Mismatch Negativity Amplitude Research Articles

Systematic review and meta-analysis of the visual mismatch negativity in schizophrenia.

Mismatch negativity (MMN) is an event-related potential component automatically elicited by events that violate predictions based on prior events. To elicit this component, researchers use stimulus repetition to induce predictions, and the MMN is obtained by subtracting the brain response to rare or unpredicted stimuli from that of frequent stimuli. Under the Predictive Processing framework, one increasingly popular interpretation of the mismatch response postulates that MMN represents a prediction error. In this context, the reduced MMN amplitude to auditory stimuli has been considered a potential biomarker of Schizophrenia, representing a reduced prediction error and the inability to update the mental model of the world based on the sensory signals. It is unclear, however, whether this amplitude reduction is specific for auditory events or if the visual MMN reveals a similar pattern in schizophrenia spectrum disorder. This review and meta-analysis aimed to summarise the available literature on the vMMN in schizophrenia. A systematic literature search resulted in 10 eligible studies that resulted in a combined effect size of g = -.63, CI [-.86, -.41], reflecting lower vMMN amplitudes in patients. These results are in line with the findings in the auditory domain. This component offers certain advantages, such as less susceptibility to overlap with components generated by attentional demands. Future studies should use vMMN to explore abnormalities in the Predictive Processing framework in different stages and groups of the SSD and increase the knowledge in the search for biomarkers in schizophrenia.

Identify Potential Causal Relationships Between Cortical Thickness, Mismatch Negativity, Neurocognition, and Psychosocial Functioning in Drug-Naïve First-Episode Psychosis Patients.

Cortical thickness (CT) alterations, mismatch negativity (MMN) reductions, and cognitive deficits are robust findings in first-episode psychosis (FEP). However, most studies focused on medicated patients, leaving gaps in our understanding of the interrelationships between CT, MMN, neurocognition, and psychosocial functioning in unmedicated FEP. This study aimed to employ multiple mediation analysis to investigate potential pathways among these variables in unmedicated drug-naïve FEP. We enrolled 28 drug-naïve FEP and 34 age and sex-matched healthy controls. Clinical symptoms, neurocognition, psychosocial functioning, auditory duration MMN, and T1 structural magnetic resonance imaging data were collected. We measured CT in the superior temporal gyrus (STG), a primary MMN-generating region. We found a significant negative correlation between MMN amplitude and bilateral CT of STG (CT_STG) in FEP (left: r = -.709, P < .001; right: r = -.612, P = .008). Multiple mediation models revealed that a thinner left STG cortex affected functioning through both direct (24.66%) and indirect effects (75.34%). In contrast, the effects of the right CT_STG on functioning were mainly mediated through MMN and neurocognitive pathways. Bilateral CT_STG showed significant association with MMN, and MMN plays a mediating role between CT and cognition. Both MMN alone and its interaction with cognition mediated the effects of structural alterations on psychosocial function. The decline in overall function in FEP may stem from decreased CT_STG, leading to subsequent MMN deficits and neurocognitive dysfunction. These findings underline the crucial role of MMN in elucidating how subtle structural alterations can impact neurocognition and psychosocial function in FEP.

Effect of Abstract Phonemic Complexity on Mismatch Negativity (MMN) Amplitude.

Mismatch negativity (MMN) reflects a pre-perceptual neurophysiological response that is generated subconsciously due to the interruption of a memory trace of ongoing sensory events in the environment. It has been widely used by researchers to understand complex perceptual mechanisms. Furthermore, it has been recommended as an objective tool to investigate disorders related to auditory cognition in hearing aid and cochlear implant users. Many researchers suggest that utilizing a larger acoustic difference between standard and deviant stimuli within the oddball paradigm will lead to a more robust MMN response. The purpose of the present study is to examine if increasing the abstract phonemic contrast between standard and deviant stimuli in the oddball paradigm leads to a more robust MMN response. Fourteen young female adults participated in the present study. To ensure that the MMN response was elicited by phonemic and not acoustic differences in the stimuli, a one-to-many ratio was created for the abstract phonemic features while controlling the acoustic features when designing the oddball paradigm as described by Phillips et al. (2000). MMN amplitude was measured at the Cz and Fz electrodes in 2 conditions, with 2 trials in each condition. In condition 1, the standards and deviants differed by one distinctive feature: voicing in trial 1 (/tӕ/ was standard and /dӕ/ was deviant), and place of articulation in trial 2 (/bӕ/ was standard and /dӕ/ was deviant). In condition 2, the standards and deviants differed across two distinctive features: voicing and place of articulation. In trial 1, /pӕ/ was standard and /dӕ/ was deviant; in trial 2, /dӕ/ was standard and /pӕ/ was deviant. MMN amplitudes elicited by two distinctive features were significantly larger than MMN amplitudes elicited by one distinctive feature (p<0.001). Trials 1 and 2 in each condition showed no statistical difference, and they were repeatable and highly correlated. Recordings from the Cz and Fz electrodes showed no statistical difference and were highly correlated and similar in morphology. It is known in the literature that increasing acoustic complexity elicits a more robust MMN. The present study showed that this assumption can be extended to abstract phonemic complexity. Increasing the phonemic complexity by utilizing more distinctive features in the oddball paradigm increased the amplitude and robustness of the MMN.

