事件相关电位N400神经发生源研究

目的事件相关电位(event-related potentials,ERPs)N400是与语境歧义处理相关的高级认知电位,研究应用于精神分裂症的认知功能障碍。有关N400神经发生源,国内外均少有研究报道。本研究应用“低分辩率电磁断层扫描术(low resolution electromagnetic tomography,LORETA)”技术研究 N400的神经发生源。方法ERPs应用汉词语词对(S1-S2)诱发。S1-S2的关系为:语义关联对、语义非关联对和汉词-人造词对。脑电信号应用17导电极记录。被试为18例正常健康者,男9,女9,平均年龄25．2±4．4岁。应用LORETA软件中内含的“统计学非参数地形图(statistical non-parametric mapping,SnPM)”程序分析被试处理不同类语词时所激活的脑功能区差异。结果与语义关联词对中S2诱发ERPs相比,语义非关联词对中S2诱发出潜伏期在300-500 ms左右的负向偏转成分N400。分别比较S2开始后300-350 ms、350-400 ms、400-450 ms和450-500 ms时间窗内两类刺激语词激活的脑功能区,发现具有显著性差异的脑功能区集中在左半球的颞上回、颞中回、岛回、梭状回、后扣带回和海马旁回等区域。结论事件相关电位N400的神经发生源位于优势半球的颞叶及扣带回-海马结构。     

The N1 complex to gaps in noise: effects of preceding noise duration and intensity.

OBJECTIVE: To study the effects of duration and intensity of noise that precedes gaps in noise on the N-Complex (N(1a) and N(1b)) of Event-Related Potentials (ERPs) to the gaps. METHODS: ERPs were recorded from 13 normal subjects in response to 20 ms gaps in 2-4.5 s segments of binaural white noise. Within each segment, the gaps appeared after 500, 1500, 2500 or 4000 ms of noise. Noise intensity was either 75, 60 or 45 dBnHL. Analysis included waveform peak measurements and intracranial source current density estimations, as well as statistical assessment of the effects of pre-gap noise duration and intensity on N(1a) and N(1b) and their estimated intracranial source activity. RESULTS: The N-Complex was detected at about 100 ms under all stimulus conditions. Latencies of N(1a) (at approximately 90 ms) and N(1b) (at approximately 150 ms) were significantly affected by duration of the preceding noise. Both their amplitudes and the latency of N(1b) were affected by the preceding noise intensity. Source current density was most prominent, under all stimulus conditions, in the vicinity of the temporo-parietal junction, with the first peak (N(1a)) lateralized to the left hemisphere and the second peak (N(1b)) - to the right. Additional sources with lower current density were more anterior, with a single peak spanning the duration of the N-Complex. CONCLUSIONS: The N(1a) and N(1b) of the N-Complex of the ERPs to gaps in noise are affected by both duration and intensity of the pre-gap noise. The minimum noise duration required for the appearance of a double-peaked N-Complex is just under 500 ms, depending on noise intensity. N(1a) and N(1b) of the N-Complex are generated predominantly in opposite temporo-parietal brain areas: N(1a) on the left and N(1b) on the right. SIGNIFICANCE: Duration and intensity interact to define the dual peaked N-Complex, signaling the cessation of an ongoing sound.     

When the brain remembers, but the patient doesn’t: Converging fMRI and EEG evidence for covert recognition in a case of prosopagnosia

The role of the occipito-temporal cortex in visual awareness remains an open question and with respect to faces in particular, it is unclear to what extent the fusiform face area (FFA) may be involved in conscious identification. An answer may be gleaned from prosopagnosia, a disorder in which familiar faces are no longer recognized. This impairment has sometimes been reported to be associated with implicit processing of facial identity, although the neural substrates responsible for unconscious processing remain unknown. In this study, we addressed these issues by investigating the functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) responses to familiar and unfamiliar faces in a well-known prosopagnosic patient (P.S.). Our fMRI results show that faces known prior to the onset of prosopagnosia produce an increase in activation in the lateral fusiform gyrus encompassing the FFA, as well as the right middle frontal gyrus, when compared to unknown faces. This effect is not observed with photographs of celebrities dating after the onset of prosopagnosia. Furthermore, electrophysiological responses show that previously familiar faces differ from unfamiliar ones at around 550 msec.Since covert processing of familiarity is associated with activation in FFA, this structure does not appear to be sufficient to produce awareness of identity. Furthermore, the results support the view that FFA participates in face individuation.     

