Do tone duration changes that elicit the mismatch negativity also affect the preceding middle latency responses?

The human brain can automatically detect sound changes. Previous studies have reported that rare sounds presented within a sequence of repetitive sounds elicit the mismatch negativity (MMN) in the absence of attention in the latency range of 100-250 ms. On the other hand, a previous study discovered that occasional changes in sound location enhance the middle latency response (MLR) elicited in the latency range of 10-50 ms. Several studies have reported an increase in the amplitude of the MLR within the frame of oddball paradigms such as frequency and location changes. However, few studies have been conducted on paradigms employing a duration change. The purpose of the present study was to examine whether the peak amplitudes of the MLR components are enhanced by a change in duration. Twenty healthy Japanese men (age: 23.9 ± 2.9 years) participated in the present study. We used an oddball paradigm that contained standard stimuli with a duration of 10 ms and deviant stimuli with a duration of 5 ms. The peak amplitudes of the MLR for the deviant stimuli were then compared with those for the standard stimuli. No changes were observed in the peak amplitude of the MLR resulting from a duration change, whereas a definite MMN was elicited. The amplitude of the MLR was increased within the frame of oddball paradigms such as frequency and location changes. By contrast, the amplitude of the MLR was not changed within the duration change oddball paradigm that elicited the MMN.

Plasma levels of dopamine metabolite correlate with mismatch negativity in patients with schizophrenia.

AIM: Mismatch negativity (MMN) deficit is one of the most robust and replicable findings in schizophrenia, and primarily reflects deficient functioning of the N-methyl-D-aspartate (NMDA) receptor system. Although the dopamine receptor is known not to modulate MMN over the short term, it is unclear whether the dopamine system affects MMN in the long term. METHODS: We explored correlations between MMN and levels of plasma dopamine and serotonin metabolites in 18 patients with schizophrenia psychiatrically evaluated with the Positive and Negative Syndrome Scale (PANSS). RESULTS: A significant negative correlation exists between MMN amplitude and plasma levels of dopamine metabolites. Plasma serotonin metabolite levels were not correlated with MMN. The PANSS total score and Negative score also showed negative correlations with MMN amplitude. CONCLUSION: The usual strong therapeutic blockade of dopamine receptors applied in cases of schizophrenia may reduce MMN over the long term.

The Relationship between Mismatch Negativity and the COMTVal108/158Met Genotype in Schizophrenia.

Mismatch negativity (MMN) is a component of auditory event-related potentials that reflects automatic change detection in the brain, showing qualities of endophenotypes in schizophrenia. MMN deficiency is one of the robust findings in patients, and it reflects both cognitive and functional decline. Catechol-o-methyltransferase (COMT) is a key enzyme involved in regulating dopamine transmission within the prefrontal cortex. A preliminary study suggested that the COMTVal108/158Met genotype (rs4680) is related to cognitive function in schizophrenia. Both the COMTVal108/158Met genotype and MMN are related to cognitive function, but no studies have reported on the relationship between MMN and the COMTVal108/158Met genotype in schizophrenia. This study therefore examined the relationship between COMTVal108/158Met genotype and MMN. The duration of MMN was measured, and the COMTVal108/158Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in 49 Japanese schizophrenia patients (Val/Val, n = 21; Met carriers, n = 28). Amplitude and latency of MMN were compared between Val/Val and Met carriers.

Switching antipsychotics to aripiprazole or blonanserin and plasma monoamine metabolites levels in patients with schizophrenia.

OBJECTIVE: Blonanserin is a novel atypical antipsychotic drug that has efficacy equal to risperidone. We investigated the effects of aripiprazole and blonanserin on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenylglycol in the switching strategy of schizophrenia. METHODS: Twenty two Japanese patients with schizophrenia were enrolled into this open study. The antipsychotics of all patients were switched to aripiprazole or blonanserin for the improvement of clinical symptoms or side effects. Plasma monoamine metabolites levels were analyzed with high-performance liquid chromatography. RESULTS: There were no significant effects for time (p = 0.346) or time × group interaction (p = 0.27) on the changes of positive and negative syndrome scale (PANSS) total score, although blonanserin decreased PANSS scores. We observed negative correlation between pHVA at baseline and the change in PANSS total score (rs = -0.450, p = 0.046). We also found positive correlation between the changes in pHVA and the changes in PANSS total (rs = 0.536, p = 0.015) and positive (rs = 0.572, p = 0.008) scores. CONCLUSIONS: There were no differences between blonanserin and aripiprazole in the improvement of clinical symptoms. Our results suggest that pHVA may be useful indicator for the switching strategy to aripiprazole or blonanserin in schizophrenia.