Effect of music integrated phonological awareness program on preschool cochlear implant users

ObjectivesChildren with cochlear implants exhibit lower phonological awareness and sound discrimination skills compared to their normal-hearing peers. However, music training has been shown to have a positive effect on speech discrimination and awareness skills. MethodsOur study included 23 cochlear implant users and 23 normal hearing participants aged 5–6 years with language skills. The aim was to observe the effect of a music-integrated phonological awareness program on cochlear implant users and to compare the phonological awareness skills of children with cochlear implants before and after online training with their normal hearing peers. ResultsResults showed that the trained study group scored higher on the Scale of Early Childhood Phonological Awareness (PASECP) after training than the control group (p < 0.05). In addition, SMRT scores increased between before and after training in the study group, and Mismatch Negativity (MMN) amplitudes increased and latencies decreased as a result of training (p < 0.05). ConclusionsThe study suggests that phonological awareness training integrated with music can effectively improve the phonological awareness skills of children with cochlear implants and has the potential to enable them to achieve phonological awareness levels similar to or even better than their normal hearing peers.

Tracking the habituation of the event-related EEG potential in automatic change detection using an auditory two-tone oddball paradigm.

The mismatch negativity and the P3a of the event-related EEG potential reflect the electrocortical response to a deviant stimulus in a series of stimuli. Although both components have been investigated in various paradigms, these paradigms usually incorporate many repetitions of the same deviant, thus leaving open whether both components vary as a function of the deviant's position in a series of deviant stimuli-i.e. whether they are subject to qualitative/quantitative habituation from one instantiation of a deviant to the next. This is so because the detection of mismatch negativity/P3a in the event-related EEG potential requires an averaging over dozens or hundreds of stimuli, i.e. over many instantiations of the deviant per participant. The present study addresses this research gap. We used a two-tone oddball paradigm implementing only a small number of (deviant) stimuli per participant, but applying it to a large number of participants (n> 230). Our data show that the mismatch negativity amplitude exhibits no decrease as a function of the deviant's position in a series of (standard and) deviant stimuli. Importantly, only after the very first deviant stimulus, a distinct P3a could be detected, indicative of an orienting reaction and an attention shift, and thus documenting a dissociation of mismatch negativity and P3a.

Auditory mismatch negativity in pre-manifest and manifest Huntington’s disease

AimThe aim of this study was to investigate the characteristics of the electrophysiological brain response elicited in a passive acoustic oddball paradigm, i.e. mismatch negativity (MMN), in patients with Huntington’s disease (HD) in the premanifest (pHD) and manifest (mHD) phases. In this regard, we correlated the results of event-related potentials (ERP) with disease characteristics. Methods: This was an observational cross-sectional MMN study. In addition to the MMN recording of the passive oddball task, all subjects with first-degree inheritance for HD underwent genetic testing for mutant HTT, the Huntington’s Disease Rating Scale, the Total Functional Capacity Scale, the Problem Behaviors Assessment short form, and the Mini-Mental State Examination. Results: We found that global field power (GFP) was reduced in the MMN time window in mHD patients compared to pHD and normal controls (NC). In the pHD group, MMN amplitude was only slightly and not significantly increased compared to mHD, while pHD patients showed increased theta coherence between trials compared to mHD. In the entire sample of HD gene carriers, the main MMN traits were not correlated with motor performance, cognitive impairment and functional disability. Conclusion: These results suggest an initial and subtle deterioration of pre-attentive mechanisms in the presymptomatic phase of HD, with an increasing phase shift in the MMN time frame. This result could indicate initial functional changes with a possible compensatory effect. Significance: An initial and slight decrease in MMN associated with increased phase coherence in the corresponding EEG frequencies could indicate an early functional involvement of pre-attentive resources that could precede the clinical expression of HD.

