Interictal and postictal contingent negative variation in migraine without aura

Cortical hyperexcitability is thought to explain the more enhanced contingent negative variation (CNV) amplitudes and impaired CNV habituation that have been found during the interictal period in migraine without aura. These CNV characteristics have been shown to normalize to the level of healthy controls during an attack. This study aimed to replicate the interictal findings, and additionally examine whether migraineurs show reduced CNV amplitudes during the postattack period. Of 12 patients with migraine without aura and their sex- and age-matched healthy controls, CNV characteristics were recorded once in an interictal period, once during the postattack period within 30 hours after an attack that was treated with sumatriptan, and once after an attack that was treated with habitual nonvasoactive medication (counterbalanced). The present results did not confirm the enhanced CNV early and late wave amplitudes or impaired habituation, and cortical hyperexcitability that have previously been reported in the interictal period in patients with migraine without aura. During the postattack period, a decrease in CNV early and late amplitudes was found but only after sumatriptan use. This reduction in CNV amplitudes was most prominent over the frontal cortex and could reflect cortical hypoexcitability, possibly related to a suppression of central catecholaminergic activity by sumatriptan.     

Developmental changes of the contingent negative variation in migraine and healthy children

It has been hypothesized that abnormalities of information processing in migraine may be attributed to impairment of cerebral maturation. However, the most evidences for this hypothesis have come from cross-sectional studies during childhood. We performed a longitudinal study and recorded contingent negative variation (CNV), an event-related slow cortical potential, in migraine children (n = 27) and age-matched healthy individuals (n = 23) in 1998 and 8 years later (2006). Amplitudes of all CNV components were reduced and habituation of the initial CNV (iCNV) increased in the observed time. However, the reduction of the iCNV amplitude was more pronounced in migraine patients who were in remission in 2006 and in healthy subjects and less pronounced in migraineurs with persisting headaches. Patients with the worsened migraine demonstrated the most pronounced loss of iCNV habituation in 1998 and significantly increased iCNV amplitudes in 2006. This longitudinal study supports the hypothesis of impaired cerebral maturation in migraine and shows that migraine manifestation is a key factor interfering with the natural maturation process of central information processing.     

Influence of MTHFR genotype on contingent negative variation and MRI abnormalities in migraine

BACKGROUND: The MTHFR C677T genotype has been associated with increased risk of migraine, particularly of migraine with aura (MA) in selected clinical samples and with elevated homocysteine. The hyper-homocysteinemia may favor the vascular and neuronal mechanism underlying migraine, and the risk of stroke. OBJECTIVE: The first aim of the present study was to examine the Contingent Negative Variation (CNV) amplitude and habituation pattern in a migraine sample versus non-migraine subjects, at the light of the MTHFR genotype, according to an unrelated and clinical based case-control panel. The second aim was to compare the frequency of Magnetic Resonance Imaging (MRI) subclinical brain lesions across the different C677 genotypes in the same migraine sample, selected for the young age and the absence of any cardiovascular risk factor. METHODS: One hundred and five 18-45 year old out-patients, 90 affected by migraine without aura (MO) and 15 by MA, and 97 non-migraine healthy subjects, age and sex matched, were selected for the genetic analysis. All subjects had a common ethnic origin from Puglia. Sixty-four migraine subjects and 33 control subjects were submitted to the recording of the CNV. All migraine subjects underwent the MRI evaluation. RESULTS: The frequency of homozygosis was 14.33% in normal subjects, versus 25.7% in MA + MO group (chi2-test: 10.80 P= .001). The frequency of homozygosis in MO patients, was 25.5% (MA versus N: chi2-test: 9 P= .003), in MA group it was 26.6%. Considering the MTHFR genotype in migraine patients and controls, the C677TT subjects exhibited a reduced habituation index of the early CNV (iCNV), in respect with both C677TC and C677CC; in the migraine group, there was a significant decrease of CNV habituation in patients with homozygosis and a positive correlation between the habituation index values and the homocysteine levels. Nineteen migraine patients exhibited subclinical brain lesions (18.05%): patients with C677T homozygosis did not exhibit a higher risk for MRI abnormalities. CONCLUSIONS: This unrelated and clinical based case-control study showed that genetically induced hyper-homocysteinemia may favor the neuronal factors predisposing to migraine, while it does not influence the presence of subclinical vascular brain lesions probably linked with increased risk of stroke.     

