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.

Sources of non-physiologic noise in simultaneous EEG-fMRI data: a phantom study.

Simultaneous EEG-fMRI studies require an understanding of the noise characteristics of the acquisition environment so that appropriate pre-processing steps may be taken to remove known artifacts from the data stream. Using a phantom approach, we have developed a general methodology for characterizing non-physiologic noise in EEG signal and demonstrate the use of this methodology for a specific MR scanner and EEG data acquisition system configuration. Our results show the δ frequency band is significantly impacted by baseline drift or baseline correction algorithms while the ß and γ bands are impacted by residual gradient artifact and gradient corrections.

Mismatch negativity with visual-only and audiovisual speech.

The functional organization of cortical speech processing is thought to be hierarchical, increasing in complexity and proceeding from primary sensory areas centrifugally. The current study used the mismatch negativity (MMN) obtained with electrophysiology (EEG) to investigate the early latency period of visual speech processing under both visual-only (VO) and audiovisual (AV) conditions. Current density reconstruction (CDR) methods were used to model the cortical MMN generator locations. MMNs were obtained with VO and AV speech stimuli at early latencies (approximately 82-87 ms peak in time waveforms relative to the acoustic onset) and in regions of the right lateral temporal and parietal cortices. Latencies were consistent with bottom-up processing of the visible stimuli. We suggest that a visual pathway extracts phonetic cues from visible speech, and that previously reported effects of AV speech in classical early auditory areas, given later reported latencies, could be attributable to modulatory feedback from visual phonetic processing.

Spatiotemporal dynamics of audiovisual speech processing.

The cortical processing of auditory-alone, visual-alone, and audiovisual speech information is temporally and spatially distributed, and functional magnetic resonance imaging (fMRI) cannot adequately resolve its temporal dynamics. In order to investigate a hypothesized spatiotemporal organization for audiovisual speech processing circuits, event-related potentials (ERPs) were recorded using electroencephalography (EEG). Stimuli were congruent audiovisual/ba/, incongruent auditory/ba/synchronized with visual/ga/, auditory-only/ba/, and visual-only/ba/and/ga/. Current density reconstructions (CDRs) of the ERP data were computed across the latency interval of 50-250 ms. The CDRs demonstrated complex spatiotemporal activation patterns that differed across stimulus conditions. The hypothesized circuit that was investigated here comprised initial integration of audiovisual speech by the middle superior temporal sulcus (STS), followed by recruitment of the intraparietal sulcus (IPS), followed by activation of Broca's area [Miller, L.M., d'Esposito, M., 2005. Perceptual fusion and stimulus coincidence in the cross-modal integration of speech. Journal of Neuroscience 25, 5884-5893]. The importance of spatiotemporally sensitive measures in evaluating processing pathways was demonstrated. Results showed, strikingly, early (<100 ms) and simultaneous activations in areas of the supramarginal and angular gyrus (SMG/AG), the IPS, the inferior frontal gyrus, and the dorsolateral prefrontal cortex. Also, emergent left hemisphere SMG/AG activation, not predicted based on the unisensory stimulus conditions was observed at approximately 160 to 220 ms. The STS was neither the earliest nor most prominent activation site, although it is frequently considered the sine qua non of audiovisual speech integration. As discussed here, the relatively late activity of the SMG/AG solely under audiovisual conditions is a possible candidate audiovisual speech integration response.

Neurophysiological indices of attention to speech in children with specific language impairment.

