Frontal Mismatch Negativity Research Articles

An observational study of auditory-evoked potential mismatch negativity response in individuals at high genetic risk for schizophrenia

Objectives: This study presents a novel approach by investigating the abnormal mismatch negativity (MMN) found during response to auditory-evoked potential (ERP) in schizophrenia (SZ) patients. Our unique focus is on the genetic high-risk (GHR) for SZ, comparing it with healthy controls (HC). In addition, we aim to illuminate the interrelationship of MMN with socio-occupational functioning in the GHR group, a novel aspect of our research. Material and Methods: We conducted this study with a rigorous methodology, ensuring the reliability and validity of our findings. Thirty first-degree relatives of SZ patients (GHR) who met the inclusion and exclusion criteria were recruited by purposive sampling and compared with thirty HCs. We collected sociodemographic and clinical data from all study participants, which were assessed by the Family Interview of Genetic Studies. GHR was evaluated for current socio-occupation functioning using the Social and Occupational Functioning Assessment Scale (SOFAS). All the participants underwent 128-channel electroencephalographic recording using an auditory-evoked responses paradigm. The MMN was calculated at the frontal electrode clusters, ensuring accurate and reliable data collection. Results: The study revealed a statistically significant difference in frontal MMN latency between GHR and HC. Moreover, a positive relationship was noted between the SOFAS score and MMN amplitude, and a negative relationship was found between the latencies at the frontal region. Conclusion: Our research has made a significant breakthrough in understanding SZ. Our findings reveal that individuals with a genetic susceptibility to SZ exhibit a unique response in a particular test known as MMN. This test measures the automatic auditory change detection mechanism, which detects minor alterations in the acoustic environment and is referred to as MMN. This newfound insight could prove instrumental in developing more effective diagnoses and treatments for SZ.

Mismatch negativity generation in subjects at risk for psychosis: source analysis is more sensitive than surface electrodes in risk prediction.

Deficits of mismatch negativity (MMN) in patients with schizophrenia have been demonstrated many times and there is growing evidence that alterations of MMN already exist in individuals at risk for psychosis. The present study examines differences in MMN between subjects fulfilling ultra-high risk (UHR) or only basic symptoms criteria and it addresses the question, if MMN source analysis can improve prediction of transition to psychosis. The MMN to duration, frequency, and intensity deviants was recorded in 50 healthy controls and 161 individuals at risk for psychosis classified into three subgroups: only basic symptoms (n = 74), only ultra-high risk (n = 13) and persons who fulfill both risk criteria (n = 74). Based on a three-source model of MMN generation, we conducted an MMN source analysis and compared the amplitudes of surface electrodes and sources among the three groups. Significant differences in MMN generation among the four groups were revealed at surface electrodes Cz and C4 (p < 0.05) and at the frontal source (p < 0.001) for duration deviant stimuli. The 15 subjects from the risk groups who subsequently developed a manifest psychosis had a significantly lower MMN amplitude at frontal source (p = 0.019) without showing significant differences at surface electrodes. Low activity at frontal MMN source increased the risk of transition to manifest disease by the factor 3.12 in UHR subjects. MMN activity differed significantly between subjects presenting only basic symptoms and subjects which additionally meet UHR criteria. The largest differences between groups as well as between individuals with and without transition were observed at the frontal source. The present results suggest that source analysis is more sensitive than surface electrodes in psychosis risk prediction by MMN.

The dopamine D2 agonist quinpirole impairs frontal mismatch responses to sound frequency deviations in freely moving rats.