Contingent negative variation in childhood migraine

Adult migraineurs without aura have an increased amplitude of the Contingent Negative Variation (CNV) between attacks. Given the potential diagnostic importance of this finding and the difficulties associated with diagnosing migraine in childhood it seemed important to assess CNV in children suffering from this disorder. Ninety-seven children aged between 8 and 14 years were recruited. Forty-two suffered from migraine, 34 from tension-type headache. Twenty-one healthy controls were also studied. CNV was recorded from Fz, Cz and Pz referenced to linked earlobes during 20 trials consisting of two tones of moderate intensity with an interstimulus interval (ISI) of 4 sec and an intertrial interval (ITI) of 10 to 14 sec. The second tone of each trial required a button press. EOG was recorded from the left eye. The 10 CNV responses with the least EOG artefact were selected and averaged. Children with migraine had a highly significantly more negative mean CNV amplitude at all three electrode sites than children with tension-type headache and also a more pronounced Post-Imperative-Negative-Variation (PINV). Migrainous children differed from controls only at Cz (ISI). There was also a highly significant increase of mean CNV amplitude and PINV at all three electrode sites in the control group compared to the tension headache group.     

Is increased amplitude of contingent negative variation in migraine due to cortical hyperactivity or to reduced habituation?

The aim of this study was to compare the habituation kinetics of contingent negative variation (CNV) between 12 migraineurs without aura and matched healthy controls. CNV was studied with a 3 sec interval between the warning stimulus (WS) and the imperative stimulus (IS). The data from (a) the total interval (WS-IS), (b) early component, and (c) late component were analyzed. During successive trials the habituation kinetics were determined using regression analysis. On CNV averaged over 32 trials, migraine patients had a significantly higher negativity in the total interval compared to controls. When sequential blocks of four trials were analyzed, the most significant finding in migraineurs was lack of habituation of the early CNV component. The present study indicates that a delayed habituation, rather than a general increased cortical activity, is responsible for the CNV abnormalities in migraine without aura. We suggest that migraineurs between attacks not only have a cortical hyperexcitability, but also a lack of cortical inhibition causing delayed habituation.     