Influence of monaural auditory stimulation combined with music on brain activity.

Recently, the increasing attention to mental states and psychophysical health has fueled the research into methods that can aid in relaxation and recovery. Traditional methods like meditation and sauna, while effective, have their limitations; thus, the need for more accessible and convenient alternatives. Our innovative approach combines monaural beats with music, attempting to replicate the relaxing effects of a sauna in the auditory domain. In comparison to normal music and silent condition, the power of the theta active band significantly increased when listening to our modified music. Furthermore, after listening to modified music, there was a significant increase in mismatch negativity (MMN) amplitude in the oddball task. Additionally, participants' subjective responses to a questionnaire indicated significant changes in body relaxation and other metrics after listening to the processed music. This state is considered similar to the "totonou" state, which manifests in physical and mental feelings of relaxation, pleasure, and mental clarity in the sauna. Thus, the present research proposes a convenient method for achieving relaxation, opening an avenue for individuals to customize their "totonou" music based on personal preferences.

Effects of the cardiac cycle on auditory processing: A preregistered study on mismatch negativity.

The systolic and diastolic phases of the cardiac cycle are known to affect perception and cognition differently. Higher order processing tends to be facilitated at systole, whereas sensory processing of external stimuli tends to be impaired at systole compared to diastole. The current study aims to examine whether the cardiac cycle affects auditory deviance detection, as reflected in the mismatch negativity (MMN) of the event-related brain potential (ERP). We recorded the intensity deviance response to deviant tones (70 dB) presented among standard tones (60 or 80 dB, depending on blocks) and calculated the MMN by subtracting standard ERP waveforms from deviant ERP waveforms. We also assessed intensity-dependent N1 and P2 amplitude changes by subtracting ERPs elicited by soft standard tones (60 dB) from ERPs elicited by loud standard tones (80 dB). These subtraction methods were used to eliminate phase-locked cardiac-related electric artifacts that overlap auditory ERPs. The endogenous MMN was expected to be larger at systole, reflecting the facilitation of memory-based auditory deviance detection, whereas the exogenous N1 and P2 would be smaller at systole, reflecting impaired exteroceptive sensory processing. However, after the elimination of cardiac-related artifacts, there were no significant differences between systole and diastole in any ERP components. The intensity-dependent N1 and P2 amplitude changes were not obvious in either cardiac phase, probably because of the short interstimulus intervals. The lack of a cardiac phase effect on MMN amplitude suggests that preattentive auditory processing may not be affected by bodily signals from the heart.

The accuracy of different mismatch negativity amplitude representations in predicting the levels of consciousness in patients with disorders of consciousness.

The mismatch negativity (MMN) index has been used to evaluate consciousness levels in patients with disorders of consciousness (DoC). Indeed, MMN has been validated for the diagnosis of vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS). In this study, we evaluated the accuracy of different MMN amplitude representations in predicting levels of consciousness. Task-state electroencephalography (EEG) data were obtained from 67 patients with DoC (35 VS and 32 MCS). We performed a microstate analysis of the task-state EEG and used four different representations (the peak amplitude of MMN at electrode Fz (Peak), the average amplitude within a time window -25- 25 ms entered on the latency of peak MMN component (Avg for peak ± 25 ms), the average amplitude of averaged difference wave for 100-250 ms (Avg for 100-250 ms), and the average amplitude difference between the standard stimulus ("S") and the deviant stimulus ("D") at the time corresponding to Microstate 1 (MS1) (Avg for MS1) of the MMN amplitude to predict the levels of consciousness. The results showed that among the four microstates clustered, MS1 showed statistical significance in terms of time proportion during the 100-250 ms period. Our results confirmed the activation patterns of MMN through functional connectivity analysis. Among the four MMN amplitude representations, the microstate-based representation showed the highest accuracy in distinguishing different levels of consciousness in patients with DoC (AUC = 0.89). We discovered a prediction model based on microstate calculation of MMN amplitude can accurately distinguish between MCS and VS states. And the functional connection of the MS1 is consistent with the activation mode of MMN.

