m stimulus blocks over the course of the experiment. Two types of LTH were observed. The N1 showed stimulus-specific LTH in that N1 amplitudes declined during the presentation of a stimulus, but returned to control levels when a different stimulus was presented in the subsequent condition. In contrast, the P3 elicited by the deviant stimuli showed non-specific LTH, being reduced across successive blocks containing different stimuli. P3s elicited by target stimuli remained stable in amplitude.     

规律短音中极短间隔短音诱发的失匹配负电位

失匹配负电位是听觉事件相关电位的一个成分,它由一系列重复的,同性质的“标准刺激”的物理性质稍有偏离的“偏差刺激”所诱发,在规律性的标准刺激中,偶然的物理性质稍有偏离的刺激,如频率,强度,久度等的些微变化均可诱发ＭＭＮ。偶然地给于时间上“过早出现”的同样刺激,即频率,强度,久度完全相同,只是在规律性的标准刺激中过早地出现的刺激,作为偏差刺激,也可以诱发出ＮＮＭ。本研究在恒定刺激间隔ＩＳＩ＝６００ｍｓ