OBJECTIVE: The aim was to determine whether children with specific language impairment (SLI) differed from children with typical language development (TLD) in their allocation of attention to speech sounds. METHODS: Event-related potentials were recorded to non-target speech sounds in two tasks (passive-watch a video and attend to target tones among speech sounds) in two experiments, one using 50-ms duration vowels and the second using 250-ms vowels. The difference in ERPs across tasks was examined in the latency range of the early negative difference wave (Nd) found in adults. Analyses of the data using selected superior and inferior sites were compared to those using electrical field power (i.e., global field power or GFP). The topography of the ERP at the maximum GFP was also examined. RESULTS: A negative difference, comparable to the adult Nd, was observed in the attend compared to the passive task for both types of analysis, suggesting allocation of attentional resources to processing the speech stimuli in the attend task. Children with TLD also showed greater negativity than those with SLI in the passive task for the long vowels, suggesting that they allocated more attentional resources to processing the speech in this task than the SLI group. This effect was only significant using the GFP analysis and was seen as smaller GFP for the TLD than SLI group. The SLI group also showed significantly later latency than the TLD group in reaching the maximum GFP. In addition, a significantly greater proportion of children with SLI compared to those with typical language showed left-greater-than-right frontocentral amplitude at the latency determined from each child's maximum GFP peak. CONCLUSIONS: Children generally showed greater attention to speech sounds when attention is directed to the auditory modality compared to the visual modality. However, children with TLD, unlike SLI, also appear to devote some attentional resources to speech even in a task in which they are instructed to attend to visual information and ignore the speech. SIGNIFICANCE: These findings suggest that children with SLI have limited attentional resources, that they are poorer at dividing attention, or that they are less automatic in allocating resources to speech compared to children with typically developing language skills.

Simultaneous 3-T fMRI and high-density recording of human auditory evoked potentials.

We acquired simultaneous high-field (3 T) functional magnetic resonance imaging (fMRI) and high-density (64- and 128-channel) EEG using a sparse sampling technique to measure auditory cortical activity generated by right ear stimulus presentation. Using dipole source localization, we showed that the anatomical location of the grand mean equivalent dipole of auditory evoked potentials (AEPs) and the center of gravity of fMRI activity were in good agreement in the horizontal plane. However, the grand mean equivalent dipole was located significantly superior in the cortex compared to fMRI activity. Interhemispheric asymmetry was exhibited by fMRI, whereas neither the AEP dipole moments nor the mean global field power (MGFP) of the AEPs showed significant asymmetry. Increasing the number of recording electrodes from 64 to 128 improved the accuracy of the equivalent dipole source localization but decreased the signal-to-noise ratio (SNR) of MR images. This suggests that 64 electrodes may be optimal for use in simultaneous recording of EEG and fMRI.

Subtitled videos and mismatch negativity (MMN) investigations of spoken word processing.

The purpose of this study was to determine whether the presence of subtitles on a distracting, silent video affects the automatic mismatch negativity (MMN) response to simple tones, consonant-vowel (CV) nonwords, or CV words. Two experiments were conducted in this study, each including ten healthy young adult subjects. Experiment 1 investigated the effects of subtitles on the MMN response to simple tones (differing in frequency, duration, and intensity) and speech stimuli (CV nonwords and CV words with a /d/-/g/ contrast). Experiment 2 investigated the effects of subtitles on the MMN response to a variety of CV nonword and word contrasts that incorporated both small (e.g., /d/ vs. /g/) and/or large (e.g., /e:/ vs. /el/) acoustic deviances. The results indicated that the presence or absence of subtitles on the distracting silent video had no effect on the amplitude of the MMN or P3a responses to simple tones, CV nonwords, or CV words. In addition, the results also indicated that movement artifacts may be statistically reduced by the presence of subtitles on a distracting silent video. The implications of these results are that more "engaging" (i.e., subtitled) silent videos can be used as a distraction task for investigations into MMN responses to speech and nonspeech stimuli in young adult subjects, without affecting the amplitude of the responses.

Automatic auditory processing of english words as indexed by the mismatch negativity, using a multiple deviant paradigm.

