Tryptophan depletion effects on EEG and MEG responses suggest serotonergic modulation of auditory involuntary attention in humans

Involuntary attention shifting, i.e., detecting and orienting to unexpected stimulus changes, may be altered at low brain serotonin (5-hydroxytryptamine; 5-HT) levels. This was studied in 13 healthy subjects (21–30 years old; 6 females) by using a dietary challenge, acute tryptophan depletion (ATD), which decreases 5-HT synthesis in the brain. Five hours after ingestion of either ATD or control mixture (randomized, double-blinded, crossover design), brain responses indexing involuntary attention were measured with simultaneous 64-channel electroencephalography (EEG) and 122-channel magnetoencephalography (MEG). During the measurement, the subjects were instructed to discriminate equiprobable 200- and 400-ms tones by pressing one of two buttons rapidly. Occasionally, the frequency of the tones changed (10% increase/decrease), causing involuntary attention shifting. ATD significantly lowered plasma tryptophan concentrations (total tryptophan decreased by 75%, free tryptophan decreased by 35%). As compared to the control condition, ATD reduced the amplitude of the deviant-tone N2 wave, including the overlapping mismatch negativity (MMN) and N2b subcomponents, which are suggested to reflect change detection in the brain. The EEG results were accompanied by a significant increase in the peak latency of the magnetic counterpart of MMN. However, no ATD effects were observed in P3 to task-irrelevant frequency change. Reaction time (RT) to deviants per se was not significantly affected, but RT in trials succeeding the deviant-frequency tones was increased by ATD, which suggested impaired reorienting to the task-relevant activity. In conclusion, the results suggest that decreased level of central 5-HT function after ATD may decrease involuntary attention shifting to task-irrelevant sound changes and thus modulate resource allocation to the task-relevant activity.     

膀胱癌相关基因的研究进展

膀胱癌在中国为最常见的泌尿系统肿瘤。膀胱癌的发生发展是一个多步骤的过程,异常基因型的长期积累导致恶性表型的出现。与膀胱癌相关的基因主要有癌基因（如H-ras、FGFR3、erbB2、CCND1、mdm2等）、抑癌基因（如INK4A/ARF、Rb、TP53、PTEN、TSC1、PTCH、DBCCR1等）及DNA错配修复基因等。本文就与膀胱癌相关的几类主要基因的研究进展作一综述。     

The perception of speech sounds by the human brain as reflected by the mismatch negativity (MMN) and its magnetic equivalent (MMNm)

The present article outlines the contribution of the mismatch negativity (MMN), and its magnetic equivalent MMNm, to our understanding of the perception of speech sounds in the human brain. MMN data indicate that each sound, both speech and nonspeech, develops its neural representation corresponding to the percept of this sound in the neurophysiological substrate of auditory sensory memory. The accuracy of this representation, determining the accuracy of the discrimination between different sounds, can be probed with MMN separately for any auditory feature (e.g., frequency or duration) or stimulus type such as phonemes. Furthermore, MMN data show that the perception of phonemes, and probably also of larger linguistic units (syllables and words), is based on language-specific phonetic traces developed in the posterior part of the left-hemisphere auditory cortex. These traces serve as recognition models for the corresponding speech sounds in listening to speech. MMN studies further suggest that these language-specific traces for the mother tongue develop during the first few months of life. Moreover, MMN can also index the development of such traces for a foreign language learned later in life. MMN data have also revealed the existence of such neuronal populations in the human brain that can encode acoustic invariances specific to each speech sound, which could explain correct speech perception irrespective of the acoustic variation between the different speakers and word context.     

Sound presentation rate is represented logarithmically in human cortex

The encoding of temporal information is critical to auditory processing. Since the mismatch negativity component of the auditory event-related brain potential is thought to reflect properties of auditory sensory memory, we used it to examine the representation of acoustic time intervals in the human cortex. The mismatch negativity occurs in response to deviations in acoustic regularities, which are stored in sensory memory. We used 16 stimulus conditions, randomly presenting short trains of tones with fixed onset-to-onset intervals of 100, 200, 300 or 400 ms (all tones in the study were identical). The first four intervals between the tones established the acoustic regularity on each train (i.e. the 'standard'). The fifth tone in each train was preceded by an interval that varied randomly among the same four intervals. If this interval was different from the standard for that trial, it violated the acoustic regularity (i.e. it was a 'deviant'). The mismatch response to the fifth tone differed significantly among stimulus conditions and was proportional to the absolute value of the logarithm of the deviant/standard interval ratio. This indicates that short acoustic time intervals are represented with a ratio scale in the human cortex. When the fifth tone occurred 100 ms after the fourth, it elicited a somewhat different, although proportional response, supporting the hypothesis that a special integration mechanism may exist for very short time intervals.     

Contribution of attentional and cognitive factors to laser evoked brain potentialsModulation attentionnelle et cognitive des réponses évoquées par laser

Painful stimuli delivered by infrared laser stimulators elicit laser-evoked potentials (LEP) or magnetic fields in respective electroencephalogram (EEG) and magnetoencephalogram (MEG). Evidence is reviewed that LEP represent a series of event-related potentials (ERP) that depend on vigilance and arousal, selective spatial attention and contextual task variables. Paradigms adopted from other stimulus modalities in the assessment of attention and cognition in ERP and applied to LEP allow the view that middle-latency (N1) and long latency (N2-P2) components of LEP can be overlapped or supplemented by endogenous components such as the processing negativity and distinct members (P3a and P3b) of the "P300" activities, each of which is considered in detail in this review. This composite entity needs to be considered when LEP are experimentally or clinically used in the assessment of sensory and cognitive phenomena and abnormalities of pain sensation.     