AimA reduced mismatch negativity (MMN) response is a promising electrophysiological endophenotype of schizophrenia that reflects neurocognitive impairment. Dopamine dysfunction is associated with symptoms of schizophrenia. However, whether the dopamine system is involved in MMN impairment remains controversial. In this study, we investigated the effects of the dopamine D2‐like receptor agonist quinpirole on mismatch responses to sound frequency changes in an animal model.MethodsEvent‐related potentials were recorded from electrocorticogram electrodes placed on the auditory and frontal cortices of freely moving rats using a frequency oddball paradigm consisting of ascending and equiprobable (ie, many standards) control sequences before and after the subcutaneous administration of quinpirole. To detect mismatch responses, difference waveforms were obtained by subtracting nondeviant control waveforms from deviant waveforms.ResultsHere, we show the significant effects of quinpirole on frontal mismatch responses to sound frequency deviations in rats. Quinpirole delayed the frontal N18 and P30 mismatch responses and reduced the frontal N55 MMN‐like response, which resulted from the reduction in the N55 amplitude to deviant stimuli. Importantly, the magnitude of the N55 amplitude was negatively correlated with the time of the P30 latency in the difference waveforms. In contrast, quinpirole administration did not clearly affect the temporal mismatch responses recorded from the auditory cortex.ConclusionThese results suggest that the disruption of dopamine D2‐like receptor signaling by quinpirole reduces frontal MMN to sound frequency deviations and that delays in early mismatch responses are involved in this MMN impairment.

Aberrant Frequency Related Change-Detection Activity in Chronic Tinnitus.

Tinnitus is the perception of sound without the occurrence of an acoustic event. The deficit in auditory sensory or echoic memory may be the cause of the perception of tinnitus. This study considered the mismatch negativity (MMN) to investigate the potential difference between and within groups of persons with normal hearing (NH) and tinnitus. Using an auditory multi-feature paradigm to elicit the MMN, this study considered the MMN peak amplitude at two central frequencies for two MMN subcomponents. These central frequencies were 1 and 5 kHz, which the latter was closer to the perceived tinnitus frequency in the group with tinnitus. The deviants were higher frequency, lower frequency, higher intensity, lower intensity, duration, location (left), location (right), and gap. The pure tone audiometry (PTA) test and distortion product otoacoustic emissions (DPOAE) test showed no meaningful difference between the two groups. For the frontal subcomponent, the mean amplitudes of the MMN peak for the two groups illustrated less negative meaningful MMN peak amplitudes in the group of persons with tinnitus. For the supratemporal component at 5 kHz central frequency, amplitudes were lower for the group of persons with tinnitus, whereas for the central frequency of 1 kHz, most deviants exhibited meaningful differences. Additionally, within-group comparisons indicated that mean amplitudes for both groups were more negative at the central frequency of 1 kHz for the frontal MMN subcomponent. In comparison, the supratemporal component illustrated a lower peak amplitude at 5 kHz central frequency in the group of persons with tinnitus and no difference in the NH group, which is a unique observation of this study. Results of the between-groups are in accordance with previous studies and within-group comparisons consider the probability of decreasing the change detection capability of the brain. The results of this study indicate that increasing the frequency of the stimuli close to the tinnitus perceived frequencies decreases the prediction error, including the prediction error of the silence. Such a decrease may cause the prediction error of the spontaneous neural activity in the auditory pathway to exceed the silence prediction error, and as a result, increases the probability of occurrence of tinnitus in higher frequencies according to the predictive coding model.

Neurologic Characterization of Craniosynostosis: Can Direct Brain Recordings Predict Language Development?

Nonsyndromic craniosynostosis (NSC) is associated with language deficits. Conventional tests, such as the Bayley Scales of Infant Development (BSID), may not reflect accurate long-term cognition. Alternatively, mismatch negativity (MMN) waves recorded via electroencephalogram (EEG) measure neural responses to speech and may objectively predict language development. This study aimed to (1) correlate infant MMN to future language achievement and (2) compare MMN among subtypes of NSC. Pre and postoperatively (mean operative age 9.5 months), NSC participants received the BSID and EEG phoneme-discrimination paradigm(80 dB,250 Hz). The MMN was the largest negative amplitude in the difference wave 80 to 300 ms after stimuli. To measure cognitive outcome, patients completed a neurodevelopmental battery (Wechsler-Abbreviated Scale of Intelligence and Wechsler-Fundamentals) at >6 years of age. Eleven NSC patients with EEG testing in infancy were neurocognitively tested (average age 8.0 years; 27% female; 55% sagittal, 27% metopic, 9% unicoronal, 9% sagittal/metopic). The left frontal cluster MMN strongly correlated with word-reading (r = 0.713, P = 0.031), reading-comprehension (r = 0.745, P = 0.021), and language-composites (r = 0.0771, P = 0.015). Conversely, BSID scores did not yield significant predictive value (r < 0.5, P > 0.05). Follow-up event related potentials (ERP) comparison included 39 normal control, 18 sagittal, 17 metopic, 6 unilateral-coronal infants. Preoperatively, sagittal (P = 0.003) and metopic (P = 0.003) patients had attenuated left frontal MMN compared to controls. Postoperatively, the sagittal cohort was normalized to controls while metopic patients retained attenuations (P = 0.041). ERP assessment in NSC had significantly better predictive value for future neurocognition than the BSID. Preoperatively, sagittal and metopic patients had attenuated neural response to language; postoperatively, sagittal patients had improved responses in comparison to metopic patients. Use of ERP assessment may help tailor treatment for language deficits earlier in development.