The mismatch negativity as an index of cognitive impairment in adults with Down syndrome

AbstractBackgroundPeople with Down syndrome (DS) have a high risk of developing Alzheimer’s disease (AD; Zis and Strydom 2018). The mismatch negativity (MMN) is an event‐related potential that can be used to index cognitive decline (Näätänen et al., 2011). Given its relative independence from attentional processes (Naatanen and Näätänen 1992), the MMN may be particularly useful when studying populations with intellectual disability, who may find sustained attention tasks challenging. We therefore investigated the MMN in people with DS and its association with cognitive abilities.MethodsMMN responses to a passive auditory oddball task were recorded from 27 adults with DS (aged 18 to 59) without any hearing impairments. Associations between MMN and age, as well as memory, language, IQ, and attention scores were examined.ResultsThe MMN was present only in young adults up to the age of 40 and the latency was prolonged. Attenuation of MMN amplitude was associated with poorer memory scores. Finally, longer MMN latencies were associated with increased inter‐individual performance variability and worse performance on memory, verbal, and general IQ tasks.ConclusionOverall, our results indicate that MMN amplitude may be associated with AD‐related memory loss, while increased MMN latency seems to reflect verbal abilities in people with DS. Furthermore, the association between MMN latency and inter‐individual performance variability may suggest the presence of AD‐driven white matter degenerations affecting the brian’s frontal lobe. Therefore, the MMN may represent a valuable tool for studying cognitive abilities and AD pathology in DS.

Mismatch negativity in schizophrenia spectrum and bipolar disorders: Group and sex differences and associations with symptom severity.

Research increasingly implicates glutamatergic dysfunction in the pathophysiologies of psychotic disorders. Auditory mismatch negativity (MMN) is an electroencephalography (EEG) waveform linked to glutamatergic neurotransmission and is consistently attenuated in schizophrenia (SCZ). MMN consists of two subcomponents, the repetition positivity (RP) and deviant negativity (DN) possibly reflecting different neural mechanisms. However, whether MMN reduction is present across different psychotic disorders, linked to distinct symptom clusters, or related to sex remain to be clarified. Four hundred participants including healthy controls (HCs; n=296) and individuals with SCZ (n=39), bipolar disorder (BD) BD typeI (n=35), or BD type II (n=30) underwent a roving MMN paradigm and clinical evaluation. MMN, RP and DN as well their memory traces were recorded at the FCZ electrode. Analyses of variance and linear regression models were used both transdiagnostically and within clinical groups. MMN was reduced in SCZ compared to BD (p=0.006, d=0.55) and to HCs (p<0.001, d=0.63). There was a significant group×sex interaction (p<0.003) and the MMN impairment was only detected in males with SCZ. MMN amplitude correlated positively with Positive and Negative Syndrome Scale total score and negatively with Global Assessment of Functioning Scale score. The deviant negativity was impaired in males with SCZ. No group differences in memory trace indices of the MMN, DN, or RP. MMN was attenuated in SCZ and correlated with greater severity of psychotic symptoms and lower level of functioning. Our results may indicate sex-dependent differences of glutamatergic function in SCZ.

Rapid improvements and subsequent effects in major depressive disorder patients with somatic pain using rTMS combined with sertraline

This study aims to explore changes in depression and pain for major depressive disorder (MDD) patients with somatic pain after repetitive transcranial magnetic stimulation (rTMS) using the event-related potentials (ERPs) technique. Eighty MDD patients with somatic pain were randomly assigned to drug therapy (DT) and combined therapy (CT) groups. CT group underwent intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) with 800 pulses and 1 Hz over the right DLPFC with 800 pulses, 5 times a week for 3 weeks. All patients were given sertraline at 50–100 mg per day. All subjects were evaluated at baseline and at weeks three and six of therapy using the Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Scale (HAMA), and Numerical Rating Scales (NRS), and the latency and amplitude of P300 and mismatch negativity (MMN) were measured. There were no significant differences in all indices between groups at baseline. At 3 weeks, HAMD subscale scores of Cognitive Impairment and NRS scores were significantly lower in the CT group than in the DT group. At 6 weeks, NRS and HAMD total scores in the CT group decreased significantly in the CT group compared with the DT group, especially for anxiety and pain, and the MMN and P300 latencies and P300 amplitude showed greater improvements. Our findings highlight that rTMS in combination with antidepressants is a rapid method of symptom improvement in patients with somatic pain with MDD and is helpful for cognitive impairment and anxiety.

