Early Contingent Negative Variation Research Articles

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.

Reduced activation of midline frontal areas in human elderly subjects: a contingent negative variation study

Contingent negative variation (CNV) was recorded from electrodes F7, F3, Fz, F4, F8, T7, C3, Cz, C4, T8, P7, P3, Pz, P4 and P8 in 19 young (mean age: 23 years) and 15 elderly (mean age: 66 years) healthy right-handed subjects, using a S2-choice paradigm. Young subjects showed early peak negativity shortly after the warning stimulus over mid-frontal areas, whereas for the remaining electrodes the negativity increased continuously. The amplitude of the early CNV was selectively reduced in elderly subjects over midline but not lateral frontal areas. We conclude that the activation of frontal midline areas as pre-supplementary motor area or anterior cingulate might be impaired in higher age.

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 children with anorexia nervosa.

Central catecholamines, particularly dopaminergic and noradrenergic systems, have affected the appetitive behavior in patients with anorexia nervosa (AN). The purpose of this study is to distinguish the characteristics of contingent negative variation (CNV) and postimperative negative variation (PINV), which may reflect the level of catecholamine in children with AN. Eight children with AN aged 10 to 15 years and 23 age-matched healthy children were recruited. Contingent negative variation was recorded from the frontal midline (Fz), central midline (Cz) and parietal midline (Pz) referenced to linked earlobes during 30 trials consisting of a warning stimulus and an imperative stimulus with an interstimulus interval of 2 s and an intertrial interval of 10 s. The imperative stimulus of each trial required a button press. Children with AN had a diminished amplitude of the CNV. They had a significantly more attenuated early CNV and late CNV amplitude at Cz than normal children. No significant differences were observed between AN children and normal children in the amplitude of PINV at all three electrode sites. No difference could be found between the two groups in the frequencies of normal and abnormal duration of PINV. These findings suggest that early CNV may be diminished by norepinephrine deficiency and late CNV may be attenuated by dopaminergic deficiency in children with AN. Reduced CNV may represent impaired cognitive processes which reflect impaired appetitive behavior in AN children.

Contingent negative variation indicates phasic arousal for externally cued unilateral eye blink in human subjects

The contingent negative variation (CNV) as a slow cortical potential was used to investigate cortical processing of externally cued, voluntary unilateral eye blink. Probands blinked as a response within a modified two-stimulus reaction time paradigm. Reaction time and amplitudes of CNV were determined. The activity of the orbicularis oculi muscles (OO) was registered by surface electromyography (EMG). Probands who performed unilateral eye blinks with accurately inhibiting contralateral OO activity showed a significantly higher negativity of the early CNV component compared with the bilateral eye blink condition. This effect was confined to the beginning of unilateral blinking performance. It is suggested that the unilateral eye blink is a challenging motor task, initially requiring an increased cortically driven arousal and attention as revealed by increased early CNV components.

Correlation between contingent negative variation and regional cerebral blood flow.

The relationship between contingent negative variation (CNV) and regional cerebral blood flow was investigated, using the stable xenon computed tomography method. Seventeen cases of chronic multiple cerebral infarction in the perforating artery areas (vascular dementia, mean age 67.0), 6 cases of Alzheimer's disease (mean age 69.5) and 8 healthy controls (mean age 62.5) were studied. Regional cerebral blood flows in the frontal, temporal, parietal and occipital cortex, frontal, temporal and occipital white matter, caudate nucleus, putamen and thalamus were measured. The amplitude of early CNV was significantly smaller in the vascular dementia group than in the healthy control group. The blood flows in the parietal cortex and thalamus were significantly lower in the vascular dementia group than in the healthy control group. There was a significant positive correlation between the amplitude of early CNV and frontal cortex blood flow. No significant correlations were present between the CNV and the other regional cerebral blood flows nor in healthy controls. The amplitude of CNV has been reported to be decreased in dementia. From the present study, the amplitude of early CNV was considered to be influenced by the blood flow in the frontal cortex.