Elucidating the glutamatergic processes underlying mismatch negativity deficits in early stage bipolar disorder and schizophrenia: A combined 1H-MRS and EEG study

Impairments in mismatch negativity (MMN) in schizophrenia are well-established; these findings have been extended to show impairments at early illness stages and in bipolar disorder. A substantial literature supports MMN as an index of NMDA receptor output, however, few studies have conducted in vivo assessments to elucidate the neurochemical underpinnings of MMN. Sixty young (16–33 years) participants with bipolar disorder (n = 47) or schizophrenia (n = 13) underwent 1H-MRS and MMN assessment. Glutamate over creatine (Glu/Cr) levels in the anterior cingulate cortex (ACC) and hippocampus were determined and MMN was measured frontally and temporally. Correlational analyses assessed the relationship between MMN amplitudes and Glu/Cr. Any significant relationships were assessed for specificity with a follow up correlation analysis of MMN and n-acetyleaspartate (NAA/Cr). No associations between frontal or temporal MMN and ACC or hippocampal Glu/Cr were noted in the bipolar group. In the schizophrenia group, frontal and right temporal MMN amplitudes corresponded with increased ACC Glu/Cr at the trend-level. Right temporal MMN was similarly significantly associated with NAA/Cr. MMN was not associated with hippocampal Glu/Cr. This work provides in vivo evidence that glutamatergic processes may underlie MMN generation in early stage schizophrenia but not in early stage bipolar disorder suggesting differences in the MMN mechanism in these groups. The negative association between ACC Glu/Cr and MMN is consistent with findings of reduced MMN and increased in vivo glutamatergic neurometabolite levels in early stage schizophrenia. Furthermore, these results indicate that examining in vivo NAA/Cr may have provide additional insights into the MMN mechanism in schizophrenia.

Pre-attentive Mismatch Response and Involuntary Attention Switching to a Deviance in an Earlier-Than-Usual Auditory Stimulus: An ERP Study.

An acoustic stimulus elicits an electroencephalographic response called auditory event-related potential (ERP). When some members of a stream of standard auditory stimuli are replaced randomly by a deviant stimulus and this stream is presented to a subject who ignores the stimuli, two different ERPs to deviant and standard stimuli are recorded. If the ERP to standard stimuli is subtracted from the ERP to deviant stimuli, the difference potential (DP) waveform typically exhibits a series of negative-positive-negative deflections called mismatch negativity (MMN), P3a, and reorienting negativity (RON), which are associated with pre-attentive change detection, involuntary attention switching, and reorienting of attention, respectively. The aim of the present study was to investigate how these pre-attentive processes are affected if the change occurs earlier than its usual timing implied by isochronous standard stimuli. In the MMN paradigm employed, 15% of the standards were randomly replaced by deviant stimuli which differed either in their pitch, their earlier onset time, or in both. Event-related responses to these three deviants [timely pitch change (RTP), earlier onset (REO), earlier pitch change (REP)] and to standards (RS) were recorded from 10 reading subjects. To maintain identical stimulation histories for the responses subtracted from each other, “deviant-standard” difference potentials (DP) for “timely” and “early” pitch deviances were derived as follows: DPTP = RTP − RS and DPEP = REP − REO. Interestingly, the MMN components of the DPs to timely and early pitch deviances had similar amplitudes, indicating that regularity of stimulus timing does not provide any benefit for the pre-attentive auditory change detection mechanism. However, different scalp current density (SCD) dynamics of the MMN/P3a complexes, elicited by timely and early pitch deviances, suggested that an auditory change in a stimulus occurring earlier-than-usual initiates a faster and more effective call-for-attention and causes stronger attention switching than a timely change. SCD results also indicated that the temporal, frontal, and parietal MMN components are simultaneously present rather than emerging sequentially in time, supporting the MMN models based on parallel deviance processing in the respective cortices. Similarity of the RONs to timely and early pitch deviances indicated that reorienting of attention is of the same strength in two cases.