Longitudinal change in mismatch negativity (MMN) but not in gamma-band auditory steady-state response (ASSR) is associated with psychological difficulties in adolescence.

Adolescence is a critical period for psychological difficulties. Auditory mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are representative electrophysiological indices that mature during adolescence. However, the longitudinal association between MMN/ASSR and psychological difficulties among adolescents remains unclear. We measured MMN amplitude for duration and frequency changes and ASSR twice in a subsample (n = 67, mean age 13.4 and 16.1years, respectively) from a large-scale population-based cohort. No significant longitudinal changes were observed in any of the electroencephalography indices. Changes in SDQ-TD were significantly associated with changes in duration MMN, but not frequency MMN and ASSR. Furthermore, the subgroup with higher SDQ-TD at follow-up showed a significant duration MMN decrease over time, whereas the subgroup with lower SDQ-TD did not. The results of our population neuroscience study suggest that insufficient changes in electroencephalography indices may have been because of the short follow-up period or non-monotonic change during adolescence, and indicated that the longitudinal association with psychological difficulties was specific to the duration MMN. These findings provide new insights that electrophysiological change may underlie the development of psychosocial difficulties emerging in adolescence.

Trait and State Anxiety Effects on Mismatch Negativity and Sensory Gating Event-Related Potentials.

We used the auditory roving oddball to investigate whether individual differences in self-reported anxiety influence event-related potential (ERP) activity related to sensory gating and mismatch negativity (MMN). The state-trait anxiety inventory (STAI) was used to assess the effects of anxiety on the ERPs for auditory change detection and information filtering in a sample of thirty-six healthy participants. The roving oddball paradigm involves presentation of stimulus trains of auditory tones with certain frequencies followed by trains of tones with different frequencies. Enhanced negative mid-latency response (130-230 ms post-stimulus) was marked at the deviant (first tone) and the standard (six or more repetitions) tone at Fz, indicating successful mismatch negativity (MMN). In turn, the first and second tone in a stimulus train were subject to sensory gating at the Cz electrode site as a response to the second stimulus was suppressed at an earlier latency (40-80 ms). We used partial correlations and analyses of covariance to investigate the influence of state and trait anxiety on these two processes. Higher trait anxiety exhibited enhanced MMN amplitude (more negative) (F(1,33) = 14.259, p = 6.323 × 10-6, ηp2 = 0.302), whereas state anxiety reduced sensory gating (F(1,30) = 13.117, p = 0.001, ηp2 = 0.304). Our findings suggest that high trait-anxious participants demonstrate hypervigilant change detection to deviant tones that appear more salient, whereas increased state anxiety associates with failure to filter out irrelevant stimuli.

Intact Mismatch Negativity Responses in Clinical High Risk for Psychosis and First-Episode Psychosis: Evidence From Source-Reconstructed Event-Related Fields and Time-Frequency Data

BackgroundThis study examined whether mismatch negativity (MMN) responses are impaired in participants at clinical high risk for psychosis (CHR-P) and patients with first-episode psychosis (FEP) and whether MMN deficits predict clinical outcomes in CHR-Ps. MethodsMagnetoencephalography data were collected during a duration-deviant MMN paradigm for a group of 116 CHR-P participants, 33 FEP patients (15 antipsychotic-naïve), clinical high risk negative group (n = 38) with substance abuse and affective disorder, and 49 healthy control participants. Analysis of group differences of source-reconstructed event-related fields as well as time-frequency and intertrial phase coherence focused on the bilateral Heschl’s gyri and bilateral superior temporal gyri. ResultsSignificant magnetic MMN responses were found across participants in the bilateral Heschl’s gyri and bilateral superior temporal gyri. However, MMN amplitude as well as time-frequency and intertrial phase coherence responses were intact in CHR-P participants and FEP patients compared with healthy control participants. Furthermore, MMN deficits were not related to persistent attenuated psychotic symptoms or transitions to psychosis in CHR-P participants. ConclusionsOur data suggest that magnetic MMN responses in magnetoencephalography data are not impaired in early-stage psychosis and may not predict clinical outcomes in CHR-P participants.

