非空间线索相容性事件相关电位研究

目的:通过考察前置线索与刺激在颜色与形状2个维度上的重合关系对目标刺激的影响,探讨刺激与反应在不相容程度条件下,线索与刺激的相容性对反应产生影响的神经基础。方法:实验于2003-11在北京师范大学心理学院实验室完成。对象为北京师范大学本科生12人。均为右利手,视力或矫正视力正常,颜色知觉正常。实验在隔音的暗室中进行,刺激是红、绿、蓝3种颜色的平面图形和立体图形,自变量是线索和目标的4个对应关系。每次实验开始前,屏幕中央呈现注视点1000ms,间隔300ms之后呈现线索1000ms,再间隔300ms呈现目标,要求被试按反应盒上的1,2,4键对目标做出反应。实验216次,按随机顺序呈现。记录从刺激呈现前200ms到呈现后1000ms前部的15个电极和后部的8个电极,并按照4个时间窗口(100～160ms,前部N1,后部P1;170～230ms,N2;280～400ms,前部P3;320～420ms,后部P3)的峰值和潜伏期进行统计分析。结果:12人均获检测,全部进入结果分析。①额叶与顶叶N1和P3的峰值分析:在刺激呈现以后100～160ms,额叶和顶叶的N1波的不同条件的主效应显著,电极位置的主效应显著。电极与条件的交互作用不显著。在刺激呈现之后280～400ms,P3波的条件主效应也接近显著,电极位置的主效应显著。②枕叶P1、N2、P3的峰值分析:在刺激呈现之后100～160ms,枕叶P1波条件的主效应不显著,而电极位置的主效应显著。在170～230ms,N2波主效应接近显著,线索与目标形状相同颜色不同时诱发了更负的波。电极位置的主效应也是接近显著的。但P1和N2的条件和电极交互作用均不显著。P3(320～420ms)波的条件和电极位置的交互作用显著。简单效应分析结果显示,除在P4和P12个电极上,4种条件的差异接近显著,在其他6个电极上,4种条件的差异都非常显著。线索和目标在2个维度完全重合条件下诱发了更正的波,颜色相同形状不同时峰值居中,而形状和颜色都不同、形状相同颜色不同时峰值最小。③潜伏期的分析:额叶和顶叶N1波的条件主效应显著。P3波的条件主效应也显著,与额叶和顶叶相比,枕叶的3种事件相关电位成分P1、N2和P3的潜伏期的主效应均不显著。额叶和顶叶的N1波在早期刺激-反应相容性任务加工中对形状较为敏感,P3波对颜色较为敏感。结论:额叶和顶叶对刺激-反应相容性任务加工的早期起着主要作用,枕叶在刺激-反应相容性任务加工后期选择反映阶段的作用更为明显。额叶和顶叶的N1波在早期刺激-反应相容性任务加工中表现出对形状判断较为敏感,P3波对颜色的状判断较为敏感。刺激-反应相容性效应可能是视觉-动作转换或是对不同反应的选择造成的,注意在刺激-反应相容性任务中对形状加工起着十分重要的作用。     

