Mismatch negativity (MMN), the deviance-elicited auditory deflection, explained

The current review constitutes the first comprehensive look at the possibility that the mismatch negativity (MMN, the deflection of the auditory ERP/ERF elicited by stimulus change) might be generated by so-called fresh-afferent neuronal activity. This possibility has been repeatedly ruled out for the past 30 years, with the prevailing theoretical accounts relying on a memory-based explanation instead. We propose that the MMN is, in essence, a latency- and amplitude-modulated expression of the auditory N1 response, generated by fresh-afferent activity of cortical neurons that are under nonuniform levels of adaptation.     

Cognitive vs. affective listening modes and judgments of music - An ERP study

The neural correlates of processing deviations from Western music rules are relatively well known. Less is known of the neural dynamics of top-down listening modes and affective liking judgments in relation with judgments of tonal correctness. In this study, subjects determined if tonal chord sequences sounded correct or incorrect, or if they liked them or not, while their electroencephalogram (EEG) was measured. The last chord of the sequences could be congruous with the previous context, ambiguous (unusual but still enjoyable) or harmonically inappropriate. The cognitive vs. affective listening modes were differentiated in the event-related potential (ERP) responses already before the ending chord, indicating different preparation for the judgment tasks. Furthermore, three neural events tagged the decision process preceding the behavioral responses. First, an early negativity, peaking at about 280 ms, was elicited by chord incorrectness and by disliking judgments only over the right hemisphere. Second, at about 500 ms from the end of the sequence a positive brain response was elicited by the negative answers of both tasks. Third, at about 1200 ms, a late positive potential (LPP) was elicited by the liking judgment task whereas a large negative brain response was elicited by the correctness judgment task, indexing that only at that late latency preceding the button press subjects decided how to judge the cadences. This is the first study to reveal the dissociation between neural processes occurring during affective vs. cognitive listening modes and judgments of music.     

Alcohol dependence and anxiety increase error‐related brain activity

Aims Detection of errors is crucial for efficient goal‐directed behaviour. The ability to monitor behaviour is found to be diminished in patients with substance dependence, as reflected in decreased error‐related brain activity, i.e. error‐related negativity (ERN). The ERN is also decreased in other psychiatric disorders with impaired response inhibition, such as attention‐deficit hyperactivity disorder and borderline personality disorder, but increased in anxiety disorders. The objective of the current study was to assess error monitoring in alcohol‐dependent patients in relation to psychiatric comorbidity. We expected decreased error monitoring in alcohol‐dependent patients with impulse control disorders and increased error monitoring in anxious alcohol‐dependent patients. Design In a case–control design alcohol‐dependent patients were compared with healthy controls. Setting and participants A consecutive series of 29 male alcohol‐dependent patients, between 18 and 55 years of age, applying for in‐patient detoxification were recruited at Novadic Kentron Center for Addiction Treatment. Fifteen age‐matched healthy controls were recruited through advertisements in regional newspapers. Measurements Event‐related potentials were recorded while performing a speeded choice‐reaction task, from which ERN amplitudes were calculated. Axis‐I and ‐II psychiatric comorbidity were assessed using the MINI International Neuropsychiatric Interview and the Structured Interview for DSM‐IV Personality disorders. All participants completed the Temperament and Character Inventory and Profile of Mood States. Findings ERN amplitudes were increased for alcohol‐dependent patients compared to healthy controls, particularly in patients with comorbid anxiety disorders. Conclusions Increased error monitoring in alcohol‐dependent patients, particularly those with comorbid anxiety disorders, is in contrast with previous studies that suggested decreased error monitoring to be a general feature in substance use disorders. Psychiatric disorders co‐occurring with alcohol dependence, such as anxiety disorders, may indicate subpopulations of alcohol‐dependent patients, with distinct neurobiological and genetic characteristics, possibly requiring different treatment strategies.     

Differential expression of hMLH1 in sporadic human colorectal cancer tumors and distant metastases

Somatic defects in the mismatch repair system constitute an important pathway in colorectal carcinogenesis. We have examined the expression of mismatch repair proteins in sporadic stage IV colorectal tumors and their derived metastases. Sporadic tumors were further examined for differences in expression between the tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver metastases. In cases with loss of mismatch repair protein expression, lymph node metastases were also examined. Clinicopathological parameters and Ki‐67 staining indexes were evaluated and compared. Four tumors displayed a complete loss of hMLH1/hPMS2 expression at the transition zone; however, three of these expressed both proteins at the invasive front and in liver and lymph node metastases. A further four were predominantly hMLH1/hPMS2 negative at the transition zone, but with distinct subclones of hMLH1/hPMS2‐expressing cells at the transition zone. All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No significant difference in the proliferative index was observed for the hMLH1/hPMS2‐compromised group. In stage IV tumors re‐expression of hMLH1/hPMS2 occurred, leading to different patterns of expression within the primary tumor and between tumor and metastases. This may have functional importance for the chemosensitivity of metastases compared to the primary tumor.     