Electrophysiological correlates for response inhibition in a Go/NoGo task

OBJECTIVE: Event-related brain potentials (ERPs) during a Go/NoGo task were investigated to elucidate the electrophysiological basis for executive and inhibitory control of responses. METHODS: We studied Go/NoGo ERPs in 13 healthy subjects during a modified continuous performance test using high-density electroencephalogram (EEG) recording. We measured peak latency, amplitude, and topographic distribution of the components, and analyzed the neural sources using low-resolution electromagnetic tomography. RESULTS: There were no differences between the Go and NoGo conditions in the latency, amplitude, scalp topography, or the electrical source localization of the P1 and N1 components. The N2 component was seen only in the NoGo ERP, and its source was located in the right lateral orbitofrontal and cingulate cortex. The NoGo-P3 component had larger amplitude and longer latency, and was more anteriorly localized than Go-P3; Go-P3 was located mainly in the medial part of the parietal cortex, whereas the NoGo-P3 activity was observed in the left lateral orbitofrontal cortex. CONCLUSIONS: These results suggest that the lateral orbitofrontal and anterior cingulate areas play critical roles in the inhibitory control of behavior and that both hemispheres are involved in inhibitory cognitive function.     

P300和脑功能成像在定向术治疗海洛因依赖中的应用

目的探讨定向毁损术治疗海洛因依赖者手术前后P300和脑功能成像的变化及其关系。方法对77例海洛因依赖者定向术术前和术后6~12个月随访期内进行P300和正电子发射断层摄影术(PET)、功能磁共振成像(fMR I)检查,评估P300和脑功能成像的变化及其与手术疗效的关系,并与30名正常人比较,进行相关统计学分析。结果海洛因依赖者术前及术后随访复吸者P300中的P3波潜伏期延长和波幅降低,与术后未复吸者和正常对照组比较均存在显著性差异(P<0.01)。P300、PET、fMR I异常术前分别为63例、69例和54例,而随访时分别为32例、18例和13例,其中,疗效优者异常分别有9例、3例和2例,疗效差者有23例、15例和11例;而且,fMR I异常病例PET和P300均异常,PET异常病例P300均异常。各检查项目术前和随访时比较,及手术疗效优与手术疗效差组间比较均具有统计意义(P<0.05)。结论海洛因依赖者存在一定认知障碍和脑功能异常区,定向手术可以改善患者认知功能。手术前后事件相关电位P300和PET、fMR I的改变具有一定相关性并可以作为评估海洛因依赖者手术治疗效果的客观指标。     

Selective anterior cingulate cortex deficit during conflict solution in schizophrenia: an event-related potential study

BACKGROUND: Schizophrenia research has gained a new focus on identification and further characterization of neurocognitive deficits in the search for behavioural endophenotypes of this disorder. The objective of this study was to explore differential cortical processing during executive control in schizophrenia as assessed with the attention network test (ANT). METHODS: Sixteen schizophrenic patients and sixteen healthy controls matched for gender, age, education, and nicotine consumption were tested with the ANT while recording 29-channel-electroencephalogram (EEG). Visual event-related potentials (ERP) N200 and P300 were topographically analyzed and cortical mapping using low resolution brain electromagnetic tomography (LORETA) was applied to localize neuroelectric generators of ERP. RESULTS: Behaviourally, significant differences between schizophrenic patients and controls were found only for the conflict condition (p<0.05) and for conflict adjusted by mean reaction time (p<0.01). Examining ERP of control subjects, N200 failed to show robust flanker congruency effects. P300 amplitude was reduced at Pz (p<0.05) and P300 latency was increased at Cz (p<0.005) for the conflict condition. Schizophrenic patients differed significantly in P300 latency at Cz during late conflict processing (p<0.005). Source analysis revealed a deficit in anterior cingulate cortex (p<0.05). CONCLUSION: Our results are in line with previous reports about dysfunctional ACC activation in schizophrenia and argue in favour of a selective deficit of cortical conflict resolution. It is further proposed that dysfunctional ACC activation during executive processing may be a neurophysiologic endophenotype candidate of schizophrenia.     