非空间线索相容性事件相关电位研究

目的：通过考察前置线索与刺激在颜色与形状2个维度上二的重合关系对目标刺激的影响，探讨刺激与反应在不相容程度条件下，线索与刺激的相容性对反应产生影响的神经基础。方法：实验于2003—11在北京师范大学心理学院实验室完成。对象为北京师范大学本科生12人。均为右利手，视力或矫正视力正常，颜色知觉正常。实验在隔音的暗室中进行，刺激是红、绿、蓝3种颜色的平面图形和立体图形，自变量是线索和目标的4个对应关系。每次实验开始前，屏幕中央呈现注视点1000ms，间隔300ms之后呈现线索1000ms．再问隔300ms呈现目标，要求被试按反应盒上的1，2，4键对目标做出反应。实验216次，按随机顺序呈现。记录从刺激呈现前200ms到呈现后1000ms前部的15个电极和后部的8个电极，并按照4个时间窗口（100～160ms，前部N1，后部P1；170～230ms，N2；280～400ms，前部P3；320-420ms，后部P3）的峰值和潜伏期进行统计分析。结果：12人均获检测，全部进入结果分析、①额叶与顶叶N1和P3的峰值分析：在刺激呈现以后100-160ms，额叶和顶叶的N1波的不同条件的主效应显著，电极位置的主效应显著。电极与条件的交互作用不显著．在刺激呈现之后280～400ms，P3波的条件主效应也接近显著．电极位置的主效应显著。②枕叶P1、N2、P3的峰值分析：在刺激呈现之后100-160ms，枕叶P1波条件的主效应不显著．而电极位置的主效应显著。在170-230ms，N2波主效应接近显著．线索与目标形状相同颜色不同时诱发了更负的波。电极佗置的主效应也是接近显著的．但P1和N2的条件和电极交互作用均不显著。P3（320～420ms）波的条件和电极位置的交互作用显著。简单效应分析结果显示，除在P4和P12个电极上，4种条件的差异接近显著，在其他6个电极上，4种条件的差异都非常显著．线索和目标在2个维度完全重合条件下诱发了更正的波．颜色相同形状不同时峰值居中，而形状和颜色都不同、形状相同颜色不同时峰值最小．③潜伏期的分析：额叶和顶叶N1波的条件主效应显著．P3波的条件主效应也显著，与额叶和顶叶相比，枕叶的3种事件相关电位成分P14、N2和P3的潜伏期的主效应均不显著。额叶和顶叶的N1波在早期刺激-反应相容性任务加工中对形状较为敏感．P3波对颜色较为敏感。结论：额叶和顶叶对刺激一反应相容性任务加工的早期起着主要作用，枕叶在刺激-反应相容性任务加工后期选择反映阶段的作用更为明显：额叶和顶叶的N1波在早期刺激-反应相容性任务加丁中表现出对形状判断较为敏感，P3波对颜色的状判断较为敏感。刺激-反应相容性效应可能是视觉-动作转换或是对不同反应的选择造成的，注意在刺激-反应相容性任务中对形状加工起着十分重要的作用．     

Separating distractor rejection and target detection in posterior parietal cortex--an event-related fMRI study of visual marking

Successful survival in a competitive world requires the employment of efficient procedures for selecting new in preference to old information. Recent behavioral studies have shown that efficient selection is dependent not only on properties of new stimuli but also on an intentional bias that we can introduce against old stimuli. Event-related analysis of functional magnetic resonance imaging data from a task involving visual search across time as well as space indicates that the superior parietal lobule is specifically involved in processes leading to the efficient segmentation of old from new items, whereas the temporoparietal junction area and the ascending limb of the right intraparietal sulcus are involved in the detection of salient new items and in response preparation. The study provides evidence for the functional segregration of brain regions within the posterior parietal lobe.     

Using voxel-specific hemodynamic response function in EEG-fMRI data analysis: An estimation and detection model

Research groups who study epileptic spikes with simultaneous EEG-fMRI have used mostly the general linear model (GLM). A shortcoming of the GLM is that the specification of a simple hemodynamic response function (HRF) may lead to biased results. Other methods, which predict the hemodynamic response from the measured data, have been termed "recognition models". The merit of recognition models lies in the power of estimating the region-specific or voxel-specific HRF. We propose an approach that merges these two models in a general framework: estimate the HRF on the training data sets, and applying the estimated HRF on the other part of the data sets. The merit of this framework is that it can utilize the advantages of both models. A comparison of performance is made between the GLM with three fixed HRFs and the new model with voxel-specific HRFs. The main results are as follows: (1) in 18 of the 21 patients, the new model has a higher adjusted coefficient of multiple determination than the GLM with fixed HRF; (2) in some subjects, with the new model, we found areas of activation that had not been detected with the three fixed HRFs at our threshold of significance. The results suggest that the new model can do better than the fixed HRF GLM for the analysis of epileptic activity with EEG-fMRI.     

Novelty and target processing during an auditory novelty oddball: a simultaneous event-related potential and functional magnetic resonance imaging study

Recent evidence suggests that both spatiotemporally distinct and overlapping brain regions are involved in bottom-up- and top-down-driven attentional processing. However, existing studies are based on a variety of different approaches, including electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), raising the question of how EEG and fMRI findings in this field are related to each other. The present study aimed at disentangling common from specific regions underlying bottom-up novelty-processing and top-down target-processing. Simultaneous EEG and fMRI recordings were employed to investigate how fMRI-identified brain regions contribute to event-related potential (ERP) signatures of novelty- and target-processing. Fourteen subjects performed a modified novelty oddball task in which either rare tones or novel sounds served as targets in different blocks, allowing us to separate novelty-related from mere distractor-related effects. ERP signatures of novelty- and target-processing could be identified, confirming previous research based on recordings outside the scanner. fMRI analyses revealed that, despite considerable overlap of regions activated during novelty- and target-processing, bilateral superior temporal and right inferior frontal areas showed pronounced activation related to novelty-processing. fMRI-informed ERP dipole seeding was used to integrate both signals. The source modeling results further implicated temporal and inferior frontal sources in novelty-processing. Target-related fMRI activation on the other hand was confirmed in a network comprising distributed frontoparietal regions as well as bilateral caudate nucleus and cerebellum. Most regions identified by fMRI showed a contribution to target-related ERP signatures. This pattern of findings underscores the potential of simultaneous EEG/fMRI recordings for the spatiotemporal characterization of target- and novelty-processing.     