Abnormal Temporal Window of Integration in Auditory Sensory Memory in Schizophrenia.

Mismatch negativity (MMN) is automatically elicited by incoming sound deviation compared to the neural representation of preceding homogenous sounds stored in the brain's auditory sensory memory. This study aimed to assess time-functional deviation sensitivity in auditory sensory memory associated with a temporal window of integration (TWI) of 160-170 msec in patients with schizophrenia. To this end, we measured the magnetic counterpart of the MMN (MMNm) in 20 patients with schizophrenia on medication and 20 healthy age-matched adults as a control group responding to an omitted tone segment incorporated into a complex sound of 176 ms duration corresponding to the TWI duration. Overall, the magnitude of the MMNm was smaller in the patients with schizophrenia than in the healthy control group. The peak latency of the MMNm was prolonged in the latter omitted segments for both groups, but to a greater extent in patients with schizophrenia. These results indicate that deviation detection is impaired in the later part of the TWI, corresponding to the duration of auditory sensory memory in patients with schizophrenia. Thus, the specific impairment of MMN in response to duration deviants (duration MMN), as previously reported, might result from a damaged mechanism in the later part of the TWI of sensory memory, suggesting that a decline in sensory memory causes distorted perception or disturbances in cognitive function in patients with schizophrenia.

Effect of the Temporal Window of Integration of Speech Sound on Mismatch Negativity.

Speech-sound stimuli have a complex structure, and it is unclear how the brain processes them. An event-related potential (ERP), known as mismatch negativity (MMN), is elicited when an individual's brain detects a rare sound. In this study, MMNs were measured in response to an omitted segment of a complex sound consisting of a Japanese vowel. The results indicated that the latency from onset in the right hemisphere was significantly shorter than that in the frontal midline and left hemispheres during left ear stimulation. Additionally, the results of latency from omission showed that the latency of stimuli omitted in the latter part of the temporal window of integration (TWI) was longer than that of stimuli omitted in the first part of the TWI. The mean peak amplitude was found to be higher in the right hemisphere than in the frontal midline and left hemispheres in response to left ear stimulation. In conclusion, the results of this study suggest that would be incorrect to believe that the stimuli have strictly the characteristics of speech-sound. However. the results of the interaction effect in the latencies from omission were insignificant. These results suggest that the detection time for deviance may not be related to the stimulus ear. However, the type of deviant stimuli on latencies was found to be significant. This is because the detection of the deviants was delayed when a deviation occurred in the latter part of the TWI, regardless of the stimulation of the ear.

Effect of oxytocin nasal spray on auditory automatic discrimination measured by mismatch negativity.

RATIONALE: As a treatment for cognitive dysfunction in schizophrenia, oxytocin nasal sprays potentially improve social cognition, facial expression recognition, and sense of smell. Mismatch negativity (MMN) is an event-related potential (ERP) reflecting auditory discrimination while MMN deficits reflect cognitive function decline in schizophrenia. OBJECTIVES: To determine whether oxytocin nasal spray affects auditory MMN METHODS: We measured ERPs in healthy subjects during an auditory oddball task, both before and after oxytocin nasal spray administration. Forty healthy subjects were randomly assigned to either the oxytocin or placebo group. ERPs were recorded during the oddball task for all subjects before and after a 24 international unit (IU) intranasal administration, and MMN was compared between the two groups. RESULTS: Participants who received oxytocin had significantly shorter MMN latencies than those who received a placebo. Oxytocin had no significant effect on the Change in MMN amplitude. CONCLUSIONS: The shortened MMN latencies that were observed after oxytocin nasal spray administration suggest that oxytocin may promote the comparison-decision stage.

Socioeconomic status, damage-related conditions, and PTSD following the Fukushima-daiichi nuclear power plant accident:The Fukushima Health Management Survey.