The critical role of the inferior frontal cortex in establishing a prediction model for generating subsequent mismatch negativity (MMN): A TMS-EEG study

BackgroundThe prediction violation account of automatic or pre-attentive change detection assumed that the inferior frontal cortex (IFC) is involved in establishing a prediction model for detecting unexpected changes. Evidence supporting the IFC’s contribution to prediction model is mainly based on the Mismatch Negativity (MMN) to deviants violating predictions that are established based on the frequently presented standard events. However, deviant detection involves processes, such as events comparison, other than prediction model establishment.ObjectiveThe current study investigated the critical role of the IFC in establishing a prediction model during standards processing for subsequent deviant detection.MethodsTranscranial Magnetic Stimulation (TMS) was applied at the IFC to disrupt the processing of the initial 2 or 5 standards of a 3-, 6-, or 9-standard train, while the MMN responses to pitch deviant presented after the standard trains were recorded and compared.ResultsAn abolishment of MMN was only observed when TMS was delivered to the IFC at the initial 2 standards of the 3-standard train, but not at the initial 5 standards, or when TMS at the vertex or TMS sound recording was applied. The MMNs were also preserved when IFC TMS, vertex TMS, or TMS sound recording was applied at the initial 2 or 5 standards of longer trains.ConclusionThe IFC plays a critical role in processing the initial standards of a short standard train for subsequent deviant detection. This result is consistent with the prediction violation account that the IFC is important for establishing the prediction model.     

The use of neuroimaging to study behavior in patients with epilepsy

Structural and functional neuroimaging continues to play an increasing role in the presurgical evaluation of patients with epilepsy. In addition to its value in localizing the epileptogenic zone and eloquent cortex, neuroimaging is contributing to our understanding of mood comorbidity in epilepsy. Although the vast majority of research has focused on patients with temporal lobe epilepsy (TLE), neuroimaging studies of patients with extratemporal epilepsy and primary generalized epilepsy are increasing in number. In this review, structural and functional imaging modalities that have received considerable research attention in recent years are reviewed, and their strengths and limitations for understanding behavior in epilepsy are assessed. In addition, advances in multimodal imaging are discussed along with their potential application to the presurgical evaluation of patients with seizure disorders.     

The Potential for New Understandings of Normal and Abnormal Cognition by Integration of Neuroimaging and Behavioral Data: Not an Exercise in Carrying Coals to Newcastle

Discovering the means to prevent and cure schizophrenia is a vision that motivates many scientists. But in order to achieve this goal, we need to understand its neurobiological basis. The emergent metadiscipline of cognitive neuroscience fields an impressive array of tools that can be marshaled towards achieving this goal, including powerful new methods of imaging the brain (both structural and functional) as well as assessments of perceptual and cognitive capacities based on psychophysical procedures, experimental tasks and models developed by cognitive science. We believe that the integration of data from this array of tools offers the greatest possibilities and potential for advancing understanding of the neural basis of not only normal cognition but also the cognitive impairments that are fundamental to schizophrenia. Since sufficient expertise in the application of these tools and methods rarely reside in a single individual, or even a single laboratory, collaboration is a key element in this endeavor. Here, we review some of the products of our integrative efforts in collaboration with our colleagues on the East Coast of Australia and Pacific Rim. This research focuses on the neural basis of executive function deficits and impairments in early auditory processing in patients using various combinations of performance indices (from perceptual and cognitive paradigms), ERPs, fMRI and sMRI. In each case, integration of two or more sources of information provides more information than any one source alone by revealing new insights into structure-function relationships. Furthermore, the addition of other imaging methodologies (such as DTI) and approaches (such as computational models of cognition) offers new horizons in human brain imaging research and in understanding human behavior.

