Mismatch negativity: no difference between controls and abstinent alcoholics.

Deficient information processing in ADHD theoretically results in sensory overload and may underlie the symptoms of the disorder. Mismatch negativity (MMN) and P3a amplitude reflect an individual's detection and subsequent change in attention to stimulus change in their environment. Our primary aim was to explore MMN and P3a amplitude in adult ADHD patients and to examine the effects of methylphenidate (MPH) on these measures. Forty initially psychostimulant-naïve, adult ADHD patients without comorbid ASD and 42 matched healthy controls (HC) were assessed with an MMN paradigm at baseline. Both groups were retested after 6 weeks, in which patients were treated with MPH. Neither significant group differences in MMN nor P3a amplitude were found at baseline. Although 6-week MPH treatment significantly reduced symptomatology and improved daily functioning of the patients, it did not significantly affect MMN amplitude; however, it did significantly reduce P3a amplitude compared to the HC. Furthermore, more severe ADHD symptoms were significantly associated with larger MMN amplitudes in the patients, both at baseline and follow-up. We found no evidence for early information processing deficits in patients with ADHD, as measured with MMN and P3a amplitude. Six-week treatment with MPH decreased P3a but not MMN amplitude, although more severe ADHD-symptoms were associated with larger MMN amplitudes in the patients. Given that P3a amplitude represents an important attentional process and that glutamate has been linked to both ADHD and MMN amplitude, future research should investigate augmenting MPH treatment of less responsive adults with ADHD with glutamatergic antagonists.

Several studies have examined the mismatch negativity (MMN) evoked potential as a measure of a brain inhibitory deficit in alcoholics or those at risk for alcoholism. This study examined MMN in actively drinking treatment-naive alcohol-dependent individuals. This study examined the association of MMN with risk factors for alcoholism, postalcohol withdrawal hyperexcitability, and alcohol use variables. Electroencephalograms were gathered on 84 subjects (42 controls and 42 treatment-naive alcohol-dependent individuals) during a nonattending MMN experiment. Alcoholism family history density, the number of externalizing disorder symptoms, and psychological indices of deviance proneness served as measures of risk factors associated with the vulnerability to alcoholism. Alcohol use variables were used as measures of alcoholism severity. There were no differences in the MMN integral, amplitude, or latency between control and treatment-naive alcohol-dependent subjects. There also were no significant associations of MMN measures with any of the measures of alcoholism vulnerability, with any of the alcohol use variables, or with the prevalence or severity of symptoms of postalcohol withdrawal hyperexcitability. Although there is a strong association between alcohol abuse and symptoms of disinhibition and deviance proneness, the MMN response does not offer any direct physiological evidence of this phenomenon.

ObjectiveThe mismatch negativity (MMN) event-related potential is an index of the pre-attentive stage of neural auditory information processing and an electrophysiological signal indicative of the integrity of auditory information processing with regard to the attention deficit symptom of attention deficit hyperactivity disorder (ADHD). We investigated the association between the MMN amplitude and latency in frontal brain regions and symptom severity in children with ADHD and subclinical ADHD symptoms.MethodsThis study included 29 children: 16 (10 boys; mean age, 13.06 ± 3.67 years) with ADHD (ADHD group) and 13 (eight boys; mean age, 13.40 ± 3.31 years) with sub-clinical ADHD symptoms (subclinical ADHD group). We performed the following assessments: Korean ADHD rating scale-IV (K-ARS-IV), children depression inventory, state/trait anxiety inventory for children, and MMN (measured at Fz, FCz, Cz, and CPz).ResultsThere were no sex or mean age differences between the groups (c2 = −0.01, p = 0.958; Z = −1.88, p = 0.060, respectively). The ADHD group had a significantly higher mean K-ARS-IV score (26.13 ± 9.56 vs. 17.15 ± 11.73, Z = −2.11, p = 0.035). Significant differences were found according to symptom severity in the MMN amplitude at FCz (Z = −2.11, p = 0.035) and MMN latency at Fz and FCz (Z = −2.48, p = 0.013; Z = −2.57, p = 0.010). The K-ARS-IV, K-ARS inattention subscale, and K-ARS hyperactivity-impulsivity subscale scores in the ADHD group correlated significantly with the MMN amplitude at Cz and CPz.ConclusionThis study found differences in the MMN amplitude and latency according to the severity of ADHD symptoms and identified MMN as a potential adjunct to the diagnosis of ADHD.