Event-Related Potentials Associated With Judgment: Comparison of S1- and S2-Choice Conditions in a Contingent Negative Variation (CNV) Paradigm

To elucidate the functional role of association cortex in judgment and decision-making about external stimuli, the scalp topography of contingent negative variation (CNV) recorded in 9 normal volunteers was compared in two settings; dichotomous S1- and S2-choice paradigms using right wrist extension or flexion movement upon S2 as the choice reaction task with an S1-S2 interstimulus interval of 2 s. Two main findings were obtained. First, early CNV in the S1-choice paradigm consisted of a frontal to frontopolar midline negative potential, most likely representing judgment more than orienting response, and a left-sided parietal positive potential, at least partially representing P3b, whereas in the S2-choice paradigm it consisted only of a smaller frontal negative potential shift, most likely representing merely an orienting response. This suggests that the prefrontal and left parietal association cortexes might be active in the judgment and decision-making process. Second, after S2, two positive peaks (334 and 545 ms after S2) were observed at the midline central to left parietal areas only in the S2-choice paradigm. In the S1-choice paradigm, one large negative peak (275 ms after S2) was observed. We postulate that the first peak of the S2-choice paradigm is related to decision making or judgment and that the second peak is related to the following cognitive process. We conclude that at least the prefrontal and parietal association cortexes generate transient potentials accompanying judgment, and possibly decision making.

Effects of reduction in arousal level caused by long-lasting task on CNV.

The present study aimed at investigating an inverted-U relationship between contingent negative variation (CNV) and arousal level by examining the effects on CNV of gradually reduced arousal level by long-lasting task. The subjects conducted a simple reaction time task consisting of warning stimuli (S1) and imperative stimuli (S2). This task consisted of 200 trials and lasted about 40 minutes. During this task, spontaneous EEG before S1 and SPL (skin potential level) were measured as indicators for arousal level. The 200 CNV, EEG and SPL data were classified into 5 blocks each of which included 40 trials of data. Analysis was made in seven subjects in whom reduction in the arousal level in long-lasting task was shown by increase in the relative power values of alpha waves before S1 and decrease in the SPL. As a result, the amplitude of early CNV at Fz was observed to increase from the earlier half phase (block 1) to the middle phase (block 3) and to decrease from the middle phase (block 3) to the latter half (block 5). In the middle phase, the amplitude was the greatest. The low amplitude of early CNV in the early half of the task (block 1) was inferred to have been induced by excessive arousal state because of the low relative power values of alpha waves and the high SPL at this time. On the other hand, the low amplitude in the later phase (block 5) was inferred to have been induced by reduction in arousal level because of the high relative power values of alpha waves and the low SPL. These results suggested that CNV amplitude and arousal level was in an inverted-U relationship.

Effects of changes in arousal level by continuous light stimulus on contingent negative variation (CNV).

The purpose of the present study was to investigate an inverted-U relationship between contingent negative variation (CNV) and arousal level which was influenced by extraneous environment. As an extraneous stimulant, stimulation by light was adopted, and five levels of luminance conditions, 10 cd/m2, 100 cd/m2, 320 cd/ m2, 1,000 cd/m2, and 1,800 cd/m2 were provided randomly. Under five luminance conditions, seven subjects who had been accustomed a measurement of CNV executed simple reaction time tasks to evoke CNV. Outside CNV, spontaneous EEG prior to S1 was measured as an indicator for arousal level. As a result, a negative correlation existed between the logarithm of luminance and the relative power value of alpha waves at Fz. Otherwise, an increase in luminance caused an increase in CNV amplitude until the luminance level reached 320 cd/m2, beyond which however CNV amplitude was found to decrease. These tendencies were most remarkable in the phase of early CNV at Fz. The low amplitude of early CNV seen in the high luminance conditions was inferred to have been induced by excessive arousal state because of the low relative power value of alpha waves, while the low amplitude in the low luminance conditions was inferred to have been induced by low arousal state because of the high relative power value of alpha waves. However, changes in arousal level by light stimulus caused no effect on reaction time. From these findings, it was suggested that a definite "inverted-U" relationship existed between the change in arousal level by light stimulation and resultant CNV, and that it could be discriminated as to whether reduction in CNV is caused by excessive arousal effect of environment by analyzing spontaneous EEG preceding S1.