Inferior frontal cortex as a key generator of mismatch negativity: a repetitive transcranial magnetic stimulation study

Background: Auditory mismatch negativity (MMN) measured by electroencephalography is widely utilized in neuroscience research and is considered a robust biomarker of schizophrenia. Electroencephalography and magnetoencephalography source localization and functional magnetic resonance imaging studies consistently recognized superior temporal cortex as a main generator of MMN. A second frontal generator was reported by several studies as well, but the results were inconsistent. In this study, we examined the causal relationship of inferior frontal region and MMN by using repetitive transcranial magnetic stimulation (rTMS).

One Way or Another: Evidence for Perceptual Asymmetry in Pre-attentive Learning of Non-native Contrasts.

Research investigating listeners’ neural sensitivity to speech sounds has largely focused on segmental features. We examined Australian English listeners’ perception and learning of a supra-segmental feature, pitch direction in a non-native tonal contrast, using a passive oddball paradigm and electroencephalography. The stimuli were two contours generated from naturally produced high-level and high-falling tones in Mandarin Chinese, differing only in pitch direction (Liu and Kager, 2014). While both contours had similar pitch onsets, the pitch offset of the falling contour was lower than that of the level one. The contrast was presented in two orientations (standard and deviant reversed) and tested in two blocks with the order of block presentation counterbalanced. Mismatch negativity (MMN) responses showed that listeners discriminated the non-native tonal contrast only in the second block, reflecting indications of learning through exposure during the first block. In addition, listeners showed a later MMN peak for their second block of test relative to listeners who did the same block first, suggesting linguistic (as opposed to acoustic) processing or a misapplication of perceptual strategies from the first to the second block. The results also showed a perceptual asymmetry for change in pitch direction: listeners who encountered a falling tone deviant in the first block had larger frontal MMN amplitudes than listeners who encountered a level tone deviant in the first block. The implications of our findings for second language speech and the developmental trajectory for tone perception are discussed.

Influence of mental workload on detecting information varieties revealed by mismatch negativity during flight simulation

Behavioral and physiological measures indexed by frontal mismatch negativity (MMN), temporal MMN and eye blink rate derived from electrooculogram (EOG) were used to assess the mental workload related to flight simulation tasks. A total of 14 healthy flying cadets carried out flight simulation tasks under high and low mental workload conditions respectively. The mental workload conditions were manipulated by the complexity of abnormal attitude identification task presented on the head-up display (HUD) during the cruise phase. In this experiment, the increasing mental workload was associated with decreased accuracy rate of detecting abnormal information and longer reaction time. The frontal MMN was enhanced under the high mental workload condition whereas the temporal MMN was decreased, reflecting different information processing mechanisms. In addition, the eye blink rate, an additional assessment of mental workload, also showed high sensitivity and decreased significantly with the increase of mental workload. These results suggested that high mental workload might influence operator's pre-attentive change detection.

Is There an Association Between Mismatch Negativity and Cortical Thickness in Schizophrenia Patients?

