Habituation Of Contingent Negative Variation Research Articles

Disease duration of episodic migraine correlates with modified amplitudes and habituation of contingent negative variation.

Cortical habituation in episodic migraine patients without medication overuse headache (MOH), recorded by contingent negative variation (CNV), is often reduced compared with healthy controls. There is evidence that with longer duration of migraine disease (DOD) amplitudes and habituation of CNV become progressively abnormal. The aim of the study was to examine habituation characteristics of contingent negative variation in episodic migraine patients suffering from short- and long-lasting migraine compared to matched healthy controls. 32 migraine patients without aura and without MOH diagnosed according to the revised ICHD-II criteria and 16 age- and sex-matched healthy controls were included. According to DOD, the total sample of migraine patients was divided into two groups (group a: DOD <121 months, n = 17 subjects, group b: DOD >120 months, n = 15 subjects). Both migraine groups did not differ in the number of days of migraine and the duration of attacks. Overall CNV and initial CNV differed significantly between migraine patients and controls, whereas the former produced more negative amplitudes. In the migraine group lack of or deficient habituation occurred, whilst controls showed habituation. There were middle range correlations between the DOD and overall CNV, initial CNV, and y-intercept. Patients suffering from long-lasting migraine produced higher CNV amplitudes with a higher y-intercept. The results are interpreted as "maladaptive plasticity" with a risen intercept in long-lasting migraine.

Behavioural treatment programme contributes to normalization of contingent negative variation in children with migraine

Migraine is a disorder of central information processing which may be characterized by increased amplitudes and reduced habituation of evoked and event-related potentials. In this pilot study, special behavioural training of habituation to aversive stimuli (MIPAS-Family = Migraine Patient Seminar for Families) was developed and proven effective in children suffering from migraine without aura. 13 children with migraine participated in the MIPAS-Family programme and 13 other children with migraine were treated with biofeedback. The influence of both treatments on abnormal cortical information processing in migraine was assessed using recordings of the contingent negative variation (CNV), an event-related slow cortical potential. Both MIPAS training and biofeedback caused an equal reduction of migraine frequency and severity. However, MIPAS treatment was associated with a significant increase in iCNV habituation. Changes in the clinical course of migraine correlated positively with normalization of habituation: the greater the reduction in headache frequency, the greater the increase in CNV habituation was. These effects were not observed in the biofeedback group. This study demonstrates that the specific treatment programme which was evolved from knowledge of pathogenetic mechanisms of migraine influences central information processing and leads to a clinical effect.

Effects of Pregnancy on Slow Cortical Potentials in Migraine Patients and Healthy Controls

Increased negative amplitudes and lack of habituation of contingent negative variation (CNV) in migraine are well established and are supposed to reflect an altered cortical excitability level. Migraine attacks occur less during pregnancy but often relapse after delivery. We investigated the effect of pregnancy on slow cortical potentials and reaction time in migraine patients and healthy controls. Four groups were examined: 14 pregnant migraine patients, 12 non-pregnant migraine patients, 15 pregnant healthy women and 16 non-pregnant healthy women aged 19-38 years. Two recordings were performed in the pregnant subjects: in the 36th week of gestation and 4 weeks after delivery. The non-pregnant subjects were recorded at the same time interval of 8 weeks. Pregnant migraine patients showed significantly fewer migraine days during the third trimester of pregnancy and returned to nearly the former level 4 weeks post delivery. Non-pregnant migraine patients demonstrated a significant reduction of migraine days at the second measurement. There was no effect of pregnancy on CNV amplitudes, but there was an effect of pregnancy on the habituation coefficient and reaction time of migraine patients. Faster habituation from a higher preactivation level was found. As an explanation for the changed habituation level we favour the model of correlation between preactivation level and habituation level, the so-called law of initial value. We found a correlation between preactivation level and habituation. Our study confirms a specific effect of pregnancy on slow cortical potentials in migraine patients.