胃癌组织hMLH1启动子甲基化是造成其蛋白表达降低的主要原因

目的：通过研究胃癌中错配修复基因hMLH1启动子区5CpG岛甲基化及蛋白表达情况，探讨hMLH1启动子Ⅸ甲基化对蛋白表达的影响及在胃癌发病中的作用。方法：收集诊断明确且未经放化疗的胃癌手术切除标本41例及同病例癌旁黏膜。应用免疫组化SP法检测标本hMLH1蛋白表达情况。应用甲基化特异性PCR（MSP）榆测标本hMLH1启动子区甲基化情况。结果：胃癌组与癌旁组，hMLH1蛋白阳性表达率分别为58．54％（24／41）和80．49％（33／41）（P〈0．05）；启动子甲基化率分别为80．49％（33／41）和24．39％（10／41）（P〈0．05）；完全甲基化率分别为41．46％（17／41）和19．51％（8／41）（P〈0．05）；部分甲基化率分别为39．02％（16／41）和4．88％（2／41）（P〈0．05）。无论胃癌组织还是癌旁组织，完全甲基化病例均出现hMLH1蛋白表达缺失，部分甲基化病例和启动子未甲基化病例均有hMLH1蛋白表达。hMLHI基因启动子甲基化率与胃癌患者性别、年龄、癌组织分化程度、浸润深度和淋巴结转移均无明显相关性（P〉0．05）。结论：hM—LH1基因启动子甲基化是导致hMLH1蛋白表达降低的主要原因；胃黏膜hMLH1蛋白表达降低有助于胃癌的预警。     

Effects of water on cortical excitability in humans

The effects of water on cortical excitability, measured using magnetoencephalographic recordings, were investigated in a sample of 19 healthy volunteers in a double-blind, placebo experiment comparing water with saline solution. Spontaneous magnetoencephalogram as well as auditory-evoked magnetic fields were recorded before and after the drinking of 750 mL water (9 subjects) or saline solution (10 subjects) and during and after hyperventilation following the drinking conditions. Hyperventilation was used to enhance the hypothesized synchronizing effect of water on spontaneous magnetoencephalographic activity. In addition, the magnetic fields were measured during a dichotic listening task under attended and unattended conditions. The prediction, that intake of water, because of induced cell swelling, will increase neuronal excitability and lead to an increased synchronization of the spontaneous magnetoencephalogram during hyperventilation was confirmed. Hyperventilation induced an increase of spectral power in all frequency bands particularly theta and delta power after water drinking. Furthermore, there was an increase of magnetic mismatch negativity (MMNm) amplitude in attended conditions and a simultaneous decrease in unattended conditions after water drinking. N1m (magnetic N1 wave) revealed significant changes during experimental conditions: increase after drinking and decrease after hyperventilation in both groups. MMNm for attended conditions showed a high positive correlation with osmolality changes (difference in the mol solute per kg water before and after drinking); N1m and PNm (magnetic processing negativity) as well as MMNm for unattended conditions showed significant correlations with subjective ratings of thirst and mood state.     

Photodynamic therapy of DNA mismatch repair-deficient and -proficient tumour cells

Loss of DNA mismatch repair is a common finding in hereditary nonpolyposis colon cancer as well as in many types of sporadic human tumours. DNA mismatch repair-deficient cells have been reported to be resistant to many chemotherapeutic agents and to radiotherapy, and to have the potential of rapidly acquiring additional mutations leading to tumour progression. Photodynamic therapy is a new treatment modality using light to activate a photosensitiser that preferentially localises in tumour cells. An oxygen dependent photochemical reaction ensues, resulting in selective tumour necrosis. The effect of loss of DNA mismatch repair activity on the sensitivity to photodynamic therapy was tested using pairs of cell lines proficient or deficient in mismatch repair due to loss of either MLH1 or MSH2 protein function. Cells were incubated with the photosensitiser 5,10,15,20-meta-tetra(hydroxyphenyl)chlorin and exposed to laser light at 652 nm with various optical doses ranging from 0-1 J cm(-2). Cell survival was assessed using the clonogenic assay. Loss of MLH1 or MSH2 function was not associated with resistance to photodynamic therapy. MCF-7 cells repeatedly treated with photodynamic therapy expressed parental levels of MLH1, MSH2, MSH6, and PMS2. DNA mismatch repair-deficient and -proficient cells showed similar subcellular distributions of meta-tetra(hydroxyphenyl)chlorin as analysed by laser scanning and fluorescence microscopy. Therefore, repeated exposure of tumour cells to photodynamic therapy does not seem to result in loss of DNA mismatch repair, and loss of mismatch repair, in turn, does not seem to contribute to resistance to photodynamic therapy. Our results suggest recommending photodynamic therapy as a strategy for circumventing resistance due to loss of DNA mismatch repair.     

听神经病患者失匹配负波特征与言语识别率的关系

目的观察听神经病(auditory neuropathy,AN)患者失匹配负波(mismatch negativity,MMN)的基本特征及其与最大言语识别率(phonetic balanced maximum,PBmax)的关系。方法用IHS3099(Version3.82)型诱发电位仪对14例(19耳)AN患者和24例(24耳)听力正常者行MMN测试,用GSI-61双通道诊断型听力计和SONY Tc-Fx25盒式双声道立体声录音机及自行录制的单音节音素平衡词表磁带分别测试14例(19耳)AN患者和19例(19耳)听力正常者的PBmax,比较两组MMN潜伏期和振幅差异有无显著性意义,并分析MMN潜伏期和振幅与PBmax的相关性。结果与对照组相比,AN组MMN(强度差异和频率差异)潜伏期显著延长(P<0.01),AN组强度差异MMN振幅与对照组相比有显著性差异(P=0.019),两组频率差异MMN振幅无显著性差异(P=0.128);AN组频率差异和强度差异MMN潜伏期与PBmax呈部分负相关(r=-0.647,P<0.01;r=-0.708,P<0.01),对照组强度差异MMN潜伏期与PBmax也呈部分负相关(r=-0.643,P<0.05),但对照组频率差异MMN潜伏期与PBmax无相关性(r=-0.027,P=0.913)。结论MMN潜伏期相对稳定,振幅变异较大。AN组MMN潜伏期明显比对照组延长,在群体水平与PBmax呈部分负相关。MMN潜伏期在预估AN患者的言语识别能力方面有一定的意义。