Mismatch negativity (MMN) is thought to reflect preattentive, automatic auditory processing. Reduced MMN amplitude is among the most robust findings in schizophrenia research. MMN generators have been shown to be located in the temporal and frontal cortices, which are key areas in the pathophysiology of schizophrenia. This study investigated whether frontotemporal cortical thickness was associated with reduced MMN current source density (CSD) strength in patients with schizophrenia. Sixteen schizophrenia patients and 18 healthy controls (HCs) were examined using magnetoencephalography while they performed a passive auditory oddball paradigm. All participants underwent a T1 structural magnetic resonance imaging scan in a separate session. We evaluated MMN CSD and cortical thickness, and their associations, in the superior and transverse temporal gyri, as well as in the inferior and middle frontal gyri. Patients exhibited significantly reduced CSD strength in all temporal and frontal areas of interest relative to HCs. There was a positive correlation between CSD strength and cortical thickness in both temporal and frontal areas in HCs. However, schizophrenia patients showed negative correlations between CSD strength and cortical thickness in the bilateral inferior frontal gyri. Additionally, we found positive correlations between frontal cortical thickness and negative and total scores on the Positive and Negative Syndrome Scale (PANSS). Our findings provide evidence for deficient temporal and frontal MMN generators and a disruption of normal structure-function relationship in patients with schizophrenia.

Mismatch negativity: Alterations in adults from the general population who report subclinical psychotic symptoms

BackgroundDeficits of mismatch negativity (MMN) in schizophrenia and individuals at risk for psychosis have been replicated many times. Several studies have also demonstrated the occurrence of subclinical psychotic symptoms within the general population. However, none has yet investigated MMN in individuals from the general population who report subclinical psychotic symptoms. MethodsThe MMN to duration-, frequency-, and intensity deviants was recorded in 217 nonclinical individuals classified into a control group (n=72) and three subclinical groups: paranoid (n=44), psychotic (n=51), and mixed paranoid-psychotic (n=50). Amplitudes of MMN at frontocentral electrodes were referenced to average. Based on a three-source model of MMN generation, we conducted an MMN source analysis and compared the amplitudes of surface electrodes and sources among groups. ResultsWe found no significant differences in MMN amplitudes of surface electrodes. However, significant differences in MMN generation among the four groups were revealed at the frontal source for duration-deviant stimuli (P=0.01). We also detected a trend-level difference (P=0.05) in MMN activity among those groups for frequency deviants at the frontal source. ConclusionsIndividuals from the general population who report psychotic symptoms are a heterogeneous group. However, alterations exist in their frontal MMN activity. This increased activity might be an indicator of more sensitive perception regarding changes in the environment for individuals with subclinical psychotic symptoms.

Background Noise Degrades Central Auditory Processing in Toddlers.

Noise, as an unwanted sound, has become one of modern society's environmental conundrums, and many children are exposed to higher noise levels than previously assumed. However, the effects of background noise on central auditory processing of toddlers, who are still acquiring language skills, have so far not been determined. The authors evaluated the effects of background noise on toddlers' speech-sound processing by recording event-related brain potentials. The hypothesis was that background noise modulates neural speech-sound encoding and degrades speech-sound discrimination. Obligatory P1 and N2 responses for standard syllables and the mismatch negativity (MMN) response for five different syllable deviants presented in a linguistic multifeature paradigm were recorded in silent and background noise conditions. The participants were 18 typically developing 22- to 26-month-old monolingual children with healthy ears. The results showed that the P1 amplitude was smaller and the N2 amplitude larger in the noisy conditions compared with the silent conditions. In the noisy condition, the MMN was absent for the intensity and vowel changes and diminished for the consonant, frequency, and vowel duration changes embedded in speech syllables. Furthermore, the frontal MMN component was attenuated in the noisy condition. However, noise had no effect on P1, N2, or MMN latencies. The results from this study suggest multiple effects of background noise on the central auditory processing of toddlers. It modulates the early stages of sound encoding and dampens neural discrimination vital for accurate speech perception. These results imply that speech processing of toddlers, who may spend long periods of daytime in noisy conditions, is vulnerable to background noise. In noisy conditions, toddlers' neural representations of some speech sounds might be weakened. Thus, special attention should be paid to acoustic conditions and background noise levels in children's daily environments, like day-care centers, to ensure a propitious setting for linguistic development. In addition, the evaluation and improvement of daily listening conditions should be an ordinary part of clinical intervention of children with linguistic problems.