情感障碍患者关联性负变实验观察

背景：关联性负变是与精神医学和心理学关系最为密切的一种脑诱发电位。 目的：探讨情感障碍患者与正常成人在关联性负变检测中的不同表现。 设计：病例一对照实验。 单位：山东省淄博市精神病医院功能科。对象：选择2005—02／2006—01在山东省淄博市第五人民医院就诊和住院的情感障碍患者29例，男14例，女15例，监护人均知情同意，所有患者均符合精神病诊断与分类手册DSM—IV的躁狂抑郁症诊断标准。将情感障碍患者按入院时的精神状态分为躁狂相和抑郁相2组。躁狂相组11例，Bech—Rataelson躁狂量表评分大于16分。抑郁相组18例，分为单相（目前抑郁以往无躁狂）11例及双相（目前抑郁有过躁狂）7例，汉密顿抑郁量表评分大于24分。选择27例身心健康的医院职工作为对照组，男14例，女13例，年龄21～53岁，平均年龄（32．5&;#177;5．9）岁，3组受试者年龄、性别差异无显著性。 方法：实验在屏蔽的隔音室中进行，被试者坐于软椅上，双眼向前看一目的物，在实验过程中，保持清醒。记录电极用8mm铂金头皮电极，位置参照国际脑电图学会10／20标准。颅顶有效电极置于Cz，参考电极置于右乳突。两眉中点上2cm处接地。关联性负变波形用函数记录仪描记。标准的关联性负变模式由光信号及短声信号组成。闪光灯和扬声器置于被试者正后方，被试者双耳接受短声信号后，即用右手指按手握式电键，瞬时切断短声。从同步光信号发出开始，全程持续2500ms为一次关联性负变记录，每20次叠加为一轮实验。每例被试者接受2轮实验，实验结束后，以20μV标准电压输入上述系统作同样次数叠加处理，作为波幅测量标准。主要观察指标：各组受试者的关联性负变的潜伏期，波幅B、指令信号前负相期待波面积、指令信号后负变化面积。结果：纳入患者56例全部进入结果分析。躁狂相组患者关联性负变波幅B较对照组高[（22．8&;#177;4．8）μV；（16．0&;#177;5．7）μV；P〈0．01]，抑郁相组患者指令信号前负相期待波面积较对照组小[（292．8&;#177;161．6）μV。；（412．8&;#177;-159．9）μV。；P〈0．01]，抑郁相组患者关联性负变指令信号后负变化潜伏期延长[（261．9&;#177;79．3）ms；（211．9&;#177;36．3）ms；P〈0．05]，抑郁相单相组比双相组的关联性负变指令信号后负变化潜伏期显著延长[（344．5&;#177;66．9）ms；（230．4&;#177;83．8）ms；P〈0．01]。 结论：关联性负变和指令信号后负变化等提示关联性负变潜伏期延长可能是抑郁相单相患者的素质标记，而关联性负变波幅的变化则可能是情感障碍患者的状态标记。     

情感障碍患者关联性负变实验观察

背景:关联性负变是与精神医学和心理学关系最为密切的一种脑诱发电位。目的:探讨情感障碍患者与正常成人在关联性负变检测中的不同表现。设计:病例-对照实验。单位:山东省淄博市精神病医院功能科。对象:选择2005-02/2006-01在山东省淄博市第五人民医院就诊和住院的情感障碍患者29例,男14例,女15例,监护人均知情同意,所有患者均符合精神病诊断与分类手册DSM-IV的躁狂抑郁症诊断标准。将情感障碍患者按入院时的精神状态分为躁狂相和抑郁相2组。躁狂相组11例,Bech-Rataelson躁狂量表评分大于16分。抑郁相组18例,分为单相(目前抑郁以往无躁狂)11例及双相(目前抑郁有过躁狂)7例,汉密顿抑郁量表评分大于24分。选择27例身心健康的医院职工作为对照组,男14例,女13例,年龄21～53岁,平均年龄(32.5±5.9)岁,3组受试者年龄、性别差异无显著性。方法:实验在屏蔽的隔音室中进行,被试者坐于软椅上,双眼向前看一目的物,在实验过程中,保持清醒。记录电极用8mm铂金头皮电极,位置参照国际脑电图学会10/20标准。颅顶有效电极置于Cz,参考电极置于右乳突。两眉中点上2cm处接地。关联性负变波形用函数记录仪描记。标准的关联性负变模式由光信号及短声信号组成。闪光灯和扬声器置于被试者正后方,被试者双耳接受短声信号后,即用右手指按手握式电键,瞬时切断短声。从同步光信号发出开始,全程持续2500ms为一次关联性负变记录,每20次叠加为一轮实验。每例被试者接受2轮实验,实验结束后,以20μV标准电压输入上述系统作同样次数叠加处理,作为波幅测量标准。主要观察指标:各组受试者的关联性负变的潜伏期、波幅B、指令信号前负相期待波面积、指令信号后负变化面积。结果:纳入患者56例全部进入结果分析。躁狂相组患者关联性负变波幅B较对照组高[(22.8±4.8)μV;(16.0±5.7)μV;P<0.01],抑郁相组患者指令信号前负相期待波面积较对照组小[(292.8±161.6)μV2;(412.8±159.9)μV2;P<0.01],抑郁相组患者关联性负变指令信号后负变化潜伏期延长[(261.9±79.3)ms;(211.9±36.3)ms;P<0.05],抑郁相单相组比双相组的关联性负变指令信号后负变化潜伏期显著延长[(344.5±66.9)ms;(230.4±83.8)ms;P<0.01]。结论:关联性负变和指令信号后负变化等提示关联性负变潜伏期延长可能是抑郁相单相患者的素质标记,而关联性负变波幅的变化则可能是情感障碍患者的状态标记。     