Early contingent negative variation (CNV) shows symmetrical negativity in a somatosensory paradigm

Early contingent negative variation (CNV) shows symmetrical negativity in a somatosensory paradigm

木質材料 針葉樹材のニオイが随伴性陰性変動（ＣＮＶ）に及ぼす影響

In order to clarify the effect of odors of seven coniferous woods on human, contingent negative variation (CNV) and electroencephalogram (EEG) were measured. Four of the species used, hinoki (Chamaecyparis obtusa), sugi (Cryptomeria japonica), akamatsu (Pinus densiflora), and hiba (Thujopsis dolabrata var. hondai), were grown in Japan, and three of them, Alaska cedar (Chamaecyparis nootkatensis), Douglas fir (Pseudotsuga menziesii), and western red cedar (Thuja plicata), were grown in the United States. The concentrations of their wood odors were analysed by gas-liquid chromatography. The total concentration of monoterpene hydrocarbon in the wood odors was held to less than 3ppb.The amplitudes of early components of CNV and the α/β wave ratio of EEG at the frontal (Fz) and central (Cz) regions between in the presence and absence of wood odors were compared. 5 male and 5 female volunteers ranging in age from 20 to 26 were examinated. The result obtained are summerized as follows:(1) In the presence of wood odors, the early CNV amplitudes at Fz decreased at a statistical level of significance of 5% or better.(2) The α/β wave ratio of EEG increased significantly at Cz with hiba wood odor (p<0.01).(3) The decrease of the early CNV amplitude at Fz is related to the concentration of α-pinene in the wood odors.

Contingent negative variation and movement-related cortical potentials in parkinsonism

The contingent negative variation (CNV) and movement-related cortical potentials (MRCPs) were recorded in 10 cases of Parkinson's disease, 10 cases of vascular parkinsonism and 10 age-matched healthy controls. The amplitude of the early CNV was smaller in the Parkinson's disease group and the vascular parkinsonism group than in the healthy control group. The latencies of Bereitschaftspotential (BP) and negative slope (NS′) were longer and the amplitude of BP was smaller in the Parkinson's disease group and the vascular parkinsonism group than in the healthy control group. These abnormalities in CNV and MRCPs were improved by intravenous injection of l-DOPA.

PS-13-1 Early contingent negative variation (CNV) is small in a somatosensory paradigm

A novel discriminant method, termed local discriminative spatial patterns (LDSP), is proposed for movement-related potentials (MRPs)-based single-trial electroencephalogram (EEG) classification. Different from conventional discriminative spatial patterns (DSP), LDSP explicitly considers local structure of EEG trials in the construction of scatter matrices in the Fisher-like criterion. The underlying manifold structure of two-dimensional spatio-temporal EEG signals contains more discriminative information. LDSP is an extension to DSP in the sense that DSP can be formulated as a special case of LDSP. By constructing an adjacency matrix, LDSP is calculated as a generalized eigenvalue problem, and so is computationally straightforward. Experiments on MRPs-based single-trial EEG classification show the effectiveness of the proposed LDSP method.

Contingent negative variation during migraine attack and interval: evidence for normalization of slow cortical potentials during the attack.

The contingent negative variation (CNV) amplitudes of 16 subjects with migraine without aura were studied during pain-free intervals and during attacks and the results were compared with those of 22 healthy subjects. In 32 trials the CNV amplitudes were calculated for (a) "total interval", (b) "early CNV component", (c) "late CNV component", and (d) habituation. There was a significantly higher total CNV amplitude in migraine subjects during pain-free intervals compared to that of the healthy subjects and migraine patients during an attack. Healthy subjects as well as subjects studied during the attack showed a significant habituation whereas migraine subjects studied during pain-free intervals did not. This suggests that the higher CNV amplitude in migraine patients studied between pain-free attacks may be due in part to impaired habituation.

Impulsivity, mood and the contingent negative variation in women with and without premenstrual changes in impulsive behaviour

Contingent negative variation (CNV), postimperative variation (PIV) and reaction time (RT) were recorded in a signalled Go/No Go avoidance paradigm, verbal and visuo-spatial versions of a match/mismatch paradigm, and an auditory forewarned RT paradigm at 3 menstrual cycle phases—menstrual, mid-cycle and premenstrual—in 3 samples of women: women without significant premenstrual changes (PMCs) in mood and behaviour; women with documented PMCs in mood and behaviour excluding premenstrual impulsivity; and women with documented PMCs in mood and behaviour including changes in impulsive behaviour. Subjective stress and arousal were also measured at each cycle phase. Recordings were repeated in a small sample of women with PMCs during treatment with fluoxetine/ placebo. There was no relationship between either state or trait measures of impulsivity and Go/No Go CNV, in contrast with previous findings in males. MANOVA revealed significant Group × Phase interactions for early CNV amplitude and laterality in the forewarned RT paradigm, and for subjective stress, supporting a “disordered state regulation” hypothesis of premenstrual syndrome (PMS). Other measures (subjective arousal, PIV in the Go/No Go paradigm) showed significant effects of Group independent of cycle phase, with PMS groups showing lower arousal and greater postimperative positivity than controls.