OBJECTIVE: The aim of this study was to investigate mismatch negativity (MMN) responses to a variety of speech stimuli (/de:/, /ge:/, /deI/ "day", and /geI/ "gay") in a multiple deviant paradigm. It was hypothesized that all speech stimulus contrasts in the multiple deviant paradigm, including the fine acoustic speech contrast [d/g], would elicit robust MMN responses and that consonant vowel (CV) real word deviants (e.g., "day" and "gay") would elicit larger MMN responses than CV nonword deviants (e.g., "de" and "ge") within and across experimental contrasts. DESIGN: Ten healthy, right-handed, native English-speaking adults (23.4 +/- 2.27 yr) with normal hearing were presented with 12 blocks of stimuli, using a multiple deviant oddball paradigm. Each of the four speech stimuli were presented as standards (p = 0.7) in three blocks, with the remaining stimuli acting as deviants (p = 0.1 each). Subjects were also presented with the same stimuli in a behavioral discrimination task. RESULTS: MMN responses to the fine acoustic speech contrast [d/g] (e.g., "de" versus "ge", "day" versus "gay") did not reach significance. However, a significant and larger MMN response was obtained at an earlier latency to the real word deviants among nonword standards with the same initial consonant (i.e., de-->day, ge-->gay) when compared with the responses to nonword deviants among word standards (day-->de, gay-->ge). CONCLUSIONS: The results showed that MMN responses could be elicited by speech stimuli with large, single acoustic deviances, within a multiple deviant paradigm design. This result has positive clinical implications for the testing of subjects who may only tolerate short testing sessions (e.g., pathological populations) in that responses to a wider range of speech stimuli may be recorded without necessarily having to increase session length. The results also demonstrated that MMN responses were elicited by large, single acoustic deviances but not fine acoustic deviances within the speech stimuli. The poor results for the fine acoustic deviances support previous studies that have used single contrast paradigms and found that when carefully controlled methodological designs and strict methods of analysis are applied, robust responses to fine-grained CV syllable contrasts may be difficult to obtain. The enhanced MMN observed in response to the real word deviants among nonword standards may provide further evidence for the presence of long-term neural traces for words in the brain, however possible contextual effects limit the interpretation of these data. Further research is needed to investigate the ability of the MMN response to accurately reflect speech sounds with fine acoustic contrasts, as well as the ability of the MMN to reflect neural traces for words in the brain, before it can be reliably used as a clinical tool in the investigation of spoken word processing in pathological populations.

Processing of English words with fine acoustic contrasts and simple tones: a mismatch negativity study.

The purpose of this study was to compare the robustness of the event-related potential (ERP) response, called the mismatch negativity (MMN), when elicited by simple tone stimuli (differing in frequency, duration, or intensity) and speech stimuli (CV nonword contrast /de:/ vs. /ge:/ and CV word contrast /del/ vs. /gel/). The study was conducted using 30 young adult subjects (Groups A and B; n = 15 each). The speech stimuli were presented to Group A at a stimulus onset asynchrony (SOA) of 610 msec and to Group B at an SOA of 900 msec. The tone stimuli were presented to both groups at an SOA of 610 msec. MMN responses were elicited by the simple tone stimuli (66.7%-96.7% of subjects with MMN "present," or significantly different from zero, p < 0.05) but not the speech stimuli (10% subjects with MMN present for nonwords, 10% for words). The length of the SOA (610 msec or 900 msec) had no effect on the ability to obtain consistent MMN responses to the speech stimuli. The results indicated a lack of robust MMN elicited by speech stimuli with fine acoustic contrasts under carefully controlled methodological conditions. The implications of these results are discussed in relation to conflicting reports in the literature of speech-elicited MMNs, and the importance of appropriate methodological design in MMN studies investigating speech processing in normal and pathological populations.

Differential ear effects of profound unilateral deafness on the adult human central auditory system.