汉语成语N400在神经衰弱和抑郁症患者事件相关电位检测中的应用研究

目的采用汉语成语作为N400刺激物,探讨神经衰弱与抑郁症患者事件相关点位N400的关系。方法选择2011年3月—2013年3月在本院心理门诊和住院的神经衰弱和抑郁症患者,并选取40例正常人作为对照组。采用汉语成语作为N400刺激物,观察受试者的N400的测量。结果 MMSE评分B组、A组、C组呈上升趋势,且两两之间比较均有显著差异（P均〈0.01）;HAMD-17总分B组、A组、C组呈逐渐下降趋势,且两两之间比较也均有显著差异（P均〈0.01）;N400潜伏期B组、A组、C组呈逐渐下降趋势,且两两之间比较均有显著差异（P均〈0.05）;N400波幅C组、A组、B组呈逐渐下降趋势,且A组与C组、B组与C组间存在显著差异（P均〈0.01）;抑郁症患者组的N400潜伏期延长与HAMD-17评分呈正相关关系（r=0.321,P=0.026）。结论相较于正常人,神经衰弱与抑郁症患者的思维减慢,对汉语成语的理解、抽象概括能力降低,且抑郁症患者表现得更为突出;抑郁症患者Cz脑区的N400潜伏期与HAMD-17评分是呈正相关的。     

Real-time detection of event-related brain activity

The complexity and inter-individual variation of brain signals impedes real-time detection of events in raw signals. To convert these complex signals into results that can be readily understood, current approaches usually apply statistical methods to data from known conditions after all data have been collected. The capability to provide meaningful visualization of complex brain signals without the requirement to initially collect data from all conditions would provide a new tool, essentially a new imaging technique, that would open up new avenues for the study of brain function. Here we show that a new analysis approach, called SIGFRIED, can overcome this serious limitation of current methods. SIGFRIED can visualize brain signal changes without requiring prior data collection from all conditions. This capacity is particularly well suited to applications in which comprehensive prior data collection is impossible or impractical, such as intraoperative localization of cortical function or detection of epileptic seizures.     

Lactate: biomarker and potential therapeutic target

Lactate levels are frequently elevated in critically ill patients and correlate well with disease severity. Elevated lactate levels are prognostic in prehospital, emergency department, and intensive care unit settings. This review discusses the role of lactate as a biomarker in diagnosing and assessing the severity of systemic hypoperfusion, as well as the role of serum lactate measurements in guiding clinical care and enabling prognosis in critically ill patients.     

Overview of artifact reduction and removal in evoked potential and event-related potential recordings

Artifact in one form or another needs to be contended with in all EEG and EP studies. Various methods have been employed to avoid, eliminate, or minimize artifact. This article has described the methods that have been available for some time and newer methods and their advantages. It is the authors' hope that through the use of these methods the accuracy of all EP and ERP measurements will be improved and promote the validity and general acceptance of EP and ERP recordings. Genuine and valuable data are contained in EPs and ERPs. The challenge is to extract relatively small voltage signals often occurring within a higher voltage background of artifact. The computing power required to perform the artifact removal/reduction procedures now is available with basic laptop and desktop computers, as are the software programs that provide the artifact removal/reduction capabilities. It may be of interest for a prudent researcher to integrate the currently available artifact rejection methods before subjecting the ERP and EP data for further analysis and subsequent publication.     

Context effects on odor processing: an event-related potential study

The present study aimed to investigate the effects of cognitive/emotional bias on central nervous odor processing. Forty-five female participants were divided into three groups and were either led to believe the odor was a natural, healthy extract (positive bias), potentially hazardous (negative bias), or a common test odorant (control). The odor (isobornyl acetate) was presented via a constant-flow olfactometer and the EEG was recorded from 60 scalp locations. In the negative bias condition, participants reported reduced well-being and judged the odor as less pleasant. However, neither the thresholds nor the intensity ratings were changed by the context condition. Chemosensory event-related potential (CSERP) analysis revealed that the latencies of the N1 and P2 components were prolonged in the negative bias condition and shortened in the positive bias condition. Current source densities were most prominent in the frontal lobe in negatively biased participants. The findings show that expecting to perceive an emotionally significant odor affects the early encoding of odors.     