Stereotyped topography of different elevated contingent negative variation components in children with migraine without aura points towards a subcortical dysfunction

Increased negativity during contingent negative variation (CNV) is thought to reflect abnormal neural activation in adult migraineurs' attention related processing. Findings in childhood and adolescence have yielded less clear results. This study characterizes the age-dependent development of CNV topography in migraine during childhood in order to elucidate the origin and cerebral generators of described CNV elevations. A large sample of children with primary headache (migraine with/without aura, tension type headache) and healthy controls aged 6-18 years was examined in a CNV paradigm using 64-channel high resolution DC-EEG. Patients were tested for diagnose-related topographic group differences of initial CNV (iCNV), late CNV (lCNV) and postimperative negative variation (PINV). All three CNV components of 6-11-year-old migraineurs without aura showed elevated negativity over the supplementary motor area (SMA) and around the vertex. Migraine children lacked age-dependent development of late CNV around Cz as previously reported. However, they showed a normal development of late CNV over pre-/primary motor cortex (MI). There was no marked elevation of iCNV amplitude over frontal areas (orienting reaction) nor specific amplitude elevations over "motor" or "sensory" areas during sustained attention (late CNV). Additional "pre-mature" activation e.g., in the locus coeruleus (leading to diffuse cortical activation summing up to a maximum over the vertex) or the basal ganglia (interacting with SMA) explained the rather stereotyped CNV elevation around the vertex better than a specific implication of the cortical systems responsible for orienting, motor preparation or sensory attention.     

Electrophysiological studies on headache: the contingent negative variation

The contingent negative variation (CNV) is a slow cortical potential recorded from the scalp. This method allows the pathophysiology of chronic headaches to be elucidated. When assessed during the pain-free interval patients suffering from migraine without aura show significantly more negative amplitudes than healthy controls. This negativity reflects the activity of cerebral noradrenergic systems. Some studies using repeated recordings of the CNV show a periodicity in amplitude change. When migraine patients are assessed a few days before a migraine attack occurs, they show pronounced negativity, which normalized during the attack. Despite these interesting findings that are based on group comparisons, evaluating the CNV on an individual basis does not allow specific conclusions. Thus, assessment of the CNV is an important tool to examine pathophysiological aspects of chronic headaches, but is not suitable as a diagnostic procedure.     

Contingent negative variation and efficacy of beta-blocking agents in migraine

Thirty-three patients with common migraine underwent contingent negative variation (CNV) recordings before receiving prophylactic beta-blocker treatment with either metoprolol (27 patients) or propranolol (6 patients) at mean daily dosages of 110 mg and 122 mg, respectively. After 3 months the therapeutic efficacy of the beta-blocker was assessed in each patient by means of a global severity score and compared with the initial CNV recordings. The mean clinical improvement was 62%. A significant positive correlation was found between CNV amplitude before prophylaxis and the clinical response to beta-blockers: patients with higher CNV tended to respond better to therapy. Eight of 10 patients with a CNV amplitude higher than -25 microV had a more than 50% reduction of the severity score--that is, a good or excellent response to the beta-blocking agent--whereas only 2 of 9 patients with an amplitude lower than -20 microV had a good response.     