Altered Processing of Auditory Distractions Under Competing Inputs in Children With Attention-Deficit/Hyperactivity Disorder.

Background:Comorbid risky alcohol use in bipolar disorder (BD) is recognized for its high prevalence and clinical relevance, though understanding of its neurobiological underpinning is limited. The N-methyl-D-aspartate (NMDA) receptor has recognized alterations in BD and is a major site of ethanol’s effects in the brain. The present study aimed to examine the NMDA receptor system in adolescents and young adults with BD by evaluating the longitudinal changes in a robust marker of NMDA function, mismatch negativity (MMN), in relation to changes in alcohol use patterns.Methods:Forty-six BD patients (aged 16–30) were recruited at baseline and 59% (n = 27) returned for follow-up 17.9 +/- 7.3 months later. At both time-points a two-tone, passive, duration-deviant MMN paradigm was conducted and alcohol measures were collected. Pearson’s correlations were performed between changes in MMN amplitudes and changes in alcohol use. Multiple regression was used to assess whether MMN amplitudes at baseline could predict alcohol use at follow-up.Results:Reduction in risky drinking patterns was associated with increased temporal MMN and decreased fronto-central MMN. Larger temporal MMN at baseline was a significant predictor of greater alcohol use at follow-up.Conclusions:Results suggest risky alcohol use in BD may further compound pre-existing NMDA receptor abnormalities and, importantly, reducing alcohol use early in stages of illness is associated with changes in MMN. This highlights the importance of monitoring alcohol use from first presentation. In addition, preliminary results present an exciting potential for utility of MMN as a neurobiological marker used to determine risk for alcohol misuse in BD.

Multiple sclerosis (MS) is one of the most common neurological diseases in North America and it is frequently associated with sensory processing difficulties, cognitive deficits, and psychiatric illness. While many studies have examined cognitive deficits in MS measured by behavioural responses and neuroimaging techniques, only a few studies have examined neurophysiological measures of auditory functioning in MS, such as the mismatch negativity (MMN). The MMN is an event-related potential that indicates automatic auditory change detection. This study examined whether MMN endpoints measured by electroencephalography (EEG) differ in individuals with relapsing-remitting MS compared to healthy controls and whether the symptomatology of MS, including symptoms of depression and fatigue, are related to MMN measures. A multi-feature MMN paradigm, which includes five distinct deviant tones, was used to assess auditory cortex function in MS. There were no significant differences in MMN amplitudes or latencies between the MS and control group (p < 0.05) and corresponding effect sizes were small. However, there was a correlation between reduced MMN amplitudes in response to an intensity deviant and physician-reported disability. The intensity MMN may be more sensitive to deterioration in this population. Ultimately, this study provides a comprehensive profile of early auditory processing abilities in MS and suggests that a reduction in the MMN response may be representative of disease severity in MS.

Based on results showing that the "deviant-minus-standard" estimate of the mismatch negativity (MMN) amplitude increases with increasing amounts of deviance, it has been suggested that the MMN amplitude reflects the amount of difference between the neural representations of the standard and the deviant sound. However, the deviant-minus-standard waveform also includes an N1 difference. We tested the effects of the magnitude of deviance on MMN while minimizing this N1 confound. We found no significant magnitude of deviance effect on the genuine MMN amplitude. Thus we suggest that the average MMN amplitude does not reflect the difference between neural stimulus representations; rather it may index the percentage of detected deviants, each of which elicits an MMN response of uniform amplitude. These results are compatible with an explanation suggesting that MMN is involved in maintaining a neural representation of the auditory environment.

Deficient mismatch negativity (MMN) has been proposed as a candidate biomarker in schizophrenia and may therefore be potentially useful in early identification and intervention in early onset psychosis. In this study we explored whether deficits in the automatic orienting and reorienting responses, measured as MMN and P3a amplitude, are present in young adolescents with first-episode psychosis (FEP) and whether findings are specific to psychosis compared to young adolescents with attention deficit hyperactivity disorder (ADHD). MMN and P3a amplitude were assessed in young adolescents (age 12-17 years) with either FEP (N = 27) or ADHD (N = 28) and age- and gender-matched healthy controls (N = 43). The MMN paradigm consisted of a four-tone auditory oddball task with deviant stimuli based on frequency, duration and their combination. Significantly less MMN was found in patients with psychosis compared to healthy controls in response to frequency and duration deviants. MMN amplitudes in the group of patients with ADHD were not significantly different from patients with psychosis or healthy controls. No significant group differences were found on P3a amplitude. Young adolescents with FEP showed impaired MMN compared to healthy controls while intermediate and overlapping levels of MMN were observed in adolescents with ADHD. The findings suggest that young FEP patients already exhibit pre-attentive deficits that are characteristic of schizophrenia albeit expressed on a continuum shared with other neuropsychiatric disorders.