The time-course of auditory and visual distraction effects in a new crossmodal paradigm

Vision often dominates audition when attentive processes are involved (e.g., the ventriloquist effect), yet little is known about the relative potential of the two modalities to initiate a “break through of the unattended”. The present study was designed to systematically compare the capacity of task-irrelevant auditory and visual events to withdraw attention from the other modality. Sequences of auditory and visual stimuli were presented with different amounts of temporal offset to determine the presence, strength, and time-course of attentional orienting and reorienting as well as their impact on task-related processing. One of the streams was task-relevant, while crossmodal distraction caused by unexpected events in the other stream was measured by impairments of behavioral task performance and by the N2, P3a, and reorienting negativity (RON) components of the event-related potential (ERP). Unexpected events in the visual modality proved to be somewhat more salient than those in the auditory modality, yet crossmodal interference caused by auditory stimuli was more pronounced. The visual modality was relatively constrained in terms of a critical time-range within which distraction effects could be elicited, while the impact of auditory stimuli on task-related processing extended over a longer time-range. These results are discussed in terms of functional differences between the auditory and visual modalities. Further applications of the new crossmodal protocol are deemed promising in view of the considerable size of the obtained distraction effects.     

Semantic integration processes at different levels of syntactic hierarchy during sentence comprehension: An ERP study

An event-related potential (ERP) study was conducted to investigate the temporal neural dynamics of semantic integration processes at different levels of syntactic hierarchy during Chinese sentence reading. In a hierarchical structure, subject noun + verb + numeral + classifier + object noun, the object noun is constrained by selectional restrictions of the classifier at the lower-level and of the verb at the higher-level and the classifier is also constrained by the verb at the higher-level. Semantic congruencies between verb, classifier, and noun were manipulated, resulting in five types of sentences: correct sentences, sentences with the single classifier-noun mismatch, sentences with the single verb-noun mismatch, sentences with the double-mismatch in classifier-noun and verb-noun, and sentences with the triple-mismatch in classifier-noun, verb-noun and verb-classifier. Compared with correct sentences, all four types of mismatches elicited N400 effects on the noun, with the effect in the double-mismatch equal to the effect in the single classifier-noun mismatch but larger than the effect in the single verb-noun mismatch. In addition, the single verb-noun mismatch and the double-mismatch elicited a left-posterior positivity effect and an anterior negativity effect in the 550-800 ms time window on the noun, with the effects larger in the double-mismatch than in the single-mismatch. The classifier-noun mismatch also elicited the late anterior negativity effect on the noun. Although the triple-mismatch did not induce a significant late positivity effect on the noun, it did on the classifier. The pattern of the N400 effects suggests that semantic processes at different levels of syntactic hierarchy interact in integrating the incoming word into the prior sentence context with neither process overriding the other. The late-posterior positivity effect may reflect the coordination of various semantic integration processes across hierarchical levels during sentence comprehension.     

Feedback‐related potentials are sensitive to sequential order of decision outcomes in a gambling task

The feedback negativity (FN) has been repeatedly linked to expectancies about decision outcomes. Sequential outcome order is likely to influence such expectancies but has been widely disregarded. We therefore investigated whether the three‐trial order of decision outcomes in a gambling task influences the FN as well as the P200 and P300. All three deflections were not only influenced by the outcome valence of the current trial but also by the outcomes of the two preceding trials. In detail, the FN and P300 to any current trial outcome were largest when the outcomes in the two preceding trials had an opposite valence. The P200 was highest in the context of two directly preceding wins, indicating that it may reflect representations of local outcome history. Our findings demonstrate that neural systems involved in decision outcome processing dynamically and continuously integrate the local outcome history for the evaluation of present outcomes.     

急性脑卒中后脑诱发电位失匹配负波的变化观察

目的观察急性脑卒中后患者脑诱发电位失匹配负波的变化特点。方法对70例脑卒中患者和40例正常人进行失匹配负波（MMN）检查。结果与正常对照组比较，脑卒中患者脑诱发电位的MMN潜伏期延长、波幅降低，2组比较差异有统计学意义（P〈0．05）。结论脑卒中患者存在认知功能损害，MMN是敏感的检测工具。     

Parkinson病患者认知功能障碍与失匹配负波相关性研究

目的：探讨失匹配负波（MMN）与额叶认知功能测试在评价Parkinson病（PD）患者认知功能中的作用及其临床价值。方法：对28例早期非痴呆非抑郁PD患者和31例年龄、教育年限相匹配的正常对照组分别进行额叶认知功能测试和MMN测定。结果：与正常对照组相比，非痴呆非抑郁PD患者额叶认知测试评分较差，MMN潜伏期延长（P〈0．001）；波幅虽呈下降趋势，但无统计学意义；MMN潜伏期延长与额叶认知功能障碍程度呈正相关（P〈0．01～0．05）。结论：MMN能较客观地反映非痴呆非抑郁PD患者早期额叶认知功能障碍。