Abnormality of Auditory Mismatch Negativity in Depression and Its Dependence on Stimulus Intensity.

Mismatch negativity (MMN) is thought to reveal several abnormalities of cognitive functioning. Although depression often affects cognitive functioning, previous studies concerning MMN in depressed patients provided conflicting results. In recent reports, it has been suggested that depressed patients may show abnormal auditory response to regular auditory stimuli presented with at a relatively high intensity. We thus recorded acoustic MMN in 16 drug-free patients suffering from moderate depression and in 10 healthy subjects at 2 different stimulus intensities. Differences in MMN latency and amplitude between depressed patients and healthy subjects reached the significance level only for high intensity stimulation, and they were consistent with a dysfunction of frontal MMN subcomponents in depressed patients. This finding suggests that consistent MMN abnormalities can be observed in depressed patients by using high-intensity stimulation; moreover, it supports the hypothesis of disturbances of frontal networks in depression even in early stages of disease.

Decoding of Single Auditory Features Investigated by Mismatch Negativity

Event Abstract Back to Event Decoding of Single Auditory Features Investigated by Mismatch Negativity Melissa Larsen1, 2*, Morten Mørup2, Michelle Rosgaard Birknow3, 4, Elvira Fischer1, 5, William Baaré1, Thomas Werge5 and Hartwig Siebner6, 7 1 Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Danish Research Centre for Magnetic Resonance, Denmark 2 Technical University of Denmark, DTU Compute, Denmark 3 H. Lundbeck A/S, Synaptic Transmission 2, Denmark 4 University of Copenhagen , Department of Neurology, Psychiatry and Sensory Sciences, Denmark 5 Mental Health Centre Sct. Hans Copenhagen University Hospital, Research Institute of Biological Psychiatry, Denmark 6 Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Danish Research Centre for Magnetic Resonance, Denmark 7 Bispebjerg Hospital, University of Copenhagen, Department of Neurology, Denmark A fundamental task our brain successfully masters on a daily basis is to detect unexpected changes in our environment. This process can be studied electrophysiologically with electroencephalography (EEG) by measuring the event related response to auditory irregularities in a stream of standard tones. Such irregularities give rise to the so-called mismatch negativity (MMN), an evoked fronto-central response emerging 100 - 150 ms after onset of an oddball stimulus (R. Naatanen et. al 2007). Previous studies used a classical oddball paradigm to test up to five different deviant types within one paradigm, but failed to investigate the memory trace effect for each of the different oddballs and how this leads to the prediction of sensory changes. Here we propose a multiplex MMN roving paradigm, independently introducing pitch and duration deviants, which then become the new standard within their domain, pitch and duration respectively. This paradigm evokes specific responses to distinct auditory changes and allows to characterize the memory trace to single auditory features. We successfully separated the frontal MMN responses to pitch from duration deviants within our multiplex roving paradigm in healthy human subjects. We compared these signals to responses from a pure pitch roving paradigm using a simple parametric comparison between the standards and the deviants. Our results show similar MMN prefrontal responses to pitch in the pure pitch and the multiplex paradigm. This is in line with previous studies on mismatch negativity and predictive coding suggesting prefrontal regions to play a role in integrating bottom-up sensory signals with top-down predictive signals (Rao and Ballard, 1999). Further, our results imply that single auditory features are decoded independently from each other and hence our findings may contribute to the characterization of change detection responses in the human cortex. Keywords: EEG, predictive coding, auditory processing, MMN, change detection Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Sensation and Perception Citation: Larsen M, Mørup M, Rosgaard Birknow M, Fischer E, Baaré W, Werge T and Siebner H (2015). Decoding of Single Auditory Features Investigated by Mismatch Negativity. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00217 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Ms. Melissa Larsen, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Danish Research Centre for Magnetic Resonance, Hvidovre, Denmark, melissal@drcmr.dk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Melissa Larsen Morten Mørup Michelle Rosgaard Birknow Elvira Fischer William Baaré Thomas Werge Hartwig Siebner Google Melissa Larsen Morten Mørup Michelle Rosgaard Birknow Elvira Fischer William Baaré Thomas Werge Hartwig Siebner Google Scholar Melissa Larsen Morten Mørup Michelle Rosgaard Birknow Elvira Fischer William Baaré Thomas Werge Hartwig Siebner PubMed Melissa Larsen Morten Mørup Michelle Rosgaard Birknow Elvira Fischer William Baaré Thomas Werge Hartwig Siebner Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Mismatch negativity in recent-onset and chronic schizophrenia: a current source density analysis.