Mismatch negativity amplitude in first-degree relatives of individuals with psychotic disorders: Links with cognition and schizotypy

The aim was to evaluate the mismatch negativity (MMN) component, a correlate of the automatic detection of changes in the acoustic environment, in healthy adults, and adults with amnestic mild cognitive impairment (aMCI). Forty-three aMCI subjects and 43 healthy Chinese older adults were arranged into experimental group and control group, respectively. Their MMN amplitude and latency were measured at the FZ, FCZ, and CZ electrode sites under a passive auditory oddball task. The results showed that the latencies obtained from the FZ, FCZ, and CZ electrode sites were significantly longer in the aMCI adults than in the control adults (P < 0.01) while there were no significant differences in MMN amplitude between two groups (P > 0.05). The MMN latency was found to be a sensitive and specific biomarker of aMCI.

Effects of auditory hallucinations on the mismatch negativity (MMN) in schizophrenia as measured by a modified ‘optimal’ multi-feature paradigm

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Cochlear implant provides a great opportunity for children with severe to profound sensorineural hearing loss to restore normal hearing. Identifying mismatch negativity (MMN) in cochlear implant recipients helps to assess the role of central auditory structures in processing speech stimuli in those patients. The objective of the present study is to evaluate tone and speech discrimination in cochlear implanted children using mismatch negativity test.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; MMN was recorded in 35 children. They were divided into two groups. Control group consisted of 15 normal hearing children, their age ranged from 3-11 years. Study group consisted of 20 children fitted with unilateral CI, and their age matched the control group. Two oddball paradigms were used; the first was tone bursts (1000 Hz as standard stimulus and 1050 Hz as deviant stimulus). The second was synthesized speech stimuli (/da/ as standard stimulus and /ga/ as deviant one). Both paradigms were presented at 75dB SPL.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; All cochlear implanted children included showed MMN on using both oddball paradigms. Comparing results of both groups revealed statistically significant differences in MMN latency and amplitude. There was a significant positive correlation between MMN latencies and the implantation age as well as the duration of hearing loss before implantation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; MMN provides an objective tool to assess the auditory discrimination abilities in cochlear implanted children which may help in their rehabilitation and also in the optimum setting of their devices.&lt;/p&gt;

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.

Validation of mismatch negativity and P3a for use in multi-site studies of schizophrenia: Characterization of demographic, clinical, cognitive, and functional correlates in COGS-2

BackgroundThe Mismatch Negativity (MMN) is an event-related potential (ERP) sensitive to early auditory deviance detection and has been shown to be reduced in schizophrenia patients. Moreover, MMN amplitude reduction to duration deviant tones was found to be related to functional outcomes particularly, to neuropsychological (working memory and verbal domains) and psychosocial measures. While MMN amplitude is thought to be correlated with deficits of early sensory processing, the functional significance of MMN latency remains unclear so far. The present study focused on the investigation of MMN in relation to neuropsychological function in schizophrenia.MethodForty schizophrenia patients and 16 healthy controls underwent a passive oddball paradigm (2400 binaural tones; 88% standards [1 kHz, 80 db, 80 ms], 11% frequency deviants [1.2 kHz], 11% duration deviants [40 ms]) and a neuropsychological test-battery. Patients were assessed with regard to clinical symptoms.ResultsCompared to healthy controls schizophrenia patients showed diminished MMN amplitude and shorter MMN latency to both deviants as well as an impaired neuropsychological test performance. Severity of positive symptoms was related to decreased MMN amplitude to duration deviants. Furthermore, enhanced verbal memory performance was associated with prolonged MMN latency to frequency deviants in patients.ConclusionThe present study corroborates previous results of a diminished MMN amplitude and its association with positive symptoms in schizophrenia patients. Both, the findings of a shorter latency to duration and frequency deviants and the relationship of the latter with verbal memory in patients, emphasize the relevance of the temporal aspect of early auditory discrimination processing in schizophrenia.