癫(癎)患者抑郁情绪及其事件相关电位研究

目的:探讨癫癎患者抑郁情绪及其事件相关电位特征,为癫癎病情判定寻找更多的实验室依据。方法:52例癫癎患者和50例健康对照者分别进行汉密尔顿抑郁量表评定和事件相关电位测定,将结果进行对比分析。结果:癫癎组事件相关电位测定的异常率为73.1%(38/52),事件相关电位中N2,P3波潜伏期较对照组延长,P3波幅降低,差异有统计学意义(P<0.01),汉密尔顿抑郁量表评定中相关因子分和总分值与对照组相比,差异有统计学意义(P<0.01)。事件相关电位成分中P3波潜伏期与汉密尔顿抑郁量表评定中相关因子分呈正相关(P<0.01),而P3波幅与其呈负相关(P<0.01)。结论:癫癎患者抑郁情绪及认知障碍明显,事件相关电位测定可作为癫癎患者认知功能的判定指标。     

Regional differences in the refractory period of the hemodynamic response: an event-related fMRI study.

We investigated the characteristics of the hemodynamic response (HDR) to paired presentations of visual face stimuli using functional magnetic resonance imaging (fMRI). Photographs of faces were presented singly or in pairs with either a 1-s or 6-s intrapair interval (IPI). Each trial (single face or face pairs) was followed by an intertrial interval of 16-20 s. Faces were presented at fixation and passively viewed by the 10 subjects. Images were acquired at 1.5 Tesla using a gradient-echo echo-planar imaging sequence sensitive to blood-oxygenation-level-dependent (BOLD) contrast. To examine the refractory properties of the HDR, we subtracted the single-stimulus hemodynamic response from the composite response evoked by face pairs for all voxels significantly active on single face trials. The residual represents the contribution of the second stimulus to the fMRI signal. Event-related presentation of faces evoked activity in medial calcarine cortex and the fusiform gyrus bilaterally. In both calcarine and fusiform regions, the hemodynamic response to the second face in a pair was of lower amplitude and of increased latency at 1 s IPI, with significant recovery of both amplitude and latency toward single-stimulus values at 6 s IPI. At 1 s IPI, significantly greater recovery was found in posterior fusiform regions (50-60%) than in midfusiform regions (10-40%). These regional differences were not apparent at 6 s IPI. No differences were found across slices in calcarine cortex. There was a significant difference in mean latency to HDR peak between calcarine and fusiform cortex, with the HDR peaking about 400 ms earlier in calcarine cortex. We conclude that characteristics of the HDR, notably its amplitude, latency, and refractory properties, differ across visual cortical areas.     

Single-trial P3 amplitude and latency informed event-related fMRI models yield different BOLD response patterns to a target detection task

Using single-trial parameters as a regressor in the General Linear Model (GLM) is becoming an increasingly popular method for informing fMRI analysis. However, the parameter used to characterise or to differentiate brain regions involved in the response to a particular task varies across studies (e.g. ERP amplitude, ERP latency, reaction time). Furthermore, the way in which the single-trial information is used in the fMRI analysis is also important. For example, the single-trial parameters can be used as regressors in the GLM or to modify the duration of the events modelled in the GLM. The aim of this study was to investigate the BOLD response to a target detection task when including P3 amplitude, P3 latency and reaction time parameters in the GLM. Simultaneous EEG-fMRI was recorded from fifteen subjects in response to a visual choice reaction time task. Including P3 amplitude as a regressor in the GLM yielded activation in left central opercular cortex, left postcentral gyrus, left insula, left middle frontal gyrus, left insula and left parietal operculum. Using P3 latency and reaction time as an additional regressor yielded no additional activation in comparison with the conventional fMRI analysis. However, when P3 latency or reaction time was used to determine the duration of events at a single-trial level, additional activation was observed in the left postcentral gyrus, left precentral gyrus, anterior cingulate cortex and supramarginal gyrus. Our findings suggest that ERP amplitudes and latencies can yield different activation patterns when used to modify relevant aspects of the GLM.     