Mismatch negativity (MMN) is a component of the event-related potential elicited by deviant auditory stimuli. It is presumed to index pre-attentive monitoring of changes in the auditory environment. MMN amplitude is smaller in groups of individuals with schizophrenia compared to healthy controls. We compared duration-deviant MMN in 16 recent-onset and 19 chronic schizophrenia patients versus age- and sex-matched controls. Reduced frontal MMN was found in both patient groups, involved reduced hemispheric asymmetry, and was correlated with Global Assessment of Functioning (GAF) and negative symptom ratings. A cortically-constrained LORETA analysis, incorporating anatomical data from each individual's MRI, was performed to generate a current source density model of the MMN response over time. This model suggested MMN generation within a temporal, parietal and frontal network, which was right hemisphere dominant only in controls. An exploratory analysis revealed reduced CSD in patients in superior and middle temporal cortex, inferior and superior parietal cortex, precuneus, anterior cingulate, and superior and middle frontal cortex. A region of interest (ROI) analysis was performed. For the early phase of the MMN, patients had reduced bilateral temporal and parietal response and no lateralisation in frontal ROIs. For late MMN, patients had reduced bilateral parietal response and no lateralisation in temporal ROIs. In patients, correlations revealed a link between GAF and the MMN response in parietal cortex. In controls, the frontal response onset was 17 ms later than the temporal and parietal response. In patients, onset latency of the MMN response was delayed in secondary, but not primary, auditory cortex. However amplitude reductions were observed in both primary and secondary auditory cortex. These latency delays may indicate relatively intact information processing upstream of the primary auditory cortex, but impaired primary auditory cortex or cortico-cortical or thalamo-cortical communication with higher auditory cortices as a core deficit in schizophrenia.

Longitudinal associations between mismatch negativity and disability in early schizophrenia- and affective-spectrum disorders

Impaired mismatch negativity (MMN) is a robust finding in schizophrenia and, more recently, similar impairments have been reported in other psychotic- and affective-disorders (including at early stages of illness). Although cross-sectional studies have been numerous, there are few longitudinal studies that have explored the predictive value of this event-related potential in relation to clinical/functional outcomes. This study assessed changes in MMN (and the concomitant P3a) amplitude over time and aimed to determine the longitudinal relationship between MMN/P3a and functional outcomes in patients recruited during the early stage of a schizophrenia- or affective-spectrum disorder. Sixty young patients with schizophrenia- and affective-spectrum disorders and 30 healthy controls underwent clinical, neuropsychological and neurophysiological assessment at baseline. Thirty-one patients returned for clinical and neuropsychological follow-up 12-30months later, with 28 of these patients also repeating neurophysiological assessment. On both occasions, MMN/P3a was elicited using a two-tone passive auditory paradigm with duration deviants. Compared with controls, patients showed significantly impaired temporal MMN amplitudes and trend-level deficits in central MMN/P3a amplitudes at baseline. There were no significant differences for MMN measures between the diagnostic groups, whilst the schizophrenia-spectrum group showed reduced P3a amplitudes compared to those with affective-spectrum disorders. For those patients who returned for follow-up, reduced temporal MMN amplitude at baseline was significantly associated with greater levels of occupational disability, and showed trend-level associations with general and social disability at follow-up. Paired t-tests revealed that MMN amplitudes recorded at the central-midline site were significantly reduced in patients over time. Interestingly, those patients who did not return for follow-up showed reduced frontal MMN and fronto-central P3a amplitudes compared to their peers who did return for repeat assessment. This study provides some evidence of the predictive utility of MMN at the early stages of schizophrenia- and affective-spectrum disorders and demonstrated that MMN impairments in such patients may worsen over time. Specifically, we found that young patients with the most impaired MMN amplitudes at baseline showed the most severe levels of disability at follow-up. Furthermore, in the subset of patients with repeat neurophysiological testing, central MMN was further impaired suggestive of neurodegenerative effects. MMN may serve as a neurophysiological biomarker to more accurately predict functional outcomes and prognosis, particularly at the early stages of illness.