The usefulness of subtraction ictal SPECT coregistered to MRI in single- and dual-headed SPECT cameras in partial epilepsy

PURPOSE: To prove the clinical usefulness of SISCOM and compare SISCOM images derived from single- and dual-headed single-photon computed tomography (SPECT) cameras for localization of partial epileptic seizures. METHODS: We retrospectively studied 38 partial epilepsy patients, using subtraction SPECT coregistered to magnetic resonance imaging (MRI; SISCOM). SPECT imaging of the first 15 patients was performed by single-headed camera, and the next 23 patients by dual-headed camera. Side-by-side ictal-interictal SPECT evaluation and SISCOM images were blindly reviewed and classified as either localizing to one of 16 sites or nonlocalizing. A third reviewer evaluated cases of disagreement between primary reviewers. Results were compared with seizure localization by any of the following three traditional techniques: surgical outcome, invasive, and noninvasive video-EEG monitoring. The results from the single- and dual-headed SPECT cameras were compared. RESULTS: Reviewers localized areas of hyperperfusion with SISCOM images more often than with side-by-side SPECT evaluation (71.0 vs. 47.4%; p = 0.01). When we compared results of SPECT evaluation with traditional techniques, SISCOM showed greater concordance than side-by-side SPECT evaluation (60.53 vs. 36.84%; p = 0.006). There were no differences in localization between images derived from single- and dual-headed cameras. Concordance of seizure localization, compared with traditional techniques, also was not different between these groups [kappa = 0.38, 95% confidence interval (CI), 0.18-0.58] vs. kappa = 0.63, 95% CI (0.45-0.81)]. CONCLUSIONS: SISCOM is a worthwhile technique for preoperative evaluation in partial epilepsy patients and improves the sensitivity and specificity of seizure localization of SPECT images derived from both single- and dual-headed SPECT cameras.     

The N300 ERP component reveals developmental changes in object and action identification

Semantic mastery includes quickly identifying object and action referents in the environment. Given the relational nature of action verbs compared to object nouns, how do these processes differ in children and adults? To address this question the Event Related Potentials (EPRs) of 8–9 year olds and adults were recorded as they performed a picture-matching task in which a noun (chair) or verb (sit) was followed by a picture of an object and action (a man sitting in a chair). Adults and children displayed similar central N400 congruency effects in response to objects and actions. Developmental differences were revealed in the N300. Adults displayed N300 differences between congruent and incongruent items for both objects and actions. Children, however, exhibited an N300 congruency effect only for objects, indicating that although object noun representations may be adult-like, action verb representations continue to solidify through middle childhood. Surprisingly, adults also exhibited a posterior congruency effect that was not found in children. This is similar to the late positive component (LPC) reported by other studies of semantic picture processing, but the lack of such a response in children raises important questions about the development of semantic integration.     

The functional 5-HT1A receptor polymorphism affects response inhibition processes in a context-dependent manner

Cognitive control processes may depend on contextual information, sometimes improving performance, but impairing performance if expectancies about forthcoming events induce pre-potent responses. The neurobiological bases of these effects are not understood. Here, we examine context-dependent variations of response control processes using the AX-CPT task with respect to the relevance of the functional serotonin 1A receptor polymorphism (5-HT1A C(−1019)G) in a sample of healthy subjects (N = 90) by means of event-related potentials (ERPs).The results show that, when context information is helpful to drive behavioural performance, carriers of the −1019G allele reveal compromised cognitive control. Yet, they show enhanced task performance when strong context representations would lead to declines in behavioural control. These findings are paralleled by modulations of the (Nogo)-P3 ERP-component. These results show for the first time that, even though the −1019G allele enhances the risk to develop anxiety disorders, it also confers an advantage to its carriers in terms of better cognitive control processes in conditions where contextual information compromises cognitive control. Effects of the 5-HT1A C(−1019)G polymorphism were further modulated by anxiety sensitivity. As the functional effect of the 5-HT1A C(−1019)G polymorphism has previously been shown to be rather specific for serotonergic 1A autoreceptors in the dorsal raphe nucleus (DRN), the results suggest that contextual modulations in cognitive control may be exerted by the DRN.     