Detection of event-related hemodynamic response to neuroactivation by dynamic modeling of brain activity

This paper presents a state-space hemodynamic model by which any event-related hemodynamic prediction function (i.e., the basis function of the design matrix in the general linear model) is obtained as an output of the model. To model the actual event-related behavior during a task period (intra-activity dynamics) besides the contrasting behavior among the different task periods and against the rest periods (inter-activity dynamics), the modular system is investigated by parametric subspace-based state-space modeling of actual hemodynamic response to an impulse stimulus. This model provides a simple and computationally efficient way to generate the event-related basis function for an experiment by just convolving the developed hemodynamic model with the impulse approximation of the experimental stimuli. The demonstration of the stated findings is carried out by conducting finger-related experiments with slow- and fast-sampling near-infrared spectroscopy instruments to model and validate the cortical hemodynamic responses. The generated basis functions of the finger-related experiments are adapted from real data to validate the incorporation of non-delayed and real-time event-related features and to effectively demonstrate a dynamic-modeling-based online framework. The proposed method demonstrates potential in estimating event-related intra- and inter-activation dynamics and thereby outperforms the classical Gaussian approximation method.     

Double dissociation between rules and memory in music: an event-related potential study

Language and music share a number of characteristics. Crucially, both domains depend on both rules and memorized representations. Double dissociations between the neurocognition of rule-governed and memory-based knowledge have been found in language but not music. Here, the neural bases of both of these aspects of music were examined with an event-related potential (ERP) study of note violations in melodies. Rule-only violations consisted of out-of-key deviant notes that violated tonal harmony rules in novel (unfamiliar) melodies. Memory-only violations consisted of in-key deviant notes in familiar well-known melodies; these notes followed musical rules but deviated from the actual melodies. Finally, out-of-key notes in familiar well-known melodies constituted violations of both rules and memory. All three conditions were presented, within-subjects, to healthy young adults, half musicians and half non-musicians. The results revealed a double dissociation, independent of musical training, between rules and memory: both rule violation conditions, but not the memory-only violations, elicited an early, somewhat right-lateralized anterior-central negativity (ERAN), consistent with previous studies of rule violations in music, and analogous to the early left-lateralized anterior negativities elicited by rule violations in language. In contrast, both memory violation conditions, but not the rule-only violation, elicited a posterior negativity that might be characterized as an N400, an ERP component that depends, at least in part, on the processing of representations stored in long-term memory, both in language and in other domains. The results suggest that the neurocognitive rule/memory dissociation extends from language to music, further strengthening the similarities between the two domains.     

Ventilatory and hemodynamic management of potential organ donors: an observational survey

OBJECTIVE: To determine the current standard ventilatory and cardiovascular management in potential organ donors. DESIGN: Prospective, multiple-center, observational survey. SETTING: A total of 15 intensive care units in 13 hospitals in Piedmont, Italy. PATIENTS: A total of 34 brain-dead patients enrolled in 6 months. MEASUREMENTS AND MAIN RESULTS: Demographics and reasons for lung transplant exclusion were recorded. Ventilatory and hemodynamic variables were compared before and after confirmation of brain death. A total of 23 potential donors were ineligible for lung donation based on pulmonary status and age. Of the 11 eligible lung donors, only two donated the lungs because five had Pao2/Fio2 ratios of <300 and four were ineligible for logistic problems. Tidal volume was 10 +/- 2 mL/kg, positive end-expiratory pressure was 3.3 +/- 2.7 cm H2O, Fio2 was 50% +/- 18% before brain death diagnosis, and no changes were made after brain death confirmation. In potential lung donors, apnea tests were performed with apneic oxygenation after disconnection from the ventilator in all cases; tracheal suction was performed with an open circuit in eight cases, and no recruitment maneuvers were performed. Crystalloid infusion was increased after diagnosis of brain death from 187 +/- 151 to 275 +/- 158 mL/hr (p < .05), and central venous pressure increased from 6 +/- 3 to 7 +/- 3 mm Hg (p < .05). Inotropic support was used in 24 donors (70%). CONCLUSIONS: Five of 11 potential lung donors (45%) had a Pao2/Fio2 ratio of <300, making them ineligible for lung donation. After the diagnosis of brain death, ventilatory management remained the same, no maneuvers for prevention of derecruitment of the lung were performed, and cardiovascular management was modified to optimize peripheral organ perfusion. These data represent the current standard of care for ventilatory management of potential organ donors and may be suboptimal in preserving lung function.     