Effects of rizatriptan on the contingent negative variation in healthy women

The effect of the antimigraine drug rizatriptan on the amplitude and habituation of the contingent negative variation (CNV) in healthy women was examined in a randomized, double-blind, placebo-controlled trial. The test persons were assigned either to a drug ( n  = 20) or a placebo group ( n  = 20). The CNV was recorded three times: before, directly after, and 24 h after drug or placebo intake. The CNV paradigm was presented in a standard, a cued and a choice version. Rizatriptan led to an increase of CNV amplitude that depended on the level of difficulty of the task. Whereas there was no drug effect in the standard version, an amplitude increase was obtained mainly in the choice task. The results are in line with the ceiling theory of migraine, which assumes a rise of CNV amplitude if the serotonin level is lowered.     

Brain activity relating to the contingent negative variation: an fMRI investigation

The contingent negative variation (CNV) is a long-latency electroencephalography (EEG) surface negative potential with cognitive and motor components, observed during response anticipation. CNV is an index of cortical arousal during orienting and attention, yet its functional neuroanatomical basis is poorly understood. We used functional magnetic resonance imaging (fMRI) with simultaneous EEG and recording of galvanic skin response (GSR) to investigate CNV-related central neural activity and its relationship to peripheral autonomic arousal. In a group analysis, blood oxygenation level dependent (BOLD) activity during the period of CNV generation was enhanced in thalamus, somatomotor cortex, bilateral midcingulate, supplementary motor, and insular cortices. Enhancement of CNV-related activity in anterior and midcingulate, SMA, and insular cortices was associated with decreases in peripheral sympathetic arousal. In a subset of subjects in whom we acquired simultaneous EEG and fMRI data, we observed activity in bilateral thalamus, anterior cingulate, and supplementary motor cortex that was modulated by trial-by-trial amplitude of CNV. These findings provide a likely functional neuroanatomical substrate for the CNV and demonstrate modulation of components of this neural circuitry by peripheral autonomic arousal. Moreover, these data suggest a mechanistic model whereby thalamocortical interactions regulate CNV amplitude.     

Contingent negative variation in subjects at risk for migraine without aura.

Migraine is a complex disease with a significant genetic background. One possible strategy to investigate the genetics of migraine is the evaluation of functional vulnerability markers or biological elementary endophenotypes in individuals with the greatest probability of developing the disorder (high-risk design). In this study the contingent negative variation (CNV) was recorded in 35 high-risk subjects with a positive family history of migraine without aura (FHP), 35 low-risk individuals without a positive family history (FHN), and 35 migraineurs (migraine without aura). FHP subjects and migraine patients differed significantly from FHN individuals with regard to amplitude and habituation slope of the early CNV component (initial CNV or iCNV). FHP participants demonstrated the same iCNV abnormalities and distribution among iCNV characteristics as migraineurs. The amplitude of the iCNV correlated significantly with the relative number of subjects suffering from migraine among first- and second-degree relatives. The higher the density of affected individuals in the family, the more pronounced were the CNV abnormalities in relatives. This study provides evidence that the familial factor contributes to the abnormal amplitude, and to a lesser degree, habituation of the iCNV, and that the iCNV may be used as a functional-genetic vulnerability marker in further research of migraine genetics.     

Preparatory visuo-motor cortical network of the contingent negative variation estimated by current density

The present report studied the intracerebral current density of the contingent negative variation (CNV) during a visuo-manual task using the gap paradigm. The CNV is usually obtained during preparatory periods for perception and action. In this experiment right-hand responses were required. The CNV potential was obtained during the preparatory period from electrodes placed at 58 scalp sites. The CNV showed an early and a late phase. Scalp voltage and source current density maps showed that the early phase was focused on frontal midline sites. The late phase had two foci, one overlying the primary motor cortex and one over occipital sites. When analyzed by low-resolution tomography, the early phase of the CNV showed activations in the supplementary motor area (SMA), the anterior cingulate cortex (ACC), and some posterior areas. The late phase had anterior activations in the left prefrontal cortex, middle frontal cortex, primary motor cortex, ACC, and SMA; and several posterior activations including those in the medial occipital cortex, middle inferior occipital cortex, posterior cingulate cortex, and temporal and parietal areas. Results from the activated areas and their temporal dynamics during the preparatory period suggest that the ACC and the SMA areas recruit the action- and perception-related areas needed to process the expected subsequent imperative task.     