The Great East Japan Earthquake severely damaged the Tohoku and Kanto districts, and Fukushima Prefecture faced a subsequent nuclear disaster. Few studies have reported the effects of socioeconomic stressors on individuals' mental status following disasters. We analyzed the responses of 60,704 adult residents of a designated restricted area to the PTSD Checklist-Stressor-Specific Version (PCL-S). The relationships between the PCL-S scores and demographic, socioeconomic, and damage-related variables were analyzed using regression analysis to predict participants' severity of PTSD symptoms. Approximately 14.1% of evacuees had severe PTSD symptoms (PCL-S ≥50) eighteen months post-earthquake. The PCL-S scores were higher among women, older adults, less educated people, those with a history of mental illness, and those living outside Fukushima Prefecture. The PCL-S scores increased with participants' scores on the Kessler Psychological Distress Scale. The number of trauma-exposure stressors and socioeconomic stressors were associated with 1.52 and 3.77 increases in the PCL-S score, respectively. Furthermore, psychological distress, unemployment, decreased income, house damage, tsunami experience, nuclear power plant accident experience, and loss of someone close due to the disaster were associated with the prevalence of severe PTSD symptoms. The complex triple disaster of a major earthquake, tsunami, and nuclear accident created significant socioeconomic changes that may be important determinants of PTSD among residents of restricted access areas in Fukushima.

Effects of benzodiazepine and orexin receptor antagonist on cognitive function revealed by auditory event-related potentials.

BACKGROUND: Cognitive decline after oral administration of sedatives, such as benzodiazepines, is a serious side effect. Suvorexant, an orexin receptor antagonist, has a favorable tolerability and a limited side-effect profile. AIM: The purpose of this study was to estimate the cognitive decline 1 day after oral medication with lormetazepam, a benzodiazepine, and suvorexant by comparing mismatch negativity (MMN) and P300 reflecting auditory discrimination function. METHODS: Sixty healthy subjects (42 males) were randomly assigned to three groups receiving suvorexant 20 mg, lormetazepam 2 mg, or placebo in this double-blind, randomized control study. Event-related potential recordings during an auditory oddball task and a digit symbol substitution test (DSST) were performed 1 day after oral administration. RESULTS: MMN, on the day after oral administration, was significantly attenuated in the lormetazepam group compared with the other two groups, but there was no difference between the suvorexant and placebo groups. No significant difference was found in P300 amplitudes and DSST scores among the three groups. CONCLUSION: These findings suggest that suvorexant, unlike benzodiazepine, is not associated with cognitive deficits, as revealed by MMN but not P300. This study shows a neurophysiological difference in the effects of suvorexant and benzodiazepine on cognitive function.

Omission mismatch negativity of speech sounds reveals a functionally impaired temporal window of integration in schizophrenia.

OBJECTIVE: We hypothesized that sensory memory associated with the temporal window of integration (TWI) would be impaired in patients with schizophrenia, an issue that had not been evaluated using omission mismatch negativity (MMN) of complex speech sounds. We aimed to assess the functional changes in auditory sensory memory associated with the TWI in patients with schizophrenia by investigating the effect of omission of complex speech stimuli on the MMN. METHODS: In total, 17 patients with schizophrenia and 15 control individuals participated in the study. The MMN in response to omission deviants of complex speech sounds was recorded, while the participants were instructed to ignore the series of speech sounds. RESULTS: The MMN latency in patients with schizophrenia was significantly prolonged by deviant stimuli to omissions corresponding to the early and late parts of the temporal TWI. There were no significant group differences in the amplitude of the MMN to omissions at different time points across the TWI. CONCLUSIONS: Our results suggested that sensory tracing function in patients with schizophrenia is impaired in the early and the later half of the TWI. SIGNIFICANCE: We showed that certain MMN abnormalities in patients with schizophrenia may be caused by an impaired TWI.

Estimation of frequency difference at which stream segregation precedes temporal integration as reflected by omission mismatch negativity.

Both stream segregation and temporal integration are considered important for auditory scene analysis in the brain. Several previous studies have indicated that stream segregation may precede temporal integration when both processes are required. In the present study, we utilized mismatch negativity (MMN)-which reflects automatic change detection-to systematically estimate the threshold of the frequency difference at which stream segregation occurs prior to temporal integration when these functions occur together during a state of inattention. Electroencephalography (EEG) data were recorded from 22 healthy Japanese men presented with six blocks of alternating high pure tones (high tones) and low pure tones (low tones). Only high tones were omitted with 5 % probability in all blocks. Our results indicated that stream segregation should cancel temporal integration of close sounds, as indicated by omission-MMN elicitation, when the frequency difference is 1000 Hz or larger.