Processing of acoustic and phonological information of lexical tones at pre-attentive and attentive stages

ABSTRACT While Mismatch Negativity (MMN) and P300 have been found to correlate with the processing of acoustic and phonological information involved in speech perception, there is controversy surrounding how these two components index acoustic and/or phonological processing at pre-attentive and attentive stages. The current study employed both passive and active oddball paradigms to examine neural responses to lexical tones at the two stages in Cantonese speakers, using the paradigm of categorical perception (CP) where the between- and within-category deviants share the same acoustic distance from the standard but differ in the involvement of phonological information. We failed to observe a CP effect in P300, which might indicate that this component doesn’t necessarily index phonological processing, while MMN does, as reflected by the finding of a greater MMN amplitude elicited from the between-category than within-category deviant. Nevertheless, phonological processing might be overridden by acoustic processing among participants who were sensitive to pitch.

Delirium is associated with loss of feedback cortical connectivity.

Post-operative delirium (POD) is associated with increased morbidity and mortality but is bereft of treatments, largely due to our limited understanding of the underlying pathophysiology. We hypothesized that delirium reflects a disturbance in cortical connectivity that leads to altered predictions of the sensory environment. High-density electroencephalogram recordings during an oddball auditory roving paradigm were collected from 131 patients. Dynamic causal modeling (DCM) analysis facilitated inference about the neuronal connectivity and inhibition-excitation dynamics underlying auditory-evoked responses. Mismatch negativity amplitudes were smaller in patients with POD. DCM showed that delirium was associated with decreased left-sided superior temporal gyrus (l-STG) to auditory cortex feedback connectivity. Feedback connectivity also negatively correlated with delirium severity and systemic inflammation. Increased inhibition of l-STG, with consequent decreases in feed-forward and feed-back connectivity, occurred for oddball tones during delirium. Delirium is associated with decreased feedback cortical connectivity, possibly resulting from increased intrinsic inhibitory tone. Mismatch negativity amplitude was reduced in patients with delirium. Patients with postoperative delirium had increased feedforward connectivity before surgery. Feedback connectivity was diminished from left-side superior temporal gyrus to left primary auditory sensory area during delirium. Feedback connectivity inversely correlated with inflammation and delirium severity.

Mismatch negativity as a marker of auditory pattern separation.

To what extent does incidental encoding of auditory stimuli influence subsequent episodic memory for the same stimuli? We examined whether the mismatch negativity (MMN), an event-related potential generated by auditory change detection, is correlated with participants' ability to discriminate those stimuli (i.e. targets) from highly similar lures and from dissimilar foils. We measured the MMN in 30 young adults (18-32years, 18 females) using a passive auditory oddball task with standard and deviant 5-tone sequences differing in pitch contour. After exposure, all participants completed an incidental memory test for old targets, lures, and foils. As expected, participants at test exhibited high sensitivity in recognizing target items relative to foils and lower sensitivity in recognizing target items relative to lures. Notably, we found a significant correlation between MMN amplitude and lure discrimination, but not foil discrimination. Our investigation shows that our capacity to discriminate sensory inputs at encoding, as measured by the MMN, translates into precision in memory for those inputs.

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 mismatch negativity as an index of cognitive abilities in adults with Down syndrome.

Down syndrome (DS) is associated with an ultra-high risk of developing Alzheimer's disease (AD). Understanding variability in pre-AD cognitive abilities may help understand cognitive decline in this population. The mismatch negativity (MMN) is an event-related potential component reflecting the detection of deviant stimuli that is thought to represent underlying memory processes, with reduced MMN amplitudes being associated with cognitive decline. To further understand the MMN in adults with DS without AD, we explored the relationships between MMN, age, and cognitive abilities (memory, language, and attention) in 27 individuals (aged 17-51) using a passive auditory oddball task. Statistically significant MMN was present only in 18 individuals up to 41years of age and the latency were longer than canonical parameters reported in the literature. Reduced MMN amplitude was associated with lower memory scores, while longer MMN latencies were associated with poorer memory, verbal abilities, and attention. Therefore, the MMN may represent a valuable index of cognitive abilities in DS. In combination with previous findings, we hypothesize that while MMN response and amplitude may be associated with AD-related memory loss, MMN latency may be associated with speech signal processing. Future studies may explore the potential impact of AD on MMN in people with DS.