The hemodynamic response in children with Simplex Autism

BackgroundNumerous functional magnetic resonance imaging (fMRI) studies of the brain-bases of autism have demonstrated altered cortical responses in subjects with autism, relative to typical subjects, during a variety of tasks. These differences may reflect altered neuronal responses or altered hemodynamic response. This study searches for evidence of hemodynamic response differences by using a simple visual stimulus and elementary motor actions, which should elicit similar neuronal responses in patients and controls.MethodsWe acquired fMRI data from two groups of 16 children, a typical group and a group with Simplex Autism, during a simple visuomotor paradigm previously used to assess this question in other cross-group comparisons. A general linear model estimated the blood-oxygen-level-dependent (BOLD) signal time course, and repeated-measures analysis of variance tested for potential cross-group differences in the BOLD signal.ResultsThe hemodynamic response in Simplex Autism is similar to that found in typical children. Although the sample size was small for a secondary analysis, medication appeared to have no effect on the hemodynamic response within the Simplex Autism group.ConclusionsWhen fMRI studies show BOLD response differences between autistic and typical subjects, these results likely reflect between-group differences in neural activity and not an altered hemodynamic response.     

Influence of the OPRM1 gene polymorphism upon children's degree of withdrawal and brain activation in response to facial expressions

Genetic variation of the A118G polymorphism of the μ-opioid receptor gene (OPRM1) predicts individual sensitivity to social rejection and fMRI activation during simulated social rejection in adults, while data on these relationships during childhood are lacking. We investigated whether this polymorphism predicts childhood withdrawal - a predictor of sensitivity to social rejection -, and the face-specific N170 event-related waveform in response to facial expressions. Among facial expressions, 'anger' was expected to be particularly evocative, as it communicates social rejection. Forty-nine children aged 8-10 years were characterised for their OPRM1 genotype, their score at the Withdrawn Scale of the Child Behavior Checklist (CBCL), and for N170 latencies and amplitudes recorded during a task of implicit processing of happy, neutral, and angry expressions of other children. Children carrying the OPRM1-G allele had higher CBCL Withdrawn scores and enhanced N170 amplitudes in response to facial expressions. Multiple linear regressions showed that the Withdrawn scale score predicts larger N170 amplitudes at the Pz and C4 electrodes, only for the anger expression. Children who carry one or two copies of the OPRM1 G-allele are more likely to manifest withdrawn behaviours, and differ for electrophysiological responses to the early phases of processing affective stimuli.     

The effect of deep brain stimulation on the frontal N30 component of somatosensory evoked potentials in advanced Parkinson's disease patients.

OBJECTIVES: In the present study we investigated whether in advanced Parkinson's disease (PD) patients the frontal component of short somatosensory evoked potentials (SEPs) to median nerve stimulation may be modified by basal ganglia deep brain stimulation (DBS). METHODS: We recorded the SEPs in 6 PD patients undergoing bilateral functional neurosurgery in the internal globus pallidus (GPi) (4 patients) and in the nucleus subthalamicus (STN) (two patients) during ineffective and effective bilateral BDS. Pre-operatively, the SEPs were also recorded in off therapy and during apomorphine infusion. RESULTS: From the evaluation of the latency and the amplitude characteristics of the major parietal (N20 and P25) and frontal (N30) components, we observed that whereas the parietal waves did not vary in any condition, the N30 potential showed a remarkable amplitude increase during apomorphine as well as during effective bilateral GPi or STN DBS. Furthermore, after the stimulators were turned off we noticed that the N30 amplitude potential progressively faded almost in parallel with the attenuation of DBS clinical effects. CONCLUSIONS: Our results lead to the conclusion that the bilateral DBS of both GPi and STN is really effective in producing a selective increase of frontal N30 amplitude probably improving the supplementary motor area functional activity, but these results do not clarify whether this amelioration is due to a central or a 'long loop' mechanism.     