Young patient with treatment-resistant schizophrenia drastically improved by combination of clozapine and maintenance electroconvulsive therapy: a case report.

Objectives: Although clozapine is considered the only effective pharmacological option for patients with treatment-resistant schizophrenia (TRS), around 30-40% of patients show clozapine resistance. Modified electroconvulsive therapy augmentation is reportedly clinically effective for clozapine-resistant schizophrenia, but few case reports have described the efficacy of combining clozapine and continuous/maintenance ECT for patients with TRS. Methods: We present the case of a young patient with TRS who was treated using combination therapy with clozapine and maintenance ECT (m-ECT). Results: The patient achieved drastic improvement under combination therapy with clozapine and m-ECT. Total Positive and Negative Syndrome Scale (PANSS) score fell markedly by 36 (from 108 to 72) using the combination of clozapine and m-ECT. Behaviors not reflected directly by PANSS score also improved. For example, the problem of being unable to take oral drugs stably because of delusions of poisoning was resolved. Furthermore, the patient maintained improvement under m-ECT, and long-term homestays became possible. Conclusion: Combination therapy with clozapine and m-ECT proved greatly effective in this case. Further clinical trials of this combination therapy for TRS are needed to confirm the effectiveness. Further studies are also expected to examine effective periods for this therapy.

The Relationship between Sleep Time and Mental Health Problems According to the Strengths and Difficulties Questionnaire in Children after an Earthquake Disaster: The Fukushima Health Management Survey.

A cross-sectional study was performed on the adverse effects of sleep time on the mental health of children after the Great East Japan Earthquake and subsequent nuclear reactor accident in March 2011. The target participants were children aged 4-15 years living inside the government-designated evacuation zone as of 11 March 2011 (n = 29,585). The participants' parents/guardians completed the Strengths and Difficulties Questionnaire (SDQ) and sleep time data were obtained from the 2011 Fukushima Health Management Survey. A total of 18,745 valid responses were returned. We excluded questionnaires with incomplete answers leaving 13,272 responses for the final analysis. First, we divided the children into three age groups for analysis. Second, we divided each age group into four or five groups based on sleep time per day. We used SDQ scores ≥16 to indicate a high risk of mental health problems. In the 4-6-year-old group, those with a sleep time of <9 h had a higher risk. In the 7-12-year-old group, those with ≥10 h of sleep time had a higher risk. In the 13-15-year-old group, those with ≥9 h of sleep time had a higher risk. Shorter sleep time was associated with a higher risk of mental health in 4-6-year-olds. On the other hand, oversleeping was associated with a high risk of mental health in 7-15-year-olds.

Alteration of Duration Mismatch Negativity Induced by Transcranial Magnetic Stimulation Over the Left Parietal Lobe.

Mismatch negativity (MMN) is generated by a comparison between an incoming sound and the memory trace of preceding sounds stored in sensory memory without any attention to the sound. N100 (N1) is associated with the afferent response to sound onset and reflects early analysis of stimulus characteristics. MMN generators are present in the temporal and frontal lobe, and N1 generators are present in the temporal lobe. The parietal lobe is involved in MMN generation elicited by a change in duration. The anatomical network connecting these areas, lateralization, and the effect of the side of ear stimulation on MMN remain unknown. Thus, we studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the left parietal lobe on MMN and N1 in 10 healthy subjects. Low-frequency rTMS over the left parietal lobe decreased the amplitude of MMN following right ear sound stimulation, but the amplitude was unaffected with left ear sound stimulation. We observed no significant changes in the amplitude of N1 or the latency of MMN or N1. These results suggest that low-frequency rTMS over the left parietal lobe modulates the detection of early auditory changes in duration in healthy subjects. Stimulation that is contralateral to the side of the ear experiencing sound may affect the generation of duration MMN more than ipsilateral stimulation.

The efficacy of antipsychotics for prolonged delirium with renal dysfunction.