Seasonal variation in migraine

Our group has previously shown that migraineurs, as opposed to individuals with other headaches, are more likely to have headache during the bright arctic summer than during the polar night season. We set out to investigate the impact of seasonal light exposure in migraine with and without aura. We performed a questionnaire-based study of 169 female volunteer migraineurs in an arctic area where light conditions during summer and winter seasons are extreme. We included 98 patients with migraine with aura (MA) and 71 with migraine without aura (MoA). One hundred and seven patients (63%) reported seasonal variation in migraine attack frequency. Close to half (47%) of patients with aura, but only 17% of patients without aura, reported more frequent attacks during the light season (P < 0.001). Patients with MA reported interictal light hypersensitivity and light exposure as an attack precipitating factor significantly more often than individuals with MoA. They also reported significantly more frequent use of sunglasses to prevent attacks. We found no significant differences between MA and MoA as regards sleep disturbances, use of oral contraceptives, impact of headache or circadian variations. Seasonal periodicity of migraine in an arctic population with more frequent attacks during the light season is a convincing phenomenon in MA but not in MoA. The amount of light exposure seems to be pivotal to this variation.     

脑电图、经颅多普勒及P300检测技术在偏头痛诊断中的应用价值、

目的探讨脑电图（EEG）、经颅多普勒（TCD）及P300检测技术诊断偏头痛的表现。方法选取2008年3月-2011年6月在神经内科门诊就诊的90例偏头痛患者为疾病组,90例健康体检者为对照组,两组均进行EEG、TCD、P300检测,并对临床检查结果进行分析。结果疾病组EEG异常率、TCD异常率均高于对照组（P〈0．05）;P300电位潜伏期、波幅与对照组比较有显著性差异（P〈0．05）;对P300靶刺激识别错误率高于对照组（P〈0．05）。结论脑电图、经颅多普勒和P300检测可以为偏头痛的临床诊断提供参考,多种检查技术结合患者的病史、临床表现等资料可以明确诊断,指导临床预防和正确治疗偏头痛。     

Contingent negative variation-findings and perspectives in migraine

Contingent negative variation (CNV) is a negative cerebral potential which is related to attention and arousal. CNV occurs during an experimental situation in which stimuli and responses are serially organized. Between attacks migraine patients have on average higher negative amplitudes compared to healthy controls or patients with tension-type headache. Successful treatment with beta-blocking agents decreases CNV amplitudes. In spite of encouraging findings in neurological disorders, CNV is not widely used. In this review some possible reasons for this are pointed out.     

应用P300电位变化评估消化道恶性肿瘤患者的负性情绪

目的:消化道恶性肿瘤患者负性情绪与其对疾病的认知状态相关,用P300可客观评估这一现象。方法:对60例消化道恶性肿瘤患者和62例健康志愿者分别进行了P300电位测定和负性情绪量表评定。结果:消化道恶性肿瘤组负性情绪比较明显。其P300电位成分中N2,P3波潜伏期[(246.1±23.0)ms和(339.7±26.6)ms]延长,P3波幅[(3.14±2.01)μV]降低,与对照组比较差异有显著性意义(t=2.53～14.23,P<0.01或P<0.05)。结论:P300电位可作为消化道恶性肿瘤患者的认知状况的评价指标。     

Minipig negative slow wave demonstrates target/nontarget differences in P300 paradigm

The negative slow wave (NSW) is a late component of the event-related potential (ERP) in man modulated like the P300 by the stimulus, the task, and the response demand. Aiming at the development of a minipig model of schizophrenia, we investigated scalp ERPs in an auditory P300 paradigm in six G?ttingen minipigs. Before training, we observed no difference between target and nontarget NSW. After training, target NSW amplitude was increased 50% compared to nontarget. A P350 was recognized, but the finding of a lack of target/nontarget difference is not conclusive.