Phantom calibration method for improved temporal characterization of hemodynamic response in event-related fMRI

In event-related functional MRI, there exist limits on the time length of the experiments on human subjects and the imaging speed. Due to these limitations, data truncation and undersampling have to be used in functional MRI signal acquisition. The effect of these factors on the hemodynamic deconvolution is investigated experimentally and a phantom calibration method to improve the hemodynamic response is developed. It is observed that the high frequency components generated due to data truncation can fold back into low frequencies when the sampling rate is not sufficiently high. This aliasing can introduce significant noise in hemodynamic deconvolution and can reduce the accuracy of the temporal characterization of hemodynamic response. A SMARTPHANTOM BOLD simulator is used to calibrate the aliasing effect in an event-related functional MRI experiment. With the calibration, an anti-aliasing method is used to suppress the aliasing and this resulted in an improved temporal characterization of hemodynamic response in event-related fMRI.     

血管性痴呆患者事件相关电位P300的实验

背景在对血管性痴呆的诊断和治疗效果的评价过程中,最突出的问题是缺乏一种客观、敏感的手段来评估患者的痴呆程度及其变化,以便及时对患者作出诊断或对其疗效进行考核.事件相关电位的内源成分P300,与受试者的认知加工过程密切相关,而与刺激的性质无关,是客观反映大脑高级心理活动最有价值的可靠指标之一.目的探讨事件相关电位P300对血管性痴呆患者的作用和意义,为血管性痴呆的临床诊断和疗效考核提供客观依据.设计以患者为研究对象,非随机同期化对照的验证性研究.单位一所省级医院的神经内科和肌电图室和一所大学医院的神经内科.对象2000-02/2001-06重庆医科大学附属第二医院神经内科门诊及住院的血管性痴呆患者64例(血管性痴呆组),其中,男38例,女26例,平均年龄(66.0±4.6)岁.文化程度中学以上19人,小学31例,文盲14例.同期住院的未发生血管性痴呆的脑卒中患者60例(非血管性痴呆组),其中,男35例,女25例,平均年龄(68.0±3.7)岁.文化程度中学以上15例,小学29例,文盲16例.方法用简易智能量表考核血管性痴呆组和非血管性痴呆组患者的智能状况,并对其进行P300检测,观察患者P300的潜伏期及波幅的改变,并比较二者在血管性痴呆组和非血管性痴呆组患者间的差异,同时观察患者P300潜伏期与简易智能量表得分相关性.主要观察指标P300的潜伏期及波幅的改变.P300潜伏期与简易智能量表得分相关性.结果血管性痴呆组和非血管性痴呆组患者P300潜伏期延长率分别为74%和7%,两组患者间差异有显著性,同时患者P300潜伏期与简易智能量表得分有明显相关性(r=0.609 6,P＜0.05).结论P300潜伏期可以作为血管性痴呆患者早期诊断和疗效考核的客观指标.     

Neuronal inhibition and excitation, and the dichotomic control of brain hemodynamic and oxygen responses

Brain's electrical activity correlates strongly to changes in cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO(2)). Subthreshold synaptic processes correlate better than the spike rates of principal neurons to CBF, CMRO(2) and positive BOLD signals. Stimulation-induced rises in CMRO(2) are controlled by the ATP turnover, which depends on the energy used to fuel the Na,K-ATPase to reestablish ionic gradients, while stimulation-induced CBF responses to a large extent are controlled by mechanisms that depend on Ca(2+) rises in neurons and astrocytes. This dichotomy of metabolic and vascular control explains the gap between the stimulation-induced rises in CMRO(2) and CBF, and in turn the BOLD signal. Activity-dependent rises in CBF and CMRO(2) vary within and between brain regions due to differences in ATP turnover and Ca(2+)-dependent mechanisms. Nerve cells produce and release vasodilators that evoke positive BOLD signals, while the mechanisms that control negative BOLD signals by activity-dependent vasoconstriction are less well understood. Activation of both excitatory and inhibitory neurons produces rises in CBF and positive BOLD signals, while negative BOLD signals under most conditions correlate to excitation of inhibitory interneurons, but there are important exceptions to that rule as described in this paper. Thus, variations in the balance between synaptic excitation and inhibition contribute dynamically to the control of metabolic and hemodynamic responses, and in turn the amplitude and polarity of the BOLD signal. Therefore, it is not possible based on a negative or positive BOLD signal alone to decide whether the underlying activity goes on in principal or inhibitory neurons.