AIM: Delirium is commonly encountered in daily clinical practice. To identify predictors influencing outcomes, we retrospectively examined the characteristics of inpatients with delirium who required psychiatric medication during hospitalization. METHODS: We extracted all new inpatients (n=523) consulted for psychiatric symptoms at Fukushima Medical University Hospital between October 2011 and September 2013. We selected 203 inpatients with delirium diagnosed by psychiatrists. We analyzed data from 177 inpatients with delirium who received psychiatric medication. We defined an "early improvement group" in which delirium resolved in ≤3 days after starting psychiatric medication, and a "prolonged group" with delirium lasting for >3 days. Among the 83 inpatients with renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2), we defined an "early improvement group with renal dysfunction" in which delirium resolved in ≤3 days after starting psychiatric medication and a "prolonged group with renal dysfunction" with delirium lasting for >3 days. We then examined differences between groups for different categorical variables. RESULTS: Dose of antipsychotic medication at end point was significantly lower in the prolonged group with renal dysfunction than in the early improvement group with renal dysfunction. CONCLUSION: The results suggest that maintaining a sufficient dose of antipsychotics from an early stage may prevent prolongation of delirium even in inpatients with renal dysfunction.

Mental Health Status of Children After the Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant Accident.

The disaster at the Fukushima Daiichi Nuclear Power Plant after the Great East Japan Earthquake on March 11, 2011, might have affected the mental health status of children. To assess the mental health status, we measured the Strengths and Difficulties Questionnaire (SDQ) in 15 274 children (aged 4-15 years). The proportions of those who scored above the cutoff (≥16) of SDQ, reflecting the clinical range of the mental health status, were 25.0% (aged 4-6 years), 22.0% (aged 7-12 years, and 16.3% (aged 13-15 years), which were higher than that in the usual state (9.5%). We also explored the possibility that the distribution on the Fukushima prefectural map of the proportions of those who scored above the cutoff (≥16) of SDQ might correspond with the environmental radiation levels, but there was no significant correlation.

Dynamic changes in near-infrared spectroscopy (NIRS) findings in first-episode schizophrenia: a case report.

The clinical course of schizophrenia is characterized by recurrence and chronicity and has a large burden on society.　Nevertheless, diagnosis of schizophrenia is based only on distinctive symptoms and the disease course.　Near-infrared spectroscopy (NIRS) is a useful method for measuring changes in the hemoglobin concentration in the cortical surface area and reflects brain function.　We measured NIRS four times during the clinical course in a patient with first-episode schizophrenia.A 17-year-old woman admitted to our hospital because of hallucinations, delusions and appetite loss. After treatment with low-dose antipsychotics, NIRS findings showed a prompt increase in the cerebral blood volume in the frontal region.　On the basis of the clinical course of this patient, we introduce a new point of view, namely, that NIRS findings may be useful as a state marker that indicates the severity of schizophrenia in some cases.

Severe Psychological Distress of Evacuees in Evacuation Zone Caused by the Fukushima Daiichi Nuclear Power Plant Accident: The Fukushima Health Management Survey.

BACKGROUND: Following the Great East Japan Earthquake on March 11, 2011, the nuclear disaster at the Fukushima Daiichi Nuclear Power Plant has continued to affect the mental health status of residents in the evacuation zone. To examine the mental health status of evacuee after the nuclear accident, we conducted the Mental Health and Lifestyle Survey as part of the ongoing Fukushima Health Management Survey. METHODS: We measured mental health status using the Kessler 6-item psychological distress scale (K6) in a total of 73,569 (response rate: 40.7%) evacuees aged 15 and over who lived in the evacuation zone in Fukushima Prefecture. We then dichotomized responders using a 12/13 cutoff on the K6, and compared the proportion of K6 scores ≥13 and ≤12 in each risk factor including demographic information, socioeconomic variables, and disaster-related variables. We also performed bivariate analyses between mental health status and possible risk factors using the chi-square test. Furthermore, we performed multivariate regression analysis using modified Poisson regression models. RESULTS: The median K6 score was 5 (interquartile range: 1-10). The number of psychological distress was 8,717 (14.6%). We found that significant differences in the prevalence of psychological distress by almost all survey items, including disaster-related risk factors, most of which were also associated with increased Prevalence ratios (PRs). Additionally, we found that psychological distress in each evacuation zone was significantly positively associated with the radiation levels in their environment (r = 0.768, p = 0.002). CONCLUSION: The earthquake, tsunami and subsequent nuclear accident likely caused severe psychological distress among residents in the evacuation zone in Fukushima Prefecture. The close association between psychological distress and the radiation levels shows that the nuclear accident seriously influenced the mental health of the residents, which might be exacerbated by increased risk perception. To provide prompt and appropriate support, continued psychosocial intervention for evacuees is strongly recommended.