Effects of topiramate and levetiracetam vs placebo on habituation of contingent negative variation in migraine patients

Migraine is characterized by reduced habituation of multimodal evoked potentials, which in turn reflects an abnormal pattern of cortical excitability. We assessed the effects of a 2-month treatment with topiramate or levetiracetam vs placebo on contingent negative variation (CNV) habituation and amplitude in a cohort of migraine without aura (MO) patients. Forty-five MO patients were selected from a university-based outpatient clinic and randomly assigned to 100mg topiramate or 1000mg levetiracetam or placebo in a double-blind design. Twenty-four control subjects were also recruited. The initial CNV (iCNV) amplitude and habituation were assessed by Cz/A1-A2 derivation recordings in the basal condition (T0) and after 2 months of treatment (T1). Both topiramate and levetiracetam produced a significant reduction in migraine frequency compared to placebo, they also reversed the abnormal iCNV habituation pattern which characterized the MO patients in the basal condition and which was not present in controls. For migraine patients, the reduced migraine frequency and habituation index following treatment were significantly correlated. A lack of habituation of evoked responses is an interictal endophenotypic marker in migraine, the reversion of which may improve disease outcome. These results suggest a role for neurophysiological methods in the management of migraine.

Central Mechanisms of Controlled-Release Metoprolol in Migraine: A Double-Blind, Placebo-Controlled Study

beta-Blockers are widely used in the prophylaxis of migraine and have been described as very effective drugs in many studies. Some investigators have demonstrated that the clinical improvement of migraine corresponds to the normalization of the contingent negative variation (CNV), a slow cortical potential measuring cortical information processing. However, most of these studies have contained a variety of methodological pitfalls, which we attempted to address in the current study. Twenty patients suffering from migraine without aura were randomly divided into two groups. The groups were treated either with controlled-release metoprolol or placebo for 3 months, using a double-blind design. Twice before and once after each month of the treatment the CNV was recorded. After 3 months, a significant reduction of migraine frequency, duration and intensity was demonstrated for the metoprolol compared with the placebo group. The CNV was characterized by a marked reduction of the amplitude of the total CNV and postimperative negative variation and normalization of the eartly CNV habituation following treatment. Therefore, metoprolol may exert its prophylactic effect in migraine through the influence on cortical information processing and excitability represented by the CNV.

Influence of MTHFR Genotype on Contingent Negative Variation And MRI Abnormalities in Migraine

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. 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. 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. 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. 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.

Slow cortical potentials in migraine families.

Amplitude and habituation of event-related potentials are abnormal in migraine. We investigated 43 migraine and 41 healthy families to evaluate the influences of age, sex and familial contribution on the variance of amplitude and habituation of the contingent negative variation (CNV). Analysis of individual differences in relation to the CNV habituation was performed. The study demonstrated that habituation of the early CNV component characterizes migraine considerably better than the CNV amplitudes. Habituation, however, is strongly influenced by age. Migraine adults and children generally showed reduced habituation. Surprisingly, more than 30% of the healthy adults demonstrated a marked loss of habituation. The reduced CNV habituation represented a high sensitivity but low specificity to migraine, especially in children. CNV amplitude and habituation parameters revealed a considerable familial contribution associated with migraine. No familial influence on either morphology or habituation of the CNV in healthy families or between healthy members of migraine families was observed. The low specificity and familial transmission of CNV parameters in members of migraine families suggest that increased amplitudes and reduced habituation of CNV do not constitute a primary risk factor for migraine, but rather represent a predisposition. Genetic components probably affect variation of the CNV amplitude and habituation.

Are the periodic changes of neurophysiological parameters during the pain-free interval in migraine related to abnormal orienting activity?