This study investigates the effects of profound acquired unilateral deafness on the adult human central auditory system by analyzing long-latency auditory evoked potentials (AEPs) with dipole source modeling methods. AEPs, elicited by clicks presented to the intact ear in 19 adult subjects with profound unilateral deafness and monaurally to each ear in eight adult normal-hearing controls, were recorded with a 31-channel system. The responses in the 70-210 ms time window, encompassing the N1b/P2 and Ta/Tb components of the AEPs, were modeled by a vertically and a laterally oriented dipole source in each hemisphere. Peak latencies and amplitudes of the major components of the dipole waveforms were measured in the hemispheres ipsilateral and contralateral to the stimulated ear. The normal-hearing subjects showed significant ipsilateral-contralateral latency and amplitude differences, with contralateral source activities that were typically larger and peaked earlier than the ipsilateral activities. In addition, the ipsilateral-contralateral amplitude differences from monaural presentation were similar for left and for right ear stimulation. For unilaterally deaf subjects, the previously reported reduction in ipsilateral-contralateral amplitude differences based on scalp waveforms was also observed in the dipole source waveforms. However, analysis of the source dipole activity demonstrated that the reduced inter-hemispheric amplitude differences were ear dependent. Specifically, these changes were found only in those subjects affected by profound left ear unilateral deafness.

Auditory-evoked potential studies of cortical maturation in normal hearing and implanted children: correlations with changes in structure and speech perception.

Human auditory system maturation as assessed by means of auditory-evoked potential recording is compared to maturation of axon neurofilaments and some critical stages in speech perception. The parallels strongly suggest that the emergence of the N1 component reflects the maturation of the axons in layer II and upper layer III of the auditory cortex. This is also the time period during which the perception of speech in noise and degraded speech markedly improves. The absence of N1 in cochlear implant subjects who have been deaf for a period of at least 3 years below the age of 6 years suggests a critical period in the maturation of the upper cortical layers and potentially poor future performance in the perception of masked and degraded speech.

Maturation of human central auditory system activity: the T-complex.

OBJECTIVE: The purpose of this study was to evaluate and describe the maturation of a set of auditory evoked potentials (AEPs) described as the T-complex from a large group of children, adolescents, and young adults who ranged in age from 5 to 20 years of age. METHODS: The AEPs evoked by brief trains of clicks presented to the left ear were measured at 30 scalp-electrode locations. Analyses focused on age-related latency and amplitude changes in the T-complex recorded at the temporal electrode sites T3 and T5 over the left hemisphere and T4 and T6 over the right hemisphere. The maturation of the T-complex components Na, Ta, and Tb was contrasted with those of the obligatory AEPs P1, N1b, and P2 measured at electrodes C3 and C4. RESULTS: T-complex activity was present in the grand average AEPs of all 14 age groups spanning ages 5-20 years. T-complex components recorded at electrodes T3 and T4 differed in both morphology and maturation rate from those recorded at T5 and T6. In contrast to the prolonged maturation of AEP latency measured at electrodes T5 and T6, the T-complex components measured at electrodes T3 and T4 did not show a significant overall change in peak latency as a function of age. Consistent amplitude and latency correlations were found between the obligatory AEP components P1, N1b and P2 recorded at C3 and C4 and the T-complex components measured at T5 and T6, but not T3 and T4. CONCLUSIONS: Distinct patterns of AEP maturation were measured at electrode sites commonly used to record the T-complex. At scalp electrodes located over more posterior temporal areas (T5 and T6), the AEPs were characterized by a prolonged pattern of maturation very similar to that measured at the central electrodes C3 and C4. These findings and others reported in this paper provide strong evidence that the AEPs recorded at electrodes T5 and T6 are not T-complex peaks. In contrast, the AEPs measured at electrodes T3 and T4 over more anterior temporal scalp areas appear largely independent of activity measured at the central electrode locations. The T-complex peaks Ta and Tb measured at these scalp locations mature early, with no overall significant age-related changes in peak latencies. SIGNIFICANCE: The T-complex is recorded from the temporal electrodes T3 and T4 represents activity of secondary auditory cortex better than, and independent from, midline potentials. Its robust presence in 5-8 year olds supports its potential usefulness in assessing language impairment.

The neurophysiology of auditory perception: from single units to evoked potentials.