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.

Changes in bit-mapped contingent negative variation (CNV) activity due to initial normal involutional processes of the human brain

Bit-color mapped multicomponent CNV complexes and RTs to S2 evoked with a simple warned CNV/RT paradigm were recorded and measured in 20 selected right-handed very healthy volunteers (10 young adults and 10 presenile subjects, mean age 28.3 and 59.6, respectively). EEG and CNV components (post S1, N1, P2, P3; early CNV; N1200; late CNV; CNV resolution) were recorded from Fz, C3, Cz, C4, P3, Pz, and P4 referenced to linked mastoid electrodes. EOG, RT and stimuli were also recorded. The presenile group differed significantly from the younger group in the auditory post-S1 N1 and early (O-wave) and late (P-wave) CNV complex components. A progressive amplitude reduction limited to frontal leads between O-wave and P-wave, the lowest point being reached in the P-wave, was characteristic in the presenile group. Moreover, presenile subjects showed relatively flat CNV waveshapes of low amplitude and, on the whole, performed a little less well than young ones. This finding suggests that the statistically significant changes in auditory post-S1 N1 and CNV activity recorded in our presenile subjects, without any appreciable deficits in behavioral or mental performance, could be alerting signs of early brain involutional processes related to minimal and subclinical decline in orienting, attentiveness and response preparation capabilities. If such is the case, and it could be confirmed in a larger sample of very healthy subjects, these age-related changes in the presenium might prove to be of considerable practical importance for clinical research.

随伴陰性変動(CNV)の意義と臨床応用

In this review, we discuss the psychophysiological properties of human contingent negative variation (CNV) observed during S1-S2 (warning stimulus-imperative stimulus)tasks. The CNV can be divided into three components. The early CNV seems to be induced by S1 and be associated with the information processing of the S1. The middle component, which emerges between the early and late CNV may be also induced by S1. Its nature and properties are, however, not fully understood. The late CNV may be induced by S2 and seems to be related to the attention paid to the S2 as well as to the preparation for the motor response.We also provided an overview of studies of CNV under psychopathological conditions in adults subjects. The abnormal features of the CNV described in psychiatric patients are related to its amplitude (often decreased, but sometimes increased) and its duration after the imperative stimulus (S2).In the field of otolaryngology, CNV is used in objective audiometry for psychogenic deafness and in objective olfactory sensory testing.In our study, CNV amplitude was larger for tinnitus patients with no hearing loss than in controls. This results is interpreted as evidence of abnormalities in the central orienting mechanism in such tinnitus patients.

The contingent negative variation in psychopaths.

There have been persistent claims that the contingent negative variation (CNV) is absent or greatly attenuated in psychopaths. However, these claims are based on a few studies with serious methodological and diagnostic problems. The present study attempted to avoid these problems. The subjects were male prison inmates divided into psychopaths and nonpsychopaths on the basis of scores on the Psychopathy Checklist. CNV was recorded while the subject performed a forewarned reaction time task with a relatively long interval (6 s) between the warning stimulus and the imperative stimulus. Motivation to perform well was ensured by having reaction times to the imperative stimulus determine how much money would be won or lost on a given trial. The early CNV of psychopaths was significantly larger than was that of the nonpsychopaths. There were no group differences in the late CNV or in reaction time. To the extent that the early CNV reflects processing of the warning stimulus and attention to task demands, the results are consistent with the hypothesis that psychopaths are proficient at focusing attention on events that interest them.

CNV abnormalities following closed head injury.

Event-related potentials (ERPs) were recorded in a GO/NO-GO reaction time task from 20 closed head injury patients, at least 6 months postinjury, and from 20 controls. In this task the pitch of an initial tone (Sl) indicated whether or not a response was required to a second tone (S2) occurring 1.5 s later. In the control group both the early, frontal-maximum, and the later vertex-maximum, components of the contingent negative variation (CNV) were larger on GO than NO-GO trials. In the patients, the early frontal CNV wave did not differentiate GO and NO-GO trials, and the late CNV showed a smaller separation between these trial types than did the late CNV of the control group. These CNV abnormalities may reflect impairments in selectively orienting to salient stimuli, and in differential response preparation. Such impairments might in turn reflect the damage to the frontal lobes and/or their connections that commonly occurs as a result of closed head injury.