The effect of stimulation type,head modeling,and combined EEG and MEG on the source reconstruction of the somatosensory P20/N20 component

Modeling and experimental parameters influence the Electro‐ (EEG) and Magnetoencephalography (MEG) source analysis of the somatosensory P20/N20 component. In a sensitivity group study, we compare P20/N20 source analysis due to different stimulation type (Electric‐Wrist [EW], Braille‐Tactile [BT], or Pneumato‐Tactile [PT]), measurement modality (combined EEG/MEG – EMEG, EEG, or MEG) and head model (standard or individually skull‐conductivity calibrated including brain anisotropic conductivity). Considerable differences between pairs of stimulation types occurred (EW‐BT: 8.7 ± 3.3 mm/27.1° ± 16.4°, BT‐PT: 9 ± 5 mm/29.9° ± 17.3°, and EW‐PT: 9.8 ± 7.4 mm/15.9° ± 16.5° and 75% strength reduction of BT or PT when compared to EW) regardless of the head model used. EMEG has nearly no localization differences to MEG, but large ones to EEG (16.1 ± 4.9 mm), while source orientation differences are non‐negligible to both EEG (14° ± 3.7°) and MEG (12.5° ± 10.9°). Our calibration results show a considerable inter‐subject variability (3.1–14 mS/m) for skull conductivity. The comparison due to different head model show localization differences smaller for EMEG (EW: 3.4 ± 2.4 mm, BT: 3.7 ± 3.4 mm, and PT: 5.9 ± 6.8 mm) than for EEG (EW: 8.6 ± 8.3 mm, BT: 11.8 ± 6.2 mm, and PT: 10.5 ± 5.3 mm), while source orientation differences for EMEG (EW: 15.4° ± 6.3°, BT: 25.7° ± 15.2° and PT: 14° ± 11.5°) and EEG (EW: 14.6° ± 9.5°, BT: 16.3° ± 11.1° and PT: 12.9° ± 8.9°) are in the same range. Our results show that stimulation type, modality and head modeling all have a non‐negligible influence on the source reconstruction of the P20/N20 component. The complementary information of both modalities in EMEG can be exploited on the basis of detailed and individualized head models.     

N10 component in median nerve somatosensory evoked potentials (SEPs) is not an antidromic motor potential.

OBJECTIVE: To test the hypothesis that the N10 far-field potential in median nerve somatosensory evoked potentials is generated by the motor axons by examining patients with amyotrophic lateral sclerosis (ALS). METHODS: Subjects were 5 ALS patients showing pronounced or complete denervation of median-innervated small hand muscles. We evaluated N10 over scalp, and proximal plexus volleys (PPVs) at lateral or anterior cervical electrode. RESULTS: N10 and PPVs were definitely preserved for every ALS subject. N10 amplitudes of ALS subjects were even significantly larger than control subjects. In one ALS patient completely lacking motor axons, N10 was larger than the largest one among control subjects. CONCLUSIONS: Present results clearly indicate that N10 is not predominantly generated by motor axons but by the whole median nerve dominated by sensory axons. We propose a theory that N10 is a junctional potential generated by the entrance of the median nerve into bone at the intervertebral foramen, producing a positive pole at the non-cephalic reference electrode. Significantly larger N10 in ALS subjects may be due to the lack of cancellation by slower motor axons. SIGNIFICANCE: The hypothesis that N10 is generated by motor axons is refuted, and a new theory of its generation is presented.     

The role of neuroimaging in the surgical treatment of epilepsy

ABSTRACT— Resective surgical treatment of medically intractable epilepsy requires accurate identification of the site and extent of the epileptogenic zone responsible for habitual seizures. Epileptogenicity per se is demonstrated electrophysiologically, but interictal and ictal EEG transients, whether recorded extracranially or intracranially, propagate widely and can give rise to false lateralizing and false localizing information. Neuroimaging techniques provide additional important information which greatly enhances confidence in localization derived electrophysiologically. Structural imaging with X-ray computed tomography and magnetic resonance imaging, as well as functional imaging with positron emission tomography, single photon emission computed tomography, and computerized mapping of electromagnetic activity, used together with other tests of focal functional deficit, 1) increase the confidence with which surgical resection can be performed on the basis of noninvasive tests alone, 2) aid in developing appropriate strategy for intracranial electrode recording when this is necessary, and 3) supplement results of invasive studies sufficiently to justify surgical resection in some patients who otherwise might be rejected for surgery. Addition of these new techniques, therefore, has increased the number of patients considered candidates for surgery, decreased the number of invasive procedures necessary before surgery can be performed, and increased the accuracy of surgical resection.