Evoked electric potential and magnetic field studies have the immense benefit that they can be conducted in awake, behaving humans and can be directly correlated with aspects of perception. As such, they are powerful objective indicators of perceptual properties. However, given a set of evoked potential and/or evoked field waveforms and their source locations, obtained for an exhaustive set of stimuli and stimulus contrasts, is it possible to determine blindly, i.e. predict, what the stimuli or stimulus contrasts were? If this can be done with some success, then a useful amount of information resides in scalp-recorded activity for, e.g., the study of auditory speech processing. In this review, we compare neural representations based on single-unit and evoked response activity for vowels and consonant-vowel phonemes with distinctions in formant glides and voice onset time. We conclude that temporal aspects of evoked responses can track some of the dominant response features present in single-unit activity. However, N1 morphology does not reliably predict phonetic identification of stimuli varying in voice onset time, and the reported appearance of a double-peak onset response in aggregate recordings from the auditory cortex does not indicate a cortical correlate of the perception of voicelessness. This suggests that temporal aspects of single-unit population activity are likely not inclusive enough for representation of categorical perception boundaries. In contrast to population activity based on single-unit recording, the ability to accurately localize the sources of scalp-evoked activity is one of the bottlenecks in obtaining an accessible neurophysiological substrate of perception. Attaining this is one of the requisites to arrive at the prospect of blind determination of stimuli on the basis of evoked responses. At the current sophistication level of recording and analysis, evoked responses remain in the realm of extremely sensitive objective indicators of stimulus change or stimulus differences. As such, they are signs of perceptual activity, but not comprehensive representations thereof.

Visual speech perception without primary auditory cortex activation.

Speech perception is conventionally thought to be an auditory function, but humans often use their eyes to perceive speech. We investigated whether visual speech perception depends on processing by the primary auditory cortex in hearing adults. In a functional magnetic resonance imaging experiment, a pulse-tone was presented contrasted with gradient noise. During the same session, a silent video of a talker saying isolated words was presented contrasted with a still face. Visual speech activated the superior temporal gyrus anterior, posterior, and lateral to the primary auditory cortex, but not the region of the primary auditory cortex. These results suggest that visual speech perception is not critically dependent on the region of primary auditory cortex.

Maturation of human central auditory system activity: separating auditory evoked potentials by dipole source modeling.

OBJECTIVES: Previous studies have shown that observed patterns of auditory evoked potential (AEP) maturation depend on the scalp location of the recording electrodes. Dipole source modeling incorporates the AEP information recorded at all electrode locations. This should provide a more robust description of auditory system maturation based on age-related changes in AEPs. Thus, the purpose of this study was to evaluate central auditory system maturation based dipole modeling of multi-electrode long-latency AEPs recordings. METHODS: AEPs were recorded at 30 scalp-electrode locations from 118 subjects between 5 and 20 years of age. Regional dipole source analysis, using symmetrically located sources, was used to generate a spatio-temporal source model of age-related changes in AEP latency and magnitude. RESULTS: The regional dipole source model separated the AEPs into distinct groups depending on the orientation of the component dipoles. The sagittally oriented dipole sources contained two AEP peaks, comparable in latency to Pa and Pb of the middle latency response (MLR). Although some magnitude changes were noted, latencies of Pa and Pb showed no evidence of age-related change. The tangentially oriented sources contained activity comparable to P1, N1b, and P2. There were various age-related changes in the latency and magnitude of the AEPs represented in the tangential sources. The radially oriented sources contained activity comparable to the T-complex, including Ta, and Tb, that showed only small latency changes with age. In addition, a long-latency component labeled TP200 was observed. CONCLUSIONS: It is possible to distinguish 3 maturation groups: one group reaching maturity at age 6 and comprising the MLR components Pa and Pb, P2, and the T-complex. A second group that was relatively fast to mature (50%/year) was represented by N2. A third group was characterized by a slower pattern of maturation with a rate of 11-17%/year and included the AEP peaks P1, N1b, and TP200. The observed latency differences combined with the differences in maturation rate indicate that P2 is not identical to TP200. The results also demonstrated the independence of the T-complex components, represented in the radial dipoles, from the P1, N1b, and P2 components, contained in the tangentially oriented dipole sources.