Early and late auditory event-related potentials in cognitively high functioning male adolescents with autism spectrum disorder

Event-related potentials (ERP) studies have offered diverging results in characterizing the basic nature of abnormal sensory processing and discrimination in autism spectrum disorders (ASDs). In the present study we report duration mismatch negativity (MMN) and later ERP components (P3a and P3b) derived from auditory odd-ball paradigms in a homogenous sample of cognitively high functioning male adolescents with ASD. We find significantly reduced frontal and temporal MMN amplitudes and no differences in P3a or P3b amplitudes or latencies compared to controls. These findings are in contrast to recent studies reporting enhanced ERP amplitudes to auditory stimuli, and are more in support of a weakened automatic auditory sensory processing as being central to the abnormal auditory behavioral responses commonly encountered in ASD.

Mismatch negativity/P3a complex in young people with psychiatric disorders: a cluster analysis.

BackgroundWe have recently shown that the event-related potential biomarkers, mismatch negativity (MMN) and P3a, are similarly impaired in young patients with schizophrenia- and affective-spectrum psychoses as well as those with bipolar disorder. A data driven approach may help to further elucidate novel patterns of MMN/P3a amplitudes that characterise distinct subgroups in patients with emerging psychiatric disorders.MethodsEighty seven outpatients (16 to 30 years) were assessed: 19 diagnosed with a depressive disorder; 26 with a bipolar disorder; and 42 with a psychotic disorder. The MMN/P3a complex was elicited using a two-tone passive auditory oddball paradigm with duration deviant tones. Hierarchical cluster analysis utilising frontal, central and temporal neurophysiological variables was conducted.ResultsThree clusters were determined: the ‘globally impaired’ cluster (n = 53) displayed reduced frontal and temporal MMN as well as reduced central P3a amplitudes; the ‘largest frontal MMN’ cluster (n = 17) were distinguished by increased frontal MMN amplitudes and the ‘largest temporal MMN’ cluster (n = 17) was characterised by increases in temporal MMN only. Notably, 55% of those in the globally impaired cluster were diagnosed with schizophrenia-spectrum disorder, whereas the three patient subgroups were equally represented in the remaining two clusters. The three cluster-groups did not differ in their current symptomatology; however, the globally impaired cluster was the most neuropsychologically impaired, compared with controls.ConclusionsThese findings suggest that in emerging psychiatric disorders there are distinct MMN/P3a profiles of patient subgroups independent of current symptomatology. Schizophrenia-spectrum patients tended to show the most global impairments in this neurophysiological complex. Two other subgroups of patients were found to have neurophysiological profiles suggestive of quite different neurobiological (and hence, treatment) implications.

Intelligence and Information Processing

The relationship between mental ability (MA, Raven Progressive Matrices) and speed of information processing was examined by recording mismatch negativity (MMN) parameters from 41 women during passive listening to auditory standard and deviant stimuli with backward masking. The intertone interval (ITI) between the offset of the standard or deviant tone and the onset of the masking tone was varied between conditions (25, 50, or 150 ms). Three versions of a trail-making test (Zahlen-Verbindungs-Test, ZVT) were also presented to obtain a behavioral index of information processing speed. Multiple regression analysis showed that the more difficult versions of the ZVT and midline frontal MMN latency at 25-ms ITI were both significant predictors of MA. Across all ITI conditions, the higher ability (HA) group exhibited a shorter MMN latency than the lower ability (LA) group. Finally, the HA group also had a larger MMN amplitude than the LA group for the 25-ms ITI condition. These results indicate that low-level auditory discrimination, indexed by MMN, contributes to individual differences in fluid intelligence. In this regard, MMN provides a valuable tool for examining individual differences in intelligence in individuals who are not able to comply with psychometric testing.