Migraine patients are characterized by increased amplitude and reduced habituation of contingent negative variation (CNV). Furthermore, the CNV underlies periodic changes during the pain-free interval, being maximal before attack. The periodicity of CNV is related to periodic changes in habituation, probably due to variation of orienting activity during the pain-free interval. CNV and orienting response (OR) were studied in 20 females suffering from migraine without aura and in 12 matched healthy females. The neurophysiological recordings in the group of patients were performed 1-4 days before and 4 days after a migraine attack. The amplitudes and habituation of early and late components and total CNV were calculated. The OR was assessed using the habituation of the skin conductance response (SCR) and alpha blocking (AB). The non-parametric tests were employed for statistical analysis. There were no differences between the two groups for habituation of all CNV components and of SCR following an attack. However, the habituation of AB was significantly reduced in migraine. Before attack we observed a significantly reduced habituation of the early and total CNV and of the AB compared to controls and recordings performed after an attack. The habituation of the late component and of SCR remained unchanged. The abnormal habituation could be explained by the periodic changes of physiological parameters during the pain-free interval. The impaired habituation of early CNV in migraine is associated with increased orienting activity seen only in the central component (AB) of OR.

Migraine in childhood – are periodically occurring migraine attacks related to dynamic changes of cortical information processing?

Amplitudes and habituation of contingent negative variation (CNV) were analyzed in relation to spontaneously occurring migraine attacks in ten children suffering from migraine without aura. Recording took place during feedback training and instrumental conditioning of slow brain potentials. Both the amplitude of the early CNV component and its habituation deficit increase during the 5 days prior to a migraine attack, with maximum abnormalities the day before the ictal episode. Abrupt reduction of the amplitude and normalization of the CNV habituation were observed during the attack. This study provides evidence for neurophysiological periodicity in young migraineurs and emphasizes that the time relative to the migraine attacks must be considered in studies of juvenile migraine during the headache-free period.

Contingent negative variation in patients with chronic daily headache.

The aim of this study was the investigation of amplitude and habituation of contingent negative variation (CNV) in migraine and chronic daily headache (CDH) patients in order to describe possible neurophysiological features responsible for the clinical transformation and worsening of the headache. Fifteen females suffering from migraine without aura and 15 females diagnosed with CDH evolved from migraine without aura with interparoxysmal chronic tension-type headache (transformed migraine), underwent CNV recording. Fifteen healthy females matched for age served as controls. CNV was obtained from C3 and C4 using the standard reaction time paradigm and 3 sec ISI. The amplitudes and habituation of total CNV, early and late components, and of post-imperative negative variation (PINV) were calculated. The migraine patients were characterized by significantly more pronounced negativity of the early component and total CNV, compared to CDH sufferers and controls. CDH patients demonstrated significantly reduced negativity of the late component and pronounced PINV compared to the other groups. The early component of CNV did not habituate in migraine or CDH patients. However, the impaired habituation in CDH was related to significantly lower amplitudes. These results support the diagnostic and scientific value of habituation in migraine research and therapy. Late components of CNV and PINV can be considered as predictive variables for transformation of migraine. The results are discussed in terms of the relationship between late CNV, PINV, environment control abilities and susceptibility for development of depression.

Potentiation instead of habituation characterizes visual evoked potentials in migraine patients between attacks

We have studied habituation of the pattern-reversal visual evoked potential (VEP) in healthy volunteers (n = 16) and in patients suffering from migraine without (n = 27) or with aura (n = 9). Five blocks of 50 responses at a stimulation rate of 3.1 Hz were sequentially averaged and analyzed separately for latencies, peak-to-peak amplitudes of N1-P1 and P1-N2, and the area under the N2 component Latencies of N1, P1, or N2 components were not significantly different between the sequential trial blocks, or between groups. Mean amplitudes of N1-P1 and P1-N2 in the first and subsequent blocks of SO responses were not statistically different among groups. In healthy subjects, there was a decrement of N1-P1 and P1-N2 amplitudes and N2 area on successive averagings. This habituation was maximal in the third and fourth blocks, but tended to disappear in the fifth block. In marked contrast to healthy subjects, migraine patients were characterized by a transient amplitude increment (i.e. potentiation) of VEP components which reached its maximum in the second to fourth blocks. Amplitude changes in sequential blocks were not dependent on attention and differed significantly between healthy subjects and migraineurs, but not between migraine with and without aura. Taken together with previous studies showing deficient habituation of contingent negative variation in migraine, these results indicate a dysfunction of central information processing which might have behavioral and pathogenic correlates.